GeneBe

FSHR

protein-coding

follicle stimulating hormone receptor, the group of Glycoprotein hormone receptors

Gene summary

The protein encoded by this gene belongs to family 1 of G-protein coupled receptors. It is the receptor for follicle stimulating hormone and functions in gonad development. Mutations in this gene cause ovarian dysgenesis type 1, and also ovarian hyperstimulation syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

Previous symbols:
  • ODG1

MANE transcript

NM_000145.4

Inheritance

AD, AR

ClinVar variants

P:36U:115B:20

Top phenotype

Ovarian hyperstimulation syndrome; Ovarian dysgenesis 1

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr2:48,962,157-49,154,527

External References & Databases

Ensembl (ENSG00000170820)NCBI Gene (2492)OMIM (136435)HGNC:3969GenCCUniProt (P23945)AlphaFoldClinVar (FSHR)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~192.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

46 XX gonadal dysgenesisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0009299

Submitter: Orphanet

ovarian dysgenesis 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0024463

Submitter: PanelApp Australia

ovarian hyperstimulation syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011972

Submitter: Labcorp Genetics (formerly Invitae)

ovarian hyperstimulation syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011972

Submitter: PanelApp Australia

ovarian dysgenesis 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0024463

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Ovarian hyperstimulation syndrome; Ovarian dysgenesis 1AD/AR

Manifestation: Endocrine; Genitourinary; Obstetric

Intervention: Obstetric

Rationale: 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

Refs: 7553856; 9769327; 12498425; 11889179; 12930928; 12930927; 12930924; 17721928; 20087398Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FSHR variants in ClinVar

11 Conditions Cataloged
Inborn genetic diseasesTotal: 73
Ovarian dysgenesis 1Total: 63
not providedTotal: 60
Ovarian hyperstimulation syndromeTotal: 54
FSHR-related disorderTotal: 7
Genetic non-acquired premature ovarian failureTotal: 7
not specifiedTotal: 3
Dizygotic twinsTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000145.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
14
clinvar
10
clinvar
 24
missense
9
clinvar
18
clinvar
99
clinvar
10
clinvar
 136
nonsense
1
clinvar
2
clinvar
 3
start loss
1
clinvar
1
clinvar
 2
frameshift
3
clinvar
2
clinvar
 5
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total1422115200171

Highest pathogenic variant AF is 0.00027881595

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000145.4RefSeqNP_000136.210MANE Select
ENST00000406846.7EnsemblENSP00000384708.210MANE Select
NM_181446.3RefSeqNP_852111.29Standard
ENST00000304421.8EnsemblENSP00000306780.49Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
fshrDanio rerio

Structure: germ line cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

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

Molecular Function

  • follicle-stimulating hormone receptor activity
  • protein binding
  • G protein-coupled peptide receptor activity

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • integral component of membrane
  • receptor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000406846
Coding exons
10
Length
192381
Individuals with no LoFs
125701
Homozygous LoFs
0
Heterozygous LoFs
47
Defined
125748
p
0.000187
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.7994013581.120.00001784602
Missense (PolyPhen)93108.910.853931372
Synonymous-2.701781381.290.000006941356
Loss of Function0.7651923.00.8280.00000106314

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American0.000140.00014rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.000190.00018rare
European (Non-Finnish)0.000210.00021rare
South Asian0.000290.00029rare
Other0.000330.00033rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.400

Intolerance Scores

LoFtool
0.411
RVIS EVS
-0.11
RVIS percentile EVS
45.49

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.297

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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