SRD5A3

Chr 4AR

steroid 5 alpha-reductase 3

Also known as: CDG1P, CDG1Q, KRIZI, S5AR, S5AR 3, SRD5A2L, SRD5A2L1

NCBI Gene: 79644 ENSG00000128039 UniProt: Q9H8P0 OMIM: 611715

The protein functions as a polyprenol reductase that converts polyprenol to dolichol in the early steps of protein N-linked glycosylation and also converts testosterone to dihydrotestosterone. Biallelic mutations cause congenital disorder of glycosylation type Iq and Kahrizi syndrome, both presenting with intellectual disability and developmental delays along with multisystem involvement including cerebellar ataxia and ophthalmologic abnormalities. This follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the steroid 5-alpha reductase family, and polyprenol reductase subfamily. It is involved in the production of androgen 5-alpha-dihydrotestosterone (DHT) from testosterone, and maintenance of the androgen-androgen receptor activation pathway. This protein is also necessary for the conversion of polyprenol into dolichol, which is required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-linked glycosylation of proteins. Mutations in this gene are associated with congenital disorder of glycosylation type Iq. [provided by RefSeq, Mar 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.972 OMIM phenotypes

Clinical Summary— SRD5A3

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Gene-Disease Validity (ClinGen)

SRD5A3-congenital disorder of glycosylation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

25 unique Pathogenic / Likely Pathogenic· 125 VUS of 256 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.000

Z-score 1.64

OE 0.54 (0.32–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.76Z-score

OE missense 0.83 (0.72–0.96)

136 obs / 163.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.32–0.97)

0≤0.351.4

Missense OE?0.83 (0.72–0.96)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 8 / 14.8Missense obs/exp: 136 / 163.3Syn Z: 0.80

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSRD5A3-related congenital disorder of glycosylationLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7228th %ile

GOF

0.6542th %ile

LOF

0.2190th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

256 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic11

VUS125

Likely Benign61

Benign28

Conflicting11

Pathogenic

Likely Pathogenic

125

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	13	0	1	0	14
Likely Pathogenic	7	2	1	1	11
VUS	2	74	47	2	125
Likely Benign	0	4	29	28	61
Benign	0	0	27	1	28
Conflicting	—				11
Total	22	80	105	32	250

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap SRD5A3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →