FSHR

follicle stimulating hormone receptor, the group of Glycoprotein hormone receptors

Basic information

Region (hg38): 2:48962156-49154527

Previous symbols: [ "ODG1" ]

Links

ENSG00000170820 ∙ NCBI:2492 ∙ OMIM:136435 ∙ HGNC:3969 ∙ Uniprot:P23945 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 46 XX gonadal dysgenesis (Supportive), mode of inheritance: AD
• ovarian dysgenesis 1 (Strong), mode of inheritance: AR
• ovarian hyperstimulation syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ovarian hyperstimulation syndrome; Ovarian dysgenesis 1	AD/AR	Obstetric	In Ovarian hyperstimulation syndrome, diagnosis may be beneficial for preconception/reproductive planning (eg, in order to avoid precipitating factors related to ovarian hyperstimulation); In Ovarian dysgenesis 1, genetic knowledge may be beneficial to allow Interventions such as preserving eggs in women with premature ovarian insufficiency	Endocrine; Genitourinary; Obstetric	7553856; 9769327; 12498425; 11889179; 12930928; 12930927; 12930924; 17721928; 20087398

ClinVar

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

• not provided (65 variants)
• Ovarian hyperstimulation syndrome (54 variants)
• Ovarian dysgenesis 1 (53 variants)
• Inborn genetic diseases (18 variants)
• not specified (6 variants)
• Ovarian dysgenesis (3 variants)
• Ovarian hyperstimulation syndrome;Ovarian dysgenesis 1 (2 variants)
• Amenorrhea (2 variants)
• Ovarian response to FSH stimulation (1 variants)
• FSHR-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FSHR 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			12	6		18
missense		3	39	2	2	46
nonsense						0
start loss	1		1			2
frameshift	1		1			2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2	1		3
non coding			6	11	26	43
Total	2	3	60	19	28

Highest pathogenic variant AF is 0.00000657

Variants in FSHR

This is a list of pathogenic ClinVar variants found in the FSHR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-48962159-A-G		Ovarian hyperstimulation syndrome • Ovarian dysgenesis 1	Uncertain significance (Jan 12, 2018)
2-48962170-A-G		Ovarian hyperstimulation syndrome • Ovarian dysgenesis 1	Likely benign (Jan 12, 2018)
2-48962412-T-A		Ovarian hyperstimulation syndrome • Ovarian dysgenesis 1	Conflicting classifications of pathogenicity (Jan 13, 2018)
2-48962477-G-A		Ovarian dysgenesis 1 • Ovarian hyperstimulation syndrome	Benign (Nov 11, 2018)
2-48962487-A-T		Ovarian dysgenesis 1 • Ovarian hyperstimulation syndrome	Likely benign (Mar 29, 2019)
2-48962534-T-C		Ovarian dysgenesis • Ovarian hyperstimulation syndrome	Uncertain significance (Jun 14, 2016)
2-48962560-C-T		Ovarian dysgenesis 1 • Ovarian hyperstimulation syndrome	Uncertain significance (Jan 13, 2018)
2-48962622-A-G		Ovarian dysgenesis 1 • Ovarian hyperstimulation syndrome	Likely benign (Jan 13, 2018)
2-48962755-A-G		Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
2-48962782-C-T		Ovarian hyperstimulation syndrome • not specified • Ovarian dysgenesis 1	Benign (Aug 10, 2021)
2-48962833-T-G		Inborn genetic diseases	Uncertain significance (Feb 10, 2022)
2-48962839-G-A		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
2-48962919-G-A		Ovarian hyperstimulation syndrome • Ovarian dysgenesis 1	Uncertain significance (Jan 13, 2018)
2-48962936-A-T		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
2-48962959-G-A		Ovarian dysgenesis 1	Likely pathogenic (Oct 01, 2020)
2-48962990-G-C		Ovarian dysgenesis 1 • Ovarian hyperstimulation syndrome	Uncertain significance (Jan 13, 2018)
2-48963009-C-T			Likely benign (Dec 31, 2019)
2-48963020-G-C		Ovarian dysgenesis 1	Likely pathogenic (-)
2-48963058-A-G		Genetic non-acquired premature ovarian failure	Likely pathogenic (Oct 01, 2019)
2-48963061-G-T		Ovarian dysgenesis 1	Pathogenic/Likely pathogenic (Jun 01, 2010)
2-48963069-G-A		FSHR-related disorder	Likely benign (Mar 24, 2020)
2-48963097-G-A		Ovarian dysgenesis 1	Likely pathogenic (-)
2-48963104-G-A		Ovarian dysgenesis 1	Pathogenic (Oct 01, 1998)
2-48963122-C-T		Ovarian hyperstimulation syndrome	Pathogenic (Aug 21, 2003)
2-48963135-CACGATGT-C		Genetic non-acquired premature ovarian failure	Pathogenic (Oct 01, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FSHR	protein_coding	protein_coding	ENST00000406846	10	192381

