ERBB3

Chr 12ARAD

erb-b2 receptor tyrosine kinase 3

Also known as: ErbB-3, FERLK, HER3, LCCS2, MDA-BF-1, VSCN1, c-erbB-3, c-erbB3

This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Lethal congenital contractural syndrome 2MIM #607598
AR
{?Erythroleukemia, familial, susceptibility to}MIM #133180
AD
Visceral neuropathy, familial, 1, autosomal recessiveMIM #243180
AR
7
Active trials
167
Pubs (1 yr)
P/LP submissions
P/LP missense
0.69
LOEUF
Multiple*
Mechanism· predicted
📖
GeneReview available — ERBB3
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.69LOEUF
pLI 0.000
Z-score 3.71
OE 0.52 (0.400.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.39Z-score
OE missense 0.86 (0.800.91)
633 obs / 739.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.52 (0.400.69)
00.351.4
Missense OE?0.86 (0.800.91)
00.61.4
Synonymous OE?1.05
01.21.6
LoF obs/exp: 36 / 69.4Missense obs/exp: 633 / 739.4Syn Z: -0.61

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Advanced Solid Tumor

A Clinical Study of SYS6023 in Patients With Advanced Solid Tumors

RECRUITING
NCT07110883Phase PHASE1CSPC Megalith Biopharmaceutical Co.,Ltd.Started 2024-08-15
SYS6023
Breast Cancer

NeoadjuVAnt muLti-agENT Chemotherapy or Patritumab Deruxtecan With or Without endocrINE Therapy for High-risk HR+/HER2- Breast Cancer - VALENTINE Trial

ACTIVE NOT RECRUITING
NCT05569811Phase PHASE2SOLTI Breast Cancer Research GroupStarted 2022-11-25
Patritumab deruxtecanChemotherapyLetrozole
HER2-positive Metastatic Breast CancerFirst-line Treatment

Disitamab Vedotin + Pyrotinib Versus THP in the First-line Treatment for HER2+ Advanced Breast Cancer Clinical Trial

RECRUITING
NCT06278870Phase PHASE3Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityStarted 2023-09-06
disitamab vedotinPyrotinibtrastuzumab
Non-Small Cell Lung CancerPancreatic CancerLocally Advanced Solid Tumor

Study 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 RECRUITING
NCT05919537Phase PHASE1Hummingbird BioscienceStarted 2023-09-06
HMBD-001DocetaxelNab-paclitaxel
Locally Advanced Lung Non-Small Cell CarcinomaMetastatic Lung Non-Small Cell CarcinomaStage III Lung Cancer AJCC v8

Sotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation

RECRUITING
NCT07012031Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2026-06-17
Biopsy ProcedureBiospecimen CollectionComputed Tomography
Bladder CancerTriple Negative Breast CancerCastration-resistant Prostate Cancer

A Phase I/IIa Trial of HMBD-001 in Advanced HER3 Positive Solid Tumours

ACTIVE NOT RECRUITING
NCT05057013Phase PHASE1, PHASE2Cancer Research UKStarted 2021-11-10
HMBD-001HMBD-001 and enzalutamide
Solid Tumor, Adult

Patritumab Deruxtecan in Patients With Solid Tumor Harboring an NRG1 Fusion

RECRUITING
NCT06383884Phase PHASE2Samsung Medical CenterStarted 2024-08-13
Patritumab Deruxtecan