EGFR

Summary

EGFR (epidermal growth factor receptor, HGNC:3236) is a protein-coding gene on chromosome 7p11.2, encoding Epidermal growth factor receptor (P00533). Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. In precision oncology, EGFR L858R confers sensitivity to Erlotinib in Lung Non-small Cell Carcinoma (CIViC Level A); 302 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 17.5% of cell lines).

The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor, thus inducing receptor dimerization and tyrosine autophosphorylation leading to cell proliferation. Mutations in this gene are associated with lung cancer. EGFR is a component of the cytokine storm which contributes to a severe form of Coronavirus Disease 2019 (COVID-19) resulting from infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Source: NCBI Gene 1956 — RefSeq curated summary.

At a glance

• Gene–disease (curated): non-small cell lung carcinoma (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 35 (top 3% of genes corpus-wide)
• Clinical variants (ClinVar): 4,015 total — 61 pathogenic, 38 likely-pathogenic (top 1% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 7 regions constrained (≈4% of expected missense variation)
• GTEx eGene: eQTL in 30 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 21
• Drug target: yes — 70 curated mechanism-of-action drugs, 4 via a complex or family; 175 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 15 — Afatinib Dimaleate, Amivantamab, Brigatinib, +12 more
• Approved drugs acting on a complex or family including it: 1 — Vandetanib (Epidermal growth factor receptor)
• Precision-oncology evidence (CIViC): 303 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 13 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 17.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.98 (loss-of-function intolerant), LOEUF 0.47 (moderately constrained)
• MANE Select transcript: NM_005228
• Interaction hub: 10,618 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3236
Approved symbol	EGFR
Name	epidermal growth factor receptor
Location	7p11.2
Locus type	gene with protein product
Status	Approved
Aliases	ERBB1, ERRP
Ensembl gene	ENSG00000146648
Ensembl biotype	protein_coding
OMIM	131550
Entrez	1956

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 16 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000275493

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 3: 2, TSL 4: 2

ENST00000275493, ENST00000342916, ENST00000344576, ENST00000420316, ENST00000450046, ENST00000455089, ENST00000459688, ENST00000463948, ENST00000485503, ENST00000700144, ENST00000700145, ENST00000700146, ENST00000700147, ENST00000898199, ENST00000898200, ENST00000898201, ENST00000898202, ENST00000998125, ENST00001110465, ENST00001112636, ENST00001118378, ENST00001124896, ENST00001134423

RefSeq mRNA: 9 — MANE Select: NM_005228 NM_001346897, NM_001346898, NM_001346899, NM_001346900, NM_001346941, NM_005228, NM_201282, NM_201283, NM_201284

CCDS: CCDS47587, CCDS5514, CCDS5515, CCDS5516, CCDS87507, CCDS94105

Canonical transcript exons

ENST00000275493 — 28 exons

Exon	Start	End
ENSE00001084926	55157663	55157753
ENSE00001084927	55163733	55163823
ENSE00001084929	55156533	55156659
ENSE00001084931	55156759	55156832
ENSE00001084939	55161499	55161631
ENSE00001084941	55160139	55160338
ENSE00001245887	55205256	55211628
ENSE00001601336	55181293	55181478
ENSE00001623732	55154011	55154152
ENSE00001627115	55165280	55165437
ENSE00001631695	55192766	55192841
ENSE00001652975	55152546	55152664
ENSE00001681524	55191719	55191874
ENSE00001683983	55151294	55151362
ENSE00001704157	55143305	55143488
ENSE00001751179	55155830	55155946
ENSE00001756460	55174722	55174820
ENSE00001768076	55171175	55171213
ENSE00001773562	55201735	55201782
ENSE00001778519	55173921	55174043
ENSE00001790701	55200316	55200413
ENSE00001795780	55202517	55202625
ENSE00001798125	55146606	55146740
ENSE00001801208	55201188	55201355
ENSE00001841347	55019017	55019365
ENSE00002684637	55172983	55173124
ENSE00003541288	55142286	55142437
ENSE00003625684	55198717	55198863

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8363 / max 1327.4558, expressed in 1335 samples.

Highest expression (Bgee): nipple, gingiva, gingival epithelium, placenta, mammalian vulva.

Genetic regulation across tissues (GTEx eQTL / sQTL)

EGFR is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 35 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cortex	eqtl	2.1e-15	-0.49	7:54853213:C:T
Nerve Tibial	eqtl	2.9e-13	+0.21	7:55151918:A:G
Adipose Subcutaneous	eqtl	6.8e-12	-0.16	7:55120299:G:A
Brain Nucleus accumbens basal ganglia	eqtl	2.5e-11	-0.40	7:54886678:G:A
Skin Sun Exposed Lower leg	eqtl	4.9e-10	+0.15	7:55152484:A:G
Skin Sun Exposed Lower leg	sqtl	9.9e-10	-0.33	7:55186493:G:A
Brain Frontal Cortex BA9	eqtl	3.3e-09	-0.28	7:54877227:C:T
Brain Anterior cingulate cortex BA24	eqtl	1.3e-07	-0.35	7:54853213:C:T
Skin Not Sun Exposed Suprapubic	eqtl	4.2e-07	+0.14	7:55152484:A:G
Cells Cultured fibroblasts	eqtl	5.8e-07	+0.16	7:54960781:C:G
Brain Cerebellum	eqtl	7.4e-07	-0.30	7:54853213:C:T
Brain Caudate basal ganglia	eqtl	2.9e-06	-0.35	7:54853213:C:T
Brain Putamen basal ganglia	eqtl	3.7e-06	-0.38	7:54853213:C:T
Artery Tibial	eqtl	1.5e-04	+0.14	7:55077641:G:A
Brain Hypothalamus	eqtl	1.7e-04	-0.29	7:54853213:C:T
Pancreas	eqtl	1.8e-04	+0.62	7:54963313:C:T
Spleen	eqtl	1.8e-04	+0.16	7:54866438:C:CAGA
Cells Cultured fibroblasts	sqtl	4.1e-04	+0.39	7:55159371:T:C
Heart Left Ventricle	eqtl	5.7e-04	-0.14	7:55118911:AG:A
Thyroid	eqtl	7.6e-04	+0.49	7:55109539:G:A

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
78694	22.5493	1309
78696	1.6755	640
78693	1.6234	815
78695	0.7656	377
78714	0.1945	98
78709	0.0280	6

Top tissues by expression

showing 100 of 298 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	99.12	gold quality
gingiva	UBERON:0001828	98.63	gold quality
gingival epithelium	UBERON:0001949	98.62	gold quality
placenta	UBERON:0001987	98.56	gold quality
mammalian vulva	UBERON:0000997	98.48	gold quality
tongue squamous epithelium	UBERON:0006919	98.32	gold quality
skin of hip	UBERON:0001554	98.28	gold quality
superficial temporal artery	UBERON:0001614	97.94	gold quality
decidua	UBERON:0002450	97.78	gold quality
penis	UBERON:0000989	97.65	gold quality
pharyngeal mucosa	UBERON:0000355	97.63	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.49	gold quality
urethra	UBERON:0000057	97.31	gold quality
saphenous vein	UBERON:0007318	97.30	gold quality
lower lobe of lung	UBERON:0008949	96.72	gold quality
oral cavity	UBERON:0000167	96.61	gold quality
sural nerve	UBERON:0015488	96.43	gold quality
superior surface of tongue	UBERON:0007371	96.40	gold quality
upper leg skin	UBERON:0004262	96.33	gold quality
mammary duct	UBERON:0001765	96.28	gold quality
tongue	UBERON:0001723	96.21	gold quality
upper arm skin	UBERON:0004263	96.11	gold quality
hair follicle	UBERON:0002073	95.77	gold quality
synovial joint	UBERON:0002217	95.73	gold quality
zone of skin	UBERON:0000014	95.68	gold quality
body of tongue	UBERON:0011876	95.67	gold quality
cauda epididymis	UBERON:0004360	95.66	gold quality
cervix epithelium	UBERON:0004801	95.56	gold quality
skin of leg	UBERON:0001511	95.49	gold quality
skin of abdomen	UBERON:0001416	95.43	gold quality
pericardium	UBERON:0002407	95.40	gold quality
corpus epididymis	UBERON:0004359	95.05	gold quality
trachea	UBERON:0003126	94.84	gold quality
epithelium of mammary gland	UBERON:0003244	94.79	gold quality
trigeminal ganglion	UBERON:0001675	94.72	gold quality
caput epididymis	UBERON:0004358	94.69	gold quality
cardia of stomach	UBERON:0001162	94.38	gold quality
dorsal root ganglion	UBERON:0000044	94.32	gold quality
stromal cell of endometrium	CL:0002255	94.21	gold quality
germinal epithelium of ovary	UBERON:0001304	94.18	gold quality
nasal cavity epithelium	UBERON:0005384	93.99	gold quality
lateral globus pallidus	UBERON:0002476	93.97	gold quality
renal medulla	UBERON:0000362	93.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.30	gold quality
cervix squamous epithelium	UBERON:0006922	93.20	gold quality
squamous epithelium	UBERON:0006914	93.08	gold quality
liver	UBERON:0002107	92.72	gold quality
mammary gland	UBERON:0001911	92.58	gold quality
thoracic mammary gland	UBERON:0005200	92.56	gold quality
bronchial epithelial cell	CL:0002328	92.55	gold quality
nasal cavity mucosa	UBERON:0001826	92.49	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.30	gold quality
bronchus	UBERON:0002185	92.24	gold quality
epithelium of bronchus	UBERON:0002031	92.13	gold quality
vena cava	UBERON:0004087	92.06	gold quality
palpebral conjunctiva	UBERON:0001812	92.04	gold quality
uterine cervix	UBERON:0000002	91.68	gold quality
parietal pleura	UBERON:0002400	91.43	gold quality
epithelium of nasopharynx	UBERON:0001951	91.10	gold quality
nasopharynx	UBERON:0001728	91.08	gold quality
vagina	UBERON:0000996	91.07	gold quality
visceral pleura	UBERON:0002401	91.04	gold quality
adult organism	UBERON:0007023	91.01	gold quality
epithelium of esophagus	UBERON:0001976	90.90	gold quality
mouth mucosa	UBERON:0003729	90.89	gold quality
gluteal muscle	UBERON:0002000	90.86	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.71	gold quality
pleura	UBERON:0000977	90.55	gold quality
layer of synovial tissue	UBERON:0007616	90.51	gold quality
right lobe of liver	UBERON:0001114	90.38	gold quality
pylorus	UBERON:0001166	90.36	gold quality
mucosa of stomach	UBERON:0001199	90.32	gold quality
esophagus squamous epithelium	UBERON:0006920	90.15	gold quality
eye	UBERON:0000970	90.08	gold quality
minor salivary gland	UBERON:0001830	89.81	gold quality
colonic mucosa	UBERON:0000317	89.73	gold quality
triceps brachii	UBERON:0001509	89.70	gold quality
saliva-secreting gland	UBERON:0001044	89.69	gold quality
tibial nerve	UBERON:0001323	89.62	gold quality
adipose tissue	UBERON:0001013	89.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.17	gold quality
esophagus mucosa	UBERON:0002469	89.16	gold quality
connective tissue	UBERON:0002384	89.13	gold quality
biceps brachii	UBERON:0001507	89.10	gold quality
tonsil	UBERON:0002372	89.06	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.02	gold quality
esophagus	UBERON:0001043	89.00	gold quality
ectocervix	UBERON:0012249	88.83	gold quality
popliteal artery	UBERON:0002250	88.57	gold quality
tibial artery	UBERON:0007610	88.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.43	gold quality
lower esophagus	UBERON:0013473	88.42	gold quality
urinary bladder	UBERON:0001255	88.31	gold quality
calcaneal tendon	UBERON:0003701	88.13	gold quality
lung	UBERON:0002048	88.01	gold quality
endometrium	UBERON:0001295	87.76	gold quality
ventral tegmental area	UBERON:0002691	87.75	gold quality
oviduct epithelium	UBERON:0004804	87.57	gold quality
female reproductive system	UBERON:0000474	87.55	gold quality
pancreatic ductal cell	CL:0002079	87.32	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	2794.01
E-MTAB-9435	yes	2201.09
E-MTAB-8530	yes	711.48
E-HCAD-24	yes	544.92
E-CURD-114	yes	262.53
E-MTAB-10137	yes	165.83
E-MTAB-6701	yes	126.02
E-CURD-119	yes	20.27
E-MTAB-6678	yes	7.06
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Placenta	tissue	61.8	high
Skin 1	tissue	45.7	medium
Liver	tissue	32.2	medium
Choroid plexus	tissue	29.0
Nucleus accumbens	tissue	28.3
Postcentral gyrus	tissue	26.7
Adipose tissue	tissue	25.9	low
Locus coeruleus	tissue	25.0
Vagina	tissue	22.9	medium
Esophagus	tissue	21.3	medium
Hippocampus	tissue	21.3	not detected
Salivary gland	tissue	20.4	low
Tongue	tissue	19.0
Cervix	tissue	18.9	medium
Thyroid gland	tissue	18.7	medium
Breast	tissue	17.4	low
Olfactory bulb	tissue	16.2
Prostate	tissue	15.3	medium
Pancreas	tissue	14.6	medium
Ovary	tissue	14.2	low
Seminal vesicle	tissue	14.1	medium
Lung	tissue	14.1	low
Urinary bladder	tissue	13.7	medium
Thymus	tissue	12.0
Colon	tissue	11.4	low
Fallopian tube	tissue	11.3	medium
Kidney	tissue	10.8	medium
Endometrium 1	tissue	10.1	low
Adrenal gland	tissue	9.9	not detected
Rectum	tissue	9.8	medium
Epididymis	tissue	9.6	medium
Retina	tissue	9.4
Spinal cord	tissue	9.0
Stomach 1	tissue	8.6	low
Smooth muscle	tissue	8.4	low
Gallbladder	tissue	8.3	medium
Tonsil	tissue	7.8	medium
Skeletal muscle	tissue	7.7	low
Cerebellum	tissue	6.5	not detected
Superior colliculi	tissue	6.2
Periaqueductal gray	tissue	6.1
Small intestine	tissue	6.0	low
Basal ganglia	tissue	5.9	low
Thalamus	tissue	5.3
Duodenum	tissue	5.3	low
Hippocampal formation	tissue	5.1
Pons	tissue	4.8
Substantia nigra	tissue	4.8
Spleen	tissue	4.7	not detected
Medulla oblongata	tissue	4.6
Caudate putamen	tissue	4.5
Heart muscle	tissue	4.3	low
Amygdala	tissue	4.3
Midbrain	tissue	4.3
Hypothalamus	tissue	4.2
Frontal cortex	tissue	4.1
Testis	tissue	3.9	medium
Septum	tissue	3.9
Corpus callosum	tissue	3.7
Appendix	tissue	3.7	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Posterior thalamic nucleus (57.4), Globus pallidus, externus (47.6), Cerebellar nuclei (45.7), Inferior colliculus (45.7), Pulvinar (44.9).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets:

Target	Regulation
KRT14	Activation
SOX2	Activation

Upstream regulators (CollecTRI, top): AP1, AR, BCL11B, BCL3, BRCA1, CEBPB, CEBPG, CLDN19, CLDN3, CREBBP, DNMT1, E2F1, EGR1, EGR2, ELF5, EMX2, ERF, ERP29, ESR1, ESR2, ETS2, FOS, FOSL1, FOXC1, FOXN1, FOXO3, GATA3, GCFC2, GLI1, GLI2, GLI3, HDAC1, HDAC3, HOXA11, HOXA7, HOXB7, ID1, IRF1, JUN, JUNB

miRNA regulators (miRDB)

Targeting EGFR by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 110 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-7845-5P	99.88	64.88	771

Functional genomics

gnomAD constraint: pLI 0.983, LOEUF 0.475, missense Z 3.06 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000275493 splits into 7 regions with different missense tolerance; 2 are missense-constrained (≈4% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:55,019,278–55,019,362	65 / 37.8	1.72	no
7:55,019,363–55,156,558	311 / 412.3	0.75	no
7:55,156,559–55,156,770	15 / 46.5	0.32	yes (p 3.8e-06)
7:55,156,771–55,165,399	250 / 295.1	0.85	no
7:55,165,400–55,171,189	5 / 23.6	0.21	yes (p 1.3e-04)
7:55,171,190–55,200,375	348 / 451.5	0.77	no
7:55,200,376–55,205,614	313 / 312.3	1.00	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map
DepMap (CRISPR cell-line fitness): dependent in 17.5% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NCI-H1975 (-2.784), HSC-2 (-2.098), BHY (-2.047), H3118 (-2.037), LC-1-sq (-2.028), NUGC-3 (-1.988), SCC-9 (-1.883), EFO-27 (-1.836), HSC-4 (-1.781), SAS (-1.745), PE/CA-PJ49 (-1.725), MGH-ICC10-8 (-1.711), PC-14 (-1.668), LOU-NH91 (-1.658), JHU-029 (-1.649).

Literature-anchored findings (GeneRIF, showing 40)

• A truncated form of the hEGFR ectodomain comprising residues 1-501, unlike the full-length hEGFR ectodomain (residues 1-621), binds hEGF and hTGF-alpha with high affinity and is a competitive inhibitor of EGF-stimulated mitogenesis. (PMID:11467954)
• Chemical/biological model for EGFR activation. (PMID:11531336)
• EGFR has been detected in the nucleus and might function as a transcription factor to activate gene transcription. (PMID:11533659)
• The data presented here demonstrate that, in contrast to activation by the cytokine, growth hormone (GH), the activation of STAT5b by the growth factor, epidermal growth factor (EGF), requires overexpression of the EGF receptor (EGFR). (PMID:11751923)
• effects of receptor-selective retinoid ligands on EGFR-associated signal transduction (PMID:11788593)
• Interaction of the extracellular domain of the epidermal growth factor receptor with gangliosides (PMID:11796728)
• this study, 11 analogs of a fragment of the B-loop of EGF-related peptides from several species were synthesized to study binding to A431 human epidermoid carcinoma using both 125I-EGF and [3'4’-3H-Tyr(22,29), Abu(20,31)]EGF(20-31)-NH(2). (PMID:11814623)
• CsA affects EGF-r metabolism in gingival keratinocytes resulting in an increased number of cell surface receptors (PMID:11831486)
• Calmodulin binds to the EGFR (PMID:11853560)
• data demonstrate that prostaglandin E2 transactivates EGFR and triggers mitogenic signaling in gastric epithelial and colon cancer cells as well as in rat gastric mucosa in vivo (PMID:11875501)
• sequestration in non-caveolar lipid rafts inhibits lipid binding (PMID:11886870)
• Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors (PMID:11894095)
• estrogen transactivates the epidermal growth factor receptor (EGFR) to MAP K signaling axis via GPR30;implications for breast cancer biology (PMID:11897506)
• Identification of epidermal growth factor receptor as a target of Cdc25A protein phosphatase (PMID:11912208)
• contig map for the EGFR region and markers positioned on its associated physical map to the analysis of 7p11.2 amplifications in a series of glioblastomas. (PMID:11916499)
• EGFR is often strongly expressed and is a potential therapeutic target in patients with malignant thymic tumors (PMID:11935304)
• Antisense epidermal growth factor receptor RNA transfection in human glioblastoma cells down-regulates telomerase activity and telomere length. (PMID:11953893)
• epidermal growth factor receptor activity on fertilization capacity of testicular harvested spermatozoa (PMID:11966576)
• results suggest a potential mechanism by which maintenance of low levels of EGFR expression and subsequent EGFR upregulation may be attributed to the loss of transcriptional repression of EGFR gene expression in hormone-dependent breast cancer cells (PMID:11968000)
• Src-dependent phosphorylation of the EGFR at Tyr-845 is required for EGFR transactivation and zinc-induced Ras activation (PMID:11983694)
• Effects of pharmacologic antagonists of epidermal growth factor receptor, PI3K and MEK signal kinases on NF-kappaB and AP-1 activation and IL-8 and VEGF expression in human head and neck squamous cell carcinoma lines. (PMID:11992543)
• blocking of ubiquitination by inhibiting Src family kinases (PMID:11994282)
• novel mechanism of EGFR internalization that does not require ligand binding, receptor kinase activity, or ubiquitylation and does not direct the receptor into a degradative pathway (PMID:12006662)
• Dephosphorylation of the EGFR and the consequent suppression of EGFR signalling. Review. (PMID:12018405)
• second cysteine-rich region contains targeting information for caveolae/rafts (PMID:12023273)
• Helicobacter pylori-stimulated EGF receptor transactivation requires metalloprotease cleavage of HB-EGF (PMID:12099696)
• determination of decorin binding site (PMID:12105206)
• Expression of this molecule and its correlation with prognostic markers in patients with head and neck tumors (PMID:12127695)
• Detection of serum epidermal growth factor receptor in the diagnosis of proliferation of pituitary adenomas (PMID:12133497)
• These data demonstrate a distinct radiation response profile at the transcriptional level that is dependent on enhanced EGFR/Ras/MAPK signaling. (PMID:12134064)
• These results indicate that epidermal growth factor (EGF) receptors can form a ligand-independent inactive dimer and that receptor dimerization and activation are mechanistically distinct and separable events. (PMID:12134089)
• ErbB1 and ErbB2 employ different mechanisms of plasma membrane targeting during keratinocyte differentiation; cytoskeletal association may facilitate the coupling of activated ErbB1 and ERK. (PMID:12135609)
• Rac activation upon cell-cell contact formation is dependent on signaling from here (PMID:12147707)
• Differential EGFR patterns by interphase cytogenetics in malignant peripheral nerve sheath tumor and morphologically similar spindle cell neoplasms. (PMID:12152785)
• Results show that the juxtamembrane region of the epidermal growth factor receptor is necessary for accurate polarized expression of the native molecule. (PMID:12161422)
• The results of this study indicate that dual inhibition of focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) signaling pathways can cooperatively enhance apoptosis in breast cancers. (PMID:12167618)
• Stimulation of cells with EGF rapidly leads to phosphorylation of Hrs, raising the question whether the EGF receptor tyrosine kinase phosphorylates Hrs directly. Several downstream kinases, rather than the active receptor kinase are responsible. (PMID:12180964)
• These results demonstrate that 1,25(OH)(2)D(3) alters EGFR membrane trafficking and down-regulates EGFR growth signaling. (PMID:12181310)
• EGF receptor expression was elevated in the prefrontal cortex in schizophrenic (PMID:12192610)
• Cbl-directed monoubiquitination of CIN85 is involved in regulation of ligand-induced degradation of EGF receptors. (PMID:12218189)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	egfra	ENSDARG00000013847
danio_rerio		ENSDARG00000056909
mus_musculus	Egfr	ENSMUSG00000020122
rattus_norvegicus	Egfr	ENSRNOG00000004332

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715), RET (ENSG00000165731), AXL (ENSG00000167601), ROR2 (ENSG00000169071), ALK (ENSG00000171094), INSR (ENSG00000171105), ERBB4 (ENSG00000178568), CSF1R (ENSG00000182578), EPHB3 (ENSG00000182580), EPHA10 (ENSG00000183317), ROR1 (ENSG00000185483), EPHB4 (ENSG00000196411), NTRK1 (ENSG00000198400), DDR1 (ENSG00000204580)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95294) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 190 distinct phenotype terms.

Mouse phenotype (MP)	Records
waved hair	7
curly vibrissae	5
eyelids open at birth	5
thick pulmonary interalveolar septum	3
decreased body size	3
decreased embryo size	3
abnormal placenta labyrinth morphology	3
postnatal growth retardation	3
abnormal eye morphology	3
abnormal vibrissa morphology	3
small placenta	3
embryonic lethality during organogenesis, complete penetrance	3
embryonic lethality during organogenesis, incomplete penetrance	3
decreased spongiotrophoblast size	3
cleft palate	2
abnormal hair follicle morphology	2
abnormal hair follicle orientation	2
abnormal epidermal layer morphology	2
thin epidermis	2
decreased body weight	2
weight loss	2
abnormal placenta morphology	2
placental labyrinth hypoplasia	2
abnormal hair texture	2
abnormal bronchus morphology	2

+165 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P13387	100.0%	Diamond
Pongo abelii	Q5RB23	99.7%	Diamond
Macaca mulatta	P55245	99.3%	Diamond
Sus scrofa	O19064	95.3%	Diamond
Bos taurus	Q17R13	93.0%	Diamond
Canis lupus familiaris	O18735	91.8%	Diamond
Mesocricetus auratus	Q60553	90.3%	Diamond
Cyprinus carpio	Q09178	86.8%	Diamond
Xiphophorus maculatus	P13388	61.6%	Diamond
Drosophila melanogaster	Q9VZI2	55.7%	Diamond
Apis mellifera	P0CY46	51.9%	Diamond
Hydra vulgaris	P53356	47.2%	Diamond
Caenorhabditis elegans	G5EBZ8	43.1%	Diamond
Avian leukosis virus	P00534	100.0%	Diamond
Avian erythroblastosis virus (strain ts167)	P11273	100.0%	Diamond
Avian erythroblastosis virus (strain ES4)	P00535	99.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
EGFR-AS1	ncRNA	100507500
ELDR	ncRNA	102725541
SEC61G-DT	ncRNA	100996654
LANCL2	protein-coding	55915

Protein

Protein identifiers

Epidermal growth factor receptor — P00533 (reviewed: P00533)

Alternative names: Proto-oncogene c-ErbB-1, Receptor tyrosine-protein kinase erbB-1

All UniProt accessions (4): P00533, A0A8V8TPW8, C9JYS6, Q504U8

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration. Plays a role in enhancing learning and memory performance. Plays a role in mammalian pain signaling (long-lasting hypersensitivity). Isoform 2 may act as an antagonist of EGF action. (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins.

Subunit / interactions. Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation. Heterodimer with ERBB2. Forms a complex with CCDC88A/GIV (via SH2-like regions) and GNAI3 which leads to enhanced EGFR signaling and triggering of cell migration; binding to CCDC88A requires autophosphorylation of the EGFR C-terminal region, and ligand stimulation is required for recruitment of GNAI3 to the complex. Interacts with ERRFI1; inhibits dimerization of the kinase domain and autophosphorylation. Part of a complex with ERBB2 and either PIK3C2A or PIK3C2B. Interacts with GRB2; an adapter protein coupling the receptor to downstream signaling pathways. Interacts with GAB2; involved in signaling downstream of EGFR. Interacts with STAT3; mediates EGFR downstream signaling in cell proliferation. Interacts with RIPK1; involved in NF-kappa-B activation. Interacts (autophosphorylated) with CBL, CBLB and CBLC; involved in EGFR ubiquitination and regulation; interaction with CBL is reduced in the presence of tensin TNS4. Interacts with SOCS5; regulates EGFR degradation through ELOC- and ELOB-mediated ubiquitination and proteasomal degradation. Interacts with PRMT5; methylates EGFR and enhances interaction with PTPN6. Interacts (phosphorylated) with PTPN6; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with COPG1; essential for regulation of EGF-dependent nuclear transport of EGFR by retrograde trafficking from the Golgi to the ER. Interacts with TNK2; this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts with PCNA; positively regulates PCNA. Interacts with PELP1. Interacts with MUC1. Interacts with AP2M1. Interacts with FER. May interact with EPS8; mediates EPS8 phosphorylation. Interacts (via SH2 domains) with GRB2, NCK1 and NCK2. Interacts with ATXN2. Interacts with GAREM1. Interacts (ubiquitinated) with ANKRD13A/B/D; the interaction is direct and may regulate EGFR internalization after EGF stimulation. Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts (via C-terminal cytoplasmic kinase domain) with ZPR1 (via zinc fingers). Interacts with RNF115 and RNF126. Interacts with GPRC5A (via its transmembrane domain). Interacts with FAM83B; positively regulates EGFR inducing its autophosphorylation in absence of stimulation by EGF. Interacts with LAPTM4B; positively correlates with EGFR activation. Interacts with STX19. Interacts with CD44. Interacts with PGRMC1; the interaction requires PGRMC1 homodimerization. Interacts with PIKFYVE. Interacts with NEU3. Interacts with TRAF4. Interacts with the ant venom OMEGA-myrmeciitoxin(02)-Mg1a. Interacts with CD82; this interaction facilitates ligand-induced endocytosis of the receptor and its subsequent desensitization. Interacts with SNX32; the interaction is required for endolysosomal EGFR trafficking.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Golgi apparatus membrane. Nucleus membrane. Endosome. Endosome membrane. Nucleus Secreted.

Tissue specificity. Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers.

Post-translational modifications. Phosphorylated on Tyr residues in response to EGF. Phosphorylation at Ser-695 is partial and occurs only if Thr-693 is phosphorylated. Phosphorylation at Thr-678 and Thr-693 by PRKD1 inhibits EGF-induced MAPK8/JNK1 activation. Dephosphorylation by PTPRJ prevents endocytosis and stabilizes the receptor at the plasma membrane. Autophosphorylation at Tyr-1197 is stimulated by methylation at Arg-1199 and enhances interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 recruits STAT3. Dephosphorylated by PTPN1 and PTPN2. Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through ‘Lys-63’, but linkage through ‘Lys-48’, ‘Lys-11’ and ‘Lys-29’ also occurs. Deubiquitination by OTUD7B prevents degradation. Ubiquitinated by RNF115 and RNF126. Ubiquitinated by ZNRF1 or CBL at different lysines in response to EGF stimulation; leading to recruitment of the ESCRT machinery and subsequent degradation in the lysosomes. Deubiquitinated by UCHL1 leading to the inhibition of its degradation. Palmitoylated on Cys residues by ZDHHC20. Palmitoylation inhibits internalization after ligand binding, and increases the persistence of tyrosine-phosphorylated EGFR at the cell membrane. Palmitoylation increases the amplitude and duration of EGFR signaling. Neddylated; by NEDD8. Neddylation results in localization to the cell membrane when activated by EGF. Neddylation also increases protein stability. Methylated. Methylation at Arg-1199 by PRMT5 stimulates phosphorylation at Tyr-1197.

Disease relevance. Lung cancer (LNCR) [MIM:211980] A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. The gene represented in this entry is involved in disease pathogenesis. Neonatal nephrocutaneous inflammatory syndrome (NNCIS) [MIM:616069] An autosomal recessive disorder characterized by intrauterine growth retardation, premature birth, fragile skin, recurrent skin infections and sepsis, failure to thrive, nephrocalcinosis, and nephromegaly with tubular dysfunction. Some patients have chronic diarrhea, and necrotizing enterocolitis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Endocytosis and inhibition of the activated EGFR by phosphatases like PTPRJ and PTPRK constitute immediate regulatory mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR endocytosis and activity. Moreover, inducible feedback inhibitors including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative regulatory mechanisms for the EGFR signaling. Up-regulated by NEU3-mediated desialylation of N-linked glycan at Asn-528.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P00533-1	1, p170	yes
P00533-2	2, p60, Truncated, TEGFR
P00533-3	3, p110
P00533-4	4

RefSeq proteins (9): NP_001333826, NP_001333827, NP_001333828, NP_001333829, NP_001333870, NP_005219, NP_958439, NP_958440, NP_958441 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000494	Rcpt_L-dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR006211	Furin-like_Cys-rich_dom	Domain
IPR006212	Furin_repeat	Repeat
IPR008266	Tyr_kinase_AS	Active_site
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016245	Tyr_kinase_EGF/ERB/XmrK_rcpt	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR032778	GF_recep_IV	Domain
IPR036941	Rcpt_L-dom_sf	Homologous_superfamily
IPR049328	TM_ErbB1	Domain
IPR050122	RTK	Family

Pfam: PF00757, PF01030, PF07714, PF14843, PF21314

Enzyme classification (BRENDA)

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea)

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (321 total): strand 76, helix 56, sequence variant 40, mutagenesis site 37, modified residue 25, disulfide bond 25, turn 14, glycosylation site 13, cross-link 8, splice variant 6, binding site 4, compositionally biased region 2, topological domain 2, lipid moiety-binding region 2, repeat 2, region of interest 2, signal peptide 1, chain 1, active site 1, site 1, sequence conflict 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

showing 30 of 393 structures by resolution:

PDB	Title	Method	Resolution (Å)
8A27	EGFR kinase domain in complex with …	X-RAY DIFFRACTION	1.07
8A2D	EGFR kinase domain (L858R/V948R) in complex with …	X-RAY DIFFRACTION	1.11
5UG9	Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with a …	X-RAY DIFFRACTION	1.33
5HG8	EGFR (L858R, T790M, V948R) in complex with …	X-RAY DIFFRACTION	1.42
8A2A	EGFR kinase domain in complex with …	X-RAY DIFFRACTION	1.43
5UG8	Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with a …	X-RAY DIFFRACTION	1.46
3POZ	EGFR Kinase domain complexed with tak-285	X-RAY DIFFRACTION	1.5
6TFV	Crystal Structure of EGFR T790M/V948R in Complex with Covalent Pyrrolopyrimidine 18b	X-RAY DIFFRACTION	1.5
6TG0	Crystal Structure of EGFR T790M/V948R in Complex with Covalent Pyrrolopyrimidine 21a	X-RAY DIFFRACTION	1.5
3VRP	Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with …	X-RAY DIFFRACTION	1.52
5HG5	EGFR (L858R, T790M, V948R) in complex with …	X-RAY DIFFRACTION	1.52
5CNO	Crystal structure of the EGFR kinase domain mutant V924R	X-RAY DIFFRACTION	1.55
9NTP	EGFR kinase domain (T790MV948R) in complex with a strain-release covalent inhibitor	X-RAY DIFFRACTION	1.55
5UGC	Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with a …	X-RAY DIFFRACTION	1.58
3G5Y	Antibodies Specifically Targeting a Locally Misfolded Region of Tumor Associated EGFR	X-RAY DIFFRACTION	1.59
5U8L	Crystal structure of EGFR kinase domain in complex with a sulfonyl fluoride probe XO44	X-RAY DIFFRACTION	1.6
6TG1	Crystal Structure of EGFR T790M/V948R in Complex with Covalent Pyrrolopyrimidine 21b	X-RAY DIFFRACTION	1.6
7SI1	Crystal structure of apo EGFR kinase domain	X-RAY DIFFRACTION	1.6
8PO4	Discovery and Optimisation of Potent, Efficacious and Selective Inhibitors Targeting EGFR …	X-RAY DIFFRACTION	1.62
9GL8	EGFR Exon20 insertion mutant NPG bound with STX-721	X-RAY DIFFRACTION	1.63
9DF3	EGFR Exon20 insertion mutant SVD bound with …	X-RAY DIFFRACTION	1.68
8A2B	EGFR kinase domain (L858R/V948R) in complex with …	X-RAY DIFFRACTION	1.69
3W33	EGFR kinase domain complexed with compound 19b	X-RAY DIFFRACTION	1.7
6TFY	Crystal Structure of EGFR T790M/V948R in Complex with Covalent Pyrrolopyrimidine 18c	X-RAY DIFFRACTION	1.7
4I22	Structure of the monomeric (V948R)gefitinib/erlotinib resistant double mutant …	X-RAY DIFFRACTION	1.71
6WXN	EGFR(T790M/V948R) in complex with LN3844	X-RAY DIFFRACTION	1.76
9DF4	EGFR Exon20 insertion mutant SVD bound with STX-721	X-RAY DIFFRACTION	1.78
9FQS	EGFR Exon20 insertion mutant NPG bound with Compound 39	X-RAY DIFFRACTION	1.78
6V66	EGFR(T790M/V948R) in complex with LN2899	X-RAY DIFFRACTION	1.79
5GNK	Crystal structure of EGFR 696-988 T790M in complex with LXX-6-34	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00533-F1	76.29	0.48

Antibody-complex structures (SAbDab)

26 antibodies co-crystallized with this protein: 1YY9, 3B2U, 3B2V, 3C09, 3G5V, 3G5Y, 3P0Y, 4KRL, 4KRM, 4KRO, 4KRP, 4UV7, 5SX4, 5SX5, 5XWD, 6ARU, 6B3S, 7OM4, 8UKV, 9IP7, 9IPB, BAFISONTAMAB, DEMUPITAMAB, NECITUMUMAB, PANITUMUMAB (+1 more)

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Metabolic proteins, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted secreted proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, Mutated cancer genes, Mutational cancer driver genes, Disease related genes, FDA approved drug targets, Biotech drugs, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; plasma membrane; basal body; cell junctions; end piece; mid piece; primary cilium; principal piece

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2)

Position	Role
837	proton acceptor
1016	important for interaction with pik3c2b

Ligand- & substrate-binding residues (4)

Position	Role
718–726	ATP
745	ATP
790–791	ATP
855	ATP

Post-translational modifications (35)

Type	Positions
Phosphoserine	229, 695, 991, 995, 1026, 1039, 1042, 1064, 1070, 1071, 1081, 1166
Phosphothreonine	678, 693, 1041
N6-(2-hydroxyisobutyryl)lysine	745
Phosphotyrosine	869, 998, 1016, 1069, 1092, 1110, 1172, 1197
Omega-n-methylarginine	1199
S-palmitoyl cysteine	1049, 1146
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	716, 737, 754, 757, 867, 929, 960, 970

Disulfide bonds (25)

Type	Positions
Disulfide bond	31–58, 157–187, 190–199, 194–207, 215–223, 219–231, 232–240, 236–248, 251–260, 264–291, 295–307, 311–326, 329–333, 337–362, 470–499, 506–515, 510–523, 526–535, 539–555, 558–571, 562–579, 582–591, 595–617, 620–628, 624–636

Glycosylation sites (13)

Type	Positions
N-linked (glcnac…) (complex) asparagine	56
N-linked (glcnac…) asparagine	73, 128, 175, 196, 352, 361, 413, 444, 528, 568, 603
N-linked (glcnac…) (high mannose) asparagine	623

Mutagenesis-validated functional residues (37)

Position	Phenotype
275	strongly reduced autophosphorylation and activation of downstream kinases; when associated with a-309.
287	strongly reduced autophosphorylation and activation of downstream kinases; when associated with a-309.
309	strongly reduced autophosphorylation and activation of downstream kinases; when associated with a-275. strongly reduced autophosphorylation …
429	abolishes autophosphorylation and activation of downstream kinases.
525–1210	increased egf binding.
587–590	decreases intramolecular interactions and facilitates egf binding.
587	increased egf binding; when associated with a-590 and a-609.
590	increased egf binding; when associated with a-587; a-590 and a-609.
609	decreases intramolecular interactions and facilitates egf binding. increased egf binding; when associated with a-587; a-590 and a-609.
688	strongly reduced phosphorylation.
689	reduced autophosphorylation.
689	constitutively activated kinase.
690	reduced phosphorylation.
692	strongly reduced phosphorylation.
693	increased phosphorylation.
693	strongly reduced phosphorylation.
694	strongly reduced phosphorylation.
699	reduced phosphorylation.
700	abolishes phosphorylation.
704	abolishes phosphorylation.
705	abolishes phosphorylation.
706	abolishes phosphorylation.
745	abolishes kinase activity.
974	strongly reduced phosphorylation.
977	reduced phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

34 curated (TAS) of 78; 21 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 78 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-5637810	Constitutive Signaling by EGFRvIII ⚕	curated
R-HSA-1236382	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants ⚕	curated
R-HSA-9609690	HCMV Early Events ⚕	curated
R-HSA-5638303	Inhibition of Signaling by Overexpressed EGFR ⚕	curated
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry ⚕	curated
R-HSA-9665348	Signaling by ERBB2 ECD mutants ⚕	curated
R-HSA-9664565	Signaling by ERBB2 KD Mutants ⚕	curated
R-HSA-9665686	Signaling by ERBB2 TMD/JMD mutants ⚕	curated
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-9927432	Developmental Lineage of Mammary Gland Myoepithelial Cells	curated
R-HSA-8863795	Downregulation of ERBB2 signaling	curated
R-HSA-2179392	EGFR Transactivation by Gastrin	curated
R-HSA-182971	EGFR downregulation	curated
R-HSA-212718	EGFR interacts with phospholipase C-gamma	curated
R-HSA-8847993	ERBB2 Activates PTK6 Signaling	curated
R-HSA-6785631	ERBB2 Regulates Cell Motility	curated
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling	curated
R-HSA-9009391	Extra-nuclear estrogen signaling	curated
R-HSA-180292	GAB1 signalosome	curated
R-HSA-179812	GRB2 events in EGFR signaling	curated
R-HSA-9013507	NOTCH3 Activation and Transmission of Signal to the Nucleus	curated
R-HSA-1963642	PI3K events in ERBB2 signaling	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-8857538	PTK6 promotes HIF1A stabilization	curated
R-HSA-5673001	RAF/MAP kinase cascade	curated
R-HSA-180336	SHC1 events in EGFR signaling	curated
R-HSA-445144	Signal transduction by L1	curated
R-HSA-177929	Signaling by EGFR	curated
R-HSA-1227986	Signaling by ERBB2	curated
R-HSA-1236394	Signaling by ERBB4	curated
R-HSA-8866910	TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9609646	HCMV Infection ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-2219528	PI3K/AKT Signaling in Cancer ⚕	—
R-HSA-9820952	Respiratory Syncytial Virus Infection Pathway ⚕	—
R-HSA-1643713	Signaling by EGFR in Cancer ⚕	—
R-HSA-5637812	Signaling by EGFRvIII in Cancer ⚕	—
R-HSA-1227990	Signaling by ERBB2 in Cancer ⚕	—
R-HSA-5637815	Signaling by Ligand-Responsive EGFR Variants in Cancer ⚕	—
R-HSA-5638302	Signaling by Overexpressed Wild-Type EGFR in Cancer ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-422475	Axon guidance	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9734767	Developmental Cell Lineages	—
R-HSA-9734779	Developmental Cell Lineages of the Integumentary System	—
R-HSA-9924644	Developmental Lineages of the Mammary Gland	—
R-HSA-8939211	ESR-mediated signaling	—
R-HSA-416476	G alpha (q) signalling events	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-1963640	GRB2 events in ERBB2 signaling	electronic
R-HSA-881907	Gastrin-CREB signalling pathway via PKC and MAPK	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-373760	L1CAM interactions	—

MSigDB gene sets: 810 (showing top): PID_SHP2_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, BIOCARTA_PTEN_PATHWAY, REACTOME_SIGNALING_BY_NOTCH, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_COGNITION, BIOCARTA_TEL_PATHWAY, GOBP_GLAND_MORPHOGENESIS, GOBP_BEHAVIOR, REACTOME_GAB1_SIGNALOSOME, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, PID_TELOMERASE_PATHWAY

GO Biological Process (44): ossification (GO:0001503), positive regulation of protein phosphorylation (GO:0001934), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), epidermal growth factor receptor signaling pathway (GO:0007173), learning or memory (GO:0007611), positive regulation of cell population proliferation (GO:0008284), neuron differentiation (GO:0030182), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), positive regulation of peptidyl-serine phosphorylation (GO:0033138), ERBB2-EGFR signaling pathway (GO:0038134), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), negative regulation of protein catabolic process (GO:0042177), positive regulation of phosphorylation (GO:0042327), negative regulation of apoptotic process (GO:0043066), positive regulation of MAPK cascade (GO:0043410), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), positive regulation of DNA repair (GO:0045739), positive regulation of DNA replication (GO:0045740), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of fibroblast proliferation (GO:0048146), positive regulation of epithelial cell proliferation (GO:0050679), regulation of peptidyl-tyrosine phosphorylation (GO:0050730), protein insertion into membrane (GO:0051205), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), response to UV-A (GO:0070141), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to amino acid stimulus (GO:0071230), cellular response to epidermal growth factor stimulus (GO:0071364), cellular response to estradiol stimulus (GO:0071392), positive regulation of protein kinase C signaling (GO:0090037), positive regulation of canonical Wnt signaling pathway (GO:0090263), cell-cell adhesion (GO:0098609), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), positive regulation of miRNA transcription (GO:1902895), positive regulation of protein localization to plasma membrane (GO:1903078), negative regulation of cardiocyte differentiation (GO:1905208), MAPK cascade (GO:0000165), protein phosphorylation (GO:0006468), receptor-mediated endocytosis (GO:0006898), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), positive regulation of toll-like receptor 9 signaling pathway (GO:0034165), symbiont entry into host cell (GO:0046718)

GO Molecular Function (24): virus receptor activity (GO:0001618), chromatin binding (GO:0003682), double-stranded DNA binding (GO:0003690), MAP kinase kinase kinase activity (GO:0004709), protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), transmembrane signaling receptor activity (GO:0004888), epidermal growth factor receptor activity (GO:0005006), ATP binding (GO:0005524), enzyme binding (GO:0019899), kinase binding (GO:0019900), protein phosphatase binding (GO:0019903), protein tyrosine kinase activator activity (GO:0030296), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), cadherin binding (GO:0045296), epidermal growth factor binding (GO:0048408), actin filament binding (GO:0051015), ATPase binding (GO:0051117), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (27): Golgi membrane (GO:0000139), nucleus (GO:0005634), cytoplasm (GO:0005737), endosome (GO:0005768), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), focal adhesion (GO:0005925), basal plasma membrane (GO:0009925), cell surface (GO:0009986), endosome membrane (GO:0010008), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), cell junction (GO:0030054), clathrin-coated endocytic vesicle membrane (GO:0030669), early endosome membrane (GO:0031901), nuclear membrane (GO:0031965), ruffle membrane (GO:0032587), protein-containing complex (GO:0032991), signaling receptor complex (GO:0043235), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), Shc-EGFR complex (GO:0070435), multivesicular body, internal vesicle lumen (GO:0097489), intracellular vesicle (GO:0097708), extracellular region (GO:0005576), endocytic vesicle (GO:0030139)

Reactome top-level categories

11 top-level categories:

Category	Pathways
Signaling by EGFR	5
Signaling by ERBB2	4
Signaling by Receptor Tyrosine Kinases	3
Signaling by Ligand-Responsive EGFR Variants in Cancer	1
Intracellular signaling by second messengers	1
Gastrin-CREB signalling pathway via PKC and MAPK	1
PI3K/AKT Signaling in Cancer	1
L1CAM interactions	1
Signaling by EGFRvIII in Cancer	1
Signaling by Overexpressed Wild-Type EGFR in Cancer	1
MAPK1/MAPK3 signaling	1

GO top-level categories

showing 60 of 109 GO namespaces:

Category	Terms
cellular anatomical structure	4
epidermal growth factor receptor signaling pathway	3
positive regulation of cellular process	2
MAPK cascade	2
positive regulation of DNA metabolic process	2
protein tyrosine kinase activity	2
protein binding	2
enzyme binding	2
bounding membrane of organelle	2
intracellular membrane-bounded organelle	2
endomembrane system	2
organelle membrane	2
plasma membrane region	2
multicellular organismal process	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
ERBB signaling pathway	1
behavior	1
cognition	1
cell population proliferation	1
regulation of cell population proliferation	1
cell differentiation	1
generation of neurons	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
positive regulation of protein phosphorylation	1
peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation	1
ERBB2 signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of ERBB signaling pathway	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
phosphorylation	1
regulation of phosphorylation	1
positive regulation of phosphate metabolic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
intracellular signaling cassette	1
DNA repair	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
DNA replication	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 61 of 96 annotations. The rest are phylogenetic / computational / electronic (IEA).

showing 60 of 61 experimentally-supported GO terms:

GO term	NS	Evidence
ERBB2-EGFR signaling pathway	BP	direct assay
cell surface receptor signaling pathway	BP	direct assay
cell-cell adhesion	BP	mutant phenotype
cellular response to estradiol stimulus	BP	direct assay
epidermal growth factor receptor signaling pathway	BP	direct assay
negative regulation of apoptotic process	BP	mutant phenotype
negative regulation of cardiocyte differentiation	BP	mutant phenotype
negative regulation of protein catabolic process	BP	direct assay
phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	mutant phenotype
positive regulation of DNA repair	BP	direct assay
positive regulation of DNA replication	BP	direct assay
positive regulation of ERK1 and ERK2 cascade	BP	direct assay
positive regulation of G1/S transition of mitotic cell cycle	BP	mutant phenotype
positive regulation of MAPK cascade	BP	direct assay
positive regulation of canonical Wnt signaling pathway	BP	mutant phenotype
positive regulation of cell growth	BP	direct assay
positive regulation of cell migration	BP	mutant phenotype
positive regulation of cell population proliferation	BP	direct assay
positive regulation of epithelial cell proliferation	BP	direct assay
positive regulation of miRNA transcription	BP	mutant phenotype
positive regulation of peptidyl-serine phosphorylation	BP	mutant phenotype
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	mutant phenotype
positive regulation of phosphorylation	BP	direct assay
positive regulation of protein kinase C signaling	BP	direct assay
positive regulation of protein localization to plasma membrane	BP	direct assay
positive regulation of protein phosphorylation	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
regulation of peptidyl-tyrosine phosphorylation	BP	mutant phenotype
response to UV-A	BP	direct assay
signal transduction	BP	direct assay
Golgi apparatus	CC	direct assay
basolateral plasma membrane	CC	direct assay
cell junction	CC	direct assay
cell surface	CC	direct assay
cytoplasm	CC	direct assay
early endosome membrane	CC	direct assay
endosome	CC	direct assay
endosome membrane	CC	direct assay
focal adhesion	CC	high-throughput assay
intracellular vesicle	CC	direct assay
membrane	CC	direct assay
membrane raft	CC	direct assay
multivesicular body, internal vesicle lumen	CC	direct assay
nucleus	CC	direct assay
perinuclear region of cytoplasm	CC	mutant phenotype
plasma membrane	CC	direct assay
protein-containing complex	CC	direct assay
ruffle membrane	CC	direct assay
signaling receptor complex	CC	direct assay
actin filament binding	MF	direct assay
cadherin binding	MF	high-throughput assay
chromatin binding	MF	direct assay
enzyme binding	MF	physical interaction
epidermal growth factor receptor activity	MF	direct assay
identical protein binding	MF	physical interaction
kinase binding	MF	physical interaction
protein phosphatase binding	MF	physical interaction
protein tyrosine kinase activator activity	MF	direct assay
protein tyrosine kinase activity	MF	direct assay
transmembrane signaling receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 10,618 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EGFR	EGF	P01133	957
EGFR	PIK3CA	P42336	930
EGFR	PIK3CB	P42338	924
EGFR	PTEN	P60484	921
EGFR	KRAS	P01116	917
EGFR	TP53	P04637	915
EGFR	PIK3CG	P48736	915
EGFR	ESR1	P03372	898
EGFR	MTOR	P42345	884
EGFR	HBEGF	Q99075	883
EGFR	PIK3CD	O00329	882
EGFR	EML4	Q9HC35	881
EGFR	CD274	Q9NZQ7	880
EGFR	TGFA	P01135	873
EGFR	NRAS	P01111	870

IntAct

Human interaction partners of EGFR in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records, in a sample of 1,018 of 1,747 records).

showing 30 of 267 partners by confidence:

Partner	Interaction type	MIscore	Records
GRB2	physical association	0.980	39
SHC1	phosphorylation reaction	0.980	38
EGF	direct interaction	0.970	28
CBL	physical association	0.960	24
ERBB2	association	0.950	20
ERRFI1	direct interaction	0.930	9
STAT3	physical association	0.920	13
ERBB3	physical association	0.920	12
SRC	physical association	0.910	9
PTPN1	colocalization	0.900	8
HSP90AB1	physical association	0.890	6
PTPN11	physical association	0.860	7
PLCG1	physical association	0.850	6
YWHAQ	physical association	0.850	5
PLCG2	physical association	0.840	7
SFN	physical association	0.830	4
AP2M1	physical association	0.830	3
CALM1	physical association	0.830	3
HSP90AA1	association	0.820	7
MUC1	physical association	0.820	6
LYN	physical association	0.820	5
NCK1	physical association	0.820	5
HDAC6	physical association	0.810	11
PIK3C2B	physical association	0.810	9
PIK3R1	proximity	0.810	6
PTPN12	physical association	0.810	5
CAV1	physical association	0.810	3
MET	association	0.800	7
HSPA1A	physical association	0.800	4
HSPA8	physical association	0.800	3

BioGRID (5,098 interactions; top human partners by supporting records in a sample of 600 records): CBL (Affinity Capture-Western; 7 records), CTTN (Affinity Capture-MS; 4 records), PLCG2 (Two-hybrid; 4 records), STAT3 (Two-hybrid; 4 records), ACTN4 (Two-hybrid; 3 records), AKT1 (Two-hybrid; 3 records), ANKS1A (Two-hybrid; 3 records), APBB2 (Two-hybrid; 3 records), ARRB1 (Two-hybrid; 3 records), BAIAP2 (Two-hybrid; 3 records), BLK (Two-hybrid; 3 records), CAMLG (Two-hybrid; 3 records), CDC25C (Two-hybrid; 3 records), CDH1 (Two-hybrid; 3 records), CISH (Two-hybrid; 3 records)

SIGNOR signaling

showing 51 of 200 signaling interactions:

A	Effect	B	Mechanism
EGFR	“up-regulates activity”	HGS	phosphorylation
RIN1	up-regulates	EGFR	binding
EGFR	up-regulates	ERBB2	binding
EGFR	“up-regulates activity”	SHC1	binding
EGFR	up-regulates	SHC2	binding
EGFR	“up-regulates activity”	MUC1	phosphorylation
PTPN2	down-regulates	EGFR	dephosphorylation
EGFR	up-regulates	RGS16	phosphorylation
EGFR	up-regulates	STAT5B	phosphorylation
RARA	“down-regulates quantity by repression”	EGFR	“transcriptional regulation”
SNX9	down-regulates	EGFR
EGFR	up-regulates	CBL	relocalization
EGFR	up-regulates	ESR1	phosphorylation
GPER1	up-regulates	EGFR	binding
BTC	up-regulates	EGFR	binding
EGFR	up-regulates	PIK3R1	binding
EGFR	up-regulates	STAT1	phosphorylation
EGFR	“up-regulates activity”	STAT3	phosphorylation
HBEGF	up-regulates	EGFR	binding
gefitinib	down-regulates	EGFR	“chemical inhibition”
LRIG1	down-regulates	EGFR	binding
EGFR	up-regulates	EZR	phosphorylation
EGFR	unknown	EZR	phosphorylation
EGFR	up-regulates	STAT5A	binding
ERBB2	up-regulates	EGFR	binding
MAPK11	down-regulates	EGFR	phosphorylation
MAPK14	down-regulates	EGFR	phosphorylation
ABL1	up-regulates	EGFR	phosphorylation
BMS-599626	down-regulates	EGFR	“chemical inhibition”
EGFR	up-regulates	PCNA	phosphorylation
“erlotinib hydrochloride”	down-regulates	EGFR	“chemical inhibition”
PTGER2	up-regulates	EGFR
neratinib	down-regulates	EGFR	“chemical inhibition”
lapatinib	down-regulates	EGFR	“chemical inhibition”
EGFR	down-regulates	HDAC6	phosphorylation
sapitinib	down-regulates	EGFR	“chemical inhibition”
EPGN	up-regulates	EGFR	binding
EREG	up-regulates	EGFR	binding
ADAM17	up-regulates	EGFR
EGFR	up-regulates	PTK2	phosphorylation
PKN1	“down-regulates activity”	EGFR	phosphorylation
EPN1	down-regulates	EGFR	relocalization
EGFR	up-regulates	GSTP1	phosphorylation
AP2M1	down-regulates	EGFR	relocalization
EGF	“up-regulates activity”	EGFR	binding
EGFR	“up-regulates quantity by expression”	SOX2	“transcriptional regulation”
SOX2	“up-regulates quantity by expression”	EGFR	“transcriptional regulation”
afatinib	down-regulates	EGFR	“chemical inhibition”
“tyrphostin AG 1478”	down-regulates	EGFR	“chemical inhibition”
“tyrphostin B42”	down-regulates	EGFR	“chemical inhibition”
VARLITINIB	down-regulates	EGFR	“chemical inhibition”

Protein complexes (CORUM) (43)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

showing 42 of 43 complexes by size:

Complex	Subunits	Members
★ EGFR-ERBB3-LYN-PAG1-PRKCB-RACK1 complex	6	EGFR, ERBB3, LYN, PAG1, PRKCB, RACK1
★ CCDC88A-EGF-EGFR-GNAI3 complex	4	CCDC88A, EGF, EGFR, GNAI3
★ EGFR-ERBB2-PIK3C2A-PIK3C2B complex	4	ERBB2, PIK3C2A, PIK3C2B, EGFR
★ CBL-EGFR-SH3GL2-SH3KBP1 complex	4	CBL, EGFR, SH3GL2, SH3KBP1
★ EGF-EGFR-ERBB2 complex	3	EGF, EGFR, ERBB2
★ EGF-EGFR-ERBB3 complex	3	EGF, EGFR, ERBB3
★ EGFR-ERBB3-NRG1 complex	3	EGFR, ERBB3, NRG1
★ BTC-EGFR-ERBB3 complex	3	BTC, EGFR, ERBB3
★ EGF-EGFR-TRAF4 complex	3	EGF, EGFR, TRAF4
★ EGFR-EPHA2-NGEF complex	3	EGFR, EPHA2, NGEF
★ ITGAV-ITGB3-EGFR complex	3	EGFR, ITGAV, ITGB3
★ CBLB-EGFR-SH3KBP1 complex	3	CBLB, EGFR, SH3KBP1
★ EGFR-CBL-GRB2 complex	3	CBL, EGFR, GRB2
★ EGFR-RIN1-STAM2 complex	3	RIN1, STAM2, EGFR
★ CDCP1-EGFR-SRC complex	3	CDCP1, EGFR, SRC
★ EGFR-NHERF1-PTEN complex	3	PTEN, EGFR, NHERF1
★ TM4SF5-ITGA5-EGFR complex	3	ITGA5, TM4SF5, EGFR
★ EGFR-GRB2-TNK2 complex	3	EGFR, GRB2, TNK2
★ EGFR-ERRFI1-GRB2 complex	3	GRB2, EGFR, ERRFI1
★ CBL-EGFR-VAV2 complex	3	CBL, EGFR, VAV2
★ EGFR-TNK2 complex	2	EGFR, TNK2
★ EGFR-SLC5A1 complex	2	EGFR, SLC5A1
★ EGFR-SSTR5 complex	2	EGFR, SSTR5
★ EGFR-SSTR1 complex	2	EGFR, SSTR1
★ EGFR-SNX1 complex	2	EGFR, SNX1
★ EGF-EGFR complex	2	EGF, EGFR
★ AREG-EGFR complex	2	AREG, EGFR
★ BTC-EGFR complex	2	BTC, EGFR
★ EGFR-HBEGF complex	2	EGFR, HBEGF
★ EGFR-TGFA complex	2	EGFR, TGFA
★ EGFR-EREG complex	2	EGFR, EREG
★ EGFR-EPGN complex	2	EGFR, EPGN
★ EGFR-GPRC5A complex	2	GPRC5A, EGFR
★ EGFR-LAPTM4B complex	2	EGFR, LAPTM4B
★ CD44-EGFR complex	2	CD44, EGFR
★ EGFR-FER complex	2	EGFR, FER
★ EGFR-EPHA2 complex	2	EGFR, EPHA2
★ EGFR-MET complex	2	EGFR, MET
★ EGFR-ST3GAL1 complex	2	EGFR, ST3GAL1
★ EGFR-SNX1A complex	2	EGFR, SNX1
★ EGFR-SNX2 complex	2	EGFR, SNX2
★ EGFR-SNX4 complex	2	EGFR, SNX4

Ligand–receptor pairs (CellPhoneDB) (7)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

7 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
EREG	receptor	Signaling by Epidermal growth factor
AREG	receptor	Signaling by Epidermal growth factor
EPGN	receptor	Signaling by Epidermal growth factor
TGFA	receptor	Signaling by Transforming growth factor
EGF	receptor	Signaling by Epidermal growth factor
HBEGF	receptor	Signaling by Epidermal growth factor
BTC	receptor	Signaling by Epidermal growth factor

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 267 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by EGFRvIII	10	31.3×	2e-12
GAB1 signalosome	11	30.6×	2e-13
PI3K events in ERBB2 signaling	10	29.5×	5e-12
Signaling by ERBB2 ECD mutants	10	29.5×	5e-12
Regulation of signaling by CBL	13	28.3×	4e-15
Signaling by ERBB2 KD Mutants	15	27.8×	4e-17
Signaling by CSF3 (G-CSF)	11	27.6×	9e-13
SHC1 events in ERBB2 signaling	13	27.1×	8e-15

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	11	29.9×	1e-11
epidermal growth factor receptor signaling pathway	25	24.0×	5e-25
Fc-epsilon receptor signaling pathway	8	22.7×	2e-07
positive regulation of fibroblast migration	5	21.8×	1e-04
Schwann cell development	5	20.4×	2e-04
peptidyl-tyrosine phosphorylation	12	19.6×	2e-10
negative regulation of inflammatory response to antigenic stimulus	8	18.7×	7e-07
peptidyl-tyrosine dephosphorylation	5	17.2×	3e-04

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

EGFR is widely recognized for its importance in cancer. Amplification and mutations have been shown to be driving events in many cancer types. Its role in non-small cell lung cancer, glioblastoma and basal-like breast cancers has spurred many research and drug development efforts. Tyrosine kinase inhibitors have shown efficacy in EGFR amplfied tumors, most notably gefitinib and erlotinib. Mutations in EGFR have been shown to confer resistance to these drugs, particularly the variant T790M, which has been functionally characterized as a resistance marker for both of these drugs. The later generation TKI’s have seen some success in treating these resistant cases, and targeted sequencing of the EGFR locus has become a common practice in treatment of non-small cell lung cancer. Overproduction of ligands is another possible mechanism of activation of EGFR. ERBB ligands include EGF, TGF-a, AREG, EPG, BTC, HB-EGF, EPR and NRG1-4 (for detailed information please refer to the respective ligand section).

From intOGen — cancer-driver classification: activating (oncogene-like) across 13 cancer types — BRCA, COADREAD, GB, GBM, HGGNOS, LGGNOS, LUAD, LUSC, NSCLC, PAST, PCM, READ…(+1 more).

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for EGFR: 4,015 ClinVar records (99 pathogenic / likely pathogenic); 131 CIViC cancer variants; 21 PharmGKB clinical annotations; 35 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

4,015 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	61
Likely pathogenic	38
Uncertain significance	1850
Likely benign	1476
Benign	95

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 99 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
157499	NM_005228.5(EGFR):c.1283G>A (p.Gly428Asp)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
45225	NM_005228.5(EGFR):c.2156G>C (p.Gly719Ala)	Pathogenic	criteria provided, single submitter	3
45251	NM_005228.5(EGFR):c.2303G>T (p.Ser768Ile)	Pathogenic	criteria provided, single submitter	3
177620	NM_005228.5(EGFR):c.2236_2250del (p.Glu746_Ala750del)	Pathogenic	criteria provided, single submitter	3
45279	NM_005228.5(EGFR):c.2500G>T (p.Val834Leu)	Pathogenic	criteria provided, single submitter	2
45220	NM_005228.5(EGFR):c.2127_2129del (p.Glu709_Thr710delinsAsp)	Pathogenic	criteria provided, single submitter	1
45252	NM_005228.5(EGFR):c.2303_2304delinsTT (p.Ser768Ile)	Pathogenic	criteria provided, single submitter	1
638163	NM_005228.5(EGFR):c.2303_2305delinsTCT (p.Ser768_Val769delinsIleLeu)	Pathogenic	criteria provided, single submitter	1
971184	NM_005228.5(EGFR):c.3147C>A (p.Cys1049Ter)	Pathogenic	criteria provided, single submitter	1
1005727	NM_005228.5(EGFR):c.1605C>A (p.Cys535Ter)	Pathogenic	criteria provided, single submitter	1
1016241	NM_005228.5(EGFR):c.2917C>T (p.Arg973Ter)	Pathogenic	criteria provided, single submitter	1
1016463	NM_005228.5(EGFR):c.1536del (p.Glu513fs)	Pathogenic	criteria provided, single submitter	1
1043841	NM_005228.5(EGFR):c.2577del (p.Lys860fs)	Pathogenic	criteria provided, single submitter	1
1045120	NM_005228.5(EGFR):c.1418del (p.Asn473fs)	Pathogenic	criteria provided, single submitter	1
1425739	NM_005228.5(EGFR):c.2921_2928del (p.Asp974fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore EGFR’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 44 predictions of 2,334):

Position(s)	Effect	Δscore	Sites
7:55142284–55142285	acceptor_loss	1.0000	6
7:55142438	donor_loss	1.0000	3
7:55143303–55143304	acceptor_loss	1.0000	6
7:55146604–55146605	acceptor_loss	1.0000	6
7:55146741–55146742	donor_loss	1.0000	5
7:55154009–55154010	acceptor_loss	1.0000	4
7:55155828–55155829	acceptor_loss	1.0000	6
7:55155947–55155948	donor_loss	1.0000	5
7:55165278–55165279	acceptor_loss	1.0000	2
7:55172972	acceptor_gain	1.0000

AlphaMissense

3,432 missense substitutions predicted likely pathogenic (of 8,041 scored), across 737 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M971	9	0.992	1.000
M825	9	0.988	0.999
M945	9	0.980	0.999
M766	9	0.979	0.999
M952	9	0.968	0.998
M881	9	0.964	1.000
M947	9	0.945	1.000
M908	9	0.923	0.999
N842	8	1.000	1.000
D855	8	1.000	1.000
F723	8	0.999	1.000
H835	8	0.999	1.000
D837	8	0.999	1.000
D896	8	0.999	1.000
F961	8	0.990	1.000
S899	8	0.987	1.000
D379	8	0.985	0.995
F856	8	0.984	1.000
D974	8	0.981	0.999
F420	8	0.979	0.997

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Glioblastoma Multiforme)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (validation)	unfavorable	4.42e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.23e-05

Disease associations

OMIM: gene MIM:131550 | disease phenotypes: MIM:616069, MIM:167000, MIM:158350, MIM:211980, MIM:109800, MIM:275355, MIM:115700

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
lung cancer	Definitive	Autosomal dominant	2
non-small cell lung carcinoma	Definitive	Autosomal dominant
inflammatory skin and bowel disease, neonatal, 2	Strong	Autosomal recessive	5

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
non-small cell lung carcinoma	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (5 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

5 panels:

Panel	Rating
COVID-19 research	green
Intestinal failure or congenital diarrhoea	green
Rare genetic inflammatory skin disorders	green
Endocrine neoplasia	amber
Mosaic skin disorders - Deep sequencing	amber

Mondo (10): inflammatory skin and bowel disease, neonatal, 2 (MONDO:0014481), lung adenocarcinoma (MONDO:0005061), non-small cell lung carcinoma (MONDO:0005233), ovarian cancer (MONDO:0008170), Cowden syndrome 1 (MONDO:0008021), lung cancer (MONDO:0008903), urinary bladder cancer (MONDO:0001187), head and neck squamous cell carcinoma (MONDO:0010150), cataract 4 multiple types (MONDO:0007281), lip and oral cavity carcinoma (MONDO:0023644)

Orphanet (7): Neonatal erythroderma-autoinflammation-inflammatory bowel disease syndrome (Orphanet:294023), Rare ovarian cancer (Orphanet:213500), Squamous cell carcinoma of head and neck (Orphanet:67037), Cataract-microcornea syndrome (Orphanet:1377), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268), NON RARE IN EUROPE: Non-small cell lung cancer (Orphanet:488201), NON RARE IN EUROPE: Bladder cancer (Orphanet:157980)

HPO phenotypes

21 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000527	Long eyelashes
HP:0000822	Hypertension
HP:0001442	Typified by somatic mosaicism
HP:0001508	Failure to thrive
HP:0001561	Polyhydramnios
HP:0001680	Coarctation of aorta
HP:0001944	Dehydration
HP:0002013	Vomiting
HP:0003212	Increased circulating IgE concentration
HP:0003577	Congenital onset
HP:0005208	Secretory diarrhea
HP:0006519	Alveolar cell carcinoma
HP:0006532	Recurrent pneumonia
HP:0025092	Epidermal acanthosis
HP:0030078	Lung adenocarcinoma
HP:0030358	Non-small cell lung carcinoma
HP:0100501	Recurrent bronchiolitis
HP:0200034	Papule
HP:0200039	Pustule

GWAS associations

showing 30 of 35 associations:

Study	Trait	p-value
GCST004349_9	Glioblastoma	5e-34
GCST004347_6	Glioma	4e-27
GCST004349_10	Glioblastoma	5e-23
GCST90002400_197	Plateletcrit	6e-18
GCST90002401_506	Platelet distribution width	1e-17
GCST005932_2	Glioblastoma	3e-16
GCST006480_2	Glioblastoma (age-stratified)	4e-16
GCST90014033_3	Haemorrhoidal disease	3e-13
GCST005932_4	Glioblastoma	1e-12
GCST90002402_365	Platelet count	1e-12
GCST006480_15	Glioblastoma (age-stratified)	2e-12
GCST005931_7	Glioma	5e-12
GCST005931_5	Glioma	7e-12
GCST006480_9	Glioblastoma (age-stratified)	7e-12
GCST005932_3	Glioblastoma	1e-11
GCST006480_3	Glioblastoma (age-stratified)	2e-11
GCST006480_4	Glioblastoma (age-stratified)	2e-10
GCST005931_6	Glioma	2e-9
GCST006480_16	Glioblastoma (age-stratified)	2e-9
GCST90002391_102	Mean corpuscular hemoglobin concentration	2e-9
GCST90002397_216	Mean spheric corpuscular volume	3e-9
GCST009391_1861	Metabolite levels	4e-9
GCST90002393_545	Monocyte count	4e-9
GCST004348_3	Non-glioblastoma glioma	2e-8
GCST006480_17	Glioblastoma (age-stratified)	6e-8
GCST001058_1	Glioma	7e-8
GCST001058_7	Glioma	8e-8
GCST003158_4	Subjective response to lithium treatment	1e-6
GCST007160_15	Refractive astigmatism	1e-6
GCST007622_3	Impulsivity	1e-6

EFO canonical traits (from GWAS)

12 canonical traits:

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0006946	behavioural disinhibition measurement
EFO:0010348	cholesteryl ester 20:4 measurement
EFO:0010349	cholesteryl ester 20:5 measurement
EFO:0010350	cholesteryl ester 22:6 measurement
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0005091	monocyte count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D002289	Carcinoma, Non-Small-Cell Lung	C04.588.894.797.520.109.220.249; C08.381.540.140.500; C08.785.520.100.220.500
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (16): CHEMBL203 (SINGLE PROTEIN), CHEMBL2111431 (PROTEIN FAMILY), CHEMBL2363049 (PROTEIN FAMILY), CHEMBL3137284 (CHIMERIC PROTEIN), CHEMBL4523680 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523747 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523998 (PROTEIN-PROTEIN INTERACTION), CHEMBL4802031 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465557 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066839 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the EGFR protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

showing 60 of 70 curated-mechanism drugs:

Drug	Modality	Max phase
AFATINIB DIMALEATE	Small molecule	4
AMIVANTAMAB	Antibody	4
BRIGATINIB	Small molecule	4
CETUXIMAB	Antibody	4
DACOMITINIB	Small molecule	4
ERLOTINIB HYDROCHLORIDE	Small molecule	4
GEFITINIB	Small molecule	4
LAPATINIB DITOSYLATE	Small molecule	4
LAZERTINIB	Small molecule	4
MOBOCERTINIB	Small molecule	4
NECITUMUMAB	Antibody	4
NERATINIB	Small molecule	4
OLMUTINIB	Small molecule	4
OSIMERTINIB	Small molecule	4
PANITUMUMAB	Antibody	4
ABIVERTINIB	Small molecule	3
AUMOLERTINIB	Small molecule	3
CANERTINIB DIHYDROCHLORIDE	Small molecule	3
CLN-081	Small molecule	3
DEPATUXIZUMAB MAFODOTIN	Antibody drug conjugate	3
FIRMONERTINIB	Small molecule	3
FUTUXIMAB	Antibody	3
ICOTINIB	Small molecule	3
MODOTUXIMAB	Antibody	3
NAQUOTINIB	Small molecule	3
NIMOTUZUMAB	Antibody	3
PYROTINIB	Small molecule	3
RINDOPEPIMUT	Unknown	3
ROCILETINIB	Small molecule	3
RUSERONTINIB	Small molecule	3
SIMOTINIB	Small molecule	3
TESEVATINIB	Small molecule	3
ZALUTUMUMAB	Antibody	3
AEE-788	Small molecule	2
ALLITINIB	Small molecule	2
AZD-3759	Small molecule	2
BAFISONTAMAB	Antibody	2
BMS-690514	Small molecule	2
CEP-32496	Small molecule	2
CETUXIMAB SAROTALOCAN	Antibody drug conjugate	2
DEPATUXIZUMAB	Antibody	2
DULIGOTUZUMAB	Antibody	2
FALNIDAMOL	Small molecule	2
GC1118	Unknown	2
IMGATUZUMAB	Antibody	2
LOSATUXIZUMAB VEDOTIN	Antibody drug conjugate	2
MAB-425	Unknown	2
MATUZUMAB	Antibody	2
MAVELERTINIB	Small molecule	2
MDX-447	Unknown	2
NAZARTINIB	Small molecule	2
PELITINIB	Small molecule	2
PF-06459988	Small molecule	2
PIMURUTAMAB	Antibody	2
SAPITINIB	Small molecule	2
THELIATINIB	Small molecule	2
TOMUZOTUXIMAB	Antibody	2
VARLITINIB	Small molecule	2
AC-480	Small molecule	1
AV-412	Small molecule	1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes EGFR — the drug acts on the assembly or class, not necessarily on this subunit alone.

4 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
VANDETANIB	Epidermal growth factor receptor	4	4
POZIOTINIB	Epidermal growth factor receptor	4	3
TARLOXOTINIB	Epidermal growth factor receptor	4	2
KBP5209	Epidermal growth factor receptor	4	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 361,070 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 175 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1173655	AFATINIB	4	15,878
CHEMBL2105712	AFATINIB DIMALEATE	4	3,441
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2105719	DACOMITINIB	4	825
CHEMBL2110732	DACOMITINIB ANHYDROUS	4	6,949
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1079742	ERLOTINIB HYDROCHLORIDE	4	14,144
CHEMBL939	GEFITINIB	4	119,425
CHEMBL1201179	LAPATINIB DITOSYLATE	4	3,170
CHEMBL4558324	LAZERTINIB	4	1,412
CHEMBL4650319	MOBOCERTINIB	4	1,002
CHEMBL180022	NERATINIB	4	9,891
CHEMBL3786343	OLMUTINIB	4	1,900
CHEMBL3353410	OSIMERTINIB	4	9,448
CHEMBL3301610	ABEMACICLIB	4	7,497
CHEMBL3707348	ACALABRUTINIB	4	4,772
CHEMBL1738797	ALECTINIB	4	7,111
CHEMBL296419	ASTEMIZOLE	4	21,684
CHEMBL1289926	AXITINIB	4	16,510
CHEMBL1200558	BACITRACIN	4	163
CHEMBL290106	BITHIONOL	4
CHEMBL288441	BOSUTINIB	4
CHEMBL2105717	CABOZANTINIB	4
CHEMBL2403108	CERITINIB	4
CHEMBL71	CHLORPROMAZINE	4
CHEMBL1200528	CHROMIC CHLORIDE	4
CHEMBL11359	CISPLATIN	4
CHEMBL104	CLOTRIMAZOLE	4
CHEMBL6067481	COLISTIN	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL5416410	DASATINIB	4
CHEMBL1421	DASATINIB ANHYDROUS	4
CHEMBL926	DOBUTAMINE	4
CHEMBL3545252	DOCETAXEL	4
CHEMBL305660	EBASTINE	4
CHEMBL808	ECONAZOLE	4
CHEMBL1287853	FEDRATINIB	4
CHEMBL726	FLUPHENAZINE	4
CHEMBL64894	GENTIAN VIOLET	4
CHEMBL3301622	GILTERITINIB	4
CHEMBL496	HEXACHLOROPHENE	4
CHEMBL1873475	IBRUTINIB	4
CHEMBL941	IMATINIB	4
CHEMBL554	LAPATINIB	4
CHEMBL1009	LEVODOPA	4
CHEMBL3286830	LORLATINIB	4
CHEMBL459	METHYLDOPA	4
CHEMBL91	MICONAZOLE	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL58	MITOXANTRONE	4
CHEMBL787	MONTELUKAST	4
CHEMBL584	NELFINAVIR	4
CHEMBL1448	NICLOSAMIDE	4
CHEMBL75880	PERHEXILINE	4
CHEMBL1171837	PONATINIB	4
CHEMBL1614701	SELUMETINIB	4
CHEMBL1336	SORAFENIB	4
CHEMBL404849	SULOCTIDIL	4
CHEMBL535	SUNITINIB	4
CHEMBL83	TAMOXIFEN	4

Clinical evidence (CIViC)

Drug × variant × indication, from 393 curated evidence items; also 19 oncogenic, 15 prognostic, 14 functional. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

showing 30 of 303 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
EGFR L858R	Erlotinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID2994 +6
EGFR T790M	Osimertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID1592 +4
EGFR L858R	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID2997 +3
EGFR Exon 19 Deletion	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID2996 +2
EGFR Exon 19 Deletion	Erlotinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID2995 +1
EGFR L858R OR EGFR Exon 19 Deletion	Osimertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11219 +1
EGFR L858R OR EGFR Exon 19 Deletion	Gefitinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11241 +1
EGFR D770_N771insGT OR EGFR D770_N771insD OR EGFR D770_N771insF OR EGFR D770_N771insGD OR EGFR D770_N771insT OR EGFR N771delinsCH OR EGFR N771delinsGF OR EGFR N771delinsRD OR EGFR N771delinsSQRGH OR EGFR N771_P772insDN	Sunvozertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12632
EGFR D770delinsGY OR EGFR D770_N771insY OR EGFR N771_P772insT OR EGFR H773_V774insGNPH OR EGFR A767_S768insTLA OR EGFR S768_V769insLDS OR EGFR V769_D770insCV OR EGFR V769_D770insGA OR EGFR V769_D770insGVASV OR EGFR D770delinsAS	Sunvozertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12631
EGFR Exon 20 Insertion	Amivantamab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11227
EGFR Exon 20 Insertion	Mobocertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11228
EGFR Exon 20 Insertion	Chemotherapy + Amivantamab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12014
EGFR Exon 20 Insertion	Sunvozertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12718
EGFR G719	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11242
EGFR H773_V774insH OR EGFR D770_N771insG OR EGFR H773_V774insNPH OR EGFR A763_Y764insFQEA OR EGFR V774_C775insHV OR EGFR H773_V774insPH OR EGFR H773_V774insAH OR EGFR D770_N771insH OR EGFR N771dup	Sunvozertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12630
EGFR H773delinsYNPY OR EGFR H773delinsYPNPY OR EGFR H773_V774insHPH OR EGFR H773_V774insTH OR EGFR C775_R776insNPHVC	Sunvozertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12634
EGFR L858R AND EGFR T790M	Osimertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11599
EGFR L858R OR EGFR Exon 19 Deletion	Dacomitinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11239
EGFR L858R OR EGFR Exon 19 Deletion	Erlotinib + Ramucirumab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11240
EGFR L858R OR EGFR Exon 19 Deletion	Chemotherapy + Osimertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12015
EGFR L858R OR EGFR Exon 19 Deletion	Amivantamab + Lazertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12131
EGFR L858R OR EGFR Exon 19 Deletion	Amivantamab + Pemetrexed + Carboplatin	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12156
EGFR Mutation	Datopotamab Deruxtecan Regimen	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12522
EGFR Mutation	Datopotamab Deruxtecan	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12523
EGFR N771delinsGY OR EGFR P772_H773insYNP OR EGFR N771_P772insRH OR EGFR N771_P772insVDN OR EGFR P772delinsHR OR EGFR P772_H773insDNP OR EGFR P772_H773insPHP OR EGFR P772_H773insQ OR EGFR P772_H773insRNP OR EGFR H773delinsNPY OR EGFR H773delinsPNPY	Sunvozertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12633
EGFR S768I OR EGFR G719A OR EGFR L861Q	Afatinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC A	EID11229
EGFR S768_D770dup OR EGFR A767_V769dupASV	Sunvozertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12623
EGFR T790M AND EGFR Exon 19 Deletion	Osimertinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11598
EGFR T790M	Erlotinib	Lung Non-small Cell Carcinoma	Resistance	CIViC A	EID238 +3
EGFR A763_Y764insFQEA	Erlotinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID5939 +3

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

Clinical-actionability assertions (CIViC AMP/ASCO/CAP)

Curated AMP/ASCO/CAP tier assertions — the clinical-actionability classification (Tier I highest) for this gene’s variants, distilling the CIViC evidence above into a tiered call.

7 CIViC assertions:

Molecular profile	Disease	Therapy	Type	AMP tier	Significance
EGFR L858R	Lung Non-small Cell Carcinoma	Gefitinib †	Predictive	Tier I - Level A	Sensitivity/Response
EGFR T790M	Lung Non-small Cell Carcinoma	Osimertinib †	Predictive	Tier I - Level A	Sensitivity/Response
EGFR L858R	Lung Non-small Cell Carcinoma	Dacomitinib †	Predictive	Tier I - Level A	Sensitivity/Response
EGFR L858R	Lung Non-small Cell Carcinoma	Erlotinib †	Predictive	Tier I - Level A	Sensitivity/Response
EGFR L858R	Lung Non-small Cell Carcinoma	Afatinib †	Predictive	Tier I - Level A	Sensitivity/Response
EGFR T790M	Lung Non-small Cell Carcinoma		Oncogenic		Likely Oncogenic
EGFR L858R	Lung Non-small Cell Carcinoma		Oncogenic		Oncogenic

† an FDA-approved companion diagnostic exists for this assertion.

CIViC curated variants (131)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

V742A (missense variant), E746_A750del (inframe deletion), E746_T751>I, L747_P753delinsS (inframe deletion), R831H (missense variant), L838V (missense variant), L861Q (missense variant), R776C (missense variant), A864T (missense variant), N826S (missense variant), Exon 19 Deletion (inframe deletion), G719S (missense variant), G719D (missense variant), D770_N771insSVD, H773_V774insH, L838P (missense variant), T847I (missense variant), V851I (missense variant), L861R (missense variant), E868G (missense variant), S768_D770dup (inframe insertion), D770_N771insG (inframe insertion), H773_V774insNPH (inframe insertion), D770_N771insGL (inframe insertion), A763_Y764insFQEA (inframe insertion), EGFRVIII, D770_N771insGT (inframe insertion), V774_C775insHV (inframe insertion), D770_N771insNPG (inframe insertion), W731L (missense variant), E734Q (missense variant), T785A (missense variant), C797Y (missense variant), Y801H (missense variant), A767_V769dupASV (inframe insertion), L747_S752delinsQ (inframe insertion,inframe deletion,delins), N771delinsGY (inframe insertion,inframe deletion,delins), M766_A767insAI (inframe insertion), Y764_V765insHH (inframe insertion), P772_H773insYNP (inframe insertion), P772_V774insPHV (inframe insertion), Gain-of-function, Rare Exon 18-21 Mutation (exon variant), L861, L747P (missense variant), V774A (missense variant), V774M (missense variant), K806E (missense variant), N826Y (missense variant), V834I, N842S (missense variant), Amplification (transcript amplification), Copy Number Variation (copy number change), Overexpression, Wildtype (wild type), M766_A767insASV, D770delinsGY (inframe insertion,delins), R705K (missense variant), Rare Mutation, Exon 4 Deletion (exon loss variant) …(+71 more).

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

showing 20 of 21 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs121434568	Efficacy	1A	gefitinib	Non-Small Cell Lung Carcinoma
rs121434569	Efficacy	2B	erlotinib	Adenocarcinoma;Drug Resistance;Lung Neoplasms;Non-Small Cell Lung Carcinoma
rs121434569	Efficacy	2B	gefitinib	Drug Resistance;Non-Small Cell Lung Carcinoma
rs10258429	Toxicity	3	imatinib	Gastrointestinal Stromal Tumors
rs11506105	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs11568315	Efficacy	3	gefitinib	Non-Small Cell Lung Carcinoma
rs2227983	Toxicity	3	egfr inhibitors	Colorectal Neoplasms;Neoplasms;Non-Small Cell Lung Carcinoma;Pancreatic Neoplasms
rs2227983	Efficacy	3	cetuximab	Head and Neck Neoplasms
rs2293347	Efficacy	3	fluorouracil	Stomach Neoplasms
rs2293347	Efficacy	3	gefitinib	Non-Small Cell Lung Carcinoma
rs2330951	Toxicity	3	sorafenib	Hypertension
rs712829	Efficacy	3	topoisomerase I inhibitors	Neoplasms
rs712829	Efficacy	3	geldanamycin	Neoplasms
rs712829	Efficacy	3	erlotinib	Neoplasms
rs712829	Toxicity	3	erlotinib	Neoplasms
rs712829	Efficacy	3	Alkylating Agents	Neoplasms
rs712829	Efficacy	3	cetuximab;irinotecan;panitumumab	Colorectal Neoplasms
rs712829	Efficacy	3	gefitinib	Neoplasms
rs712830	Toxicity	3	cetuximab;irinotecan;leucovorin;tegafur	Colorectal Neoplasms
rs917881	Toxicity	3	sorafenib	Diarrhea

PharmGKB variants

11 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs712829	EGFR	3	4.00	7	erlotinib;topoisomerase I inhibitors;geldanamycin;Alkylating Agents;gefitinib;cetuximab;irinotecan;panitumumab
rs712830	EGFR	3	1.75	1	cetuximab;irinotecan;leucovorin;tegafur
rs2227983	EGFR	3	1.50	2	egfr inhibitors;cetuximab
rs2293347	EGFR	3	4.50	2	fluorouracil;gefitinib
rs121434568	EGFR	1A	190.00	1	gefitinib
rs121434569	EGFR	2B	9.00	2	erlotinib;gefitinib
rs11568315	EGFR	3	7.50	1	gefitinib
rs11506105	EGFR	3	2.50	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs10258429	EGFR	3	3.00	1	imatinib
rs2330951	EGFR	3	2.50	1	sorafenib
rs917881	EGFR	3	1.50	2	sorafenib

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

showing 59 of 84 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2293347	fluorouracil	Efficacy	Genotype CC is associated with decreased response to fluorouracil in people with Stomach Neoplasms as compared to genotypes CT + TT.	PMID:23816762
rs712829	cetuximab, panitumumab	Efficacy	Genotypes GT + TT is associated with increased survival when treated with cetuximab or panitumumab in people with Colorectal Neoplasms as compared to genotype GG.	PMID:23959273
rs121434568	gefitinib	Efficacy	Allele G is associated with response to gefitinib in people with Carcinoma, Non-Small-Cell Lung.	PMID:26490356
rs121434568	erlotinib	Efficacy	Allele G is associated with response to erlotinib in people with Carcinoma, Non-Small-Cell Lung.	PMID:26490356
rs121434568	erlotinib, gefitinib	Efficacy	Allele G is associated with decreased response to erlotinib or gefitinib in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.	PMID:26490356
rs2227983	cetuximab	Efficacy	Genotypes AA + AG are associated with decreased progression-free survival when treated with cetuximab in people with Head and Neck Neoplasms as compared to genotype GG.	PMID:28031227
rs11506105	peginterferon alfa-2a, peginterferon alfa-2b, ribavirin	Efficacy	Genotype AA is associated with increased rapid virological response (rvr) and sustained virological response (svr) when treated with peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotypes AG + GG.	PMID:28703131
rs10258429	imatinib	Toxicity	Genotypes CT + TT is associated with increased risk of Drug Toxicity and Eye Disorder when treated with imatinib in people with Gastrointestinal Stromal Tumors as compared to genotype CC.	PMID:28762371
rs2330951	sorafenib	Toxicity	Allele C is associated with increased risk of Hypertension when treated with sorafenib in people with Carcinoma, Renal Cell as compared to allele A.	PMID:35484400
rs917881	sorafenib	Toxicity	Allele A is associated with increased risk of Diarrhea when treated with sorafenib in people with Carcinoma, Renal Cell as compared to allele G.	PMID:35484400
rs2072454	imatinib	Toxicity	Genotype CC is associated with increased likelihood of periorbital edema when treated with imatinib in people with Gastrointestinal Stromal Tumors as compared to genotypes CT + TT.	PMID:37212851
rs763317		Efficacy	Genotype AA is associated with increased risk of Death in people with Lung Neoplasms as compared to genotypes AG + GG.	PMID:37498067
rs121434569	osimertinib	Efficacy	Allele T is associated with increased likelihood of progression-free survival or overall survival when treated with osimertinib in people with Carcinoma, Non-Small-Cell Lung as compared to allele C.	PMID:38584122
rs28929495	afatinib	Efficacy	Genotype GG is associated with decreased clinical benefit to afatinib in people with Non-Small Cell Lung Carcinoma.	PMID:40413606
rs10228436	imatinib	Toxicity	Genotypes AG + GG is associated with decreased likelihood of Hypersensitivity when treated with imatinib in people with Gastrointestinal Stromal Tumors as compared to genotype AA.	PMID:41193444
rs712829	gefitinib	Efficacy	Genotypes GT + TT are associated with increased progression-free survival (PFS) time when treated with gefitinib in people with Carcinoma, Non-Small-Cell Lung as compared to genotype GG.	PMID:17375033
rs712829			Genotype TT is associated with increased expression of EGFR NCI60 cell lines.	PMID:18006781
rs712829	egfr inhibitors	Toxicity	Allele T is associated with cytotoxicity of egfr inhibitors.	PMID:18006781
rs2227983	egfr inhibitors	Efficacy	Allele A is associated with cytotoxicity of egfr inhibitors.	PMID:18006781
rs712829	erlotinib	Toxicity	Genotype GG is associated with increased severity of Diarrhea when treated with erlotinib in people with Neoplasms as compared to genotypes GT + TT.	PMID:18309947
rs2227983	egfr inhibitors	Toxicity	Genotype GG is associated with increased likelihood of Exanthema when treated with egfr inhibitors in people with Neoplasms as compared to genotypes AA + AG.	PMID:22158333
rs121434568	erlotinib	Efficacy	Genotypes GT + TT are associated with decreased response to erlotinib in people with Carcinoma, Non-Small-Cell Lung as compared to genotype GG.	PMID:19692684
rs712830	cetuximab, irinotecan, leucovorin, tegafur	Toxicity	Genotype CC is associated with increased severity of Drug Toxicity when exposed to cetuximab, irinotecan, leucovorin and tegafur in people with Colorectal Neoplasms as compared to genotype AC.	PMID:22486600
rs121434568	erlotinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with erlotinib in people with EGFR mutation positive non-small-cell lung cancer.	PMID:21783417
rs121434568	erlotinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with erlotinib in people with EGFR mutation positive non-small-cell lung cancer.	PMID:22285168
rs121434568	gefitinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with gefitinib in people with EGFR mutation positive non-small-cell lung cancer.	PMID:20022809
rs121434568	gefitinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with gefitinib in people with EGFR mutation positive non-small-cell lung cancer.	PMID:20573926
rs121434568	gefitinib	Efficacy	Allele G is associated with increased longer median progression-free survival time when treated with gefitinib in people with EGFR mutation positive non-small-cell lung cancer.	PMID:20573926
rs121434568	gefitinib	Efficacy	Allele G is associated with increased response rate when treated with gefitinib in people with EGFR mutation positive non-small-cell lung cancer.	PMID:20573926
rs121434568	gefitinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with gefitinib in people with EGFR mutation positive non-small-cell lung cancer.	PMID:21900837
rs121434568	gefitinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with gefitinib in people with EGFR mutation positive non-small-cell lung cancer.	PMID:19692680
rs121434568	gefitinib	Efficacy	Allele T is associated with decreased progression-free survival (PFS) time when treated with gefitinib in people with EGFR mutation negative non-small-cell lung cancer.	PMID:19692680
rs121434568	erlotinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with erlotinib in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.	PMID:22982650
rs121434568	erlotinib	Efficacy	Allele G is associated with increased Overall survival (OS) time when treated with erlotinib in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.	PMID:22982650
rs121434568	erlotinib	Efficacy	Allele G is associated with increased response rate when treated with erlotinib in people with Adenocarcinoma as compared to allele T.	PMID:22740981
rs121434569	erlotinib	Efficacy	Allele T is associated with decreased progression-free survival (PFS) time when exposed to erlotinib in people with EGFR mutation positive non-small-cell lung cancer as compared to allele C.	PMID:21233402
rs121434569	erlotinib, gefitinib	Efficacy	Allele T is associated with decreased progression-free survival (PFS) time when treated with erlotinib or gefitinib in people with EGFR mutation positive non-small-cell lung cancer as compared to allele C.	PMID:18596266
rs121434568	erlotinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when exposed to erlotinib in people with advanced non-small-cell lung cancer as compared to allele T.	PMID:21969500
rs121434568	gefitinib	Efficacy	Allele G is associated with increased physical and life well-being quality of life (QoL) scales when treated with gefitinib in people with EGFR mutation positive advanced non-small-cell lung cancer.	PMID:22581822
rs121434568	erlotinib, gefitinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with erlotinib or gefitinib in EGFR mutation positive non-small-cell lung cancer patients as compared to allele T.	PMID:22760226
rs121434568	erlotinib, gefitinib	Efficacy	Allele G is associated with increased overall survival (OS) time when treated with erlotinib or gefitinib in EGFR mutation positive non-small-cell lung cancer patients as compared to allele T.	PMID:22760226
rs121434568	gefitinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with gefitinib in people with EGFR mutation positive non-small-cell lung cancer as compared to allele T.	PMID:20038723
rs121434568	carboplatin, erlotinib, paclitaxel	Efficacy	Allele G is associated with increased overall survival and progression-free survival when treated with carboplatin, erlotinib and paclitaxel in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.	PMID:16043828
rs121434568	gefitinib	Efficacy	Allele G is associated with increased response rate when treated with gefitinib in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.	PMID:16204011
rs121434568	gefitinib	Efficacy	Allele G is associated with increased response rate when treated with gefitinib in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.	PMID:17047654
rs121434568	gefitinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with gefitinib in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.	PMID:17047654
rs121434568	gefitinib	Efficacy	Allele G is associated with increased response rate when treated with gefitinib in non-small-cell lung cancer patients as compared to allele T.	PMID:17473659
rs121434568	erlotinib	Efficacy	Allele G is associated with increased response rate when treated with erlotinib in bronchioloalveolar carcinoma and adenocarcinoma patients as compared to allele T.	PMID:18349398
rs121434568	erlotinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with erlotinib in bronchioloalveolar carcinoma and adenocarcinoma patients as compared to allele T.	PMID:18349398
rs121434568	gefitinib	Efficacy	Allele G is associated with increased response rate when treated with gefitinib in non-small-cell lung cancer patients as compared to allele T.	PMID:17106442
rs121434568	gefitinib	Efficacy	Allele G is associated with increased median survial time when treated with gefitinib in non-small-cell lung cancer patients as compared to allele T.	PMID:17106442
rs121434568	gefitinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with gefitinib in non-small-cell lung cancer patients as compared to allele T.	PMID:16956694
rs121434568	gefitinib	Efficacy	Allele G is associated with increased overall survival (OS) time when treated with gefitinib in non-small-cell lung cancer patients as compared to allele T.	PMID:16956694
rs121434568	gefitinib	Efficacy	Allele G is associated with increased response rate when treated with gefitinib in non-small-cell lung cancer patients as compared to allele T.	PMID:16956694
rs121434568	gefitinib	Efficacy	Allele G is associated with increased response rate when treated with gefitinib in people with non-small-cell lung cancer as compared to allele T.	PMID:15897572
rs121434568	gefitinib	Efficacy	Allele G is associated with increased progression-free survival (PFS) time when treated with gefitinib in people with non-small-cell lung cancer as compared to allele T.	PMID:15897572
rs121434568	gefitinib	Efficacy	Allele G is associated with increased response rate when treated with gefitinib in non-small-cell lung cancer patients as compared to allele T.	PMID:16203769
rs121434568	gefitinib	Efficacy	Allele G is associated with increased response rate when treated with gefitinib in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.	PMID:17317677
rs121434568	gefitinib	Efficacy	Allele G is associated with increased response rate when treated with gefitinib in advanced non-small-cell lung cancer patients as compared to allele T.	PMID:17387341

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type I RTKs: ErbB (epidermal growth factor) receptor family

Most potent curated ligand interactions (108 total), top 25:

Ligand	Action	Affinity	Parameter
compound 56 [PMID: 8568816]	Inhibition	11.22	pIC50
asandeutertinib	Inhibition	10.7	pIC50
BPIQ-I	Inhibition	10.6	pIC50
panitumumab	Antagonist	10.3	pKd
xiliertinib	Inhibition	10.3	pKi
JBJ-09-063	Negative	10.08	pIC50
SH-1028	Inhibition	10.0	pIC50
TQB3804	Inhibition	9.66	pIC50
petosemtamab	Binding	9.66	pKd
JBJ-04-125-02	Inhibition	9.59	pIC50
CH7233163	Inhibition	9.55	pIC50
EGFR/ErbB-2/ErbB-4 inhibitor	Inhibition	9.52	pIC50
tesevatinib	Inhibition	9.52	pIC50
necitumumab	Binding	9.49	pKd
cetuximab	Binding	9.41	pKd
mifanertinib	Inhibition	9.4	pIC50
PD 174265	Inhibition	9.35	pIC50
allitinib	Inhibition	9.3	pIC50
BI-4020	Inhibition	9.22	pIC50
pelitinib	Inhibition	9.22	pIC50
emupertinib	Inhibition	9.04	pIC50
pirotinib	Inhibition	9.0	pIC50
nazartinib	Inhibition	9.0	pIC50
EGF	Binding	8.86	pKi
amivantamab	Binding	8.85	pKd

Binding affinities (BindingDB)

4761 measured of 6068 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[(3-Bromophenyl)amino]benzo[g]quinazoline	IC50	0.003 nM
PD153035 Analog	IC50	0.006 nM
4-[(3-bromophenyl)-amino]-6-(dimethylamino)pyrido[3,4-d]pyrimidine	IC50	0.006 nM
N-(3-bromophenyl)-1-methyl-1H-imidazo[4,5-g]quinazolin-8-amine	IC50	0.01 nM
8-[(3-Bromophenyl)amino]-3-methyl-3H-imidazo[4,5-g]-quinazoline	IC50	0.025 nM
CHEMBL3613702	IC50	0.037 nM
N-[4-(4,5-Dichloro-2-fluoro-phenylamino)-quinazolin-6-yl]-acrylamide	IC50	0.04 nM
CHEMBL3808884	EC50	0.04 nM
2-Chloro-N-[4-(4,5-dichloro-2-fluoro-phenylamino)-quinazolin-6-yl]-acetamide	IC50	0.07 nM
N-(3,4-dibromophenyl)-6,7-dimethoxyquinazolin-4-amine	IC50	0.072 nM
N-(4-bromophenyl)-6,7-dimethoxyquinazolin-4-amine	IC50	0.0724 nM
N-[(1S,1aS,6bS)-5-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzamide	IC50	0.079 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
N-[(1S,1aS,6bS)-5-[(2-oxo-3,4-dihydro-1H-pyrido[2,3-d]pyrimidin-5-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzamide	IC50	0.085 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
4-N-(3-bromophenyl)-7-N,7-N-dimethylpyrido[4,3-d]pyrimidine-4,7-diamine	IC50	0.09 nM
4-N-(3-bromophenyl)quinazoline-4,7-diamine	IC50	0.1 nM
Quinazolin-7-ylamine	IC50	0.1 nM
BDBM200762	IC50	0.11 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
(E)-4-Dimethylamino-but-2-enoic acid [4-(4,5-dichloro-2-fluoro-phenylamino)-quinazolin-6-yl]-amide	IC50	0.11 nM
4-N-(3-bromophenyl)quinazoline-4,6,7-triamine	IC50	0.12 nM
2-Chloro-N-[4-(3-iodo-phenylamino)-quinazolin-6-yl]-acetamide	IC50	0.12 nM
CHEMBL3930620	IC50	0.12 nM
(E)-N-[4-(3-chloro-4-fluoroanilino)-7-(3-oxabicyclo[3.1.0]hexan-6-ylmethoxy)quinazolin-6-yl]-4-(dimethylamino)but-2-enamide	IC50	0.13 nM	US-9187459: Quinazoline-7-ether compounds and methods of use
4-N-(3-bromophenyl)-7-N-methylpyrido[4,3-d]pyrimidine-4,7-diamine	IC50	0.13 nM
4-N-(3-bromophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine	IC50	0.13 nM
N-[(1S,1aS,6bS)-5-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-4-[[(3S)-3-methylpiperazin-1-yl]methyl]-3-(trifluoromethyl)benzamide	IC50	0.14 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
N-[(1S,1aS,6bS)-5-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-3-(2-aminopropan-2-yl)-5-(trifluoromethyl)benzamide	IC50	0.15 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
N-[(1S,1aS,6bS)-5-[(2-oxo-3,4-dihydro-1H-pyrido[2,3-d]pyrimidin-5-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzamide	IC50	0.15 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
4-[[(8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]methyl]-N-[(1S,1aS,6bS)-5-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-3-(trifluoromethyl)benzamide	IC50	0.16 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
N-[4-(3-Chloro-4-fluoro-phenylamino)-7-(4-morpholin-4-yl-but-1-enyl)-pyrido[3,2-d]pyrimidin-6-yl]-acrylamide	IC50	0.16 nM
N-[(1S,1aS,6bS)-5-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-4-[(1-ethylpiperidin-4-yl)methyl]-3-(trifluoromethyl)benzamide	IC50	0.17 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
N-[3-[[2-[3-fluoro-4-(4-methylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenyl]prop-2-enamide	IC50	0.17 nM	US-9586965: Pyrrolo[2,3-d]pyrimidine compounds as inhibitors of protein kinases
4-[(3-bromophenyl)amino]quinazoline-6,7-diol	IC50	0.17 nM
N-(3-bromophenyl)-6,7-dipropoxyquinazolin-4-amine	IC50	0.17 nM
N-[4-(3-Bromoanilino)pyrido[3,4-d]pyrimidin-6-yl]-N-methylacrylamide	IC50	0.17 nM
4-[(3-Bromophenyl)amino]-6-[(2,3-dihydroxypropyl)-amino]pyrido[3,4-d]pyrimidine	IC50	0.18 nM
4-[(3-Bromophenyl)amino]-6-[(2-hydroxyethyl)amino]-pyrido[3,4-d]pyrimidine	IC50	0.19 nM
4-N-(3-chlorophenyl)-6-N-methylpyrido[3,4-d]pyrimidine-4,6-diamine	IC50	0.19 nM
(4,5-Dichloro-2-fluoro-phenyl)-(6,7-dimethoxy-quinazolin-4-yl)-amine	IC50	0.21 nM
4-[(3-Bromophenyl)amino]-6-[N-(2-hydroxyethyl)-N-methylamino]pyrido[3,4-d]pyrimidine	IC50	0.22 nM
(2E)-N-{4-[(3-bromophenyl)amino]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide	IC50	0.22 nM
N-[(1S,1aS,6bS)-5-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-3-chloro-4-[(4-methylpiperazin-1-yl)methyl]benzamide	IC50	0.23 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
N-[(1S,1aS,6bS)-5-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-3-bromo-4-[(4-methylpiperazin-1-yl)methyl]benzamide	IC50	0.24 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
N-[(1S,1aS,6bS)-5-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-4-(1-methylpiperidin-4-yl)oxy-3-(trifluoromethyl)benzamide	IC50	0.24 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
2-({4-[(3-bromophenyl)amino]pyrido[4,3-d]pyrimidin-7-yl}amino)ethan-1-ol	IC50	0.24 nM
CHEMBL270696	IC50	0.245 nM
4-N-(3-chlorophenyl)quinazoline-4,7-diamine	IC50	0.25 nM
8-N-(3-bromophenyl)-2-N-[2-(1H-imidazol-4-yl)ethyl]-[1,3]diazino[5,4-d]pyrimidine-2,8-diamine	IC50	0.25 nM
N-[4-(3-Chloro-phenylamino)-quinazolin-7-yl]-acrylamide	IC50	0.25 nM
CHEMBL53426	IC50	0.251 nM
N-[(1S,1aS,6bS)-5-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-yl]-4-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-3-(trifluoromethyl)benzamide	IC50	0.26 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL176582
11.00	IC50	0.01	nM	MOBOCERTINIB
11.00	IC50	0.01	nM	CHEMBL5270693
10.80	IC50	0.016	nM	CHEMBL5790648
10.77	IC50	0.017	nM	CHEMBL5746224
10.70	IC50	0.02	nM	OSIMERTINIB
10.70	IC50	0.02	nM	NERATINIB
10.70	IC50	0.02	nM	CHEMBL4537790
10.70	IC50	0.02	nM	CHEMBL5270693
10.70	IC50	0.02	nM	CHEMBL5997498
10.70	IC50	0.02	nM	MOBOCERTINIB
10.68	IC50	0.021	nM	CHEMBL6054692
10.66	IC50	0.022	nM	CHEMBL5968640
10.60	IC50	0.025	nM	CHEMBL29197
10.60	IC50	0.025	nM	CHEMBL174426
10.60	IC50	0.025	nM	MOBOCERTINIB
10.57	IC50	0.027	nM	CHEMBL5288888
10.54	IC50	0.029	nM	CHEMBL29197
10.54	IC50	0.029	nM	ERLOTINIB
10.52	Ki	0.03	nM	CHEMBL4100860
10.52	IC50	0.03	nM	CHEMBL5594833
10.52	IC50	0.03	nM	CHEMBL1243316
10.43	IC50	0.037	nM	CHEMBL363815
10.43	IC50	0.037	nM	CHEMBL3613702
10.43	Kd	0.037	nM	CHEMBL5805801
10.42	IC50	0.038	nM	CHEMBL5993268
10.40	IC50	0.04	nM	CHEMBL1229592
10.40	IC50	0.04	nM	CANERTINIB
10.37	IC50	0.043	nM	CHEMBL4521381
10.30	IC50	0.05	nM	CHEMBL5193123
10.30	IC50	0.05	nM	CHEMBL5271803
10.30	IC50	0.05	nM	OSIMERTINIB
10.30	IC50	0.05	nM	CHEMBL5432965
10.30	IC50	0.05	nM	CHEMBL5915655
10.30	IC50	0.05	nM	CHEMBL5284924
10.28	IC50	0.053	nM	CHEMBL5282641
10.28	IC50	0.053	nM	CHEMBL5284924
10.28	IC50	0.052	nM	CHEMBL5790648
10.28	IC50	0.052	nM	CHEMBL6054692
10.28	IC50	0.052	nM	CHEMBL5811442
10.24	IC50	0.058	nM	OSIMERTINIB
10.23	IC50	0.059	nM	ERLOTINIB
10.22	IC50	0.06	nM	OSIMERTINIB
10.22	IC50	0.06	nM	LAPATINIB
10.22	IC50	0.06	nM	CHEMBL5186680
10.22	IC50	0.06	nM	CHEMBL5434495
10.22	IC50	0.06	nM	CHEMBL5393923
10.22	IC50	0.06	nM	CHEMBL5436031
10.21	IC50	0.061	nM	POZIOTINIB
10.21	IC50	0.061	nM	AFATINIB

PubChem BioAssay actives

3117 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Afatinib	1676514: Inhibition of human N-terminal GST-tagged EGFR L858R mutant (669 to 1210 residues) expressed in baculovirus infected Sf9 insect cells using TK as substrate preincubated for 30 mins followed by substrate addition and measured after 15 mins by HTRF assay	ic50	<0.0001	uM
N-[4-(4,5-dichloro-2-fluoroanilino)quinazolin-6-yl]prop-2-enamide	241077: Inhibition of EGF Receptor autophosphorylation in A431 cell lysate	ic50	<0.0001	uM
Mobocertinib	1956454: Inhibition of wild type EGFR (unknown origin) using TK-substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 25 mins by HTRF assay	ic50	<0.0001	uM
N-[4-(3,4-dichloro-5-fluoroanilino)quinazolin-6-yl]prop-2-enamide	1244850: Inhibition of epidermal growth factor receptor kinase (unknown origin) using [33P]-ATP after 20 to 30 mins by radiometric assay	ic50	<0.0001	uM
2-chloro-N-[4-(3-iodoanilino)quinazolin-6-yl]acetamide	241077: Inhibition of EGF Receptor autophosphorylation in A431 cell lysate	ic50	0.0001	uM
Gefitinib	1129567: Inhibition of EGFR (unknown origin) after 1.5 hr by FRET-based Z-lyte assay	ic50	0.0001	uM
7-[4-[4-(3-chloro-2-fluoroanilino)quinazolin-6-yl]triazol-1-yl]-N-hydroxyheptanamide	1330924: Inhibition of wild-type EGFR (unknown origin) assessed as remaining ATP level measured after 15 mins by luminescence analysis	ic50	0.0001	uM
N-[3-[[4-[5-(4-fluorophenyl)-2-methylsulfanyl-1H-imidazol-4-yl]-2-pyridinyl]amino]-4-methoxyphenyl]prop-2-enamide	1445480: Inhibition of human N-terminal GST-fused EGFR L858R mutant (669 to 1210 residues) expressed in baculovirus using TK-substrate-biotin incubated for 2 to 90 mins by HTFR assay	ki	0.0001	uM
N-[4-(3-chloro-4-fluoroanilino)-7-[(E)-4-morpholin-4-ylbut-1-enyl]pyrido[3,2-d]pyrimidin-6-yl]prop-2-enamide	67284: Inhibition of phosphorylation of a polyglutamic acid/tyrosine random copolymer by EGFR enzyme prepared from human A431 carcinoma cell vesicles by immunoaffinity chromatography	ic50	0.0002	uM
(2S)-2-[[6-[4-(hydroxymethyl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-2-phenylethanol	1713456: Inhibition of EGFR (unknown origin) using Tyr 04 peptide as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0002	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-[1-(oxetan-3-yl)indol-3-yl]-5-(trifluoromethyl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide	1709313: Inhibition of recombinant human N-terminal GST-tagged EGFR T790M/L858R double mutant using biotinylated TK peptide as substrate measured after 30 mins by HTRF assay	ic50	0.0002	uM
N-[5-[[4-(1-cyclopropylindol-3-yl)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	1709313: Inhibition of recombinant human N-terminal GST-tagged EGFR T790M/L858R double mutant using biotinylated TK peptide as substrate measured after 30 mins by HTRF assay	ic50	0.0002	uM
N-[5-[[5-chloro-4-[1-(oxetan-3-yl)indol-3-yl]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2112682: Inhibition of EGFR L858R/T790M mutant (unknown origin) by mobility shift assay	ic50	0.0002	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-5-[[4-[1-(dimethylsulfamoyl)indol-3-yl]pyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide	1709313: Inhibition of recombinant human N-terminal GST-tagged EGFR T790M/L858R double mutant using biotinylated TK peptide as substrate measured after 30 mins by HTRF assay	ic50	0.0002	uM
N-(1H-indazol-3-yl)-7,7-dimethyl-2-(1H-pyrazol-4-yl)-5H-furo[3,4-d]pyrimidin-4-amine	1274048: Inhibition of EGFR deletion (746 to 750 residues) mutant (unknown origin)	ki	0.0002	uM
2-(5-fluoro-2-hydroxyphenyl)-2-[3-oxo-5-(4-piperazin-1-ylphenyl)-1H-isoindol-2-yl]-N-(1,3-thiazol-2-yl)acetamide	2121735: Inhibition of EGFR Del19/T790M/C797S mutant (unknown origin)	ic50	0.0002	uM
7-[[(3aS,6aR)-2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]methoxy]-N-(3,4-dichloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine	1595620: Inhibition of EGFR in human A431 cells assessed as reduction in EGF-stimulated EGFR autophosphorylation preincuabted for 90 mins followed by EGF-stimulation by sandwich-ELISA	ic50	0.0003	uM
N-[4-(3-chloroanilino)quinazolin-7-yl]prop-2-enamide	69411: Inhibition of phosphorylation of glutamic acid/tyrosine random copolymer by isolated epidermal growth factor receptor (EGFR)	ic50	0.0003	uM
N-[4-(3-chloro-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]but-2-ynamide	260895: Inhibition of erbB1 fusion protein expressed in baculovirus by ELISA	ic50	0.0003	uM
4-(4-phenoxyphenyl)-10-prop-2-enoyl-2,3,7,10-tetrazatricyclo[6.4.0.02,6]dodeca-1(8),4,6-triene-5-carboxamide	1615345: Inhibition of EGFR (unknown origin) preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay	ic50	0.0003	uM
11-[(E)-4-(dimethylamino)but-2-enoyl]-4-(4-phenoxyphenyl)-2,3,7,11-tetrazatricyclo[6.4.0.02,6]dodeca-1(8),4,6-triene-5-carboxamide	1615345: Inhibition of EGFR (unknown origin) preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay	ic50	0.0003	uM
4-(4-phenoxyphenyl)-12-prop-2-enoyl-2,3,7,12-tetrazatricyclo[6.5.0.02,6]trideca-1(8),4,6-triene-5-carboxamide	1615345: Inhibition of EGFR (unknown origin) preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay	ic50	0.0003	uM
4-(4-phenoxyphenyl)-11-prop-2-enoyl-2,3,7,11-tetrazatricyclo[6.5.0.02,6]trideca-1(8),4,6-triene-5-carboxamide	1615345: Inhibition of EGFR (unknown origin) preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay	ic50	0.0003	uM
6-(4-phenoxyphenyl)-3-(1-prop-2-enoylpiperidin-4-yl)-5H-imidazo[1,2-b]pyrazole-7-carboxamide	1615345: Inhibition of EGFR (unknown origin) preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay	ic50	0.0003	uM
N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[6-(2-nitroimidazol-1-yl)hexoxy]quinazolin-4-amine	1174871: Inhibition of wild type EGFR (unknown origin) by Z’-Lyte kinase assay	ic50	0.0003	uM
N-(3-chloro-4-fluorophenyl)-6-methoxy-7-[4-(2-nitroimidazol-1-yl)butoxy]quinazolin-4-amine	1175520: Inhibition of wild type EGFR (unknown origin) by Z’-Lyte kinase assay	ic50	0.0003	uM
N-(3-chloro-4-fluorophenyl)-6-methoxy-7-[2-[2-(2-nitroimidazol-1-yl)ethoxy]ethoxy]quinazolin-4-amine	1175520: Inhibition of wild type EGFR (unknown origin) by Z’-Lyte kinase assay	ic50	0.0003	uM
N-(3-ethynylphenyl)-6-methoxy-7-[4-(2-nitroimidazol-1-yl)butoxy]quinazolin-4-amine	1175520: Inhibition of wild type EGFR (unknown origin) by Z’-Lyte kinase assay	ic50	0.0003	uM
N-(3-bromophenyl)-6-methoxy-7-[5-(2-nitroimidazol-1-yl)pentoxy]quinazolin-4-amine	1175520: Inhibition of wild type EGFR (unknown origin) by Z’-Lyte kinase assay	ic50	0.0003	uM
N-[3-[4-(1H-indazol-3-ylamino)-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]oxyphenyl]prop-2-enamide	1241296: Inhibition of EGFR L858R/T790M mutant (unknown origin) expressed in Sf9 cells by enzyme kinetics assay	ki	0.0003	uM
N-[3-[7-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-2,4-dioxo-3-propan-2-ylpyrimido[4,5-d]pyrimidin-1-yl]phenyl]prop-2-enamide	1498600: Inhibition of recombinant human GST-tagged EGFR L858R/T790M double mutant expressed in baculovirus expression system using Poly(Glu,Tyr)4:1 as substrate after 1 hr by ELISA	ic50	0.0003	uM
(2R)-2-(5-fluoro-2-hydroxyphenyl)-2-[3-oxo-5-(4-piperazin-1-ylphenyl)-1H-isoindol-2-yl]-N-(1,3-thiazol-2-yl)acetamide	2236501: Inhibition of EGFR L858R/T790M double mutant (unknown origin)	ic50	0.0003	uM
(4S,5R)-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-5-methyl-2-oxo-1,3-oxazolidine-4-carboxamide	1309513: Inhibition of recombinant human EGFR L858R mutant expressed in baculovirus infected insect cells preincubated for 5 mins followed by ATP addition for 30 mins by HTRF assay	ic50	0.0003	uM
N-[3-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-6,7-dioxo-5-propan-2-ylpteridin-8-yl]phenyl]prop-2-enamide	1627086: Inhibition of EGFR kinase domain L858R/T790M mutant (unknown origin) expressed using baculovirus expression system incubated for 1 hr using Poly(Glu,Tyr) 4:1 by ELISA method	ic50	0.0003	uM
6-[4-[4-(3-chloro-2-fluoroanilino)quinazolin-6-yl]triazol-1-yl]-N-hydroxyhexanamide	1330924: Inhibition of wild-type EGFR (unknown origin) assessed as remaining ATP level measured after 15 mins by luminescence analysis	ic50	0.0003	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-7-[(3R)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide	1424372: Inhibition of human EGFR L858R mutant expressed in mouse Ba/F3 cells	ic50	0.0004	uM
N-(3-chlorophenyl)-6,7-diethoxyquinazolin-4-amine;hydrochloride	283008: Displacement of [125I]4-(3-iodoanilino)-6,7-dimethoxyquinazoline from EGFR tyrosine kinase in human A431 cell membranes	ic50	0.0004	uM
3-methoxy-4-[4-[[(1R)-1-phenylethyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]benzamide	1713436: Inhibition of human EGFR using poly[Glu:Tyr] (4:1) as substrate in presence of [gamma33P]ATP by radiometric HotSpot assay	ic50	0.0004	uM
(2S)-2-phenyl-2-[(6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]ethanol	1713456: Inhibition of EGFR (unknown origin) using Tyr 04 peptide as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0004	uM
(2S)-2-[[6-(2-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-2-phenylethanol	1713436: Inhibition of human EGFR using poly[Glu:Tyr] (4:1) as substrate in presence of [gamma33P]ATP by radiometric HotSpot assay	ic50	0.0004	uM
N-(3-bromophenyl)-6-methoxy-7-[4-(2-nitroimidazol-1-yl)butoxy]quinazolin-4-amine	1175520: Inhibition of wild type EGFR (unknown origin) by Z’-Lyte kinase assay	ic50	0.0004	uM
N-[3-[7-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]-2,4-dioxo-3-propylpyrimido[4,5-d]pyrimidin-1-yl]phenyl]prop-2-enamide	1498600: Inhibition of recombinant human GST-tagged EGFR L858R/T790M double mutant expressed in baculovirus expression system using Poly(Glu,Tyr)4:1 as substrate after 1 hr by ELISA	ic50	0.0004	uM
N-[2-(dimethylamino)ethyl]-3,5-dimethoxy-4-[4-[[(1R)-1-phenylethyl]amino]thieno[2,3-d]pyrimidin-6-yl]benzamide	1273654: Inhibition of EGFR (unknown origin) by Z -LYTE assay	ic50	0.0004	uM
N-[3-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methylsulfanylpyrimidin-4-yl]oxyphenyl]prop-2-enamide	1298661: Inhibition of EGFR T790M/L858R mutant (unknown origin) expressed in baculovirus expression system after 1 hr by ELISA	ic50	0.0004	uM
N’,N’-dimethyl-N-[4-[4-[[(1R)-1-phenylethyl]amino]furo[2,3-d]pyrimidin-6-yl]phenyl]ethane-1,2-diamine	1317873: Inhibition of recombinant human GST-tagged EGFR cytoplasmic domain (668 to 1210 residues) expressed in baculovirus by Z’-LYTE assay	ic50	0.0004	uM
N-(3-ethynylphenyl)-6-methoxy-7-[5-(2-nitroimidazol-1-yl)pentoxy]quinazolin-4-amine	1175520: Inhibition of wild type EGFR (unknown origin) by Z’-Lyte kinase assay	ic50	0.0005	uM
N-[4-(3-methylanilino)pyrido[3,4-d]pyrimidin-6-yl]prop-2-enamide	67282: Inhibition of phosphorylation of glutamic acid/tyrosine random copolymer by isolated epidermal growth factor receptor (EGFR)	ic50	0.0005	uM
N-[4-(3-bromoanilino)quinazolin-6-yl]-3-morpholin-4-ylpropanamide	661563: Inhibition of human recombinant EGFR using Ulight-CAGAGAIETDKEYYTVKD as substrate after 15 mins by time-resolved fluorimetric analysis	ic50	0.0005	uM
N-[4-(3-bromoanilino)pyrido[4,3-d]pyrimidin-7-yl]prop-2-enamide	67282: Inhibition of phosphorylation of glutamic acid/tyrosine random copolymer by isolated epidermal growth factor receptor (EGFR)	ic50	0.0005	uM
N-[4-(3-chloro-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]-5-(4-methylpiperazin-1-yl)pent-2-ynamide	260895: Inhibition of erbB1 fusion protein expressed in baculovirus by ELISA	ic50	0.0005	uM

