ESR2

estrogen receptor 2, the group of Estrogen receptors

Basic information

Region (hg38): 14:64084232-64338112

Links

ENSG00000140009

∙ NCBI:2100 ∙ OMIM:601663 ∙ HGNC:3468 ∙ Uniprot:Q92731 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

ovarian dysgenesis 8 (Limited), mode of inheritance: AD
male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate), mode of inheritance: AR
familial medullary thyroid carcinoma (Supportive), mode of inheritance: AD
ovarian dysgenesis 8 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ovarian dysgenesis 8	AR	Endocrine	Individuals can present with features such as primary amenorrhea, and osteoporosis, and medical management (eg, with estrogen therapy) has been described as beneficial	Endocrine; Obstetric	30113650

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ESR2 gene.

not_provided (93 variants)
not_specified (71 variants)
ESR2-related_disorder (15 variants)
Ovarian_dysgenesis_8 (3 variants)
Familial_medullary_thyroid_carcinoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ESR2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001437.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	29 clinvar	7 clinvar	38
missense	1 clinvar		82 clinvar	11 clinvar	2 clinvar	96
nonsense			1 clinvar			1
start loss						0
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	91	40	9

Highest pathogenic variant AF is 0.0000014588339

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ESR2	protein_coding	protein_coding	ENST00000341099	8	253881

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.45e-8	0.830	125628	0	119	125747	0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.405	304	325	0.937	0.0000196	3477
Missense in Polyphen		78	94.441	0.82591		1073
Synonymous	-2.64	169	131	1.29	0.00000858	1036
Loss of Function	1.53	15	22.9	0.654	0.00000120	267

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000565	0.000564
Ashkenazi Jewish	0.00119	0.00119
East Asian	0.00103	0.00103
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000428	0.000422
Middle Eastern	0.00103	0.00103
South Asian	0.000695	0.000686
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual. {ECO:0000269|PubMed:20074560}.;
Pathway: Breast cancer - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Aromatase Inhibitor Pathway (Breast Cell), Pharmacodynamics;NHR;Nuclear Receptors;Ovarian Infertility Genes;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Disease;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription;PIP3 activates AKT signaling;Signaling by Nuclear Receptors;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;ESR-mediated signaling;Intracellular signaling by second messengers;Diseases of signal transduction;Validated nuclear estrogen receptor alpha network;Plasma membrane estrogen receptor signaling;Validated nuclear estrogen receptor beta network (Consensus)

Recessive Scores

pRec: 0.749

Intolerance Scores

loftool: 0.0411
rvis_EVS: -0.95
rvis_percentile_EVS: 9.27

Haploinsufficiency Scores

pHI: 0.293
hipred: Y
hipred_score: 0.564
ghis: 0.397

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.897

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Esr2
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); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; skeleton phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; normal 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); reproductive system phenotype; hematopoietic system phenotype; 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); neoplasm; limbs/digits/tail 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; immune system phenotype;

Zebrafish Information Network

Gene name: esr2a
Affected structure: subintestinal vein
Phenotype tag: abnormal
Phenotype quality: aplastic

Gene ontology

Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;transcription initiation from RNA polymerase II promoter;signal transduction;cell-cell signaling;negative regulation of cell growth;intracellular estrogen receptor signaling pathway;positive regulation of transcription, DNA-templated;positive regulation of DNA-binding transcription factor activity;extracellular negative regulation of signal transduction
Cellular component: extracellular region;nucleus;nucleoplasm;mitochondrion
Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;steroid hormone receptor activity;transcription coactivator activity;nuclear receptor activity;steroid binding;protein binding;zinc ion binding;enzyme binding;estrogen receptor activity;estrogen response element binding;identical protein binding;receptor antagonist activity