AKR1C3
Chr 10aldo-keto reductase family 1 member C3
Also known as: DD3, DDX, HA1753, HAKRB, HAKRe, HSD17B5, PGFS, hluPGFS
This gene encodes a cytosolic aldo-keto reductase that catalyzes the NADPH-dependent reduction of ketosteroids to hydroxysteroids, playing key roles in androgen and estrogen metabolism by converting precursors to potent hormones like testosterone and 17beta-estradiol. The gene is not loss-of-function intolerant (high LOEUF score), and pathogenic variants have not been established to cause recognizable human disease. While the enzyme has important roles in steroid hormone biosynthesis and prostaglandin metabolism, clinical disorders specifically attributed to AKR1C3 mutations are not currently well-defined in pediatric populations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
AKR1C3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools