ESR1
estrogen receptor 1, the group of Estrogen receptors
Basic information
Region (hg38): 6:151656690-152129619
Previous symbols: [ "ESR" ]
Links
Phenotypes
GenCC
Source:
- estrogen resistance syndrome (Limited), mode of inheritance: AR
- estrogen resistance syndrome (Supportive), mode of inheritance: AR
- estrogen resistance syndrome (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Estrogen resistance | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Endocrine | 8090165; 8961262; 9396482; 18505767; 23841731 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (120 variants)
- Emery-Dreifuss muscular dystrophy 4, autosomal dominant (23 variants)
- Autosomal recessive ataxia, Beauce type (22 variants)
- Autosomal recessive ataxia, Beauce type;Emery-Dreifuss muscular dystrophy 4, autosomal dominant (21 variants)
- Emery-Dreifuss muscular dystrophy 4, autosomal dominant;Autosomal recessive ataxia, Beauce type (16 variants)
- not specified (6 variants)
- Inborn genetic diseases (6 variants)
- Emery-Dreifuss muscular dystrophy (3 variants)
- Cerebellar ataxia (3 variants)
- Estrogen resistance syndrome;Migraine with or without aura, susceptibility to, 1;Familial cancer of breast;Myocardial infarction, susceptibility to (2 variants)
- Arthrogryposis multiplex congenita 3, myogenic type (1 variants)
- Migraine with or without aura, susceptibility to (1 variants)
- Rare genetic intellectual disability (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ESR1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 18 | 24 | ||||
| missense | 16 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 1 | 1 | 2 | |||
| non coding ? | 48 | 37 | 35 | 121 | ||
| Total | 1 | 0 | 56 | 61 | 43 |
Variants in ESR1
This is a list of pathogenic ClinVar variants found in the ESR1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-151804095-C-CAA | Benign (Oct 16, 2019) | |||
| 6-151807496-C-G | Benign (Apr 09, 2019) | |||
| 6-151807507-A-G | Benign (Mar 19, 2019) | |||
| 6-151807743-C-T | Likely benign (Sep 22, 2018) | |||
| 6-151807928-C-T | ESR1-related disorder | Conflicting classifications of pathogenicity (Mar 01, 2024) | ||
| 6-151807930-C-T | ESR1-related disorder | Likely benign (Aug 10, 2019) | ||
| 6-151807941-C-T | Uncertain significance (Jan 09, 2023) | |||
| 6-151807942-T-C | Estrogen resistance syndrome;Migraine with or without aura, susceptibility to, 1;Familial cancer of breast;Myocardial infarction, susceptibility to | Benign (Apr 19, 2022) | ||
| 6-151808027-C-T | Likely benign (Jul 01, 2022) | |||
| 6-151808086-C-T | Benign (Dec 31, 2019) | |||
| 6-151808141-G-A | Benign (Dec 31, 2019) | |||
| 6-151808173-G-C | ESR1-related disorder | Benign (May 31, 2019) | ||
| 6-151808175-C-T | not specified | Uncertain significance (Jan 03, 2024) | ||
| 6-151808181-G-A | not specified | Uncertain significance (Nov 18, 2022) | ||
| 6-151808188-C-T | Likely benign (May 31, 2018) | |||
| 6-151808202-T-C | not specified | Uncertain significance (Jun 22, 2023) | ||
| 6-151808208-C-A | Uncertain significance (-) | |||
| 6-151808208-C-G | not specified | Uncertain significance (Dec 09, 2023) | ||
| 6-151808208-C-T | not specified | Uncertain significance (Nov 07, 2022) | ||
| 6-151808227-G-A | ESR1-related disorder | Likely benign (Dec 31, 2019) | ||
| 6-151808227-G-T | Likely benign (Jun 13, 2018) | |||
| 6-151808264-T-C | Benign/Likely benign (Apr 01, 2024) | |||
| 6-151808318-C-T | Likely benign (Dec 31, 2019) | |||
| 6-151808321-A-G | ESR1-related disorder | Benign (Dec 31, 2019) | ||
| 6-151808410-A-AGGAG | Benign (Sep 14, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ESR1 | protein_coding | protein_coding | ENST00000440973 | 8 | 472929 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000801 | 125694 | 0 | 2 | 125696 | 0.00000796 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.61 | 258 | 342 | 0.755 | 0.0000193 | 3869 |
| Missense in Polyphen | 39 | 119.13 | 0.32737 | 1394 | ||
| Synonymous | -1.24 | 160 | 141 | 1.13 | 0.00000807 | 1176 |
| Loss of Function | 4.45 | 1 | 25.0 | 0.0400 | 0.00000141 | 277 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.0000992 | 0.0000993 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000880 | 0.00000880 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA- binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF- kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA- binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1. {ECO:0000269|PubMed:10681512, ECO:0000269|PubMed:10816575, ECO:0000269|PubMed:11477071, ECO:0000269|PubMed:11682626, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15078875, ECO:0000269|PubMed:15891768, ECO:0000269|PubMed:16043358, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:17932106, ECO:0000269|PubMed:18247370, ECO:0000269|PubMed:19350539, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20705611, ECO:0000269|PubMed:21330404, ECO:0000269|PubMed:22083956, ECO:0000269|PubMed:7651415, ECO:0000269|PubMed:9328340}.;
- Disease
