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: Q04828

This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reaction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]

Research Assistant →
0
Active trials
46
Pubs (1 yr)
27
P/LP submissions
0%
P/LP missense
1.59
LOEUF
DN
Mechanism· predicted
Clinical Summary— AKR1C1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 58 VUS of 105 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

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic2
VUS58
Likely Benign9
Benign3
25
Pathogenic
2
Likely Pathogenic
58
VUS
9
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
0
2
0
2
VUS
0
48
10
0
58
Likely Benign
0
1
5
3
9
Benign
0
1
1
1
3
Total05043497

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.

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
Comprehensive analysis of the deleterious nonsynonymous, non-coding SNPs and cancer variants of human aldo-keto reductase type 1 (AKR1C1) protein and their probable association with disease risk and progression: a computational study.
Nila NN et al.·Biochem Biophys Rep
2026Open Access
Role of Aldo-Keto reductase family 1 member C in cancer progression: a special focus on the role of AKR1C1 in pancreatic cancer.
Huang D et al.·Med Oncol
2025
Proteomic Profiling of Human Synovial Fluid Reveals AKR1C1 as a Biomarker of Osteoarthritis Severity.
Fernández-Puente P et al.·J Proteome Res
2026
Exploring the roles of AKR1C1, AKR1C2, and AKR1C3 in the nervous system: Mechanisms and perspectives.
Chen X et al.·Exp Neurol
2026Functional
Zingiberensis new saponin reverses sorafenib resistance by targeting lncRNA TCONS-00026762/AKR1C1 and modulating autophagy and ferroptosis in hepatocellular carcinoma.
Luo L et al.·Toxicol Appl Pharmacol
2026
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