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); 297 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) — +3 more curated relationships
• GWAS associations: 35
• Clinical variants (ClinVar): 3,911 total — 65 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes — 175 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 298 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 13 cancer types
• Cancer dependency (DepMap): dependent in 17.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005228

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: 17 — 11 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000275493, ENST00000342916, ENST00000344576, ENST00000420316, ENST00000450046, ENST00000455089, ENST00000459688, ENST00000463948, ENST00000485503, ENST00000700144, ENST00000700145, ENST00000700146, ENST00000700147, ENST00000898199, ENST00000898200, ENST00000898201, ENST00000898202

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.

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

298 total, 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

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

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)

110 targeting EGFR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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.

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)

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. 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), 1 shown:

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

UniProt features (306 total): strand 76, sequence variant 40, helix 40, mutagenesis site 37, modified residue 25, disulfide bond 25, turn 15, 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)

388 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8A27	X-RAY DIFFRACTION	1.07
8A2D	X-RAY DIFFRACTION	1.11
5UG9	X-RAY DIFFRACTION	1.33
5HG8	X-RAY DIFFRACTION	1.42
8A2A	X-RAY DIFFRACTION	1.43
5UG8	X-RAY DIFFRACTION	1.46
3POZ	X-RAY DIFFRACTION	1.5
6TFV	X-RAY DIFFRACTION	1.5
6TG0	X-RAY DIFFRACTION	1.5
3VRP	X-RAY DIFFRACTION	1.52
5HG5	X-RAY DIFFRACTION	1.52
5CNO	X-RAY DIFFRACTION	1.55
5UGC	X-RAY DIFFRACTION	1.58
3G5Y	X-RAY DIFFRACTION	1.59
5U8L	X-RAY DIFFRACTION	1.6
6TG1	X-RAY DIFFRACTION	1.6
7SI1	X-RAY DIFFRACTION	1.6
8PO4	X-RAY DIFFRACTION	1.62
9GL8	X-RAY DIFFRACTION	1.63
9DF3	X-RAY DIFFRACTION	1.68
8A2B	X-RAY DIFFRACTION	1.69
3W33	X-RAY DIFFRACTION	1.7
6TFY	X-RAY DIFFRACTION	1.7
4I22	X-RAY DIFFRACTION	1.71
6WXN	X-RAY DIFFRACTION	1.76
9DF4	X-RAY DIFFRACTION	1.78
9FQS	X-RAY DIFFRACTION	1.78
6V66	X-RAY DIFFRACTION	1.79
5GNK	X-RAY DIFFRACTION	1.8
3P0Y	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab): 21 — 1YY9, 3B2U, 3B2V, 3C09, 3G5V, 3G5Y, 3P0Y, 4KRL, 4KRM, 4KRO, 4KRP, 4UV7, 5SX4, 5SX5, 5XWD, 6ARU, 6B3S, 7OM4, 8UKV, 9IP7, 9IPB

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): 837 (proton acceptor); 1016 (important for interaction with pik3c2b)

Ligand- & substrate-binding residues (4): 718–726; 745; 790–791; 855

Post-translational modifications (35): 229, 678, 693, 695, 745, 869, 991, 995, 998, 1016, 1026, 1039, 1041, 1042, 1064, 1069, 1070, 1071, 1081, 1092 …

Disulfide bonds (25): 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 …

Glycosylation sites (13): 56, 73, 128, 175, 196, 352, 361, 413, 444, 528, 568, 603, 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
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-
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

37 pathways

ID	Pathway
R-HSA-1227986	Signaling by ERBB2
R-HSA-1236382	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1236394	Signaling by ERBB4
R-HSA-1250196	SHC1 events in ERBB2 signaling
R-HSA-1251932	PLCG1 events in ERBB2 signaling
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-177929	Signaling by EGFR
R-HSA-179812	GRB2 events in EGFR signaling
R-HSA-180292	GAB1 signalosome
R-HSA-180336	SHC1 events in EGFR signaling
R-HSA-182971	EGFR downregulation
R-HSA-1963640	GRB2 events in ERBB2 signaling
R-HSA-1963642	PI3K events in ERBB2 signaling
R-HSA-212718	EGFR interacts with phospholipase C-gamma
R-HSA-2179392	EGFR Transactivation by Gastrin
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-445144	Signal transduction by L1
R-HSA-5637810	Constitutive Signaling by EGFRvIII
R-HSA-5638303	Inhibition of Signaling by Overexpressed EGFR
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6785631	ERBB2 Regulates Cell Motility
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8847993	ERBB2 Activates PTK6 Signaling
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-8857538	PTK6 promotes HIF1A stabilization
R-HSA-8863795	Downregulation of ERBB2 signaling
R-HSA-8866910	TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9013507	NOTCH3 Activation and Transmission of Signal to the Nucleus

