AKR1C1

Chr 10

aldo-keto reductase family 1 member C1

Also known as: 2-ALPHA-HSD, 20-ALPHA-HSD, DD1, DD1/DD2, DDH, DDH1, H-37, HAKRC

NCBI Gene: 1645ENSG00000187134UniProt: Q04828OMIM: 600449

This protein functions as a cytosolic aldo-keto reductase that catalyzes the NADPH-dependent reduction of ketosteroids to hydroxysteroids, playing a key role in neurosteroid metabolism and regulating steroid hormone availability. The gene shows extremely low constraint against loss-of-function variants (pLI near zero, LOEUF 1.59), and no clear disease associations have been established in the provided data. Without established clinical phenotypes, the inheritance pattern and disease manifestations for this gene remain undefined.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.59
Clinical Summary— AKR1C1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 59 VUS of 107 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
1.59LOEUF
pLI 0.000
Z-score -0.43
OE 1.11 (0.78–1.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.42Z-score
OE missense 1.31 (1.17–1.47)
211 obs / 160.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.11 (0.78–1.59)
0≤0.351.4
Missense OE1.31 (1.17–1.47)
0≤0.61.4
Synonymous OE1.31
0≤1.21.6
LoF obs/exp: 21 / 19.0Missense obs/exp: 211 / 160.5Syn Z: -1.85
DN
0.76top 25%
GOF
0.6249th %ile
LOF
0.2777th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

107 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic2
VUS59
Likely Benign9
Benign3
26
Pathogenic
2
Likely Pathogenic
59
VUS
9
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
2
0
2
VUS
0
49
10
0
59
Likely Benign
0
1
5
3
9
Benign
0
1
1
1
3
Total05144499

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

View in ClinVar →

Protein Context — Lollipop Plot

AKR1C1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients