FSHR

Protein identityUniProt · HPA

UniProt accession

P23945

Gene

FSHR

Ensembl

ENSG00000170820

Chromosome

2

Canonical length

695 aa

Protein class

Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Secretome location

Intracellular and membrane

Quaternary structure

Homotrimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

695 residues, UniProt reviewed canonical sequence.

>P23945|FSHR
     1  MALLLVSLLA FLSLGSGCHH RICHCSNRVF LCQESKVTEI PSDLPRNAIE LRFVLTKLRV
    61  IQKGAFSGFG DLEKIEISQN DVLEVIEADV FSNLPKLHEI RIEKANNLLY INPEAFQNLP
   121  NLQYLLISNT GIKHLPDVHK IHSLQKVLLD IQDNINIHTI ERNSFVGLSF ESVILWLNKN
   181  GIQEIHNCAF NGTQLDELNL SDNNNLEELP NDVFHGASGP VILDISRTRI HSLPSYGLEN
   241  LKKLRARSTY NLKKLPTLEK LVALMEASLT YPSHCCAFAN WRRQISELHP ICNKSILRQE
   301  VDYMTQARGQ RSSLAEDNES SYSRGFDMTY TEFDYDLCNE VVDVTCSPKP DAFNPCEDIM
   361  GYNILRVLIW FISILAITGN IIVLVILTTS QYKLTVPRFL MCNLAFADLC IGIYLLLIAS
   421  VDIHTKSQYH NYAIDWQTGA GCDAAGFFTV FASELSVYTL TAITLERWHT ITHAMQLDCK
   481  VQLRHAASVM VMGWIFAFAA ALFPIFGISS YMKVSICLPM DIDSPLSQLY VMSLLVLNVL
   541  AFVVICGCYI HIYLTVRNPN IVSSSSDTRI AKRMAMLIFT DFLCMAPISF FAISASLKVP
   601  LITVSKAKIL LVLFHPINSC ANPFLYAIFT KNFRRDFFIL LSKCGCYEMQ AQIYRTETSS
   661  TVHNTHPRNG HCSSAPRVTS GSTYILVPLS HLAQN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FSHR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

2.6 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FSHR.

Disease | AllUniProt

Conditions FSHR is implicated in, by any mechanism.

• Ovarian dysgenesis 1 (ODG1) MIM:233300
• Ovarian hyperstimulation syndrome (OHSS) MIM:608115

Disease | GeneticClinVar

35 pathogenic / likely-pathogenic of 230 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Ovarian dysgenesis 1
• Ovarian hyperstimulation syndrome
• Genetic non-acquired premature ovarian failure
• Dizygotic twins
• Amenorrhea

ReferencesPubMed · IEDB

Publications for FSHR from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.22

gnomAD pLI

0

gnomAD missense Z

-0.8

DepMap mean gene effect

0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• basement membrane organization
• cellular response to follicle-stimulating hormone stimulus
• female gamete generation
• female gonad development
• follicle-stimulating hormone signaling pathway
• G protein-coupled receptor signaling pathway
• gonad development
• hormone-mediated signaling pathway
• intracellular water homeostasis
• locomotory behavior
• male gonad development
• negative regulation of bone resorption
• neuron projection development
• phospholipase C-activating G protein-coupled receptor signaling pathway
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of intracellular estrogen receptor signaling pathway
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• primary ovarian follicle growth
• regulation of chromosome organization
• regulation of hormone metabolic process
• regulation of osteoclast differentiation
• regulation of platelet-derived growth factor receptor signaling pathway
• regulation of protein kinase A signaling
• regulation of systemic arterial blood pressure
• Sertoli cell development
• Sertoli cell proliferation
• sperm DNA condensation
• spermatogenesis
• transcytosis
• uterus development
• regulation of acetylcholine metabolic process

Molecular functions

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

Cellular components

• cell surface
• endosome
• membrane
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Leucine-rich repeat N-terminal domain
• Glycoprotein hormone receptor family
• GPCR, rhodopsin-like, 7TM
• BspA-type LRR region
• Leucine-rich repeat domain superfamily
• 7 transmembrane receptor (rhodopsin family)
• Leucine rich repeat N-terminal domain
• BspA type Leucine rich repeat region (6 copies)
• Follicle stimulating hormone receptor
• Gonadotropin hormone receptor, transmembrane domain
• Gonadotropin hormone receptor transmembrane region

KeywordsUniProt

• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Leucine-rich repeat
• Membrane
• Receptor
• Repeat
• Signal
• Sulfation
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of FSHR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• APPL2
• ARRB2
• YWHAQ