SRD5A3

Chr 4AR

steroid 5 alpha-reductase 3

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

NCBI Gene: 79644ENSG00000128039UniProt: Q9H8P0

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]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IqMIM #612379
AR
Kahrizi syndromeMIM #612713
AR
273
ClinVar variants
44
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SRD5A3
🧬
Gene-Disease Validity (ClinGen)
SRD5A3-congenital disorder of glycosylation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 Pathogenic / Likely Pathogenic· 129 VUS of 273 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.97LOEUF
pLI 0.000
Z-score 1.64
OE 0.54 (0.32–0.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.76Z-score
OE missense 0.83 (0.72–0.96)
136 obs / 163.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.54 (0.32–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.72–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 8 / 14.8Missense obs/exp: 136 / 163.3Syn Z: 0.80

ClinVar Variant Classifications

273 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic11
VUS129
Likely Benign61
Benign28
Conflicting11
33
Pathogenic
11
Likely Pathogenic
129
VUS
61
Likely Benign
28
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
30
0
33
Likely Pathogenic
6
2
2
1
11
VUS
1
73
53
2
129
Likely Benign
0
4
29
28
61
Benign
0
0
27
1
28
Conflicting
—11
Total107914132273

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

View in ClinVar →

Protein Context — Lollipop Plot

SRD5A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SRD5A3-related congenital disorder of glycosylation

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital disorder of glycosylation, type Iq

MIM #612379

Molecular basis of disorder known

Autosomal recessive

Kahrizi syndrome

MIM #612713

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SRD5A3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
N-glycoproteomic and proteomic alterations in SRD5A3-deficient fibroblasts.
Garapati K et al.·Glycobiology
2024
SRD5A3-CDG: A Patient with a Novel Variant and Brain Neoplasm.
Kasapkara CS et al.·J Coll Physicians Surg Pak
2022Review
SRD5A3-CDG: 3D structure modeling, clinical spectrum, and computer-based dysmorphic facial recognition.
Ben Ayed I et al.·Am J Med Genet A
2021Functional
Adult phenotype and further phenotypic variability in SRD5A3-CDG.
Kara B et al.·BMC Med Genet
2014Case report
SRD5A3-CDG: Twins with an intragenic tandem duplication.
Rieger M et al.·Eur J Med Genet
2022
Review of SRD5A3 Disease-Causing Sequence Variants and Ocular Findings in Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation, and a Detailed New Case.
Kousal B et al.·Folia Biol (Praha)
2019Review
Over-expression of SRD5A3 and its prognostic significance in breast cancer.
Zhang YP et al.·World J Surg Oncol
2021
N6-methyladenosine-modified SRD5A3, identified by IGF2BP3, sustains cisplatin resistance in bladder cancer.
Liao K et al.·Hum Cell
2024
Unique clinical presentations and follow-up outcomes from experience with congenital disorders of glycosylation: PMM2-PGM1-DPAGT1-MPI-POMT2-B3GALNT2-DPM1-SRD5A3-CDG.
Yoldas Celik M et al.·J Pediatr Endocrinol Metab
2023Natural history
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools