SRD5A1

Chr 5

steroid 5 alpha-reductase 1

Also known as: S5AR 1

NCBI Gene: 6715 ENSG00000145545 UniProt: P18405 OMIM: 184753

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.

OMIM ResearchSummary from RefSeq, UniProt, Mechanism

Steroid 5-alpha-reductase (EC 1.3.99.5) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT). Also see SRD5A2 (MIM 607306).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.29

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.29LOEUF

pLI 0.000

Z-score 0.84

OE 0.74 (0.45–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.59Z-score

OE missense 0.86 (0.75–1.00)

129 obs / 149.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.45–1.29)

0≤0.351.4

Missense OE?0.86 (0.75–1.00)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 9 / 12.2Missense obs/exp: 129 / 149.3Syn Z: -1.09

Background carrier burden — how many people carry a rare variant somewhere in SRD5A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

325 rare PASS variants

Rare truncating (LoF)

1 in 4,400

41 rare PASS variants

Rare synonymous (reference)

1 in 310

162 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SRD5A1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 7,200
South Asian	~43k	1 in 210	1 in 3,500
Remaining (unassigned)	~30k	1 in 160	1 in 6,000
European (Finnish)	~27k	1 in 960	≈ 1 in 19,000
Admixed American	~22k	1 in 190	1 in 1,300
African / African American	~21k	1 in 230	1 in 2,300
East Asian	~20k	1 in 520	1 in 1,400
Ashkenazi Jewish	~13k	1 in 700	none seen
Middle Eastern	~2,884	1 in 380	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 5.? see exons ↓