AKR1B1

Chr 7

aldo-keto reductase family 1 member B

Also known as: ADR, ALDR1, ALR2, AR

NCBI Gene: 231ENSG00000085662UniProt: P15121

This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member catalyzes the reduction of a number of aldehydes, including the aldehyde form of glucose, and is thereby implicated in the development of diabetic complications by catalyzing the reduction of glucose to sorbitol. Multiple pseudogenes have been identified for this gene. The nomenclature system used by the HUGO Gene Nomenclature Committee to define human aldo-keto reductase family members is known to differ from that used by the Mouse Genome Informatics database. [provided by RefSeq, Feb 2009]

60
ClinVar variants
32
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— AKR1B1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 17 VUS of 60 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
1.00LOEUF
pLI 0.000
Z-score 1.57
OE 0.59 (0.36–1.00)
Tolerant

Typical tolerance to LoF variation

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.
0.40Z-score
OE missense 0.91 (0.80–1.04)
157 obs / 171.9 exp
Tolerant

Mild missense constraint

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.0.59 (0.36–1.00)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.80–1.04)
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.1.03
0≤1.21.6
LoF obs/exp: 10 / 17.0Missense obs/exp: 157 / 171.9Syn Z: -0.21

ClinVar Variant Classifications

60 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic1
VUS17
Likely Benign7
Benign4
31
Pathogenic
1
Likely Pathogenic
17
VUS
7
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
1
0
1
VUS
0
12
5
0
17
Likely Benign
0
2
1
4
7
Benign
0
0
1
3
4
Total01439760

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

View in ClinVar →

Protein Context — Lollipop Plot

AKR1B1 · 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
Uncovering the mechanism of resveratrol in the treatment of diabetic kidney disease based on network pharmacology, molecular docking, and experimental validation.
Chen S et al.·J Transl Med
2023Functional
Targeting AKR1B1 inhibits metabolic reprogramming to reverse systemic therapy resistance in hepatocellular carcinoma.
Wang Q et al.·Signal Transduct Target Ther
2025
Fructose Metabolism in Cancer.
Krause N et al.·Cells
2020Review
AKR1B1 Expression in the Colorectal Tumor Microenvironment Contributes Towards Its Prognostic Significance.
Demirkol Canlı S et al.·Cancer Med
2025
AKR1B1 bridges metabolic pathways and disease progression.
Zhang Q et al.·Cell Signal
2026Review
AKR1B1 Inhibits Ferroptosis and Promotes Gastric Cancer Progression via Interacting With STAT3 to Activate SLC7A11.
Yang K et al.·Cell Biol Int
2025
Role of aldo-keto reductase family 1 member B1 (AKR1B1) in the cancer process and its therapeutic potential.
Khayami R et al.·J Cell Mol Med
2020Review
Targeting AKR1B1 reprograms tumor-associated macrophages to enhance antitumor immunity.
Liu Y et al.·J Immunother Cancer
2026
Pomegranate peel and ellagic acid attenuate ulcerative colitis by targeting AKR1B1/B3 to inhibit NLRP3.
Li H et al.·Phytomedicine
2025
Associations of genetic factors with vascular diabetes complications: an umbrella review.
Zhou X et al.·J Glob Health
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Breast Cancer

Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer

ACTIVE NOT RECRUITING
NCT00616967Phase PHASE2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsStarted 2008-05
carboplatinpaclitaxel albumin-stabilized nanoparticle formulationvorinostat

External Resources

Links to major genomics databases and tools