EGFR

Epidermal growth factor receptor (EGFR/ERBB1/HER1) is a receptor tyrosine kinase (EC 2.7.10.1) that binds EGF family ligands (EGF, TGF-alpha, amphiregulin, betacellulin, epiregulin, epigen, HB-EGF) to initiate signal transduction cascades controlling cell proliferation, survival, differentiation, and migration. Upon ligand binding, EGFR undergoes homo- or heterodimerization (with ERBB2, ERBB3, ERBB4), which activates the intracellular tyrosine kinase domain through trans-autophosphorylation. Phosphorylated tyrosine residues in the C-terminal tail serve as docking sites for SH2/PTB domain-containing adaptor proteins (GRB2, SHC, etc.), leading to activation of RAS-RAF-MEK-ERK (MAPK), PI3K-AKT, PLCgamma-PKC, and STAT signaling pathways. EGFR localizes primarily to the plasma membrane and continues signaling from early endosomes after clathrin-mediated endocytosis. Receptor downregulation occurs through CBL-mediated ubiquitination and lysosomal degradation. EGFR mutations and overexpression drive multiple cancers including non-small cell lung cancer, colorectal cancer, and glioblastoma.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

• corticotroph_egfr_pomc_acth_activation via USP8-related pituitary adenoma 4 named in the module itself