GeneBe

FSHB

protein-coding

follicle stimulating hormone subunit beta, the group of Receptor ligands|Glycoprotein hormone subunits

Gene summary

The pituitary glycoprotein hormone family includes follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, and thyroid-stimulating hormone. All of these glycoproteins consist of an identical alpha subunit and a hormone-specific beta subunit. This gene encodes the beta subunit of follicle-stimulating hormone. In conjunction with luteinizing hormone, follicle-stimulating hormone induces egg and sperm production. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001382289.1

Inheritance

AR

ClinVar variants

P:5U:19B:13

Top phenotype

Hypogonadotropic hypogonadism 24 without anosmia

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr11:30,231,014-30,235,261

External References & Databases

Ensembl (ENSG00000131808)NCBI Gene (2488)OMIM (136530)HGNC:3964GenCCUniProt (P01225)AlphaFoldClinVar (FSHB)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~4.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypogonadotropic hypogonadism 24 without anosmiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009239

Submitter: Labcorp Genetics (formerly Invitae)

hypogonadotropic hypogonadism 24 without anosmiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009239

Submitter: Orphanet

hypogonadotropic hypogonadism 24 without anosmiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009239

Submitter: PanelApp Australia

hypogonadotropic hypogonadism 24 without anosmiaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009239

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Hypogonadotropic hypogonadism 24 without anosmiaAR

Manifestation: Endocrine; Obstetric

Intervention: Endocrine; Obstetric

Rationale: In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required

Refs: 4344039; 758600; 8220432; 9280841; 17961559Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FSHB variants in ClinVar

4 Conditions Cataloged
not providedTotal: 16
Hypogonadotropic hypogonadism 24 without anosmiaTotal: 13
Inborn genetic diseasesTotal: 12
FSHB-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001382289.1. 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
10
clinvar
1
clinvar
 11
missense
2
clinvar
18
clinvar
2
clinvar
 22
nonsense
1
clinvar
1
clinvar
 2
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total321912137

Highest pathogenic variant AF is 0.00005576367

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001382289.1RefSeqNP_001369218.12MANE Select
ENST00000533718.2EnsemblENSP00000433424.12MANE Select
NM_000510.4RefSeqNP_000501.12Standard
NM_001018080.3RefSeqNP_001018090.12Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
fshbDanio rerio

Structure: ovarian follicle stage III

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • GnRH signaling pathway - Homo sapiens (human)
  • cAMP signaling pathway - Homo sapiens (human)
  • Neuroactive ligand-receptor interaction - Homo sapiens (human)
  • Ovarian steroidogenesis - Homo sapiens (human)
  • Intracellular Signalling Through FSH Receptor and Follicle Stimulating Hormone

Biological Process

  • progesterone biosynthetic process
  • transforming growth factor beta receptor signaling pathway
  • G protein-coupled receptor signaling pathway
  • female gamete generation
  • female pregnancy

Molecular Function

  • hormone activity
  • protein binding
  • follicle-stimulating hormone activity

Cellular Component

  • extracellular region
  • extracellular space
  • cytoplasm
  • follicle-stimulating hormone complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000417547
Coding exons
2
Length
4246
Individuals with no LoFs
125581
Homozygous LoFs
0
Heterozygous LoFs
26
Defined
125607
p
0.000103
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.5645669.20.8090.00000338857
Missense (PolyPhen)1823.7760.75707287
Synonymous0.6392125.10.8380.00000127229
Loss of Function1.5214.460.2241.89e-761

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.00200.0020notable
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000440.000044rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Together with the alpha chain CGA constitutes follitropin, the follicle-stimulating hormone, and provides its biological specificity to the hormone heterodimer. Binds FSHR, a G protein-coupled receptor, on target cells to activate downstream signaling pathways (PubMed:2494176, PubMed:24692546). Follitropin is involved in follicle development and spermatogenesis in reproductive organs (PubMed:407105, PubMed:8220432). {ECO:0000269|PubMed:24692546, ECO:0000269|PubMed:2494176, ECO:0000269|PubMed:407105, ECO:0000269|PubMed:8220432}.;
Disease
DISEASE: Hypogonadotropic hypogonadism 24 without anosmia (HH24) [MIM:229070]: A form of hypogonadotropic hypogonadism, a group of disorders characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. HH24 is characterized by primary amenorrhea in women, oligo or azoospermia with low to normal testosterone levels in men, and infertility. {ECO:0000269|PubMed:8220432, ECO:0000269|PubMed:9271483, ECO:0000269|PubMed:9280841}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.818

Intolerance Scores

LoFtool
0.353
RVIS EVS
0.04
RVIS percentile EVS
56.64

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.542

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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