SRD5A1
Chr 5steroid 5 alpha-reductase 1
Also known as: S5AR 1
The protein converts testosterone to dihydrotestosterone (DHT) and metabolizes progesterone and corticosteroids, playing a central role in sexual differentiation and androgen physiology. Unlike SRD5A2 deficiency which causes well-characterized disorders of sexual development, SRD5A1 mutations have not been definitively associated with human disease. The gene appears highly tolerant to loss-of-function variation based on population genetics data.
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
155 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 105 | 0 | 105 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 35 | 2 | 0 | 37 |
Likely Benign | 0 | 3 | 1 | 1 | 5 |
Benign | 0 | 1 | 0 | 2 | 3 |
| Total | 0 | 39 | 109 | 3 | 151 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SRD5A1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
5-Alpha Reductase 2 as a Marker of Resistance to 5ARI Therapy
RECRUITINGMolecular Mechanisms of Dutasteride and Dietary Interventions to Prevent Prostate Cancer and Reduce Its Progression
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools