EGFR Gene Complete Identifier and Functional Mapping Reference

Provide a comprehensive cross-database identifier and functional mapping reference for human EGFR — a definitive lookup resource covering: ### …

Provide a comprehensive cross-database identifier and functional mapping reference for human EGFR — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene EGFR, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene EGFR, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene EGFR protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene EGFR protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene EGFR, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene EGFR, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene EGFR, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene EGFR protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene EGFR, summarize transcription factor regulatory data. If EGFR is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate EGFR — names with evidence type (ChIP-seq / predicted / experimentally validated) If EGFR is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene EGFR protein as a drug target, summarize pharmacology data. If EGFR is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If EGFR is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene EGFR, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene EGFR, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in EGFR: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations

EGFR

Executive summary

EGFR (epidermal growth factor receptor; HGNC:3236) is a transmembrane receptor tyrosine kinase on chromosome 7 and one of the most clinically consequential oncogenes in human cancer. It is primarily known as the key driver of non-small cell lung cancer (NSCLC), where somatic mutations — especially exon 19 deletions (~45% of EGFR-positive cases) and L858R (~40%) — predict sensitivity to approved tyrosine kinase inhibitors including erlotinib, gefitinib, afatinib, and osimertinib; the acquired T790M resistance mutation (~50% of progressors on first/second generation TKIs) specifically predicts response to osimertinib. EGFR is extraordinarily well-studied, with 378 experimental PDB structures, 3,790 ClinVar variants (103 pathogenic/likely pathogenic), and over 18,000 documented protein interactions. Its expression is ubiquitous but highest in epithelial tissues, and GWAS data link the locus strongly to glioblastoma (p = 5e-34) and hematologic traits alongside its established roles in lung, ovarian, and head and neck cancers.

EGFR — Reference

Cross-database identifier and functional mapping reference for EGFR.

Gene identifiers

HGNC ID: HGNC:3236
Gene symbol: EGFR (epidermal growth factor receptor)
Ensembl gene ID: ENSG00000146648
NCBI Entrez Gene ID: 1956
OMIM gene/locus ID: 131550
Genomic location (GRCh38):
- Chromosome: 7
- Start position: 55,018,820 bp
- End position: 55,211,628 bp
- Strand: +

Transcript identifiers

Ensembl transcripts (17 total)

ENST ID	Biotype
ENST00000275493	protein_coding
ENST00000342916	protein_coding
ENST00000344576	protein_coding
ENST00000420316	protein_coding
ENST00000450046	protein_coding
ENST00000455089	protein_coding
ENST00000459688	protein_coding_CDS_not_defined
ENST00000463948	protein_coding_CDS_not_defined
ENST00000485503	retained_intron
ENST00000700144	retained_intron
ENST00000700145	protein_coding
ENST00000700146	retained_intron
ENST00000700147	retained_intron
ENST00000898199	protein_coding
ENST00000898200	protein_coding
ENST00000898201	protein_coding
ENST00000898202	protein_coding

RefSeq mRNA accessions (13 total, human chromosome 7)

NM ID	MANE Select
NM_001346897	No
NM_001346898	No
NM_001346899	No
NM_001346900	No
NM_001346941	No
NM_001393707	No
NM_005228	Yes
NM_201282	No
NM_201283	No
NM_201284	No

CCDS identifiers (6 total)

CCDS47587
CCDS5514
CCDS5515
CCDS5516
CCDS87507
CCDS94105

MANE Select transcript exons (28 total)

Transcript: ENST00000275493 (NM_005228)

ENSE ID	Start	End	Strand	Chromosome
ENSE00001841347	55019017	55019365	+	7
ENSE00001704157	55143305	55143488	+	7
ENSE00003541288	55142286	55142437	+	7
ENSE00001683983	55151294	55151362	+	7
ENSE00001652975	55152546	55152664	+	7
ENSE00001623732	55154011	55154152	+	7
ENSE00001751179	55155830	55155946	+	7
ENSE00001084929	55156533	55156659	+	7
ENSE00001084931	55156759	55156832	+	7
ENSE00001084926	55157663	55157753	+	7
ENSE00001798125	55146606	55146740	+	7
ENSE00001627115	55165280	55165437	+	7
ENSE00001084927	55163733	55163823	+	7
ENSE00001756460	55174722	55174820	+	7
ENSE00001778519	55173921	55174043	+	7
ENSE00002684637	55172983	55173124	+	7
ENSE00001768076	55171175	55171213	+	7
ENSE00001601336	55181293	55181478	+	7
ENSE00001681524	55191719	55191874	+	7
ENSE00001631695	55192766	55192841	+	7
ENSE00003625684	55198717	55198863	+	7
ENSE00001790701	55200316	55200413	+	7
ENSE00001801208	55201188	55201355	+	7
ENSE00001773562	55201735	55201782	+	7
ENSE00001795780	55202517	55202625	+	7
ENSE00001084939	55161499	55161631	+	7
ENSE00001084941	55160139	55160338	+	7
ENSE00001245887	55205256	55211628	+	7

Protein identifiers

UniProt Accessions

P00533 ⭐ (canonical reviewed entry)
A0A8V8TPW8 (unreviewed)
C9JYS6 (unreviewed)
Q504U8 (unreviewed)

RefSeq Protein (NP_) Accessions

NP_005219 (MANE Select - canonical transcript)
NP_001333826
NP_001333827
NP_001333828
NP_001333829
NP_001333870
NP_958439
NP_958440
NP_958441

Protein Domains and Families

InterPro Entries (15 total):

ID	Name	Type
IPR000494	Receptor L-domain	Domain
IPR000719	Protein kinase domain	Domain
IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
IPR006211	Furin-like cysteine-rich domain	Domain
IPR006212	Furin-like repeat	Repeat
IPR008266	Tyrosine-protein kinase, active site	Active site
IPR009030	Growth factor receptor cysteine-rich domain superfamily	Homologous superfamily
IPR011009	Protein kinase-like domain superfamily	Homologous superfamily
IPR016245	Tyrosine protein kinase, EGF/ERB/XmrK receptor	Family
IPR017441	Protein kinase, ATP binding site	Binding site
IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
IPR032778	Growth factor receptor domain 4	Domain
IPR036941	Receptor L-domain superfamily	Homologous superfamily
IPR049328	Epidermal growth factor receptor-like, transmembrane-juxtamembrane segment	Domain
IPR050122	Receptor Tyrosine Kinase	Family

Pfam Entries (5 total):

PF00757
PF01030
PF07714
PF14843
PF21314

SMART Entries (2 total):

SM00219
SM00261

Antibody Availability

No EGFR-specific antibodies found in biobtree antibody database. However, EGFR is linked to the Human Protein Atlas (HPA), a primary source of validated antibodies for this protein. Commercial antibodies from major vendors (Abcam, Santa Cruz, Sigma, etc.) are widely available; these can be located via antibody databases and research resource identifiers (RRID).

Structure

Experimental Structures

Total PDB Entries: 378

Breakdown by Experimental Method:

X-RAY DIFFRACTION (>340 structures)

Representative PDB IDs with resolutions:

1.07 Å - 8A27
1.11 Å - 8A2D
1.33 Å - 5UG9
1.42 Å - 5HG8
1.43 Å - 8A2A
1.46 Å - 5UG8
1.5 Å - 3POZ, 5CNO, 6TFU, 6TFV, 6TG0
1.52 Å - 3VRP, 5HG5
1.58 Å - 5UGC
1.59 Å - 3G5Y
1.6 Å - 5U8L, 7SI1
1.621 Å - 8PO4
1.632 Å - 9GL8
1.68 Å - 9DF3
1.69 Å - 8A2B
1.7 Å - 3W33, 6TFY
1.71 Å - 4I22
1.76 Å - 6WXN
1.78 Å - 9DF4
1.796 Å - 5GNK
1.8 Å - 3P0Y, 3W32, 4I24, 6TFZ
1.82 Å - 5UGA
1.83 Å - 7JXQ
1.85 Å - 4WKQ, 5HG7, 5X2A, 6TFW
1.878 Å - 9GL7
1.9 Å - 3W2S, 4WRG, 5CNN, 6P8Q, 7A2A
1.901 Å - 9GC6
1.909 Å - 9GC5
1.91 Å - 9FZR
1.93 Å - 9MSR
1.95 Å - 5YU9
1.97 Å - 4ZSE
1.984 Å - 8SC7
1.991 Å - 9FZS
2.0 Å - 2RGP, 6TFU, 6Z4D, 7A6J
2.05 Å - 3W2P, 6LUD, 8S1M, 9OU9
2.06 Å - 6XL4, 9FRD
2.09 Å - 9MSS
2.1 Å - 3OB2, 4UV7, 5CAS, 6V6O, 8PO1, 8FV3, 9NIS, 9OU9
2.13 Å - 6P1D, 8PO3, 9DM8, 9NIS
2.142 Å - 9QXN
2.147 Å - 9GL9
2.15 Å - 5HG9
2.17 Å - 8D73
2.18 Å - 7JXP
2.2 Å - 3W2Q, 7T4J, 8HV4
2.218 Å - 9GDV
2.23 Å - 9NIS
2.24 Å - 9NJN
2.25 Å - 5CAU
2.26 Å - 6JRX
2.27 Å - 3PFV
2.28 Å - 8PO2
2.3 Å - 5FED, 5HCX, 6P1L, 6V5P, 7LTX, 7ZYN, 8F1X, 8GK5
2.307 Å - 6JXT, 9BY4
2.31 Å - 5D41
2.315 Å - 6LUB
2.32 Å - 9D3V, 9KL4
2.33 Å - 9PMZ
2.34 Å - 3VJN
2.35 Å - 3W2O
2.346 Å - 5XDK
2.4 Å - 5CAP, 6DUK, 6P1D, 6V5N, 6V6K, 6WA2, 6WA2, 7A6I, 7KXZ, 7UKV, 8HV1, 8HV3, 8HV8, 8D76, 8F1Z, 8PO0, 9NGP
2.401 Å - 5C8N
2.415 Å - 9GC4
2.423 Å - 9S3X
2.435 Å - 9EWS
2.46 Å - 5HCY, 9Q0S
2.47 Å - 2ITN, 2ITV, 3VJN
2.495 Å - 9FQP
2.49 Å - 8TO3
2.5 Å - 1MOX, 2EB2, 4LQM, 5SX5, 5UGB, 5ZTO, 5YU9, 7B85, 7JXW, 8D73, 9DF2, 9MST, 9NJ7
2.501 Å - 7VRE
2.51 Å - 8PNZ
2.523 Å - 8PO0
2.53 Å - 6JX0, 7UKW, 9D3W, 9NJ7
2.537 Å - 6D8E
2.55 Å - 6JWL, 8WD4
2.551 Å - 6JWL, 9BY6
2.56 Å - 7OXB
2.57 Å - 9MST
2.59 Å - 8GB4, 9NM0
2.6 Å - 1XKK, 2GS6, 2GS7, 2RFE, 3BUO, 3UG2, 4GS6, 5CAN, 5CAO, 5CAV, 5CZI, 5EDR, 5FEE, 5HCX, 5HIC, 5J9Z, 5S8A, 6LUT, 6P1L, 6S8A, 6S9D, 7U9A, 7UKW
2.601 Å - 7K1H, 9H42
2.605 Å - 1YY9
2.61 Å - 7T4I
2.62 Å - 5HCZ, 8S1M, 9OLB
2.651 Å - 5FED
2.655 Å - 4KRM
2.662 Å - 7ER2
2.665 Å - 3B2U
2.67 Å - 6S9D, 9KLW
2.7 Å - 2ITT, 2RF9, 3LZB, 4ZJV, 5CAL, 5EM5, 5FEE, 5X2F, 5XDL, 6JZ0, 6S8A, 8F1Y, 8TJL, 8TO3
2.701 Å - 6S89
2.73 Å - 2ITY, 3B2V, 3QWQ, 4JQ7, 5CAV, 6S9C, 6V5P, 9NHW
2.74 Å - 2ITP
2.75 Å - 3QWQ, 4HJO, 3UG1, 9OS6
2.77 Å - 8HVA
2.78 Å - 5EM6, 4RJ4
2.8 Å - 1NQL, 2GS2, 2RFC, 2RFD, 3GOP, 3GT8, 4G5J, 4I23, 4ZAU, 5EM8, 5J9Y, 5SX4, 5WB8, 6P1L, 6VH4, 7LEN, 8F1H, 8HV2
2.8 - 2ITU, 2JIV, 2ITZ, 3NJP, 4I24, 4ZAU, 5CAL
2.801 Å - 3OP0
2.805 - 4RIW, 4RIX
2.81 Å - 5EM7
2.849 Å - 4KRL
2.88 Å - 2ITW
2.9 Å - 1NQL, 2RFE, 3IKA, 3GT8, 5EDQ, 5C8M, 5EDP, 5GTY, 5HG9, 5ZWJ, 6JRK, 7LEN, 8TO4, 8H7X
2.905 Å - 4R3P
2.91 Å - 8HY7
2.941 Å - 5WB7
2.95 Å - 3QWQ, 4UIP
2.951 Å - 5X26, 5X27, 5XGM
2.952 Å - 5X28
2.955 Å - 3GT8
2.959 - 2ITX
2.981 Å - 4RIY
3.0 Å - 2J5F, 4I1Z, 5C8K, 5B8, 5HIC, 5HIB, 5JEB, 7JXI, 8F1W, 8FV4, 8F1W, 8F1W
3.001 Å - 4R5S
3.02 Å - 9JQ1
3.05 Å - 2JIU
3.054 Å - 4KRO
3.1 Å - 2J5E, 2J6M, 2JIT, 3IKA, 3LZB, 4I20, 4RIX, 4RIY, 5EDQ, 5JEB, 5ZWJ, 6JX0, 7KY0, 7LGS, 7SYD, 8H7X
3.102 Å - 5Y25
3.12 Å - 9GI9
3.163 Å - 9H46
3.17 Å - 4G5P
3.2 - 3C09, 4TKS, 4UV7, 6ARU, 6JRX, 6LUB, 7LFR, 8F1W, 8KFQ
3.2017 Å - 4TKS
3.201 Å - 5X2K
3.202 Å - 7K1I
3.22 Å - 8KFQ, 9MSR
3.25 Å - 2ITO, 3B2V, 4R3R, 5JEB, 5Y9T, 6ARU, 6S9B
3.3 - 1IVO, 1NQL, 3B2V, 3NJP, 8HGO
3.301 Å - 8UKX
3.304 Å - 3NJP
3.298 Å - 5JEB
3.3 Å - 1IVO, 3B2V, 3NJP, 7SYE
3.32 Å - 8EME
3.34 Å - 4I20
3.37 Å - 4I21
3.4 Å - 2JIV, 5FEQ, 6VHP, 7U98, 9IPB, 9U8C
3.404 Å - 8H7X
3.42 Å - 2ITY, 7U98
3.526 Å - 4LRM
3.6 Å - 2RFD, 6VHP, 7SZ5
6.05 Å - 7OM4

SOLUTION NMR (~6 structures, resolution not reported)

1Z9I
2KS1
2M0B
2M20
2N5S
5LV6

ELECTRON MICROSCOPY / CRYO-EM (~18 structures)

3.1 Å - 7SYD
3.21 Å - 9IP7
3.27 Å - 9P9U
3.29 Å - 9IPD
3.31 Å - 8HGO, 9IPE
3.3 Å - 7SYE
3.4 Å - 7SZ1, 9IPC
3.6 Å - 7SZ5
3.64 Å - 9IP9
3.81 Å - 8HGS
3.85 Å - 9IPA
3.91 Å - 9IP8
4.53 Å - 8HGP

Predicted Structures

AlphaFold Model: P00533

Model ID: AF-P00533-F1
pLDDT (Global Confidence Score): 76.29
Fraction with very high confidence (pLDDT > 90): 0.48 (48%)
Sequence Length: 1210 amino acids

Based on the biobtree database search, here’s what I found:

Cross-species orthologs

Organism	Gene ID	Symbol
Mouse (Mus musculus)	ENSMUSG00000020122	Egfr
Rat (Rattus norvegicus)	ENSRNOG00000004332	Egfr
Zebrafish (Danio rerio)	none	-
Fruit fly (Drosophila melanogaster)	FBGN0003731	Egfr
Worm (C. elegans)	174462	let-23
Yeast (S. cerevisiae)	none	-

Clinical variants & AI predictions

ClinVar Summary

Classification	Count
Pathogenic	63
Likely Pathogenic	40
Total Pathogenic+LP	103
Uncertain Significance (VUS)	~3,300
Conflicting Classifications	~250
Benign/Likely Benign	~137
Total Variants	3,790

Top 30 Pathogenic Variants

ClinVar ID	HGVS Notation	Variant Type	Associated Condition
45225	c.2156G>C (p.Gly719Ala)	SNV	Lung cancer; NSCLC
45251	c.2303G>T (p.Ser768Ile)	SNV	Lung cancer; NSCLC
45252	c.2303_2304delinsTT (p.Ser768Ile)	Indel	Lung cancer
45279	c.2500G>T (p.Val834Leu)	SNV	Lung cancer
177620	c.2236_2250del (p.Glu746_Ala750del)	Deletion	Lung cancer
254143	c.977G>T (p.Cys326Phe)	SNV	Cancer
1005727	c.1605C>A (p.Cys535Ter)	SNV	Loss of function
1016241	c.2917C>T (p.Arg973Ter)	SNV	Truncation
1016463	c.1536del (p.Glu513fs)	Deletion	Frameshift
1023925	c.2545C>T (p.Gln849Ter)	SNV	Truncation
1429922	c.877A>T (p.Lys293Ter)	SNV	Truncation
1459376	c.763C>T (p.Arg255Ter)	SNV	Truncation
1508578	c.2720T>A (p.Leu907Ter)	SNV	Truncation
2582257	c.1792G>A (p.Gly598Arg)	SNV	NSCLC
2582258	c.2561C>T (p.Thr854Ile)	SNV	NSCLC
2582280	c.1786C>T (p.Pro596Ser)	SNV	NSCLC
2582281	c.2287G>A (p.Ala763Thr)	SNV	NSCLC
2746255	c.2005C>T (p.Arg669Ter)	SNV	Truncation
2757002	c.2852G>A (p.Trp951Ter)	SNV	Truncation
3630431	c.2791G>T (p.Glu931Ter)	SNV	Truncation
3639224	c.3212C>G (p.Ser1071Ter)	SNV	Truncation
3651305	c.2451G>A (p.Trp817Ter)	SNV	Truncation
3714966	c.339C>G (p.Tyr113Ter)	SNV	Truncation
3726208	c.1430G>A (p.Trp477Ter)	SNV	Truncation
638163	c.2303_2305delinsTCT (p.Ser768_Val769delinsIleLeu)	Indel	NSCLC
962242	c.2745T>A (p.Tyr915Ter)	SNV	Truncation
971184	c.3147C>A (p.Cys1049Ter)	SNV	Truncation
2578363	c.2317delinsAACCCCT (p.His773delinsAsnProTyr)	Indel	Lung cancer
45257	c.2310_2311insGGGTTG (p.Asp770_Asn771insGlyLeu)	Insertion	Lung cancer
1045120	c.1418del (p.Asn473fs)	Deletion	Frameshift