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 (62): cell morphogenesis (GO:0000902), ossification (GO:0001503), embryonic placenta development (GO:0001892), positive regulation of protein phosphorylation (GO:0001934), hair follicle development (GO:0001942), ubiquitin-dependent protein catabolic process (GO:0006511), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), epidermal growth factor receptor signaling pathway (GO:0007173), salivary gland morphogenesis (GO:0007435), learning or memory (GO:0007611), positive regulation of cell population proliferation (GO:0008284), gene expression (GO:0010467), protein ubiquitination (GO:0016567), cerebral cortex cell migration (GO:0021795), 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), xenobiotic transport (GO:0042908), 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 epidermal growth factor receptor signaling pathway (GO:0045742), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of fibroblast proliferation (GO:0048146), digestive tract morphogenesis (GO:0048546), epithelial cell proliferation (GO:0050673), 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), morphogenesis of an epithelial fold (GO:0060571), eyelid development in camera-type eye (GO:0061029)

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 (35): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), endosome (GO:0005768), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cilium (GO:0005929), 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), ciliary basal body (GO:0036064), signaling receptor complex (GO:0043235), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), Shc-EGFR complex (GO:0070435), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), multivesicular body, internal vesicle lumen (GO:0097489), intracellular vesicle (GO:0097708), extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), endocytic vesicle (GO:0030139)

Reactome top-level categories

Rollup of top-11 pathways:

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

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
positive regulation of cellular process	2
epidermal growth factor receptor signaling pathway	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
cytoplasm	2
plasma membrane region	2
anatomical structure morphogenesis	1
multicellular organismal process	1
in utero embryonic development	1
placenta development	1
embryonic organ development	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
hair cycle process	1
anatomical structure development	1
skin epidermis development	1
protein ubiquitination	1
modification-dependent protein catabolic process	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
salivary gland development	1
gland morphogenesis	1
behavior	1
cognition	1
cell population proliferation	1
regulation of cell population proliferation	1
macromolecule biosynthetic process	1

Protein interactions and networks

STRING

11600 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EGFR	EGF	P01133	999
EGFR	HBEGF	Q99075	998
EGFR	TGFA	P01135	998
EGFR	GRB2	P29354	997
EGFR	NRG1	P98202	997
EGFR	EREG	O14944	996
EGFR	AREG	P15514	996
EGFR	CDH1	P12830	995
EGFR	CBL	P22681	995
EGFR	CD44	P16070	995
EGFR	BTC	P35070	995
EGFR	MUC1	P13931	994
EGFR	SHC1	P29353	994
EGFR	HSP90AA1	P07900	993
EGFR	HSP90AB1	P08238	993

IntAct

1747 interactions, top by confidence:

A	B	Type	Score
EGFR	GRB2	psi-mi:“MI:0915”(physical association)	0.980
EGFR	EGFR	psi-mi:“MI:0915”(physical association)	0.980
EGFR	EGFR	psi-mi:“MI:0844”(phosphotransfer reaction)	0.980
EGFR	EGFR	psi-mi:“MI:0407”(direct interaction)	0.980
EGFR	EGFR	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
EGFR	SHC1	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
EGFR	SHC1	psi-mi:“MI:0407”(direct interaction)	0.980
EGFR	SHC1	psi-mi:“MI:0915”(physical association)	0.980
EGF	EGFR	psi-mi:“MI:0407”(direct interaction)	0.970
EGFR	EGF	psi-mi:“MI:0407”(direct interaction)	0.970
EGFR	EGF	psi-mi:“MI:0915”(physical association)	0.970
EGFR	CBL	psi-mi:“MI:0915”(physical association)	0.960
ERBB2	EGFR	psi-mi:“MI:0914”(association)	0.950
ERBB2	EGFR	psi-mi:“MI:0915”(physical association)	0.950
EGFR	ERBB2	psi-mi:“MI:0915”(physical association)	0.950

BioGRID (5074): ERBB4 (FRET), ERBB4 (Affinity Capture-Western), CBL (Affinity Capture-Western), LRSAM1 (Affinity Capture-Western), SEC61A1 (Affinity Capture-Western), SEC61B (Co-fractionation), EGFR (Affinity Capture-Western), CBL (Affinity Capture-Western), EGFR (Biochemical Activity), EGFR (Affinity Capture-MS), ARL1 (Affinity Capture-MS), DSG2 (Affinity Capture-MS), SSBP1 (Affinity Capture-MS), MYO1B (Affinity Capture-MS), NGLY1 (Affinity Capture-MS)

ESM2 similar proteins: A4IGL7, D3ZB51, E9PZ19, O75882, O94779, O95970, P00533, P02469, P07942, P13590, P15209, P24503, P24786, P33150, P39038, P55245, P55283, P68500, P97300, P97527, P97546, Q01279, Q01973, Q03351, Q16288, Q16620, Q1EGL2, Q3B7N0, Q3UQ28, Q5IFJ9, Q5IS37, Q5IS82, Q5R945, Q63604, Q6IS24, Q6VNS1, Q7TPD3, Q7TT15, Q8K4Y5, Q8N475

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

200 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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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
InlB-mediated entry of Listeria monocytogenes into host cell	5	73.2×	4e-07
SHC1 events in EGFR signaling	5	68.6×	4e-07
Constitutive Signaling by EGFRvIII	5	68.6×	4e-07
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	6	65.9×	1e-07
Signaling by ERBB2 ECD mutants	5	64.6×	5e-07
VxPx cargo-targeting to cilium	6	59.9×	1e-07
Negative regulation of MET activity	6	59.9×	1e-07
SHC1 events in ERBB2 signaling	6	54.9×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking involved in exocytosis	5	55.2×	4e-06
membrane fission	6	40.4×	2e-06
epidermal growth factor receptor signaling pathway	8	32.5×	5e-08
receptor internalization	5	26.6×	9e-05
protein dephosphorylation	7	25.4×	2e-06
regulation of macroautophagy	5	24.2×	1e-04
mitotic cytokinesis	5	21.2×	2e-04
exocytosis	7	17.4×	2e-05

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).

Clinical variants and AI predictions

ClinVar

3911 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	65
Likely pathogenic	37
Uncertain significance	1789
Likely benign	1446
Benign	102

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1005727	NM_005228.5(EGFR):c.1605C>A (p.Cys535Ter)	Pathogenic
1016241	NM_005228.5(EGFR):c.2917C>T (p.Arg973Ter)	Pathogenic
1016463	NM_005228.5(EGFR):c.1536del (p.Glu513fs)	Pathogenic
1042058	NC_000007.13:g.(?55086755)(55274084_?)del	Pathogenic
1043841	NM_005228.5(EGFR):c.2577del (p.Lys860fs)	Pathogenic
1045120	NM_005228.5(EGFR):c.1418del (p.Asn473fs)	Pathogenic
1058215	NM_005228.5(EGFR):c.2650G>T (p.Glu884Ter)	Pathogenic
1425739	NM_005228.5(EGFR):c.2921_2928del (p.Asp974fs)	Pathogenic
1429922	NM_005228.5(EGFR):c.877A>T (p.Lys293Ter)	Pathogenic
1441678	NM_005228.5(EGFR):c.3061C>T (p.Gln1021Ter)	Pathogenic
1453945	NM_005228.5(EGFR):c.1860_1861delinsAA (p.Cys620_His621delinsTer)	Pathogenic
1456059	NC_000007.13:g.(?55221694)(55225456_?)del	Pathogenic
1457850	NM_005228.5(EGFR):c.113del (p.Leu38fs)	Pathogenic
1508578	NM_005228.5(EGFR):c.2720T>A (p.Leu907Ter)	Pathogenic
157499	NM_005228.5(EGFR):c.1283G>A (p.Gly428Asp)	Pathogenic
177620	NM_005228.5(EGFR):c.2236_2250del (p.Glu746_Ala750del)	Pathogenic
2032844	NM_005228.5(EGFR):c.492_511del (p.Trp164_Asp171delinsTer)	Pathogenic
2115063	NM_005228.5(EGFR):c.977_978del (p.Lys325_Cys326insTer)	Pathogenic
2129131	NM_005228.5(EGFR):c.2927del (p.Gln976fs)	Pathogenic
2425326	NC_000007.13:g.(?55223561)(55233842_?)del	Pathogenic
254143	NM_005228.5(EGFR):c.977G>T (p.Cys326Phe)	Pathogenic
2578363	NM_005228.5(EGFR):c.2317delinsAACCCCT (p.His773delinsAsnProTyr)	Pathogenic
2582257	NM_005228.5(EGFR):c.1792G>A (p.Gly598Arg)	Pathogenic
2582258	NM_005228.5(EGFR):c.2561C>T (p.Thr854Ile)	Pathogenic
2582280	NM_005228.5(EGFR):c.1786C>T (p.Pro596Ser)	Pathogenic
2582281	NM_005228.5(EGFR):c.2287G>A (p.Ala763Thr)	Pathogenic
2695031	NM_005228.5(EGFR):c.2090_2091dup (p.Ala698fs)	Pathogenic
2700802	NM_005228.5(EGFR):c.213_228del (p.Gln71fs)	Pathogenic
2701755	NM_005228.5(EGFR):c.357_361del (p.Leu119fs)	Pathogenic
2708436	NM_005228.5(EGFR):c.2956_2959del (p.Arg986fs)	Pathogenic

SpliceAI

4358 predictions. Top by Δscore:

Variant	Effect	Δscore
7:55142281:TCCA:T	acceptor_gain	1.0000
7:55142282:CCA:C	acceptor_loss	1.0000
7:55142282:CCAG:C	acceptor_gain	1.0000
7:55142283:CA:C	acceptor_loss	1.0000
7:55142283:CAGT:C	acceptor_gain	1.0000
7:55142284:A:AG	acceptor_gain	1.0000
7:55142284:AGTTT:A	acceptor_gain	1.0000
7:55142285:G:GA	acceptor_gain	1.0000
7:55142285:GT:G	acceptor_gain	1.0000
7:55142285:GTT:G	acceptor_gain	1.0000
7:55142285:GTTT:G	acceptor_gain	1.0000
7:55142285:GTTTG:G	acceptor_gain	1.0000
7:55142376:T:TA	donor_gain	1.0000
7:55142377:G:GA	donor_gain	1.0000
7:55142413:G:GT	donor_gain	1.0000
7:55142438:G:A	donor_loss	1.0000
7:55143300:CTTA:C	acceptor_loss	1.0000
7:55143302:TA:T	acceptor_loss	1.0000
7:55143303:A:AG	acceptor_gain	1.0000
7:55143303:A:T	acceptor_loss	1.0000
7:55143304:G:GA	acceptor_gain	1.0000
7:55143304:GAC:G	acceptor_gain	1.0000
7:55143304:GACC:G	acceptor_gain	1.0000
7:55143390:GAAA:G	donor_gain	1.0000
7:55143487:GG:G	donor_gain	1.0000
7:55143488:GG:G	donor_gain	1.0000
7:55146600:CCGCA:C	acceptor_loss	1.0000
7:55146601:CGCA:C	acceptor_loss	1.0000
7:55146602:GCAG:G	acceptor_loss	1.0000
7:55146603:CAGAA:C	acceptor_loss	1.0000

AlphaMissense

8041 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:55151334:G:C	W200C	1.000
7:55151334:G:T	W200C	1.000
7:55152560:T:A	C215S	1.000
7:55152560:T:C	C215R	1.000
7:55152561:G:A	C215Y	1.000
7:55152561:G:C	C215S	1.000
7:55152572:T:A	C219S	1.000
7:55152572:T:C	C219R	1.000
7:55152573:G:C	C219S	1.000
7:55152584:T:A	C223S	1.000
7:55152584:T:C	C223R	1.000
7:55152585:G:C	C223S	1.000
7:55152623:T:A	C236S	1.000
7:55152623:T:C	C236R	1.000
7:55152624:G:C	C236S	1.000
7:55152635:T:A	C240S	1.000
7:55152635:T:C	C240R	1.000
7:55152636:G:C	C240S	1.000
7:55154053:T:C	C264R	1.000
7:55154134:T:A	C291S	1.000
7:55154134:T:C	C291R	1.000
7:55154135:G:A	C291Y	1.000
7:55154135:G:C	C291S	1.000
7:55154136:C:G	C291W	1.000
7:55174014:G:C	G719R	1.000
7:55174015:G:A	G719D	1.000
7:55174015:G:T	G719V	1.000
7:55174020:G:C	G721R	1.000
7:55174020:G:T	G721C	1.000
7:55174021:G:A	G721D	1.000

dbSNP variants (sampled 300 via entrez): RS1000014555 (7:55097042 G>T), RS1000025564 (7:55105201 G>A), RS1000046500 (7:55137004 G>C), RS1000053581 (7:55131096 A>G), RS1000067126 (7:55143716 A>G), RS1000116619 (7:55145239 G>A,C), RS1000122637 (7:55134254 G>A), RS1000123493 (7:55099983 T>C), RS1000128342 (7:55061624 G>T), RS1000135996 (7:55090255 C>A,T), RS1000156821 (7:55098571 C>T), RS1000208834 (7:55127873 G>A,T), RS1000210392 (7:55044602 G>A,T), RS1000220819 (7:55083999 G>A), RS1000268809 (7:55159235 G>A)

Disease associations

OMIM: gene MIM:131550 | disease phenotypes: MIM:211980, MIM:616069, MIM:167000, MIM:275355, MIM:114480, MIM:109800, MIM:158350, MIM:108010

GenCC curated gene-disease

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

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
non-small cell lung carcinoma	Definitive	AD

Mondo (21): hereditary neoplastic syndrome (MONDO:0015356), lung cancer (MONDO:0008903), inflammatory skin and bowel disease, neonatal, 2 (MONDO:0014481), cerebral palsy (MONDO:0006497), ovarian cancer (MONDO:0008170), head and neck squamous cell carcinoma (MONDO:0010150), endometrial carcinoma (MONDO:0002447), hereditary breast carcinoma (MONDO:0016419), cholangiocarcinoma (MONDO:0019087), diffuse midline glioma, H3 K27-altered (MONDO:1060171), urinary bladder cancer (MONDO:0001187), lung adenocarcinoma (MONDO:0005061), lung carcinoma (MONDO:0005138), non-small cell lung carcinoma (MONDO:0005233), squamous cell carcinoma (MONDO:0005096)

Orphanet (11): Inherited cancer-predisposing syndrome (Orphanet:140162), Neonatal erythroderma-autoinflammation-inflammatory bowel disease syndrome (Orphanet:294023), Rare ovarian cancer (Orphanet:213500), Squamous cell carcinoma of head and neck (Orphanet:67037), Hereditary breast cancer (Orphanet:227535), Cholangiocarcinoma (Orphanet:70567), Brain arteriovenous malformation (Orphanet:46724), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), NON RARE IN EUROPE: Bladder cancer (Orphanet:157980), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268), NON RARE IN EUROPE: Non-small cell lung cancer (Orphanet:488201)

HPO phenotypes

21 total (23 of 21 shown, 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
HP:0100021	Cerebral palsy
HP:0012114	Endometrial carcinoma

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST001058_1	Glioma	7.000000e-08
GCST001058_7	Glioma	8.000000e-08
GCST003158_4	Subjective response to lithium treatment	1.000000e-06
GCST004347_11	Glioma	4.000000e-27
GCST004348_3	Non-glioblastoma glioma	2.000000e-08
GCST004349_6	Glioblastoma	5.000000e-34
GCST004349_7	Glioblastoma	5.000000e-23
GCST005931_5	Glioma	7.000000e-12
GCST005931_6	Glioma	2.000000e-09
GCST005931_7	Glioma	5.000000e-12
GCST005932_2	Glioblastoma	3.000000e-16
GCST005932_3	Glioblastoma	1.000000e-11
GCST005932_4	Glioblastoma	1.000000e-12
GCST006480_15	Glioblastoma (age-stratified)	2.000000e-12
GCST006480_16	Glioblastoma (age-stratified)	2.000000e-09
GCST006480_17	Glioblastoma (age-stratified)	6.000000e-08
GCST006480_2	Glioblastoma (age-stratified)	4.000000e-16
GCST006480_3	Glioblastoma (age-stratified)	2.000000e-11
GCST006480_4	Glioblastoma (age-stratified)	2.000000e-10
GCST006480_9	Glioblastoma (age-stratified)	7.000000e-12
GCST006633_17	Initial alcohol sensitivity	9.000000e-06
GCST007160_15	Refractive astigmatism	1.000000e-06
GCST007622_2	Impulsivity	1.000000e-06
GCST009269_24	Dental caries (decayed and filled deciduous teeth)	3.000000e-06
GCST009391_1578	Metabolite levels	4.000000e-06
GCST009391_1589	Metabolite levels	1.000000e-06
GCST009391_2011	Metabolite levels	4.000000e-09
GCST012488_45	L1-L4 bone mineral density x serum urate levels interaction	6.000000e-06
GCST90002391_220	Mean corpuscular hemoglobin concentration	2.000000e-09
GCST90002393_63	Monocyte count	4.000000e-09

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0006946	behavioural disinhibition measurement
EFO:0010349	cholesteryl ester 20:5 measurement
EFO:0010350	cholesteryl ester 22:6 measurement
EFO:0010348	cholesteryl ester 20:4 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 (9)

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
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400
D002547	Cerebral Palsy	C10.228.140.140.254
D018281	Cholangiocarcinoma	C04.557.470.200.025.450
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D002538	Intracranial Arteriovenous Malformations	C10.228.140.300.520; C10.500.190.500; C14.240.850.750.295; C14.240.850.875.500; C14.907.150.295; C14.907.253.560.400; C16.131.240.850.750.295; C16.131.240.850.875.500; C16.131.666.190.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
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
C562840	Breast Cancer, Familial (supp.)

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)

Molecules with ChEMBL bioactivity

175 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 854,879 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1009	LEVODOPA	4	103,854
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1079742	ERLOTINIB HYDROCHLORIDE	4	13,852
CHEMBL11359	CISPLATIN	4
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1200528	CHROMIC CHLORIDE	4
CHEMBL1200558	BACITRACIN	4	154
CHEMBL1200679	ZINC CHLORIDE	4	411,454
CHEMBL1201179	LAPATINIB DITOSYLATE	4	3,017
CHEMBL1229517	VEMURAFENIB	4	15,704
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1448	NICLOSAMIDE	4	14,322
CHEMBL1614701	SELUMETINIB	4	10,221
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL1738797	ALECTINIB	4	6,731
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1873475	IBRUTINIB	4
CHEMBL2105712	AFATINIB DIMALEATE	4
CHEMBL2105717	CABOZANTINIB	4
CHEMBL2105719	DACOMITINIB	4
CHEMBL2110732	DACOMITINIB ANHYDROUS	4
CHEMBL2403108	CERITINIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL24944	TRIBROMSALAN	4
CHEMBL288441	BOSUTINIB	4
CHEMBL290106	BITHIONOL	4

Clinical evidence (CIViC)

Drug × variant × indication: 298 predictive associations from 391 curated evidence items; also 15 prognostic, 14 functional, 13 oncogenic.

Variant	Therapy	Indication	Effect	Level	CIViC
EGFR L858R	Erlotinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID2994 +5
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	Dacomitinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11239 +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	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	Lazertinib + Amivantamab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID12131
EGFR L858R OR EGFR Exon 19 Deletion	Carboplatin + Pemetrexed + Amivantamab	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

+268 more predictive associations (showing top 30 by evidence level).

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

21 annotations.

Variant	Type	Level	Drugs	Phenotypes
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
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
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

18 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
rs2293348	EGFR		0.00	0
rs17172437	EGFR		0.00	0
rs73420732	EGFR		0.00	0
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
rs28929495	EGFR		0.00	0
rs10258429	EGFR	3	3.00	1	imatinib
rs2330951	EGFR	3	2.50	1	sorafenib
rs917881	EGFR	3	1.50	2	sorafenib
rs2072454	EGFR		0.00	0
rs763317	EGFR		0.00	0
rs10228436	EGFR		0.00	0

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 (106 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)

