3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency: genes and variants
3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency is linked to 1 analyzed protein (SRD5A2). 43 DNA variants are known to cause it; 26 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 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency
SRD5A2: 3-oxo-5-alpha-steroid 4-dehydrogenase 2
It converts testosterone to the more potent androgen dihydrotestosterone in androgen-responsive tissues. Biallelic loss-of-function variants cause 5-alpha-reductase type 2 deficiency, leading to undervirilization of 46,XY individuals and often increased virilization at puberty.
43 disease-causing and 24 uncertain variants in SRD5A2 are linked to 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency.
Weakly linked (only a few uncertain records): CHD7 and SOX9.
Known disease-causing variants in 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SRD5A2 G196S | 196 | Disease-causing (★★) | |
| SRD5A2 A228G | 228 | Disease-causing (★★) | |
| SRD5A2 A228V | 228 | Disease-causing (★★) | |
| SRD5A2 L55P | 55 | Disease-causing (★★) | |
| SRD5A2 L55Q | 55 | Disease-causing (★★) | |
| SRD5A2 E197K | 197 | Disease-causing (★★) | |
| SRD5A2 E197D | 197 | Disease-causing (★★) | |
| SRD5A2 A228T | 228 | Disease-causing (★★) | |
| SRD5A2 H231R | 231 | Disease-causing (★★) | |
| SRD5A2 R246Q | 246 | Disease-causing (★★) | |
| SRD5A2 R246W | 246 | Disease-causing (★★) | |
| SRD5A2 E57Q | 57 | Disease-causing (★★) | |
| SRD5A2 A65P | 65 | Disease-causing (★★) | |
| SRD5A2 N193S | 193 | Disease-causing (★★) | |
| SRD5A2 R227Q | 227 | Disease-causing (★★) | |
| SRD5A2 H232R | 232 | Disease-causing (★★) | |
| SRD5A2 H162P | 162 | Transmembrane | Disease-causing (★★) |
| SRD5A2 L20P | 20 | Transmembrane | Disease-causing (★★) |
| SRD5A2 G34R | 34 | Disease-causing (★★) | |
| SRD5A2 Y91H | 91 | Transmembrane | Disease-causing (★★) |
| SRD5A2 G115D | 115 | Disease-causing (★★) | |
| SRD5A2 T120P | 120 | Disease-causing (★★) | |
| SRD5A2 Q126R | 126 | Disease-causing (★★) | |
| SRD5A2 Y128C | 128 | Disease-causing (★★) | |
| SRD5A2 R145W | 145 | Disease-causing (★★) | |
| SRD5A2 P181L | 181 | Disease-causing (★★) | |
| SRD5A2 G183S | 183 | Disease-causing (★★) | |
| SRD5A2 G203S | 203 | Disease-causing (★★) | |
| SRD5A2 A207D | 207 | Transmembrane | Disease-causing (★★) |
| SRD5A2 T208I | 208 | Transmembrane | Disease-causing (★★) |
| SRD5A2 Y235F | 235 | Disease-causing (★★) | |
| SRD5A2 G196R | 196 | Disease-causing (★) | |
| SRD5A2 G196D | 196 | Disease-causing (★) | |
| SRD5A2 H231Y | 231 | Disease-causing (★) | |
| SRD5A2 A65T | 65 | Disease-causing (★) | |
| SRD5A2 F118L | 118 | Disease-causing (★) | |
| SRD5A2 H230P | 230 | Disease-causing (★) | |
| SRD5A2 A248D | 248 | Disease-causing (★) | |
| SRD5A2 G104E | 104 | Disease-causing (★) | |
| SRD5A2 A192T | 192 | Disease-causing (★) | |
| SRD5A2 Y242C | 242 | Disease-causing (★) | |
| SRD5A2 A12E | 12 | Transmembrane | Disease-causing |
| SRD5A2 A69S | 69 | Disease-causing |
Which prediction tools work for 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- PolyPhen-2: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 82 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 77 out of 100
- SIFT: 51 out of 100
- phyloP: 50 out of 100
Diseases related to 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency
- Differences in sex development, also linked to SRD5A2
- Prostate cancer, also linked to SRD5A2
Frequently asked questions
Which genes are linked to 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency?
In CATVariant, 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency is linked to 1 analyzed protein: SRD5A2 (3-oxo-5-alpha-steroid 4-dehydrogenase 2).
How many genetic variants are linked to 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency?
75 variants: 43 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 26 are of uncertain significance or have conflicting reports.
Which uncertain variants in 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 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 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.77, based on 38 disease-causing and 333 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.
Download every variant as CSV · Browse all diseases · Methods · About the Center