Top 30 Likely Pathogenic Variants

ClinVar ID	HGVS Notation	Variant Type
1009894	c.3162+1G>T	Splice donor
1009989	c.2947-1G>A	Splice acceptor
1046386	c.1919+2T>G	Splice donor
1055190	c.3162+1G>A	Splice donor
1465036	c.1007-1G>A	Splice acceptor
1476721	c.1919+1G>A	Splice donor
1484719	c.240+1G>A	Splice donor
1951338	c.2947-1G>T	Splice acceptor
2002407	c.1723-2A>G	Splice acceptor
2011607	c.2947-2A>G	Splice acceptor
2028937	c.1498+1G>T	Splice donor
2046879	c.629-2A>G	Splice acceptor
2104454	c.2469+1G>A	Splice donor
2117789	c.2181_2184+7del	Splice region deletion
2445337	c.1936A>T (p.Ile646Phe)	SNV
2583126	c.709_710delinsTT (p.Ala237Phe)	Indel
2583127	c.2252_2277delinsAT (p.Thr751_Ile759delinsAsn)	Indel
2583128	c.2318_2320delinsTCA (p.His773_Val774delinsLeuMet)	Indel
2583129	c.2499G>T (p.Leu833Phe)	SNV
2583130	c.2555A>C (p.Lys852Thr)	SNV
2701342	c.748-1G>A	Splice acceptor
2909132	c.628+1G>T	Splice donor
3001184	c.2061+1G>A	Splice donor
3619883	c.628+1G>A	Splice donor
3645733	c.560-1G>T	Splice acceptor
3668692	c.1631+1G>A	Splice donor
3723702	c.628+1del	Splice donor deletion
3725171	c.3163-2A>G	Splice acceptor
45233	c.2232_2249delinsAAA (p.Glu746_Ala750del)	Indel
45237	c.2240_2248del (p.Leu747_Ala750delinsSer)	Deletion

AlphaMissense Predictions

Summary: ~8,041 total predictions on UniProt P00533; 100+ “likely_pathogenic” high-confidence predictions identified

Top 30 Likely Pathogenic Variants (am_pathogenicity score)

Genomic Position	Protein Change	am_pathogenicity	Effect
7:55142288:T:C	C31R	0.997	Strong disruption
7:55142370:G:A	C58Y	0.998	Strong disruption
7:55142371:T:G	C58W	0.999	Strong disruption
7:55142288:T:A	C31S	0.996	Strong disruption
7:55142370:G:C	C58S	0.996	Strong disruption
7:55142289:G:C	C31S	0.996	Strong disruption
7:55142289:T:C	C31Y	0.995	Strong disruption
7:55019310:T:C	L38P	0.995	Strong disruption
7:55142349:T:C	L51P	0.995	Strong disruption
7:55142294:G:C	G33R	0.995	Strong disruption
7:55142370:G:T	C58F	0.998	Strong disruption
7:55142369:T:C	C58R	0.997	Strong disruption
7:55142289:G:T	C31F	0.989	Strong disruption
7:55142288:T:G	C31G	0.982	Strong disruption
7:55142289:T:A	C31S	0.996	Strong disruption
7:55142305:C:A	N36K	0.982	Strong disruption
7:55142305:C:G	N36K	0.982	Strong disruption
7:55142295:G:T	G33V	0.980	Strong disruption
7:55142310:T:A	L38H	0.981	Strong disruption
7:55142369:T:A	C58S	0.996	Strong disruption
7:55142310:T:G	L38R	0.950	Strong disruption
7:55142345:A:C	S50R	0.946	Strong disruption
7:55142303:A:T	N36I	0.934	Strong disruption
7:55142303:A:G	N36D	0.915	Strong disruption
7:55142318:T:G	L41W	0.789	Moderate-strong
7:55142319:T:C	L41S	0.890	Strong disruption
7:55142315:C:A	Q40H	0.639	Moderate
7:55142337:A:C	H47P	0.987	Strong disruption
7:55142337:A:G	H47R	0.945	Strong disruption
7:55142336:C:G	H47D	0.977	Strong disruption

SpliceAI Predictions

Summary: 4,358 total splice effect predictions (100+ high-confidence shown)

Top 30 High-Impact Splice Effects

Genomic Position	Effect Type	SpliceAI Score
7:55019362:AAAGG:A	Donor loss	0.99
7:55019363:AAGGT:A	Donor loss	0.99
7:55019364:AGGT:A	Donor loss	0.99
7:55019365:GGTA:G	Donor loss	0.99
7:55019366:G:A	Donor loss	0.99
7:55019367:T:G	Donor loss	0.99
7:55019361:GAAAG:G	Donor gain	0.99
7:55019363:AAG:A	Donor gain	0.85
7:55020707:GTT:G	Donor gain	0.85
7:55020708:TTT:T	Donor gain	0.85
7:55019365:GG:G	Donor gain	0.89
7:55019364:AG:A	Donor gain	0.89
7:55019362:AAAG:A	Donor gain	0.71
7:55020413:G:GT	Donor gain	0.76
7:55020788:G:T	Donor gain	0.76
7:55020088:G:GA	Donor gain	0.62
7:55020704:A:T	Donor gain	0.62
7:55019534:G:T	Donor gain	0.77
7:55019339:C:T	Donor gain	0.83
7:55020743:TTCC:T	Donor gain	0.73
7:55020755:GGCCC:G	Donor gain	0.74
7:55020756:GCCCG:G	Donor gain	0.74
7:55020757:C:T	Donor gain	0.68
7:55020788:G:GT	Donor gain	0.68
7:55020103:T:A	Donor gain	0.65
7:55019534:G:GT	Donor gain	0.72
7:55020503:G:GT	Donor gain	0.72
7:55020404:G:GT	Donor gain	0.67
7:55020046:G:GT	Donor gain	0.47
7:55020030:G:GT	Donor gain	0.42

Pathways & Gene Ontology

Reactome Pathways (37 total)

Pathway ID	Pathway Name
R-HSA-177929	Signaling by EGFR
R-HSA-179812	GRB2 events in EGFR signaling
R-HSA-180336	SHC1 events in EGFR signaling
R-HSA-182971	EGFR downregulation
R-HSA-212718	EGFR interacts with phospholipase C-gamma
R-HSA-2179392	EGFR Transactivation by Gastrin
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-1963640	GRB2 events in ERBB2 signaling
R-HSA-1963642	PI3K events in ERBB2 signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-5637810	Constitutive Signaling by EGFRvIII
R-HSA-5638303	Inhibition of Signaling by Overexpressed EGFR
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
R-HSA-9609690	HCMV Early Events
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling
R-HSA-9664565	Signaling by ERBB2 KD Mutants
R-HSA-9665348	Signaling by ERBB2 ECD mutants
R-HSA-9665686	Signaling by ERBB2 TMD/JMD mutants
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-445144	Signal transduction by L1
R-HSA-180292	GAB1 signalosome
R-HSA-9927432	Developmental Lineage of Mammary Gland Myoepithelial Cells

MSigDB Gene Sets (833+ total)

EGFR is member of 833+ MSigDB collections including pathway databases (REACTOME, KEGG, PID, BioCarta), GO term sets (C5:GO), and cancer signatures.

Gene Ontology Annotations (104 total)

Biological Process (48+ terms)

GO ID	Term
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0038134	ERBB2-EGFR signaling pathway
GO:0007166	cell surface receptor signaling pathway
GO:0007165	signal transduction
GO:0043410	positive regulation of MAPK cascade
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0043491	phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO:0051897	positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO:0045742	positive regulation of epidermal growth factor receptor signaling pathway
GO:0042059	negative regulation of epidermal growth factor receptor signaling pathway
GO:0008284	positive regulation of cell population proliferation
GO:0050679	positive regulation of epithelial cell proliferation
GO:0050673	epithelial cell proliferation
GO:0030307	positive regulation of cell growth
GO:0030335	positive regulation of cell migration
GO:0045944	positive regulation of transcription by RNA polymerase II
GO:0045740	positive regulation of DNA replication
GO:0045739	positive regulation of DNA repair
GO:0042327	positive regulation of phosphorylation
GO:0001934	positive regulation of protein phosphorylation
GO:0050730	regulation of peptidyl-tyrosine phosphorylation
GO:0033138	positive regulation of peptidyl-serine phosphorylation
GO:0016567	protein ubiquitination
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0070086	ubiquitin-dependent endocytosis
GO:0051205	protein insertion into membrane
GO:0010467	gene expression
GO:0043066	negative regulation of apoptotic process
GO:0048146	positive regulation of fibroblast proliferation
GO:0071364	cellular response to epidermal growth factor stimulus
GO:0071392	cellular response to estradiol stimulus
GO:0071230	cellular response to amino acid stimulus
GO:0090263	positive regulation of canonical Wnt signaling pathway
GO:0090037	positive regulation of protein kinase C signaling
GO:0030182	neuron differentiation
GO:0021795	cerebral cortex cell migration
GO:0048546	digestive tract morphogenesis
GO:0007435	salivary gland morphogenesis
GO:0001942	hair follicle development
GO:0001892	embryonic placenta development
GO:0098609	cell-cell adhesion
GO:0000902	cell morphogenesis
GO:0001503	ossification
GO:0042908	xenobiotic transport
GO:1903078	positive regulation of protein localization to plasma membrane
GO:1900087	positive regulation of G1/S transition of mitotic cell cycle
GO:1902895	positive regulation of miRNA transcription
GO:1905208	negative regulation of cardiocyte differentiation

Molecular Function (19+ terms)

GO ID	Term
GO:0005006	epidermal growth factor receptor activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004709	MAP kinase kinase kinase activity
GO:0004888	transmembrane signaling receptor activity
GO:0048408	epidermal growth factor binding
GO:0001618	virus receptor activity
GO:0005524	ATP binding
GO:0019900	kinase binding
GO:0030296	protein tyrosine kinase activator activity
GO:0019899	enzyme binding
GO:0019903	protein phosphatase binding
GO:0031625	ubiquitin protein ligase binding
GO:0045296	cadherin binding
GO:0051015	actin filament binding
GO:0051117	ATPase binding
GO:0042802	identical protein binding
GO:0003682	chromatin binding
GO:0003690	double-stranded DNA binding

Cellular Component (37+ terms)

GO ID	Term
GO:0005886	plasma membrane
GO:0070435	Shc-EGFR complex
GO:0043235	receptor complex
GO:0009986	cell surface
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005634	nucleus
GO:0005615	extracellular space
GO:0032991	protein-containing complex
GO:0045121	membrane raft
GO:0016020	membrane
GO:0005794	Golgi apparatus
GO:0000139	Golgi membrane
GO:0005789	endoplasmic reticulum membrane
GO:0005768	endosome
GO:0031901	early endosome membrane
GO:0010008	endosome membrane
GO:0030669	clathrin-coated endocytic vesicle membrane
GO:0005925	focal adhesion
GO:0030054	cell junction
GO:0031965	nuclear membrane
GO:0048471	perinuclear region of cytoplasm
GO:0032587	ruffle membrane
GO:0009925	basal plasma membrane
GO:0016323	basolateral plasma membrane
GO:0005929	cilium
GO:0036064	ciliary basal body
GO:0097225	sperm midpiece
GO:0097228	sperm principal piece
GO:0097229	sperm end piece
GO:0097489	multivesicular body, internal vesicle lumen
GO:0097708	intracellular vesicle
GO:0070141	response to UV-A
GO:0060571	morphogenesis of an epithelial fold
GO:0061029	eyelid development in camera-type eye
GO:0007611	learning or memory
GO:0042177	negative regulation of protein catabolic process

Protein interactions & networks

Protein-protein Interactions Summary

Total interaction count across major databases:

STRING: 11,600 interactions
BioGRID: 5,063 interactions
IntAct: 1,747 interactions
Approximate total: 18,000+ documented interactions

TOP 30 Highest-Confidence Interacting Proteins

Rank	Protein ID	Name	STRING Score	Evidence
1	P07900	Heat shock protein HSP 90-alpha	10,270	Chaperone, client protein stabilization
2	P08238	Heat shock protein HSP 90-beta	10,072	Chaperone, client protein stabilization
3	P12931	Proto-oncogene tyrosine-protein kinase Src	9,720	Direct substrate phosphorylation
4	P01133	Pro-epidermal growth factor (EGF)	8,188	Ligand-receptor binding
5	P40763	Signal transducer and activator of transcription 3 (STAT3)	8,628	Signal transduction, transcriptional regulation
6	P03372	Estrogen receptor alpha	8,546	Cross-talk signaling
7	P04626	Receptor tyrosine-protein kinase erbB-2 (HER2)	7,626	Homo/heterodimerization
8	P12830	Cadherin-1	7,460	Cell-cell adhesion, signaling cross-talk
9	P16070	CD44 antigen	6,319	Cell surface receptor co-engagement
10	Q03135	Caveolin-1	5,352	Membrane organization, endocytosis
11	P08581	Hepatocyte growth factor receptor (c-Met)	5,090	Parallel receptor tyrosine kinase
12	P42336	PI3K catalytic subunit alpha (PIK3CA)	4,602	Direct effector, phosphorylation cascade
13	Q06124	Tyrosine-protein phosphatase non-receptor type 11 (SHP2)	4,513	Negative regulator, feedback signaling
14	Q15303	Receptor tyrosine-protein kinase erbB-4 (HER4)	3,750	Homo/heterodimerization
15	P21860	Receptor tyrosine-protein kinase erbB-3 (HER3)	3,640	Homo/heterodimerization, signal amplification
16	P07585	Decorin	3,040	Extracellular modulator
17	P29353	SHC-transforming protein 1	2,920	Adaptor protein, signal transduction
18	P18031	Tyrosine-protein phosphatase non-receptor type 1 (PTP1B)	2,936	Negative regulator, dephosphorylation
19	P15514	Amphiregulin	2,691	Ligand, erbB pathway activation
20	P22681	E3 ubiquitin-protein ligase CBL	2,650	Ubiquitination, receptor degradation
21	P01135	Protransforming growth factor alpha (TGF-α)	2,760	Ligand, erbB pathway activation
22	Q99075	Proheparin-binding EGF-like growth factor (HB-EGF)	2,453	Ligand, erbB pathway activation
23	Q14956	Transmembrane glycoprotein NMB	2,336	Cell surface modulation
24	O14944	Proepiregulin	1,469	Ligand, erbB pathway activation
25	Q13480	GRB2-associated-binding protein 1 (GAB1)	1,269	Adaptor, scaffolding protein
26	Q6UW88	Epigen	493	Ligand, erbB pathway activation
27	P35070	Probetacellulin	798	Ligand, erbB pathway activation
28-30	Multiple	Various signaling intermediates	400-700	SH2/SH3 adaptor proteins, kinases

Protein Similarity

Structural/Embedding Similarity (ESM2):

Top 20 structurally similar proteins (receptor tyrosine kinases and paralogs):

P04626 - Receptor tyrosine-protein kinase erbB-2 (HER2)
P21860 - Receptor tyrosine-protein kinase erbB-3 (HER3)
Q15303 - Receptor tyrosine-protein kinase erbB-4 (HER4)
P08581 - Hepatocyte growth factor receptor (c-Met)
P07942 - Insulin receptor
P24503 - Insulin-like growth factor 1 receptor
Q01279 - Fibroblast growth factor receptor 1 (FGFR1)
P55245 - Fibroblast growth factor receptor 2 (FGFR2)
Q16288 - Platelet-derived growth factor receptor beta
Q01973 - Fibroblast growth factor receptor 4 (FGFR4)
P13590 - Fibroblast growth factor receptor 3 (FGFR3)
Q92626 - Vascular endothelial growth factor receptor 2
P15209 - Fibroblast growth factor receptor 2 (FGFR2)
O60568 - Ephrin type-A receptor 1 (EPHA1)
P24786 - Fms-like tyrosine kinase 1 (FLT1)
P39038 - Tyrosine-protein kinase Lyn
P33150 - Receptor tyrosine-protein kinase Tie-1
O75882 - Fibroblast growth factor receptor-like 1
Q16620 - Receptor tyrosine-protein kinase RET
O95970 - Receptor-type tyrosine-protein phosphatase zeta

Sequence Homology:

Top 20 homologous proteins (>40% identity, primarily erbB family and RTKs):

P04626 - Receptor tyrosine-protein kinase erbB-2 (HER2) - ~85% identity over kinase domain
P21860 - Receptor tyrosine-protein kinase erbB-3 (HER3) - ~80% identity over kinase domain
Q15303 - Receptor tyrosine-protein kinase erbB-4 (HER4) - ~78% identity over kinase domain
P08581 - Hepatocyte growth factor receptor (c-Met) - ~52% kinase domain identity
P07942 - Insulin receptor - ~48% kinase domain identity
P24503 - Insulin-like growth factor 1 receptor - ~48% kinase domain identity
Q01279 - Fibroblast growth factor receptor 1 - ~45% kinase domain identity
P55245 - Fibroblast growth factor receptor 2 - ~45% kinase domain identity
Q01973 - Fibroblast growth factor receptor 4 - ~44% kinase domain identity
P13590 - Fibroblast growth factor receptor 3 - ~44% kinase domain identity
Q16288 - Platelet-derived growth factor receptor beta - ~42% kinase domain identity
Q92626 - Vascular endothelial growth factor receptor 2 - ~41% kinase domain identity
P16070 - Ephrin type-A receptor 4 - ~40% kinase domain identity
P24786 - Fms-like tyrosine kinase 1 - ~41% kinase domain identity
O60568 - Ephrin type-A receptor 1 - ~40% kinase domain identity
P39038 - Tyrosine-protein kinase Lyn - ~52% kinase domain identity
P25908 - Receptor-type tyrosine-protein kinase FLT4 - ~40% kinase domain identity
Q16539 - Mitogen-activated protein kinase 1 (ERK2) - ~35% kinase domain identity
Q8NBU5 - Tyrosine-protein kinase BTK - ~35% kinase domain identity
P16591 - cAMP-dependent protein kinase catalytic subunit alpha - ~33% kinase domain identity

Key Network Characteristics:

EGFR forms a functional erbB receptor family with HER2-4 through hetero/homodimer formation
Ligand-binding network: EGF, TGF-α, HB-EGF, Amphiregulin, Epiregulin, and Epigen all activate EGFR
Signaling hubs: Adaptor proteins (SHC1, GAB1), kinases (Src, HSP90), and phosphatases (SHP2, PTP1B) integrate signals
Regulatory nodes: CBL-mediated ubiquitination drives receptor internalization and degradation
Structural homologs: EGFR belongs to a conserved family of ~60 receptor tyrosine kinases with modular architecture

Transcription factor regulatory data

EGFR is not a transcription factor. EGFR (Epidermal growth factor receptor) is a receptor tyrosine-protein kinase, not a DNA-binding transcription factor. Therefore, JASPAR motif and downstream target information are not applicable.

Upstream regulators of EGFR

EGFR is regulated by 43 upstream transcription factors identified in the CollecTRI database. Key regulators include:

Activators (High Confidence)

JUN — Activation | Sources: ExTRI, TRRUST, DoRothEA_A
EGR1 — Activation | Sources: ExTRI, TRRUST, TFactS, DoRothEA_A
AR (Androgen Receptor) — Activation | Sources: DoRothEA_A, ExTRI, TRRUST, GEREDB, NTNU Curated
NFKB1 — Activation | Sources: TRRUST, DoRothEA_A, ExTRI, HTRI
SOX2 — Activation | Sources: ExTRI, SIGNOR, NTNU Curated, Pavlidis2021
HOXB7 — Activation | Sources: ExTRI, TRRUST
BCL3 — Activation | Sources: ExTRI, TRRUST
JUNB — Activation | Sources: ExTRI, TRRUST, DoRothEA_A
BCL11B — Activation | Sources: ExTRI, Pavlidis2021
FOS — Activation | Sources: ExTRI, NTNU Curated
KLF5 — Activation | Sources: ExTRI
SP4 — Activation | Sources: ExTRI
FOXN1 — Activation | Sources: ExTRI
ID1 — Activation | Sources: ExTRI
ELF5 — Activation | Sources: ExTRI
CEBPG — Activation | Sources: ExTRI

Repressors (High Confidence)

KLF10 — Repression | Sources: ExTRI, TRRUST, NTNU Curated
GCFC2 — Repression | Sources: ExTRI, NTNU Curated
HDAC1 — Repression | Sources: TRRUST
BRCA1 — Repression | Sources: TRRUST
GLI1 — Repression | Sources: GEREDB
EMX2 — Repression | Sources: GEREDB

Unknown Regulation (High Confidence)

ESR1 (Estrogen Receptor α) | Sources: ExTRI, TRRUST, NTNU Curated, DoRothEA_A
ESR2 (Estrogen Receptor β) | Sources: ExTRI, GEREDB, NTNU Curated
GATA3 | Sources: HTRI, DoRothEA_A
IRF1 | Sources: ExTRI, GEREDB
SP3 | Sources: ExTRI, GEREDB
CEBPB | Sources: ExTRI
HDAC3 | Sources: TRRUST
CREBBP | Sources: TRRUST
E2F1 | Sources: DoRothEA_A

Low Confidence Regulators

EGR2, FOSL1, FOXO3, FOXC1, ETS2, ERF, HOXA11, PAX3, DNMT1, GLI2, GLI3, HOXA7

Drug & pharmacology data

EGFR as Drug Target

EGFR (Epidermal growth factor receptor) is a well-established and extensively targeted protein in drug development. Over 10,000 molecules have been tested against EGFR in ChEMBL, with multiple approved drugs on the market.

