FSHB

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

Basic information

Region (hg38): 11:30231014-30235261

Links

ENSG00000131808 ∙ NCBI:2488 ∙ OMIM:136530 ∙ HGNC:3964 ∙ Uniprot:P01225 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypogonadotropic hypogonadism 24 without anosmia (Supportive), mode of inheritance: AR
• hypogonadotropic hypogonadism 24 without anosmia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 24 without anosmia	AR	Endocrine; Obstetric	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	Endocrine; Obstetric	4344039; 758600; 8220432; 9280841; 17961559

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FSHB 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				5	2	7
missense			9	1		10
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding			11	1	6	18
Total	0	1	21	7	8

Variants in FSHB

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

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

Position	Type	Phenotype	Significance	ClinVar
11-30231020-C-G		Hypogonadotropic hypogonadism 24 without anosmia	Uncertain significance (Jan 13, 2018)
11-30231050-T-C		Hypogonadotropic hypogonadism 24 without anosmia	Uncertain significance (Jan 13, 2018)
11-30231642-T-G			Benign (Nov 11, 2018)
11-30231771-A-T			Benign (Mar 11, 2021)
11-30231908-G-A			Likely benign (Jul 20, 2018)
11-30231932-C-G		Hypogonadotropic hypogonadism 24 without anosmia	Uncertain significance (Jan 12, 2018)
11-30231952-G-A		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
11-30231961-G-T		Hypogonadotropic hypogonadism 24 without anosmia • FSHB-related disorder	Conflicting classifications of pathogenicity (Jan 12, 2024)
11-30231985-T-C		Hypogonadotropic hypogonadism 24 without anosmia	Uncertain significance (Nov 02, 2023)
11-30232009-G-A		Inborn genetic diseases	Uncertain significance (Sep 30, 2021)
11-30232010-T-C			Likely benign (Jul 04, 2018)
11-30232033-C-G			Likely benign (Oct 24, 2018)
11-30232049-C-T			Likely benign (Dec 10, 2021)
11-30232094-T-C			Benign (Nov 11, 2018)
11-30233594-A-T			Uncertain significance (Aug 31, 2021)
11-30233615-T-G		Hypogonadotropic hypogonadism 24 without anosmia	Pathogenic (Nov 25, 2010)
11-30233638-C-T		not specified • Hypogonadotropic hypogonadism 24 without anosmia	Benign (Jan 31, 2024)
11-30233644-AGT-A		Hypogonadotropic hypogonadism 24 without anosmia	Pathogenic/Likely pathogenic (Jun 03, 2019)
11-30233647-G-A			Likely benign (Nov 20, 2022)
11-30233655-C-T		Hypogonadotropic hypogonadism 24 without anosmia	Uncertain significance (Jan 12, 2018)
11-30233692-C-A		Hypogonadotropic hypogonadism 24 without anosmia	Pathogenic (Nov 25, 2010)
11-30233697-T-C		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
11-30233708-T-C		Hypogonadotropic hypogonadism 24 without anosmia	Pathogenic (Nov 25, 2010)
11-30233722-G-A		Hypogonadotropic hypogonadism 24 without anosmia	Conflicting classifications of pathogenicity (Aug 17, 2023)
11-30233732-G-C		Inborn genetic diseases	Uncertain significance (May 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FSHB	protein_coding	protein_coding	ENST00000417547	2	4246

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.345	0.603	125581	0	26	125607	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.564	56	69.2	0.809	0.00000338	857
Missense in Polyphen		18	23.776	0.75707		287
Synonymous	0.639	21	25.1	0.838	0.00000127	229
Loss of Function	1.52	1	4.46	0.224	1.89e-7	61

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00199	0.00199
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000441	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: 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;Follicle Stimulating Hormone (FSH) signaling pathway;Signaling by GPCR;Signal Transduction;Peptide hormone metabolism;Metabolism of proteins;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;G alpha (s) signalling events;Hormone ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);regulation of spermatogenesis by crem;GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i;Glycoprotein hormones;GPCR downstream signalling;Peptide hormone biosynthesis;FSH (Consensus)

Recessive Scores

• pRec: 0.818

Intolerance Scores

• loftool: 0.353
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.64

Haploinsufficiency Scores

• pHI: 0.367
• hipred: N
• hipred_score: 0.187
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.542

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fshb
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; reproductive system phenotype

Zebrafish Information Network

• Gene name: fshb
• Affected structure: ovarian follicle stage III
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: progesterone biosynthetic process;transforming growth factor beta receptor signaling pathway;G protein-coupled receptor signaling pathway;female gamete generation;female pregnancy;positive regulation of cell population proliferation;hormone-mediated signaling pathway;regulation of signaling receptor activity;positive regulation of steroid biosynthetic process;peptide hormone processing;positive regulation of cell migration;follicle-stimulating hormone signaling pathway;regulation of osteoclast differentiation;positive regulation of bone resorption;positive regulation of transcription by RNA polymerase II;Sertoli cell proliferation
• Cellular component: extracellular region;extracellular space;cytoplasm;follicle-stimulating hormone complex
• Molecular function: hormone activity;protein binding;follicle-stimulating hormone activity