CTD chemical–gene interactions

470 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Gefitinib	decreases expression, affects response to substance, decreases response to substance, increases response to substance, increases degradation (+13 more)	44
RTKI cpd	decreases phosphorylation, decreases activity, increases chemical synthesis, increases expression, increases phosphorylation (+7 more)	33
sodium arsenite	increases phosphorylation, increases activity, affects expression, affects methylation, increases expression (+4 more)	20
Erlotinib Hydrochloride	affects cotreatment, decreases response to substance, increases expression, decreases glycosylation, increases reaction (+9 more)	19
4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline	decreases activity, decreases reaction, increases phosphorylation, increases reaction, affects binding (+5 more)	16
bisphenol A	decreases reaction, increases phosphorylation, affects binding, decreases expression, decreases methylation (+6 more)	14
AG 1879	increases phosphorylation, increases reaction, affects binding, increases activity, decreases activity (+3 more)	12
Cisplatin	affects cotreatment, decreases expression, affects binding, increases reaction, increases phosphorylation (+8 more)	12
Cadmium Chloride	increases abundance, decreases expression, increases expression, decreases reaction, increases phosphorylation (+5 more)	12
Estradiol	increases reaction, decreases expression, affects binding, increases activity, affects reaction (+4 more)	11
Resveratrol	affects binding, affects cotreatment, decreases expression, increases reaction, increases degradation (+6 more)	10
Arsenic Trioxide	affects response to substance, affects reaction, decreases reaction, affects binding, decreases expression (+6 more)	10
Fluorouracil	increases reaction, decreases phosphorylation, affects reaction, affects cotreatment, affects response to substance (+5 more)	10
Curcumin	increases phosphorylation, increases reaction, decreases activity, decreases phosphorylation, decreases expression (+2 more)	9
Quercetin	affects activity, increases phosphorylation, affects cotreatment, increases expression, decreases phosphorylation (+4 more)	9
Tetrachlorodibenzodioxin	decreases reaction, increases activity, increases phosphorylation, affects response to substance, increases reaction (+4 more)	9
Particulate Matter	decreases methylation, increases abundance, increases expression, increases secretion, decreases reaction (+3 more)	9
bisphenol S	affects binding, affects cotreatment, decreases reaction, increases phosphorylation, decreases methylation (+1 more)	7
Valproic Acid	affects cotreatment, increases expression, decreases methylation	7
Doxorubicin	decreases expression, affects response to substance, affects reaction, decreases activity, decreases export (+5 more)	6
Tobacco Smoke Pollution	increases expression, increases phosphorylation, affects expression, decreases expression, increases activity (+1 more)	6
Tretinoin	decreases expression, increases expression	6
Asbestos, Crocidolite	affects reaction, increases phosphorylation, affects binding, decreases phosphorylation, decreases reaction (+3 more)	6
osimertinib	decreases phosphorylation, decreases reaction, decreases response to substance, decreases expression, affects reaction (+3 more)	5
arsenite	increases secretion, increases methylation, affects response to substance, increases activity, affects binding (+6 more)	5
epigallocatechin gallate	increases phosphorylation, decreases expression, affects reaction, decreases reaction, affects binding (+5 more)	5
Lapatinib	affects response to substance, affects reaction, affects binding, decreases reaction, increases reaction (+1 more)	5
Arsenic	affects cotreatment, decreases expression, increases expression, increases phosphorylation, affects response to substance	5
Cadmium	decreases reaction, increases abundance, affects binding, increases reaction, affects phosphorylation (+3 more)	5
Smoke	decreases expression, decreases nitrosation, increases abundance, increases phosphorylation, affects response to substance	5

ChEMBL screening assays

6531 unique, capped per target: 6211 binding, 173 functional, 138 admet, 9 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001226	Binding	Inhibition of EGFR	The identification of pyrazolo[1,5-a]pyridines as potent p38 kinase inhibitors. — *Bioorg Med Chem Lett*
CHEMBL1614029	Functional	PUBCHEM_BIOASSAY: Assay for Inhibitors of the ERK Signaling Pathway using a Homogeneous Screening Assay: EGFR L858R Kinase Inhibition. (Class of assay: confirmatory) [Related pubchem assays: 1454, 995 ]	PubChem BioAssay data set
CHEMBL3635803	ADMET	Inhibition of wild type EGFR phosphorylation in human A431 cells after 60 mins by mesoscale multiplex assay	Oxopyrido[2,3-d]pyrimidines as Covalent L858R/T790M Mutant Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors. — *ACS Med Chem Lett*

Cellosaurus cell lines

682 cell lines: 494 cancer cell line, 131 factor-dependent cell line, 45 spontaneously immortalized cell line, 8 transformed cell line, 3 finite cell line, 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0014	RPMI-8226	Cancer cell line	Male
CVCL_0037	A-431	Cancer cell line	Female
CVCL_0092	NALM-6	Cancer cell line	Male
CVCL_0509	RPMI-8226/MR20	Cancer cell line	Male
CVCL_0526	SK-MEL-28	Cancer cell line	Male
CVCL_0F29	DFCI-LU011	Cancer cell line	Male
CVCL_0H89	39ER22	Spontaneously immortalized cell line	Female
CVCL_0U51	NALM-6/SP-B	Cancer cell line	Male
CVCL_1063	A-388	Cancer cell line	Male
CVCL_1066	ABC-1	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 331 trials:

NCT	Phase	Status	Title
NCT00158041	Phase 4	COMPLETED	Subcutaneous Amifostine Safety Study
NCT00277160	Phase 4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00365508	Phase 4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00440960	Phase 4	COMPLETED	Anesthesia in Flexible Bronchoscopy for Lung Cancer Diagnostic
NCT00492843	Phase 4	TERMINATED	Loading Dose or Standard Dose of Intravenous Ibandronate in Treating Patients With Lung Cancer and Skeletal Metastasis
NCT00666978	Phase 4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00675168	Phase 4	UNKNOWN	Positron Emission Tomography (PET)/Computed Tomography (CT) and Roentgen in Lung Cancer: Evaluation of Patients in General Practice
NCT00712647	Phase 4	COMPLETED	Carotene and Retinol Efficacy Trial
NCT00747773	Phase 4	COMPLETED	Cryospray Ablation of Surgical Resection Specimens To Determine Safety And Histological Effect In The Lung
NCT01060137	Phase 4	COMPLETED	Fentanyl Matrix in Lung Cancer Pain
NCT01381627	Phase 4	UNKNOWN	Safety Evaluation of Dexmedetomidine for EBUS-TBNA
NCT01741506	Phase 4	COMPLETED	Coagulation Profile in Patients Undergoing Video Assisted Thorascopic Surgery (VATS) for Lung Cancer
NCT02246023	Phase 4	COMPLETED	Fractionated Versus Target-controlled Propofol Administration in Bronchoscopy
NCT02275702	Phase 4	COMPLETED	Randomized Study of Preoperative Dexamethasone for Quality of Recovery in VATS Lung Resection Patients
NCT02346318	Phase 4	UNKNOWN	The Randomized Controlled Clinical Trial of Kushen Injection
NCT02476526	Phase 4	COMPLETED	Safety of Low Dose IV Contrast CT Scanning in Chronic Kidney Disease
NCT02490059	Phase 4	COMPLETED	Ultrathin Bronchoscopy for Solitary Pulmonary Nodules
NCT02504801	Phase 4	UNKNOWN	Efficacy of Nebulized Pulmicort Respules in Primary Lung Cancer Patients With COPD
NCT02869789	Phase 4	COMPLETED	An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers
NCT03302221	Phase 4	WITHDRAWN	Regional Haemodynamic Changes in Radial Artery Assessment With Continuous Pulsed-wave Doppler Ultrasound
NCT03313544	Phase 4	UNKNOWN	Evolution of the Heart Function When Monitoring Immunotherapies Anti-cancerous Inhibiting PD-1
NCT03394222	Phase 4	COMPLETED	Effect of Preoperative Budesonide Inhalation on Arterial Blood Oxygenation and Intrapulmonary Shunt During OLV
NCT03570645	Phase 4	COMPLETED	Comparison of the Duration of Ropivacaine Combined With Dexmedetomidine or Dexamethasone on Paravertebral Block
NCT03571126	Phase 4	UNKNOWN	Olanzapine for the Prevention and Treatment of Nausea and Vomiting Induced by Chemotherapy of Lung Cancer
NCT03642457	Phase 4	TERMINATED	Efficacy Between Serratus Plane Block And Local Infiltration In Vats
NCT04145570	Phase 4	COMPLETED	A Single-Dose,ComparativeBioavailability Study ofTwo Formulations ofErlotinib150mgTabletsunderFastingConditions
NCT04155008	Phase 4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04613284	Phase 4	UNKNOWN	Rh-Endostatin Combined With CCRT(50 Gy) Followed by Durvalumab Maintenance for the Treatment of Specific Phase III NSCLC
NCT05463913	Phase 4	RECRUITING	Lung Nodule Detection Using Ultra-long FOV PET/CT
NCT05521789	Phase 4	RECRUITING	Erector Spinae Block for Thoracic Surgery
NCT05525338	Phase 4	RECRUITING	Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels
NCT05663242	Phase 4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Lung Tumors and Its Mechanism of Action
NCT05926336	Phase 4	UNKNOWN	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06105801	Phase 4	RECRUITING	EBUS-TBNA vs Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing
NCT06276933	Phase 4	NOT_YET_RECRUITING	A Study of Camrelizumab Combined With Chemotherapy ± Thalidomide in First-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
NCT06646471	Phase 4	RECRUITING	PROspective Master-protocol for Evaluation of Systemic THErapeutics in Elderly With Thoracic Malignancies
NCT07405086	Phase 4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT07743333	Phase 4	COMPLETED	Nebulized Lidocaine And Ketamine Before Fiberoptic Bronchoscopy
NCT07761351	Phase 4	RECRUITING	A Randomized Controlled Trial Comparing Percutaneous CT-Guided Biopsy and Shape-Sensing Robotic-Assisted Bronchoscopy
NCT07802847	Phase 4	NOT_YET_RECRUITING	Innovative and Cooperative Pathway Integrating Oncogeriatric, Pharmaceutical and Pharmacological Follow-up in Elderly Patients.
NCT00002550	Phase 3	COMPLETED	Chemotherapy Plus Radiation Therapy With or Without Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer
NCT00002583	Phase 3	COMPLETED	Vinorelbine + Cisplatin or No Further Therapy in Non-small Cell Lung Cancer That Has Been Surgically Removed
NCT00002623	Phase 3	COMPLETED	Chemotherapy Followed by Surgery or Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer
NCT00002822	Phase 3	COMPLETED	Combination Chemotherapy Followed by Radiation Therapy in Patients With Small Cell Lung Cancer
NCT00002823	Phase 3	COMPLETED	Combination Chemotherapy Compared With No Treatment Following Surgery in Treating Patients With Non-small Cell Lung Cancer
NCT00002858	Phase 3	UNKNOWN	Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Small Cell Lung Cancer
NCT00002911	Phase 3	COMPLETED	Marimastat in Treating Patients With Stage III Non-small Cell Lung Cancer
NCT00003011	Phase 3	COMPLETED	Marimastat Following Chemotherapy in Treating Patients With Small Cell Lung Cancer
NCT00003053	Phase 3	UNKNOWN	Combination Chemotherapy in Treating Patients With Stage I, II, or IIIA Non-small Cell Lung Cancer That Has Been Surgically Removed
NCT00003117	Phase 3	COMPLETED	Paclitaxel With or Without Carboplatin in Treating Patients With Advanced Non-small Cell Lung Cancer
NCT00003159	Phase 3	COMPLETED	Surgery With or Without Preoperative Chemotherapy in Treating Patients With Resectable Non-small Cell Lung Cancer
NCT00003235	Phase 3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer That Can Not Be Surgically Removed
NCT00003240	Phase 3	UNKNOWN	Standard Therapy Given With or Without Combination Chemotherapy in Treating Patients With Non-small Cell Lung Cancer
NCT00003279	Phase 3	COMPLETED	Vaccination Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer
NCT00003299	Phase 3	COMPLETED	Cisplatin Plus Etoposide With or Without Paclitaxel in Treating Patients With Extensive-Stage Small Cell Lung Cancer
NCT00003313	Phase 3	COMPLETED	Amifostine in Treating Patients With Stage II or Stage III Non-small Cell Lung Cancer
NCT00003317	Phase 3	COMPLETED	Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Stage IIIA Non-small Cell Lung Cancer
NCT00003364	Phase 3	COMPLETED	Radiation Therapy Plus Combination Chemotherapy In Treating Patients With Limited Stage Small Cell Lung Cancer
NCT00003387	Phase 3	COMPLETED	Carboplatin, Paclitaxel, and Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed During Surgery
NCT00003447	Phase 3	UNKNOWN	Vinorelbine and/or Gemcitabine in Treating Older Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for EGFR across ~30M SureChEMBL compounds — explore on Sugi Predict.