AKR1A1

Chr 1

aldo-keto reductase family 1 member A1

Also known as: ALDR1, ALR, ARM, DD3, HEL-S-6

NCBI Gene: 10327ENSG00000117448UniProt: P14550

The protein functions as an aldehyde reductase that catalyzes NADPH-dependent reduction of aldehydes, ketones, and other carbonyl compounds, serving important roles in detoxification and cellular metabolism. Mutations cause autosomal recessive intellectual disability with facial dysmorphism and behavioral abnormalities. This gene is not highly constrained against loss-of-function variants based on population genetics data.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.12
Clinical Summary— AKR1A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 45 VUS of 69 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.12LOEUF
pLI 0.000
Z-score 1.19
OE 0.69 (0.44–1.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.02Z-score
OE missense 1.00 (0.89–1.13)
191 obs / 190.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.69 (0.44–1.12)
0≤0.351.4
Missense OE1.00 (0.89–1.13)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 12 / 17.3Missense obs/exp: 191 / 190.2Syn Z: 0.53
DN
0.6939th %ile
GOF
0.6639th %ile
LOF
0.2583th %ile

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.

DNprediction above median
GOFprediction 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

69 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic2
VUS45
Likely Benign3
Benign2
4
Pathogenic
2
Likely Pathogenic
45
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
2
0
2
VUS
0
32
13
0
45
Likely Benign
0
0
1
2
3
Benign
0
1
1
0
2
Total03321256

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

View in ClinVar →

Protein Context — Lollipop Plot

AKR1A1 · 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
Potential drug targets for ovarian cancer identified through Mendelian randomization and colocalization analysis.
Liu S et al.·J Ovarian Res
2025
Exploring the regulatory mechanisms of paraptosis-related prognostic genes in gastric cancer using single-cell sequencing and transcriptome analysis.
Liu Z et al.·Sci Rep
2025Functional
Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA1 and Clinically Used Prostaglandins.
Díez-Dacal B et al.·Mol Pharmacol
2016
Interactions of antileukemic drugs with daunorubicin reductases: could reductases affect the clinical efficacy of daunorubicin chemoregimens?
Novotná E et al.·Arch Toxicol
2020
A novel mitochondrial metabolism-related gene signature for predicting the prognosis of oesophageal squamous cell carcinoma.
Lin W et al.·Aging (Albany NY)
2024
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Multi-omic analysis reveals nitric oxide dependent remodeling in classically activated macrophages and identifies negative regulation mediated by AKR1A1.
Arp NL et al.·Redox Biol
2026Functional
Lactylation-related gene AKR1A1 contributes to osteoporosis via metabolic-immune regulation: evidence from multi-omics integration, single-cell transcriptomics, and in vitro validation.
Shao Z et al.·Front Immunol
2025Open Access
RORα inhibits proliferation and chemoresistance through AKR1A1-induced glucose and lipid reprogramming in gastric cancer.
Wang X et al.·Cell Signal
2025
Multiomics Analyses Identify AKR1A1 as a Biomarker for Diabetic Kidney Disease.
Li D et al.·Diabetes
2024Open Access
Aldo-keto reductase family 1 member A1 (AKR1A1) exerts a protective function in alcohol-associated liver disease by reducing 4-HNE accumulation and p53 activation.
Lan YW et al.·Cell Biosci
2024Open Access
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