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.37e-11	0.185	125701	0	47	125748	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.799	401	358	1.12	0.0000178	4602
Missense in Polyphen		93	108.91	0.85393		1372
Synonymous	-2.70	178	138	1.29	0.00000694	1356
Loss of Function	0.765	19	23.0	0.828	0.00000106	314

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000330	0.000329
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000212	0.000211
Middle Eastern	0.00	0.00
South Asian	0.000294	0.000294
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: G protein-coupled receptor for follitropin, the follicle-stimulating hormone (PubMed:11847099, PubMed:24058690, PubMed:24692546). Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways (PubMed:24058690). {ECO:0000269|PubMed:11847099, ECO:0000269|PubMed:24058690, ECO:0000269|PubMed:24692546}.
• Disease: DISEASE: Ovarian dysgenesis 1 (ODG1) [MIM:233300]: An autosomal recessive disease characterized by primary amenorrhea, variable development of secondary sex characteristics, poorly developed streak ovaries, and high serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). {ECO:0000269|PubMed:10551778, ECO:0000269|PubMed:11889179, ECO:0000269|PubMed:12571157, ECO:0000269|PubMed:12915623, ECO:0000269|PubMed:7553856, ECO:0000269|PubMed:9769327, ECO:0000269|PubMed:9851774}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ovarian hyperstimulation syndrome (OHSS) [MIM:608115]: Disorder which occurs either spontaneously or most often as an iatrogenic complication of ovarian stimulation treatments for in vitro fertilization. The clinical manifestations vary from abdominal distention and discomfort to potentially life- threatening, massive ovarian enlargement and capillary leak with fluid sequestration. Pathologic features of this syndrome include the presence of multiple serous and hemorrhagic follicular cysts lined by luteinized cells, a condition called hyperreactio luteinalis. {ECO:0000269|PubMed:12930927, ECO:0000269|PubMed:12930928, ECO:0000269|PubMed:15080154, ECO:0000269|PubMed:16278261, ECO:0000269|PubMed:17721928, ECO:0000269|PubMed:24058690, ECO:0000269|PubMed:25581598}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: cAMP signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Vasopressin Regulation of Water Homeostasis;Intracellular Signalling Through FSH Receptor and Follicle Stimulating Hormone;GPCRs, Other;Follicle Stimulating Hormone (FSH) signaling pathway;Peptide GPCRs;Ovarian Infertility Genes;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Hormone ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);regulation of spermatogenesis by crem;GPCR ligand binding;GPCR downstream signalling;FSH (Consensus)

Recessive Scores

• pRec: 0.400

Intolerance Scores

• loftool: 0.411
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.49

Haploinsufficiency Scores

• pHI: 0.0825
• hipred: Y
• hipred_score: 0.610
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.297

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fshr
• Phenotype: homeostasis/metabolism 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); skeleton phenotype; immune system 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; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: fshr
• Affected structure: germ line cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;activation of adenylate cyclase activity;spermatogenesis;female gamete generation;gonad development;male gonad development;female gonad development;hormone-mediated signaling pathway;regulation of protein kinase A signaling;positive regulation of phosphatidylinositol 3-kinase signaling;follicle-stimulating hormone signaling pathway;positive regulation of adenylate cyclase activity;positive regulation of ERK1 and ERK2 cascade;cellular response to follicle-stimulating hormone stimulus
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;receptor complex
• Molecular function: follicle-stimulating hormone receptor activity;protein binding;G protein-coupled peptide receptor activity