- DISEASE: Estrogen resistance (ESTRR) [MIM:615363]: A disorder characterized by partial or complete resistance to estrogens, in the presence of elevated estrogen serum levels. Clinical features include absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, reduced bone mineral density, osteoporosis, continued growth into adulthood and very tall adult stature. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present. {ECO:0000269|PubMed:23841731, ECO:0000269|PubMed:27754803}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Breast cancer - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Aromatase Inhibitor Pathway (Breast Cell), Pharmacodynamics;Tamoxifen Action Pathway;Tamoxifen Metabolism Pathway;NHR;TGF-Ncore;Nuclear Receptors;Integrated Breast Cancer Pathway;miR-targeted genes in muscle cell - TarBase;Leptin signaling pathway;Aryl Hydrocarbon Receptor;JAK-STAT;Estrogen Receptor Pathway;Nuclear Receptors Meta-Pathway;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Estrogen signaling pathway;Transcriptional regulation by RUNX2;Disease;Signal Transduction;Gene expression (Transcription);estrogen responsive protein efp controls cell cycle and breast tumors growth;pelp1 modulation of estrogen receptor activity;downregulated of mta-3 in er-negative breast tumors;carm1 and regulation of the estrogen receptor;overview of telomerase protein component gene htert transcriptional regulation;role of erbb2 in signal transduction and oncology;Generic Transcription Pathway;Prolactin;Post-translational protein modification;Metabolism of proteins;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription;ATF-2 transcription factor network;AndrogenReceptor;TGF_beta_Receptor;Signaling events mediated by HDAC Class II;PIP3 activates AKT signaling;Ovarian tumor domain proteases;FOXA1 transcription factor network;Deubiquitination;Signaling by Nuclear Receptors;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;TFAP2 (AP-2) family regulates transcription of growth factors and their receptors;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Leptin;Constitutive Signaling by Aberrant PI3K in Cancer;Estrogen-dependent gene expression;PI3K/AKT Signaling in Cancer;Nuclear signaling by ERBB4;Signaling by ERBB4;Signaling by Receptor Tyrosine Kinases;RUNX1 regulates estrogen receptor mediated transcription;RUNX1 regulates transcription of genes involved in WNT signaling;ESR-mediated signaling;Intracellular signaling by second messengers;Transcriptional regulation by RUNX1;Signaling mediated by p38-alpha and p38-beta;Diseases of signal transduction;Validated nuclear estrogen receptor alpha network;Regulation of Telomerase;AP-1 transcription factor network;Plasma membrane estrogen receptor signaling;FOXM1 transcription factor network;Regulation of nuclear SMAD2/3 signaling;LKB1 signaling events;Regulation of RUNX2 expression and activity
(Consensus)
Recessive Scores
- pRec
- 0.951
Intolerance Scores
- loftool
- 0.00317
- rvis_EVS
- 0.24
- rvis_percentile_EVS
- 69.46
Haploinsufficiency Scores
- pHI
- 0.998
- hipred
- Y
- hipred_score
- 0.762
- ghis
- 0.415
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Esr1
- Phenotype
- respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; renal/urinary system phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype;
Zebrafish Information Network
- Gene name
- esr1
- Affected structure
- posterior lateral line primordium
- Phenotype tag
- abnormal
- Phenotype quality
- physical object quality
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;antral ovarian follicle growth;epithelial cell development;chromatin remodeling;transcription, DNA-templated;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;signal transduction;phospholipase C-activating G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;androgen metabolic process;male gonad development;negative regulation of gene expression;positive regulation of phospholipase C activity;protein deubiquitination;regulation of Wnt signaling pathway;intracellular steroid hormone receptor signaling pathway;intracellular estrogen receptor signaling pathway;response to estradiol;regulation of intracellular estrogen receptor signaling pathway;regulation of toll-like receptor signaling pathway;regulation of apoptotic process;negative regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of DNA-binding transcription factor activity;response to estrogen;positive regulation of transcription, DNA-templated;positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;positive regulation of transcription by RNA polymerase II;phosphatidylinositol phosphorylation;positive regulation of fibroblast proliferation;stem cell differentiation;regulation of inflammatory response;positive regulation of DNA-binding transcription factor activity;positive regulation of protein kinase B signaling;uterus development;vagina development;prostate epithelial cord elongation;prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis;regulation of branching involved in prostate gland morphogenesis;mammary gland branching involved in pregnancy;mammary gland alveolus development;epithelial cell proliferation involved in mammary gland duct elongation;protein localization to chromatin;cellular response to estrogen stimulus;cellular response to estradiol stimulus;negative regulation of production of miRNAs involved in gene silencing by miRNA
- Cellular component
- nuclear chromatin;nucleus;nucleoplasm;cytoplasm;Golgi apparatus;cytosol;plasma membrane;membrane;integral component of membrane;protein-containing complex;transcriptionally active chromatin;transcriptional preinitiation complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;TFIIB-class transcription factor binding;transcription coactivator binding;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;nuclear receptor activity;steroid binding;protein binding;beta-catenin binding;transcription factor binding;zinc ion binding;TBP-class protein binding;enzyme binding;protein kinase binding;nitric-oxide synthase regulator activity;estrogen receptor activity;estrogen receptor binding;estrogen response element binding;identical protein binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity;ATPase binding