Leydig cell agenesis: genes and variants
Leydig cell agenesis is linked to 1 analyzed protein (LHCGR). 10 DNA variants are known to cause it; 13 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 Leydig cell agenesis
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.
10 disease-causing and 13 uncertain variants in LHCGR are linked to Leydig cell agenesis.
Where Leydig cell agenesis variants cluster
- LHCGR Transmembrane (positions 571–594): 3 of 10 disease-causing changes, 8.7× more than its size predicts.
Known disease-causing variants in Leydig cell agenesis
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| LHCGR D578G | 578 | Transmembrane | Disease-causing (★★) |
| LHCGR S616Y | 616 | Transmembrane | Disease-causing (★★) |
| LHCGR E354K | 354 | Extracellular | Disease-causing (★) |
| LHCGR A498V | 498 | Transmembrane | Disease-causing (★) |
| LHCGR D578N | 578 | Transmembrane | Disease-causing (★) |
| LHCGR C343S | 343 | Extracellular | Disease-causing |
| LHCGR V144F | 144 | LRR 2 | Disease-causing |
| LHCGR C543R | 543 | Transmembrane | Disease-causing |
| LHCGR A593P | 593 | Transmembrane | Disease-causing |
| LHCGR L502P | 502 | Transmembrane | Disease-causing |
Which prediction tools work for Leydig cell agenesis
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: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 92 out of 100
Same protein, different disease
- Gonadotropin-independent familial sexual precocity is also caused by LHCGR variants; they fall mostly in different places as the Leydig cell agenesis variants (12 disease-causing).
Diseases related to Leydig cell agenesis
- Gonadotropin-independent familial sexual precocity, also linked to LHCGR
- Pseudohermaphroditism, also linked to LHCGR
- Leydig cell hypoplasia, also linked to LHCGR
Frequently asked questions
Which genes are linked to Leydig cell agenesis?
In CATVariant, Leydig cell agenesis is linked to 1 analyzed protein: LHCGR (Lutropin-choriogonadotropic hormone receptor).
How many genetic variants are linked to Leydig cell agenesis?
26 variants: 10 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 13 are of uncertain significance or have conflicting reports.
Which uncertain variants in Leydig cell agenesis 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 Leydig cell agenesis?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.92, based on 9 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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