EGFR

Chr 7ADSomaticAR

epidermal growth factor receptor

Also known as: ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS, PIG61, mENA

NCBI Gene: 1956 ENSG00000146648 UniProt: P00533

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). [provided by RefSeq, Jul 2020]

Primary Disease Associations & Inheritance

{Nonsmall cell lung cancer, susceptibility to}MIM #211980

ADSomatic

Adenocarcinoma of lung, response to tyrosine kinase inhibitor inMIM #211980

ADSomatic

Neonatal nephrocutaneous inflammatory syndromeMIM #616069

Nonsmall cell lung cancer, response to tyrosine kinase inhibitor inMIM #211980

ADSomatic

558

ClinVar variants

Pathogenic / LP

0.37

pLI score

Active trials

Clinical Summary— EGFR

🧬

Gene-Disease Validity (ClinGen)

non-small cell lung carcinoma · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

📋

ClinVar Variants

19 Pathogenic / Likely Pathogenic· 236 VUS of 558 total submissions

💊

Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.35LOEUF

pLI 0.368

Z-score 5.83

OE 0.23 (0.15–0.35)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.87Z-score

OE missense 0.80 (0.75–0.86)

561 obs / 700.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.23 (0.15–0.35)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.75–0.86)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13

0≤1.21.6

LoF obs/exp: 15 / 66.2Missense obs/exp: 561 / 700.5Syn Z: -1.65

ClinVar Variant Classifications

558 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic5

VUS236

Likely Benign283

Benign14

Conflicting6

Pathogenic

Likely Pathogenic

236

VUS

283

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	0	2	0	14
Likely Pathogenic	5	0	0	0	5
VUS	9	211	15	1	236
Likely Benign	1	11	105	166	283
Benign	0	0	0	14	14
Conflicting	—				6
Total	27	222	122	181	558

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EGFR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

EGFR-related inflammatory skin and bowel disease, neonatal

limited

ARUndeterminedAltered Gene Product Structure

Skin

G2P ↗

EGFR-related nonsmall cell lung cancer, susceptibility to

definitive

ADGain Of FunctionUncertain

Cancer

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

EPIDERMAL GROWTH FACTOR RECEPTOR; EGFR

MIM #131550 · *

{Nonsmall cell lung cancer, susceptibility to}

MIM #211980

Molecular basis of disorder known

Autosomal dominantSomatic mutation

Adenocarcinoma of lung, response to tyrosine kinase inhibitor in

MIM #211980

Molecular basis of disorder known

Autosomal dominantSomatic mutation

Neonatal nephrocutaneous inflammatory syndrome

MIM #616069

Molecular basis of disorder known

Autosomal recessive

Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in

MIM #211980

Molecular basis of disorder known

Autosomal dominantSomatic mutation

External Resources

Links to major genomics databases and tools

📖

GeneReview available — EGFR

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Literature

Landmark / reviewRecent case evidence

Key Publications

Landmark & review papers · by relevance

PubMed

Radiation-induced amphiregulin drives tumour metastasis.

Piffkó A et al.·Nature

2025

Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials.

Voldborg BR et al.·Ann Oncol

1997Review

Genome-Wide Association Study of CKD Progression.

Robinson-Cohen C et al.·J Am Soc Nephrol

2023Meta-analysis

Germline EGFR Mutations and Familial Lung Cancer.

Oxnard GR et al.·J Clin Oncol

2023

Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104).

Zhang C et al.·Cell Rep Med

2024Clinical trial

EGFR tyrosine kinase activity and Rab GTPases coordinate EGFR trafficking to regulate macrophage activation in sepsis.

Zhang X et al.·Cell Death Dis

2022

IL6 Mediates Suppression of T- and NK-cell Function in EMT-associated TKI-resistant EGFR-mutant NSCLC.

Patel SA et al.·Clin Cancer Res

2023

Extrachromosomal DNA-Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma.

Noorani I et al.·Cancer Discov

2025

Molecular Diagnosis and Identification of Novel Pathogenic Variants in a Large Cohort of Italian Patients Affected by Polycystic Kidney Diseases.

