EGFR

HIGH

Epidermal growth factor receptor

Chromosome: 7p11.2

Gene Overview

EGFR encodes the epidermal growth factor receptor, a receptor tyrosine kinase that binds EGF and related ligands to activate RAS-RAF-MAPK and PI3K-AKT signaling. Somatic EGFR mutations (especially exon 19 deletions and L858R) drive a subset of non-small cell lung cancers, particularly in never-smokers and East Asians. These mutations confer sensitivity to EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, osimertinib). EGFR overexpression occurs in many epithelial cancers. The receptor dimerizes upon ligand binding and autophosphorylates. Expression is highest in epithelial tissues. Germline EGFR variants may modify lung cancer risk. Resistance to TKIs commonly arises through T790M or MET amplification.

Molecular Function

  • receptor tyrosine kinase activity
  • EGF binding
  • signal transduction
  • cell proliferation

Protein class: receptor tyrosine kinase

Regulatory Annotation

Promoter activity: Epithelial-enriched; STAT and AP-1 elements.

Enhancer associations: Lung cancer GWAS variants may influence EGFR expression.

eQTL tissues: lung, skin

Tissue Expression Context

lungTPM range: 15-50GTEx vv8
skinTPM range: 10-35GTEx vv8

Pathways

Linked Diseases & Exposures

Diseases

Exposures

  • tobacco— literature, strength 0.78

Mechanistic Hypotheses

Activating EGFR mutations confer ligand-independent kinase activity; sustained PI3K and MAPK signaling drives proliferation and survival; tobacco exposure may select for EGFR wild-type tumors with different mutational profiles.

EGFR-mutant NSCLC responsive to TKIs; mutational spectrum differs between smokers and never-smokers.

HIGH

Confidence Rating

Overall evidence confidence for this gene entry: HIGH

References

  1. 1.Paez JG, et al. (2004). EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. doi:10.1126/science.1099314
  2. 2.GTEx Consortium (2020). GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science. doi:10.1126/science.aaz1776
  3. 3.Soria JC, et al. (2018). Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. New England Journal of Medicine. doi:10.1056/NEJMoa1713137