ESR1
Chr 6ADARestrogen receptor 1
Also known as: ER, ESR, ESRA, ESTRR, Era, NR3A1
The estrogen receptor 1 protein functions as a ligand-activated transcription factor that regulates estrogen-responsive genes involved in growth, metabolism, and sexual development. Mutations cause estrogen resistance syndrome with autosomal recessive inheritance, while some variants may contribute to migraine susceptibility with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variation (pLI 0.99, LOEUF 0.19), indicating that complete loss of function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ESR1 · 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
Current Status of Treatment for Chinese Patients With ESR1-mutated HR+/HER2-advanced Breast Cancer
RECRUITINGPaclitaxel & Cyclophosphamide With or Without Trastuzumab Before Surgery in Treating Previously Untreated Breast Cancer
ACTIVE NOT RECRUITINGNeoadjuvant Pembrolizumab + Decitabine Followed by Std Neoadj Chemo for Locally Advanced HER2- Breast Ca
ACTIVE NOT RECRUITINGUse of Imatinib to Convert Triple Negative Breast Cancer Into ER-positive Breast Cancer (I-CONIC)
RECRUITINGEffect of HSD3B1 (1245C) Gene Mutation on Treatment of Stage I-III Breast Cancer
RECRUITINGHormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)
ACTIVE NOT RECRUITINGThe T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases.
RECRUITINGElacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i.
RECRUITINGS1207 Hormone Therapy With or Without Everolimus in Treating Patients With Breast Cancer
ACTIVE NOT RECRUITINGElacestrant and Exemestane for Patients With Pretreated HR+/HER2- Metastatic Breast Cancer and [18F] FES-avid Lesions (COMBINE)
NOT YET RECRUITINGPErsonalized TREatment of High-risk MAmmary Cancer - the PETREMAC Trial
ACTIVE NOT RECRUITINGLow Dose Tamoxifen With or Without Omega-3 Fatty Acids for Breast Cancer Risk Reduction
RECRUITINGExternal Resources
Links to major genomics databases and tools