FSHR follicle stimulating hormone receptor [Homo sapiens (human)] - Gene

Summary

Official Symbol: FSHRprovided by HGNC
Official Full Name: follicle stimulating hormone receptorprovided by HGNC
Primary source: HGNC:HGNC:3969
See related: Ensembl:ENSG00000170820 MIM:136435
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LGR1; ODG1; FSHR1; FSHRO
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]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all

Genomic context

Location:: 2p16.3

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
109.20190607	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (48953161..49154527, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (49189296..49381666, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

GWAS for neovascular age-related macular degeneration bilaterality found new genetic loci STON1-GTF2A1L/LHCGR/FSHR.
Title: A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration.
Dynamical network analysis confirmed that TMD helices 2 and 5 may share communication pathways in the functional FSHR variants, whereas no connectivity was detected in the dysfunctional mutants, indicating that the global dynamics of the FSHR was sensitive to mutations at amino acid residue 408, a key position apparently linked to misfolding
Title: Molecular dynamics simulation of the follicle-stimulating hormone receptor. Understanding the conformational dynamics of receptor variants at positions N680 and D408 from in silico analysis.
Women homozygous for S in both FSHR N680S and LHCGR N312S had approximately 40% higher chance of having a baby compared to those with other genetic variants.
Title: Gonadotropin receptor variants are linked to cumulative live birth rate after in vitro fertilization.
There is possible relationship of FSH receptor gene Serine/Serine variant for the lower possibility of conception during the first 12 months of planned conception.
Title: The impact of FSH receptor polymorphism on time-to-pregnancy: a cross-sectional single-centre study.
the level of apoptosis was inversely proportional to the expression of bone morphogenetic protein (BMPR1B) and follicle stimulating hormone (FSH) receptors, in granulosa cells.
Title: The effect of ovarian reserve and receptor signalling on granulosa cell apoptosis during human follicle development.
In this mini-review, the complexity of FSHR-mediated intracellular signals activated in response to ligand stimulation is discussed. [Review Article]
Title: FSH Receptor Signaling: Complexity of Interactions and Signal Diversity.
In the homozygous model (GG vs AA), the FSHRThr307Ala-Asn680Ser gene polymorphism might be a protective factor against male infertility.
Title: [Relationship between the FSHR Thr307Ala-Asn680Ser gene polymorphism and male infertility: A meta-analysis].
Results indicate the frequency distribution of the common follicle stimulating hormone receptor (FSHR) single-nucleotide polymorphisms (SNPs) in Mexican subjects of Hispanic origin.
Title: Frequency of the T307A, N680S, and -29G>A single-nucleotide polymorphisms in the follicle-stimulating hormone receptor in Mexican subjects of Hispanic ancestry.
This study demonstrates that both gonadotrophin receptors9 FSH receptor (FSHR) and LH/choriogonadotrophin receptor (LHCGR) are expressed along the glandular epithelium of endometria and they mediate the effects of gonadotrophins on intracellular functions.
Title: Evidence for expression and functionality of FSH and LH/hCG receptors in human endometrium.
rs6165 and rs6166 genotypes associated with in vitro fertilization outcome
Title: Association of estrogen, progesterone and follicle stimulating hormone receptor polymorphisms with in vitro fertilization outcomes.

Submit: New GeneRIF Correction See all GeneRIFs (239)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Dizygotic twins MedGen: C0220761 OMIM: 276400 GeneReviews: Not available	Compare labs
Ovarian dysgenesis 1 MedGen: C0949595 OMIM: 233300 GeneReviews: Not available	Compare labs
Ovarian hyperstimulation syndrome MedGen: C0085083 OMIM: 608115 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Radiation pharmacogenomics: a genome-wide association approach to identify radiation response biomarkers using human lymphoblastoid cell lines. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
Follicle Stimulating Hormone (FSH) signaling pathway, organism-specific biosystem (from WikiPathways)
Follicle Stimulating Hormone (FSH) signaling pathway, organism-specific biosystemThe Follicle Stimulating Hormone (FSH) is an anterior pituitary gonadotropin belonging to the family of glycoprotein hormones that includes thyroid stimulating hormone (TSH), Leutinizing Hormone (LH)...
G alpha (s) signalling events, organism-specific biosystem (from REACTOME)
G alpha (s) signalling events, organism-specific biosystemThe general function of the G alpha (s) subunit (Gs) is to activate adenylate cyclase, which in turn produces cAMP, leading to the activation of cAMP-dependent protein kinases (often referred to col...
GPCR downstream signaling, organism-specific biosystem (from REACTOME)
GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
GPCRs, Class A Rhodopsin-like, organism-specific biosystem (from WikiPathways)
GPCRs, Class A Rhodopsin-like, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.gpcr.org/7tm/ (originally at http://www.cmbi.kun.nl/7tm/). The groupings are based on the GPCR phylogenetic tree available fr...
GPCRs, Other, organism-specific biosystem (from WikiPathways)
GPCRs, Other, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.gpcr.org/7tm/ (originally at http://www.cmbi.kun.nl/7tm/). The groupings are based on the GPCR phylogenetic tree available fr...
Hormone ligand-binding receptors, organism-specific biosystem (from REACTOME)
Hormone ligand-binding receptors, organism-specific biosystemThe class A (rhodopsin-like) GPCRs that bind to hormone ligands are annotated here. The hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and hu...
Neuroactive ligand-receptor interaction, organism-specific biosystem (from KEGG)
Neuroactive ligand-receptor interaction, organism-specific biosystem
Neuroactive ligand-receptor interaction
Neuroactive ligand-receptor interaction, conserved biosystem (from KEGG)
Neuroactive ligand-receptor interaction, conserved biosystem
Neuroactive ligand-receptor interaction
Ovarian Infertility Genes, organism-specific biosystem (from WikiPathways)
Ovarian Infertility Genes, organism-specific biosystemOvarian bottleneck genes associated with infertility. A valuable approach to the study of infertility is the comparison of mutations of individual human and mouse genes associated with infertility ph...
Ovarian steroidogenesis, organism-specific biosystem (from KEGG)
Ovarian steroidogenesis, organism-specific biosystemThe ovarian steroids, 17-beta estradiol (E2) and progesterone (P4), are critical for normal uterine function, establishment and maintenance of pregnancy, and mammary gland development. Furthermore, t...
Ovarian steroidogenesis, conserved biosystem (from KEGG)
Ovarian steroidogenesis, conserved biosystemThe ovarian steroids, 17-beta estradiol (E2) and progesterone (P4), are critical for normal uterine function, establishment and maintenance of pregnancy, and mammary gland development. Furthermore, t...
Peptide GPCRs, organism-specific biosystem (from WikiPathways)
Peptide GPCRs, organism-specific biosystem
Peptide GPCRs
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
cAMP signaling pathway, organism-specific biosystem (from KEGG)
cAMP signaling pathway, organism-specific biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
cAMP signaling pathway, conserved biosystem (from KEGG)
cAMP signaling pathway, conserved biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

FSHR__6759 (e-PCR)
- UniSTS:466192

RH69164 (e-PCR)
- UniSTS:49738

FSHR (e-PCR)
- UniSTS:264013

D2S2824 (e-PCR)
- UniSTS:74829

SHGC-105129 (e-PCR)
- UniSTS:169168

SHGC-89265 (e-PCR)
- UniSTS:104919

Homology

Homologs of the FSHR gene: The FSHR gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 181 organisms have orthologs with human gene FSHR
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
G protein-coupled peptide receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
follicle-stimulating hormone receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
follicle-stimulating hormone receptor activity	IDA Inferred from Direct Assay more info	PubMed
follicle-stimulating hormone receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
activation of adenylate cyclase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular response to follicle-stimulating hormone stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
female gamete generation	TAS Traceable Author Statement more info	PubMed
female gonad development	TAS Traceable Author Statement more info	PubMed
follicle-stimulating hormone signaling pathway	IDA Inferred from Direct Assay more info	PubMed
follicle-stimulating hormone signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
gonad development	TAS Traceable Author Statement more info	PubMed
hormone-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
male gonad development	IEP Inferred from Expression Pattern more info	PubMed
positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
positive regulation of phosphatidylinositol 3-kinase signaling	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of protein kinase A signaling	IMP Inferred from Mutant Phenotype more info	PubMed
spermatogenesis	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
integral component of membrane	IDA Inferred from Direct Assay more info	PubMed
integral component of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
receptor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: follicle-stimulating hormone receptor

Names: FSH receptor; follitropin receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008146.1 RefSeqGene

Range

4965..197335

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_536

mRNA and Protein(s)

NM_000145.3 → NP_000136.2 follicle-stimulating hormone receptor isoform 1 precursor

See identical proteins and their annotated locations for NP_000136.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC007189, AK292562, BC118548, BC125270, DB064473

Consensus CDS

CCDS1843.1

UniProtKB/Swiss-Prot

P23945

UniProtKB/TrEMBL

A0A1D5RMN4

Related

ENSP00000384708.2, ENST00000406846.6

Conserved Domains (5) summary

smart00013
Location:20 → 50

LRRNT; Leucine rich repeat N-terminal domain

sd00033
Location:48 → 71

LRR_RI; leucine-rich repeat [structural motif]

pfam00001
Location:379 → 626

7tm_1; 7 transmembrane receptor (rhodopsin family)

pfam12369
Location:282 → 349

GnHR_trans; Gonadotropin hormone receptor transmembrane region

pfam13855
Location:72 → 132

LRR_8; Leucine rich repeat
NM_181446.3 → NP_852111.2 follicle-stimulating hormone receptor isoform 2 precursor

See identical proteins and their annotated locations for NP_852111.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in a shorter isoform (2), compared to isoform 1.

Source sequence(s)

AC007189, AK292562, BC125270, DB064473

Consensus CDS

CCDS1844.2

UniProtKB/Swiss-Prot

P23945

Related

ENSP00000306780.4, ENST00000304421.8

Conserved Domains (7) summary

smart00013
Location:20 → 50

LRRNT; Leucine rich repeat N-terminal domain

COG4886
Location:93 → 273

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:72 → 96

LRR_RI; leucine-rich repeat [structural motif]

pfam00001
Location:353 → 600

7tm_1; 7 transmembrane receptor (rhodopsin family)

pfam12369
Location:256 → 323

GnHR_trans; Gonadotropin hormone receptor transmembrane region

pfam12799
Location:120 → 159

LRR_4; Leucine Rich repeats (2 copies)

pfam13855
Location:72 → 132

LRR_8; Leucine rich repeat

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p13 Primary Assembly

Range

48953161..49154527 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011532734.2 → XP_011531036.1 follicle-stimulating hormone receptor isoform X2

Conserved Domains (4) summary

sd00031
Location:38 → 61

LRR_1; leucine-rich repeat [structural motif]

sd00033
Location:136 → 166

LRR_RI; leucine-rich repeat [structural motif]

pfam00001
Location:302 → 549

7tm_1; 7 transmembrane receptor (rhodopsin family)

pfam12369
Location:205 → 272

GnHR_trans; Gonadotropin hormone receptor transmembrane region
XM_011532733.2 → XP_011531035.1 follicle-stimulating hormone receptor isoform X1

Conserved Domains (5) summary

smart00013
Location:20 → 50

LRRNT; Leucine rich repeat N-terminal domain

sd00033
Location:72 → 96

LRR_RI; leucine-rich repeat [structural motif]

pfam00001
Location:413 → 660

7tm_1; 7 transmembrane receptor (rhodopsin family)

pfam12369
Location:316 → 383

GnHR_trans; Gonadotropin hormone receptor transmembrane region

pfam13306
Location:61 → 216

LRR_5; Leucine rich repeats (6 copies)
XM_011532736.2 → XP_011531038.1 follicle-stimulating hormone receptor isoform X3

See identical proteins and their annotated locations for XP_011531038.1

Conserved Domains (2) summary

pfam00001
Location:115 → 362

7tm_1; 7 transmembrane receptor (rhodopsin family)

pfam12369
Location:18 → 85

GnHR_trans; Gonadotropin hormone receptor transmembrane region
XM_011532735.2 → XP_011531037.1 follicle-stimulating hormone receptor isoform X3

See identical proteins and their annotated locations for XP_011531037.1

Conserved Domains (2) summary

pfam00001
Location:115 → 362

7tm_1; 7 transmembrane receptor (rhodopsin family)

pfam12369
Location:18 → 85

GnHR_trans; Gonadotropin hormone receptor transmembrane region
XM_011532740.1 → XP_011531042.1 follicle-stimulating hormone receptor isoform X4

Conserved Domains (3) summary

smart00013
Location:17 → 50

LRRNT; Leucine rich repeat N-terminal domain

sd00033
Location:72 → 96

LRR_RI; leucine-rich repeat [structural motif]

pfam13306
Location:61 → 216

LRR_5; Leucine rich repeats (6 copies)