EGF
Chr 4epidermal growth factor
Also known as: HOMG4, URG
This gene encodes a member of the epidermal growth factor superfamily. The encoded preproprotein is proteolytically processed to generate the 53-amino acid epidermal growth factor peptide. This protein acts a potent mitogenic factor that plays an important role in the growth, proliferation and differentiation of numerous cell types. This protein acts by binding with high affinity to the cell surface receptor, epidermal growth factor receptor. Defects in this gene are the cause of hypomagnesemia type 4. Dysregulation of this gene has been associated with the growth and progression of certain cancers. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
Limited evidence — not for standalone diagnostic reporting
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
664 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 1 | 0 | 0 | 1 |
Likely Pathogenic | 2 | 0 | 0 | 0 | 2 |
VUS | 24 | 247 | 57 | 6 | 334 |
Likely Benign | 1 | 17 | 84 | 70 | 172 |
Benign | 2 | 8 | 104 | 5 | 119 |
Conflicting | — | 25 | |||
| Total | 29 | 273 | 245 | 81 | 653 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →13 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap EGF — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
EGF · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Safety of Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Advanced Tumors
ACTIVE NOT RECRUITINGIdentification of HER2-Positive Breast Cancer Molecular Characterization and Subtypes
NOT YET RECRUITINGTiming of ctDNA Testing in HR+/HER2- Advanced Breast Cancer
RECRUITINGBinary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR VST, Advanced HER2 Positive Solid Tumors
RECRUITINGStudy of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION)
ACTIVE NOT RECRUITINGPatritumab Deruxtecan in Patients With Solid Tumor Harboring an NRG1 Fusion
RECRUITINGBreast Cancer Proteomics and Molecular Heterogeneity
RECRUITINGA Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
RECRUITINGA Phase 1/1b Study of IAM1363 in HER2 Cancers
RECRUITINGQuaratusugene Ozeplasmid (Reqorsa) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib
RECRUITINGA Study to Assess the Efficacy of WSD0922-FU in Patients With C797S+ Advanced Non-small Cell Lung Cancer
RECRUITINGErlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools