ERBB3
Chr 12ARADerb-b2 receptor tyrosine kinase 3
Also known as: ErbB-3, FERLK, HER3, LCCS2, MDA-BF-1, VSCN1, c-erbB-3, c-erbB3
ERBB3 encodes a receptor tyrosine kinase that binds neuregulin-1 and forms heterodimers with other EGFR family members to activate cell proliferation and differentiation pathways. Mutations cause lethal congenital contracture syndrome, an autosomal recessive disorder characterized by severe arthrogryposis, hydrops fetalis, and intrauterine or neonatal death. The gene is not constrained against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern observed in this severe early-onset condition.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
257 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 | 2 | 4 | 7 | 0 | 13 |
Likely Pathogenic | 11 | 3 | 1 | 0 | 15 |
VUS | 2 | 85 | 6 | 0 | 93 |
Likely Benign | 1 | 10 | 18 | 24 | 53 |
Benign | 0 | 5 | 28 | 4 | 37 |
Conflicting | — | 3 | |||
| Total | 16 | 107 | 60 | 28 | 214 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ERBB3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Phase I/IIa Trial of HMBD-001 in Advanced HER3 Positive Solid Tumours
ACTIVE NOT RECRUITINGNeoadjuVAnt muLti-agENT Chemotherapy or Patritumab Deruxtecan With or Without endocrINE Therapy for High-risk HR+/HER2- Breast Cancer - VALENTINE Trial
ACTIVE NOT RECRUITINGNeratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic Solid Tumors With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation
ACTIVE NOT RECRUITINGStudy of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation
ACTIVE NOT RECRUITINGA Clinical Study of SYS6023 in Patients With Advanced Solid Tumors
RECRUITINGDisitamab Vedotin + Pyrotinib Versus THP in the First-line Treatment for HER2+ Advanced Breast Cancer Clinical Trial
RECRUITINGSotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation
RECRUITINGPatritumab Deruxtecan in Patients With Solid Tumor Harboring an NRG1 Fusion
RECRUITINGExternal Resources
Links to major genomics databases and tools