Gonadotropin-independent familial sexual precocity: genes and variants
Gonadotropin-independent familial sexual precocity is linked to 1 analyzed protein (LHCGR). 12 DNA variants are known to cause it; 8 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 Gonadotropin-independent familial sexual precocity
LHCGR: Lutropin-choriogonadotropic hormone receptor
It responds to luteinizing hormone and chorionic gonadotropin to stimulate gonadal steroidogenesis, ovulation, and male sexual differentiation. Activating variants can cause male-limited precocious puberty, whereas loss-of-function variants cause Leydig-cell hypoplasia or infertility.
12 disease-causing and 8 uncertain variants in LHCGR are linked to Gonadotropin-independent familial sexual precocity.
Where Gonadotropin-independent familial sexual precocity variants cluster
- LHCGR Transmembrane (positions 571–594): 5 of 12 disease-causing changes, 12.1× more than its size predicts.
- LHCGR Cytoplasmic (positions 550–570): 3 of 12 disease-causing changes, 8.3× more than its size predicts.
Known disease-causing variants in Gonadotropin-independent familial sexual precocity
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| LHCGR D578G | 578 | Transmembrane | Disease-causing (★★) |
| LHCGR D564G | 564 | Cytoplasmic | Disease-causing (★★) |
| LHCGR D564V | 564 | Cytoplasmic | Disease-causing (★★) |
| LHCGR T577I | 577 | Transmembrane | Disease-causing (★★) |
| LHCGR D578Y | 578 | Transmembrane | Disease-causing (★) |
| LHCGR A373V | 373 | Transmembrane | Disease-causing (★) |
| LHCGR D578N | 578 | Transmembrane | Disease-causing (★) |
| LHCGR M398T | 398 | Transmembrane | Disease-causing (★) |
| LHCGR A568V | 568 | Cytoplasmic | Disease-causing (★) |
| LHCGR L457R | 457 | Transmembrane | Disease-causing |
| LHCGR M571I | 571 | Transmembrane | Disease-causing |
| LHCGR L368P | 368 | Transmembrane | Disease-causing |
Which prediction tools work for Gonadotropin-independent familial sexual precocity
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 90 out of 100
Same protein, different disease
- Leydig cell agenesis is also caused by LHCGR variants; they fall mostly in different places as the Gonadotropin-independent familial sexual precocity variants (10 disease-causing).
Diseases related to Gonadotropin-independent familial sexual precocity
- Leydig cell agenesis, also linked to LHCGR
- Pseudohermaphroditism, also linked to LHCGR
- Leydig cell hypoplasia, also linked to LHCGR
Frequently asked questions
Which genes are linked to Gonadotropin-independent familial sexual precocity?
In CATVariant, Gonadotropin-independent familial sexual precocity is linked to 1 analyzed protein: LHCGR (Lutropin-choriogonadotropic hormone receptor).
How many genetic variants are linked to Gonadotropin-independent familial sexual precocity?
26 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 8 are of uncertain significance or have conflicting reports.
Which uncertain variants in Gonadotropin-independent familial sexual precocity look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Gonadotropin-independent familial sexual precocity?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.90, based on 12 disease-causing and 8 harmless variants).
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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