3356 measured of 4082 human assays (4173 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)-1H-imidazo[4,5-g]quinazolin-8-amine	IC50	0.008 nM
4-N-(3-bromophenyl)-6-N-methylpyrido[3,4-d]pyrimidine-4,6-diamine	IC50	0.008 nM
CHEMBL5633067	IC50	0.009 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
N-(3,4-dibromophenyl)-6,7-dimethoxyquinazolin-4-amine	IC50	0.072 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
2-[(10S,17E)-12-ethyl-8,10,16-trimethyl- 2,8,10,11,12,13-hexahydro-14H-3,5- ethenotripyrazolo[3,4-f:3’,4’-j:4″,3″- n][1,4]oxazacyclopentadecin-14- yl]ethan-1-ol	IC50	0.09 nM	US-20250353864: INDAZOLE CONTAINING MACROCYCLES AND THEIR USE
4-N-(3-bromophenyl)quinazoline-4,7-diamine	IC50	0.1 nM
N-[5-(1-acetylpiperidin-4-yl)-1-(4-hydroxycyclohexyl)benzimidazol-2-yl]-2-(1-methylpyrazol-4-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-11174245: Benzimidazole compounds and derivatives as EGFR inhibitors
2-[(10S,17E)-8,10,16-trimethyl-12- (propan-2-yl)-2,8,10,11,12,13- hexahydro-14H-3,5- ethenotripyrazolo[3,4-f:3’,4’-j:4″,3″- n][1,4]oxazacyclopentadecin-14- yl]ethan-1-ol	IC50	0.1 nM	US-20250353864: INDAZOLE CONTAINING MACROCYCLES AND THEIR USE
BDBM200762	IC50	0.11 nM	US-9670231: Fused tricyclic amide compounds as multiple kinase inhibitors
4-N-(3-bromophenyl)quinazoline-4,6,7-triamine	IC50	0.12 nM
{[(10S,17E)-14-(2-hydroxyethyl)- 8,10,12-trimethyl-2,10,11,12,13,14- hexahydro-8H-3,5-ethenotripyrazolo[3,4- f:3’,4’-j:4″,3″- n][1,4]oxazacyclopentadecin-16- yl]oxy}acetonitrile	IC50	0.12 nM	US-20250353864: INDAZOLE CONTAINING MACROCYCLES AND THEIR USE
(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-[(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
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
5-isopropyl-N-(2-(1-((1-(methoxymethyl)cyclopropyl)methyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-8-((2R,3S)-2-methyl-3-((methanesulfonyl)methyl)azetidin-1-yl)isoquinolin-3-amine	IC50	0.17 nM	US-20250368616: NITROGEN-CONTAINING HETEROCYCLIC DERIVATIVE INHIBITOR, AND PREPARATION METHOD THEREFOR AND USE THEREOF
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
2-cyano-N-[1-(4-hydroxycyclohexyl)benzimidazol-2-yl]-6-(1-methylpyrazol-4-yl)pyridine-4-carboxamide	IC50	0.2 nM	US-11174245: Benzimidazole compounds and derivatives as EGFR inhibitors
N-[1-(4-hydroxycyclohexyl)-6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-2-yl]-2-methyl-6-(1-methylpyrazol-4-yl)pyridine-4-carboxamide	IC50	0.2 nM	US-11174245: Benzimidazole compounds and derivatives as EGFR inhibitors
N-[1-(4-hydroxycyclohexyl)-6-(1-methylpiperidin-4-yl)benzimidazol-2-yl]-2-methyl-6-(1-methylpyrazol-4-yl)pyridine-4-carboxamide	IC50	0.2 nM	US-11174245: Benzimidazole compounds and derivatives as EGFR inhibitors
3,3-difluoro-N-[4-[3-(4-fluorophenyl)-1-methylpyrazol-4-yl]-7-methoxyquinazolin-6-yl]cyclobutane-1-carboxamide	IC50	0.2 nM	US-20250236608: EGFR INHIBITORS
3-(3-chloro-2-methoxyanilino)-2-[3-[[(2S)-1-prop-2-enoylpyrrolidin-2-yl]methoxy]-4-pyridinyl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	IC50	0.21 nM	WO-2022101184: N-[2-({4-[3-(ANILINO)-4-OXO-4,5,6,7-TETRAHYDRO-1H-PYRROLO[3,2-C]PYRIDIN-2-YL]PYRIDIN-3-YL)OXY)ETHYL]PROP-2-ENAMIDE DERIVATIVES AND SIMILAR COMPOUNDS AS EGFR INHIBITORS FOR THE TREATMENT OF CANCER
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
2-[(10S,17E)-16-ethoxy-8,10-dimethyl- 12-(propan-2-yl)-2,8,10,11,12,13- hexahydro-14H-3,5- ethenotripyrazolo[3,4-f:3’,4’-j:4″,3″- n][1,4]oxazacyclopentadecin-14- yl]ethan-1-ol	IC50	0.22 nM	US-20250353864: INDAZOLE CONTAINING MACROCYCLES AND THEIR USE
2-{(10S,17E)-12-ethyl-8,10-dimethyl-16- [(propan-2-yl)oxy]-2,8,10,11,12,13- hexahydro-14H-3,5- ethenotripyrazolo[3,4-f:3’,4’-j:4″,3″- n][1,4]oxazacyclopentadecin-14- yl}acetamide	IC50	0.22 nM	US-20250353864: INDAZOLE CONTAINING MACROCYCLES AND THEIR USE
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
6,7-dimethoxy-N-[3-(trifluoromethyl)phenyl]quinazolin-4-amine	IC50	0.24 nM
2-({4-[(3-bromophenyl)amino]pyrido[4,3-d]pyrimidin-7-yl}amino)ethan-1-ol	IC50	0.24 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

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

3093 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
N-[3-[[4-[5-(4-fluorophenyl)-2-(3-hydroxypropyl)-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
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
(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

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

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

653 cell lines: 468 cancer cell line, 130 factor-dependent cell line, 45 spontaneously immortalized cell line, 8 transformed cell line, 1 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)

329 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00158041	PHASE4	COMPLETED	Subcutaneous Amifostine Safety Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00440960	PHASE4	COMPLETED	Anesthesia in Flexible Bronchoscopy for Lung Cancer Diagnostic
NCT00492843	PHASE4	TERMINATED	Loading Dose or Standard Dose of Intravenous Ibandronate in Treating Patients With Lung Cancer and Skeletal Metastasis
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00675168	PHASE4	UNKNOWN	Positron Emission Tomography (PET)/Computed Tomography (CT) and Roentgen in Lung Cancer: Evaluation of Patients in General Practice
NCT00712647	PHASE4	COMPLETED	Carotene and Retinol Efficacy Trial
NCT00747773	PHASE4	COMPLETED	Cryospray Ablation of Surgical Resection Specimens To Determine Safety And Histological Effect In The Lung
NCT01060137	PHASE4	COMPLETED	Fentanyl Matrix in Lung Cancer Pain
NCT01381627	PHASE4	UNKNOWN	Safety Evaluation of Dexmedetomidine for EBUS-TBNA
NCT01741506	PHASE4	COMPLETED	Coagulation Profile in Patients Undergoing Video Assisted Thorascopic Surgery (VATS) for Lung Cancer
NCT02246023	PHASE4	COMPLETED	Fractionated Versus Target-controlled Propofol Administration in Bronchoscopy
NCT02275702	PHASE4	COMPLETED	Randomized Study of Preoperative Dexamethasone for Quality of Recovery in VATS Lung Resection Patients
NCT02346318	PHASE4	UNKNOWN	The Randomized Controlled Clinical Trial of Kushen Injection
NCT02476526	PHASE4	COMPLETED	Safety of Low Dose IV Contrast CT Scanning in Chronic Kidney Disease
NCT02490059	PHASE4	COMPLETED	Ultrathin Bronchoscopy for Solitary Pulmonary Nodules
NCT02504801	PHASE4	UNKNOWN	Efficacy of Nebulized Pulmicort Respules in Primary Lung Cancer Patients With COPD
NCT02869789	PHASE4	COMPLETED	An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers
NCT03302221	PHASE4	WITHDRAWN	Regional Haemodynamic Changes in Radial Artery Assessment With Continuous Pulsed-wave Doppler Ultrasound
NCT03313544	PHASE4	UNKNOWN	Evolution of the Heart Function When Monitoring Immunotherapies Anti-cancerous Inhibiting PD-1
NCT03394222	PHASE4	COMPLETED	Effect of Preoperative Budesonide Inhalation on Arterial Blood Oxygenation and Intrapulmonary Shunt During OLV
NCT03570645	PHASE4	COMPLETED	Comparison of the Duration of Ropivacaine Combined With Dexmedetomidine or Dexamethasone on Paravertebral Block
NCT03571126	PHASE4	UNKNOWN	Olanzapine for the Prevention and Treatment of Nausea and Vomiting Induced by Chemotherapy of Lung Cancer
NCT03642457	PHASE4	TERMINATED	Efficacy Between Serratus Plane Block And Local Infiltration In Vats
NCT04145570	PHASE4	COMPLETED	A Single-Dose,ComparativeBioavailability Study ofTwo Formulations ofErlotinib150mgTabletsunderFastingConditions
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04613284	PHASE4	UNKNOWN	Rh-Endostatin Combined With CCRT(50 Gy) Followed by Durvalumab Maintenance for the Treatment of Specific Phase III NSCLC
NCT05463913	PHASE4	RECRUITING	Lung Nodule Detection Using Ultra-long FOV PET/CT
NCT05521789	PHASE4	RECRUITING	Erector Spinae Block for Thoracic Surgery
NCT05525338	PHASE4	RECRUITING	Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels
NCT05663242	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Lung Tumors and Its Mechanism of Action
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06105801	PHASE4	RECRUITING	EBUS-TBNA vs Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing
NCT06276933	PHASE4	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	PHASE4	RECRUITING	PROspective Master-protocol for Evaluation of Systemic THErapeutics in Elderly With Thoracic Malignancies
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00002550	PHASE3	COMPLETED	Chemotherapy Plus Radiation Therapy With or Without Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer
NCT00002583	PHASE3	COMPLETED	Vinorelbine + Cisplatin or No Further Therapy in Non-small Cell Lung Cancer That Has Been Surgically Removed
NCT00002623	PHASE3	COMPLETED	Chemotherapy Followed by Surgery or Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer