AKR1A1

Chr 1

aldo-keto reductase family 1 member A1

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

NCBI Gene: 10327ENSG00000117448UniProt: P14550

This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member, also known as aldehyde reductase, is involved in the reduction of biogenic and xenobiotic aldehydes and is present in virtually every tissue. Multiple alternatively spliced transcript variants of this gene exist, all encoding the same protein. [provided by RefSeq, Jan 2011]

69
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AKR1A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 45 VUS of 69 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.02Z-score
OE missense 1.00 (0.89–1.13)
191 obs / 190.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.44–1.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.89–1.13)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 12 / 17.3Missense obs/exp: 191 / 190.2Syn Z: 0.53

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
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
Increased aldehyde reductase expression mediates acquired radioresistance of laryngeal cancer cells via modulating p53.
Kim JS et al.·Cancer Biol Ther
2012
A novel mitochondrial metabolism-related gene signature for predicting the prognosis of oesophageal squamous cell carcinoma.
Lin W et al.·Aging (Albany NY)
2024
Pharmacokinetic interactions of breast cancer chemotherapeutics with human doxorubicin reductases.
Hofman J et al.·Biochem Pharmacol
2015
The denitrosylase SCoR2 controls cardioprotective metabolic reprogramming.
Grimmett ZW et al.·Elife
2025
Genetic polymorphisms in the oxidative stress pathway and susceptibility to non-Hodgkin lymphoma.
Lan Q et al.·Hum Genet
2007
Validation and identification of reference genes in Chinese hamster ovary cells for Fc-fusion protein production.
Ma X et al.·Exp Biol Med (Maywood)
2020
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
Increased resistance of tumor cells to daunorubicin after transfection of cDNAs coding for anthracycline inactivating enzymes.
Plebuch M et al.·Cancer Lett
2007
Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA1 and Clinically Used Prostaglandins.
Díez-Dacal B et al.·Mol Pharmacol
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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
2025🔓 Open 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
2024🔓 Open 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
2024🔓 Open Access
Kefir peptides ameliorate osteoporosis in AKR1A1 knockout mice with vitamin C deficiency by promoting osteoblastogenesis and inhibiting osteoclastogenesis.
Chang GR et al.·Biomed Pharmacother
2022
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools