Hypogonadotropic hypogonadism: genes and variants
Hypogonadotropic hypogonadism is linked to 3 analyzed proteins (FGFR1, CHD7 and FSHR). 2 DNA variants are known to cause it; 6 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Hypogonadotropic hypogonadism
FGFR1: Fibroblast growth factor receptor 1
Its fibroblast-growth-factor signaling controls proliferation, differentiation, migration, and developmental patterning in many tissues. Germline pathogenic variants can cause hypogonadotropic hypogonadism or craniosynostosis syndromes, while fusions and other activating alterations drive selected cancers.
2 disease-causing and 5 uncertain variants in FGFR1 are linked to Hypogonadotropic hypogonadism.
CHD7: ATP-dependent chromatin remodeler CHD7
It regulates chromatin accessibility and developmental gene programs across multiple embryonic tissues. Haploinsufficiency is the major cause of CHARGE syndrome, which can affect the eyes, heart, choanae, growth, genital development, ears, and nervous system.
0 disease-causing and 1 uncertain variants in CHD7 are linked to Hypogonadotropic hypogonadism.
FSHR: Follicle-stimulating hormone receptor
FSH signaling through this pathway drives ovarian follicle maturation and supports Sertoli-cell function and spermatogenesis. Loss-of-function variants can cause ovarian resistance or infertility, whereas activating variants can produce inappropriate ovarian responsiveness.
0 disease-causing and 0 uncertain variants in FSHR are linked to Hypogonadotropic hypogonadism.
Weakly linked (only a few uncertain records): SOX10.
Known disease-causing variants in Hypogonadotropic hypogonadism
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| FGFR1 D133H | 133 | Extracellular | Disease-causing (★★) |
| FGFR1 D224H | 224 | Ig-like C2-type 2 | Disease-causing (★★) |
Same protein, different disease
- Hypogonadotropic hypogonadism 2 with or without anosmia is also caused by FGFR1 variants; they fall mostly in different places as the Hypogonadotropic hypogonadism variants (55 disease-causing).
- Pfeiffer syndrome is also caused by FGFR1 variants; they fall mostly in different places as the Hypogonadotropic hypogonadism variants (18 disease-causing).
- Hartsfield-Bixler-Demyer syndrome is also caused by FGFR1 variants; they fall mostly in different places as the Hypogonadotropic hypogonadism variants (13 disease-causing).
- Jackson-Weiss syndrome is also caused by FGFR1 variants; they fall mostly in different places as the Hypogonadotropic hypogonadism variants (5 disease-causing).
- Osteoglophonic dysplasia is also caused by FGFR1 variants; they fall mostly in different places as the Hypogonadotropic hypogonadism variants (5 disease-causing).
Diseases related to Hypogonadotropic hypogonadism
- Hypogonadotropic hypogonadism 2 with or without anosmia, also linked to FGFR1
- CHARGE syndrome, also linked to CHD7
- Pfeiffer syndrome, also linked to FGFR1
- Wiedemann-Steiner syndrome, also linked to CHD7
- Colorectal cancer, also linked to FGFR1
- Non-small cell lung carcinoma, also linked to FGFR1
- Idiopathic pulmonary fibrosis, also linked to FGFR1
- Hartsfield-Bixler-Demyer syndrome, also linked to FGFR1
- Jackson-Weiss syndrome, also linked to FGFR1
- CHD7-related CHARGE syndrome, also linked to CHD7
- Joubert syndrome, also linked to CHD7
- Hypogonadotropic hypogonadism 5 with or without anosmia, also linked to CHD7
Frequently asked questions
Which genes are linked to Hypogonadotropic hypogonadism?
In CATVariant, Hypogonadotropic hypogonadism is linked to 3 analyzed proteins: FGFR1 (Fibroblast growth factor receptor 1), CHD7 (ATP-dependent chromatin remodeler CHD7) and FSHR (Follicle-stimulating hormone receptor).
How many genetic variants are linked to Hypogonadotropic hypogonadism?
9 variants: 2 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 6 are of uncertain significance or have conflicting reports.
Which uncertain variants in Hypogonadotropic hypogonadism look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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