AKR1C2
Chr 10ARaldo-keto reductase family 1 member C2
Also known as: AKR1C-pseudo, BABP, DD, DD-2, DD/BABP, DD2, DDH2, HAKRD
AKR1C2 encodes a cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids and is required for male sex determination as a component of the 'backdoor' androgen biosynthesis pathway that generates dihydrotestosterone. Mutations cause 46XY sex reversal 8 with autosomal recessive inheritance. The gene is not highly constrained (LOEUF 1.46), consistent with recessive disease requiring biallelic variants to cause phenotype.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
AKR1C2 · 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
External Resources
Links to major genomics databases and tools