FSHR
follicle stimulating hormone receptor, the group of Glycoprotein hormone receptors
Basic information
Region (hg38): 2:48962157-49154527
Previous symbols: [ "ODG1" ]
Links
Phenotypes
GenCC
Source:
- 46 XX gonadal dysgenesis (Supportive), mode of inheritance: AD
- ovarian dysgenesis 1 (Strong), mode of inheritance: AR
- ovarian hyperstimulation syndrome (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Ovarian hyperstimulation syndrome; Ovarian dysgenesis 1 | AD/AR | Obstetric | 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 | Endocrine; Genitourinary; Obstetric | 7553856; 9769327; 12498425; 11889179; 12930928; 12930927; 12930924; 17721928; 20087398 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (66 variants)
- Ovarian_dysgenesis_1 (62 variants)
- not_provided (58 variants)
- Ovarian_hyperstimulation_syndrome (54 variants)
- FSHR-related_disorder (7 variants)
- Genetic_non-acquired_premature_ovarian_failure (7 variants)
- not_specified (3 variants)
- Dizygotic_twins (3 variants)
- Amenorrhea (2 variants)
- Ovarian_dysgenesis (2 variants)
- Hereditary_xanthinuria_type_1 (1 variants)
- Gonadal_dysgenesis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FSHR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000145.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 14 | 10 | 24 | |||
| missense | 17 | 94 | 129 | |||
| nonsense | 2 | |||||
| start loss | 1 | 1 | 2 | |||
| frameshift | 5 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 14 | 20 | 110 | 19 | 0 |
Highest pathogenic variant AF is 0.000278816
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FSHR | protein_coding | protein_coding | ENST00000406846 | 10 | 192381 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.37e-11 | 0.185 | 125701 | 0 | 47 | 125748 | 0.000187 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.799 | 401 | 358 | 1.12 | 0.0000178 | 4602 |
| Missense in Polyphen | 93 | 108.91 | 0.85393 | 1372 | ||
| Synonymous | -2.70 | 178 | 138 | 1.29 | 0.00000694 | 1356 |
| Loss of Function | 0.765 | 19 | 23.0 | 0.828 | 0.00000106 | 314 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000330 | 0.000329 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.000212 | 0.000211 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000294 | 0.000294 |
| Other | 0.000327 | 0.000326 |
dbNSFP
Source:
- 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.;
- Pathway
- 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;GPCRs, Other;Follicle Stimulating Hormone (FSH) signaling pathway;Peptide GPCRs;Ovarian Infertility Genes;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Hormone ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);regulation of spermatogenesis by crem;GPCR ligand binding;GPCR downstream signalling;FSH
(Consensus)
Recessive Scores
- pRec
- 0.400
Intolerance Scores
- loftool
- 0.411
- rvis_EVS
- -0.11
- rvis_percentile_EVS
- 45.49
Haploinsufficiency Scores
- pHI
- 0.0825
- hipred
- Y
- hipred_score
- 0.610
- ghis
- 0.401
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.297
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fshr
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- fshr
- Affected structure
- germ line cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- 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;gonad development;male gonad development;female gonad development;hormone-mediated signaling pathway;regulation of protein kinase A signaling;positive regulation of phosphatidylinositol 3-kinase signaling;follicle-stimulating hormone signaling pathway;positive regulation of adenylate cyclase activity;positive regulation of ERK1 and ERK2 cascade;cellular response to follicle-stimulating hormone stimulus
- Cellular component
- plasma membrane;integral component of plasma membrane;integral component of membrane;receptor complex
- Molecular function
- follicle-stimulating hormone receptor activity;protein binding;G protein-coupled peptide receptor activity