Nigro E et al.·Genes (Basel)

2023Cohort

Structural insights into the role and targeting of EGFRvIII.

Bagchi A et al.·Structure

2024

Top 10 resultsSearch PubMed ↗

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

Exploring Pyrazolo[3,4-b]Pyridine and Spiro-Oxindole Hybrids as Selective CDK2 or EGFR Inhibitors for Targeted Cancer Therapy: Design, Synthesis, and Molecular Modeling Insights.

Farouk AKBAW et al.·Drug Dev Res

2026Functional

COL1A1-induced LOXL2 promotes ovarian cancer metastasis via a feedback loop upon inhibiting EGFR lysosomal degradation.

Shen Z et al.·Exp Mol Med

2026

Constitutive EGFR activation induced by PTPRR downregulation confers resistance to KRAS inhibitors.

Kanemura H et al.·Cancer Res Commun

2026

Discrepancies Between Creatinine- and Cystatin C-Based eGFR Estimation in Palliative Care Patients and Their Implications on Drug Dosing.

Pelz S et al.·J Palliat Med

2026Cohort

Bisdemethoxycurcumin extends lifespan and healthspan in Caenorhabditis elegans via modulation of EGFR-linked signaling pathways.

Shi R et al.·Food Funct

2026

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Type2diabetesPreDiabetesRenal Failure

SGLT2 Inhibition in Addition to Lifestyle Intervention and Risk for Complications in Subtypes of Patients With Prediabetes

RECRUITING

NCT06054035Phase PHASE4University Hospital TuebingenStarted 2023-10-26

Dapagliflozin (Forxiga®)Placebo matching DapaglifolzinLifestyle Intervention

EGFR Tyrosine Kinase Inhibitors Plus Cyclin-dependent Kinase 4/6 Inhibitor

A Study of Almonertinib Combined With Palbociclib in Patients With Advanced Solid Tumors Harboring KRAS Mutations

RECRUITING

NCT06947811Phase PHASE1, PHASE2Sun Yat-sen UniversityStarted 2025-06-09

AlmonertinibPalbociclib

Lung Non-Small Cell Carcinoma

Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has Increased Copies of the MET Gene (An Expanded Lung-MAP Treatment Trial)

RECRUITING

NCT06116682Phase PHASE2SWOG Cancer Research NetworkStarted 2024-11-19

AmivantamabBiospecimen CollectionComputed Tomography

End-Stage Renal DiseaseEnd Stage Renal Disease on DialysisEnd Stage Renal Disease With Renal Transplant

CRISPR-Edited HLA Donor Kidney Transplant to Reduce Rejection Risk

RECRUITING

NCT07053462Phase PHASE1, PHASE2AMERICAN ORGAN TRANSPLANT AND CANCER RESEARCH INSTITUTE LLCStarted 2025-06-01

Ex Vivo CRISPR-Cas9 Gene Editing of Donor KidneyKidney Transplantation with Standard Care

Advanced Lung Non-Small Cell CarcinomaMetastatic Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

MRX-2843 and Osimertinib for the Treatment of Advanced EGFR Mutant Non-small Cell Lung Cancer

RECRUITING

NCT04762199Phase PHASE1Emory UniversityStarted 2021-02-24

Flt3/MerTK Inhibitor MRX-2843Osimertinib

Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING

NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17

AdavosertibAfatinibAfatinib Dimaleate

Non-small Cell Lung CancerEGFR Gene MutationEGFR-TKI Resistant Mutation

Nintedanib Plus EGFR TKI In EGFR-mutated Non-small Cell Lung Cancer Patients

RECRUITING

NCT06071013Phase PHASE1, PHASE2China Medical University HospitalStarted 2024-02-23

Nintedanib, gefitinib, erlotinib, afatinib, osimertinib

Advanced Breast CancerER-positive Breast CancerHER2-negative Breast Cancer

Elacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i.

ACTIVE NOT RECRUITING

NCT06382948Phase PHASE3MedSIRStarted 2024-12-05