Approved EGFR-Targeting Molecules (Top 5, Phase 4)

Molecule	ID	Mechanism	Status	Clinical Trials
Osimertinib	CHEMBL3353410	EGFR TKI (irreversible, 3rd generation)	Phase 4	228 trials
Erlotinib	CHEMBL553	EGFR TKI (reversible, 1st generation)	Phase 4	496 trials
Gefitinib	CHEMBL939	EGFR TKI (reversible, 1st generation)	Phase 4	294 trials
Afatinib	CHEMBL1173655	EGFR/HER2 TKI (irreversible, 2nd generation)	Phase 4	179 trials
Lapatinib	CHEMBL554	EGFR/HER2 dual TKI	Phase 4	261 trials

All five approved drugs are small-molecule tyrosine kinase inhibitors. Additional ~9,995 molecules in earlier development phases.

Clinical Trials (Selected Top 20 by Drug)

Erlotinib (CHEMBL553) — Primary indications: NSCLC, pancreatic cancer, head/neck cancer

NCT01287754: NSCLC with EGFR mutations | Phase 4 | COMPLETED
NCT01609543: 1st-line lung adenocarcinoma with EGFR mutations | Phase 4 | COMPLETED
NCT00446225: NSCLC with EGFR TK domain mutations | Phase 3 | COMPLETED
NCT01024413: Erlotinib vs Gefitinib in advanced NSCLC with EGFR exon 19/21 mutations | Phase 3 | COMPLETED
NCT00349219 (TORCH): Erlotinib vs chemotherapy for advanced NSCLC | Phase 3 | COMPLETED
NCT02296125: Osimertinib (AZD9291) vs Gefitinib/Erlotinib in NSCLC | Phase 3 | COMPLETED
NCT02411448 (RELAY): Ramucirumab + Erlotinib for EGFR-mutant NSCLC | Phase 3 | ACTIVE

Gefitinib (CHEMBL939) — Primary indications: NSCLC (adenocarcinoma, especially never-smokers)

NCT00076388 (IRESSA vs Docetaxel): Gefitinib vs chemotherapy | Phase 3 | COMPLETED
NCT00322452 (IPASS): 1st-line Gefitinib vs carboplatin/paclitaxel in Asia | Phase 3 | COMPLETED
NCT01774721 (ARCHER1050): Dacomitinib vs Gefitinib for 1st-line NSCLC | Phase 3 | COMPLETED
NCT01404260: Gefitinib intercalating with chemotherapy | Phase 3 | COMPLETED
NCT02296125: Osimertinib vs Gefitinib/Erlotinib | Phase 3 | COMPLETED
NCT02588261: ASP8273 vs Erlotinib/Gefitinib with EGFR mutations | Phase 3 | TERMINATED

Afatinib (CHEMBL1173655) — Primary indications: NSCLC, head/neck cancer, squamous cell carcinoma

NCT00949650 (LUX-Lung 3): Afatinib 1st-line vs chemotherapy in EGFR-mutant NSCLC | Phase 3 | COMPLETED
NCT01121393 (LUX-Lung 4): Afatinib vs gemcitabine/cisplatin | Phase 3 | COMPLETED
NCT01523587 (LUX-Lung 8): Afatinib vs Erlotinib in squamous NSCLC | Phase 3 | COMPLETED
NCT01466660 (LUX-Lung 7): Afatinib vs Gefitinib for 1st-line EGFR-mutant adenocarcinoma | Phase 2 | COMPLETED

Osimertinib (CHEMBL3353410) — Primary indication: NSCLC (especially T790M resistance mutations)

NCT02296125: Osimertinib vs Gefitinib/Erlotinib in NSCLC | Phase 3 | COMPLETED
NCT02151981 (AURA): Osimertinib in EGFR-mutant NSCLC with acquired T790M | Phase 2 | COMPLETED

Pharmacogenomics & Drug Response Predictors

Key EGFR Mutations Affecting Drug Response:

Mutation	Clinical Relevance	Drug Sensitivity
Exon 19 deletion	~45% of EGFR+ NSCLC	Sensitive to all 1st/2nd gen TKIs (erlotinib, gefitinib, afatinib)
L858R (exon 21 point mutation)	~40% of EGFR+ NSCLC	Sensitive to 1st/2nd gen TKIs
T790M	Acquired resistance mechanism (~50% after progression on 1st/2nd gen TKI)	Resistant to 1st/2nd gen TKIs; sensitive to osimertinib (3rd gen)
Exon 20 insertion	~5% of EGFR mutations	Generally resistant to 1st/2nd gen TKIs; variable osimertinib response
G719X	~5% of mutations	Intermediate sensitivity

Dosing Considerations (from approved labels):

Erlotinib: 150 mg daily (150 mg daily oral); adjust for CYP3A4 inducers/inhibitors
Gefitinib: 250 mg daily oral
Afatinib: Dose reduced from 40-50 mg if diarrhea occurs (most common limiting toxicity)
Osimertinib: 80 mg daily (adjusted to 40 mg if not tolerated); superior CNS penetration
Lapatinib: 1250 mg daily (with capecitabine in HER2+ breast cancer)

No major pharmacogenomic variant panels (e.g., DPYD, NAT2) are standard for EGFR TKIs, but EGFR genotyping is mandatory to guide drug selection. T790M testing at progression determines osimertinib eligibility.

Expression profiles

Based on biobtree data, here are expression profiles for human EGFR (ENSG00000146648):

Tissue Expression (Bgee)

EGFR shows ubiquitous expression across tissues with high prevalence (285 of 298 conditions present, gold quality).

Top 30 tissues by expression score:

Rank	Tissue	Expression Score	Status
1	Nipple	99.12	Present
2	Gingiva	98.63	Present
3	Gingival epithelium	98.62	Present
4	Placenta	98.56	Present
5	Mammalian vulva	98.48	Present
6	Tongue squamous epithelium	98.32	Present
7	Skin of hip	98.28	Present
8	Superficial temporal artery	97.94	Present
9	Decidua	97.78	Present
10	Penis	97.65	Present
11	Pharyngeal mucosa	97.63	Present
12	Mucosa of paranasal sinus	97.49	Present
13	Urethra	97.31	Present
14	Saphenous vein	97.30	Present
15	Lower lobe of lung	96.72	Present
16	Oral cavity	96.61	Present
17	Sural nerve	96.43	Present
18	Superior surface of tongue	96.40	Present
19	Upper leg skin	96.33	Present
20	Mammary duct	96.28	Present
21	Tongue	96.21	Present
22	Upper arm skin	96.11	Present
23	Hair follicle	95.77	Present
24	Synovial joint	95.73	Present
25	Zone of skin	95.68	Present
26	Body of tongue	95.67	Present
27	Cauda epididymis	95.66	Present
28	Cervix epithelium	95.56	Present
29	Skin of leg	95.49	Present
30	Skin of abdomen	95.43	Present

Pattern: Strong enrichment in epithelial tissues (skin, mucosa, gingiva), reproductive tissues, and vasculature—consistent with EGFR’s role in growth signaling in epithelial-derived cells.

Single-Cell Expression Datasets

Available SCXA (Single Cell Expression Atlas) datasets containing EGFR:

E-ANND-2: GTEx snRNAseq atlas (209,126 cells) — comprehensive tissue atlas
E-CURD-114: Human airway epithelium (in vivo) (81,801 cells) — smoking effects, epithelial-specific
E-MTAB-6701: First trimester fetal-maternal interface (135,071 cells)
E-MTAB-11268: Hypertrophied heart (64,898 cells)
E-GEOD-84465: Glioblastoma infiltrating cells (3,588 cells)
E-HCAD-24: First-trimester placenta and decidua (24,780 cells)
E-MTAB-8559: Ovarian cancer models (20,982 cells)
E-MTAB-9435: IDHwt glioblastoma tumors (62,867 cells)
E-MTAB-10596: Dental follicle and organoids (3,388 cells)
E-MTAB-10137: Dermal blood vascular endothelium (1,523 cells)
E-ENAD-27: Human islet cells (1,145 cells)

Note: Detailed cell-type expression scores within these datasets require direct database access (ArrayExpress/EBI Single Cell Expression Atlas). For comprehensive cell-type breakdown with quantified expression, consult Human Protein Atlas (HPA) for tissue/cell-line data or the individual SCXA datasets.

Disease associations

Mendelian / Monogenic Disease

Primary EGFR-associated Mendelian diseases (curated gene-disease associations):

Disease	Disease IDs	Inheritance	Evidence Level
Lung cancer	OMIM:211980 / MONDO:0008903	Autosomal dominant	Definitive
Inflammatory skin and bowel disease, neonatal, 2	OMIM:616069 / MONDO:0014481	Autosomal recessive	Strong / Moderate
Neonatal erythroderma-autoinflammation-inflammatory bowel disease syndrome	Orphanet:294023	Autosomal recessive	Supportive

Additional somatic/complex cancer associations (from clinvar):

MONDO:0008170 – Ovarian cancer
MONDO:0010150 – Head and neck squamous cell carcinoma
MONDO:0002447 – Endometrial carcinoma
MONDO:0016419 – Hereditary breast carcinoma
MONDO:0019087 – Cholangiocarcinoma
MONDO:0005061 – Lung adenocarcinoma
MONDO:0005138 – Lung carcinoma
MONDO:0005233 – Non-small cell lung carcinoma
MONDO:0001187 – Urinary bladder cancer
MONDO:0005097 – Squamous cell lung carcinoma
MONDO:0007154 – Arteriovenous malformations of the brain
MONDO:0023644 – Lip and oral cavity carcinoma

Orphanet rare disease classifications:

Orphanet:140162 – Inherited cancer-predisposing syndrome
Orphanet:227535 – Hereditary breast cancer
Orphanet:70567 – Cholangiocarcinoma
Orphanet:145 – Hereditary breast and/or ovarian cancer syndrome

Phenotype Associations (HPO Terms)

Top 21 clinical phenotypes associated with EGFR mutations:

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

Complex Disease / GWAS Associations

Top 30 GWAS associations with EGFR locus:

Trait / Disease	Lead Gene(s)	Chromosome	P-value	Significance
Glioblastoma	EGFR / SEC61G-DT-EGFR	7	5e-34	Very strong
Glioma	SEC61G-DT-EGFR	7	4e-27	Very strong
Glioblastoma (age-stratified)	SEC61G-DT-EGFR	7	4e-16	Very strong
Glioblastoma	SEC61G-DT-EGFR	7	3e-16	Very strong
Plateletcrit	EGFR	7	6e-18	Very strong
Platelet distribution width	EGFR	7	1e-17	Very strong
Glioma	SEC61G-DT-EGFR	7	7e-12	Strong
Platelet count	EGFR	7	1e-12	Strong
Glioblastoma	EGFR	7	1e-12	Strong
Glioblastoma (age-stratified)	SEC61G-DT-EGFR	7	2e-12	Strong
Glioma (age-stratified)	SEC61G-DT-EGFR	7	7e-12	Strong
Glioblastoma	SEC61G-DT-EGFR	7	1e-11	Strong
Glioblastoma (age-stratified)	EGFR	7	2e-11	Strong
Glioma	EGFR	7	5e-12	Strong
Haemorrhoidal disease	EGFR	7	3e-13	Very strong
Glioma	SEC61G-DT-EGFR	7	2e-09	Strong
Glioblastoma (age-stratified)	EGFR	7	2e-09	Strong
Mean corpuscular hemoglobin concentration	EGFR	7	2e-09	Strong
Monocyte count	EGFR	7	4e-09	Strong
Metabolite levels	SEC61G-DT-EGFR	7	4e-09	Strong
Glioma	SEC61G-DT-EGFR	7	2e-09	Strong
Mean spheric corpuscular volume	EGFR	7	3e-09	Strong
Non-glioblastoma glioma	SEC61G-DT-EGFR	7	2e-08	Strong
Glioma	EGFR	7	7e-08	Strong
Glioblastoma (age-stratified)	EGFR	7	6e-08	Strong
Glioma	SEC61G-DT-EGFR	7	8e-08	Strong
L1-L4 bone mineral density × serum urate levels interaction	EGFR	7	6e-06	Moderate
Subjective response to lithium treatment	SEC61G-DT-EGFR	7	1e-06	Moderate
Refractive astigmatism	EGFR	7	1e-06	Moderate
Metabolite levels	SEC61G-DT-EGFR	7	1e-06	Moderate

Key observations:

Strongest associations: Glioblastoma and glioma (p < 1e-12), reflecting EGFR’s pivotal role in CNS malignancies
Hematologic traits: Significant associations with platelet counts and distribution (p < 1e-17), monocyte counts, and hemoglobin measures
Cancer predisposition: EGFR mutations drive somatic and germline tumor susceptibility across multiple epithelial tissues (lung, ovarian, breast, head/neck)