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Protein / target

Aldo-keto reductase family 1 member A1

Encoded byAKR1A1P14550Homo sapiensSwiss-Prot
Small-molecule tractable
Druggability
High-Quality Ligand
1
Research papers

Protein at a glance

Biological role

Methylglyoxal reductase (NADPH) (acetol producing)

Strongest disease association

Heart Failure

Via encoding gene AKR1A1 · Genetic evidence · score 0.21

Research activity

Emerging research

1 papers · latest 2011

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols.

View complete UniProt function annotation

Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:10510318, PubMed:30538128). Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids, with a preference for negatively charged substrates, such as glucuronate and succinic semialdehyde (PubMed:10510318, PubMed:30538128). Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes (By similarity). Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic (By similarity). Involved also in the detoxification of lipid-derived aldehydes like acrolein (By similarity). Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN) (PubMed:11306097, PubMed:18276838). Also acts as an inhibitor of protein S-nitrosylation by mediating degradation of S-nitroso-coenzyme A (S-nitroso-CoA), a cofactor required to S-nitrosylate proteins (PubMed:30538128). S-nitroso-CoA reductase activity is involved in reprogramming intermediary metabolism in renal proximal tubules, notably by inhibiting protein S-nitrosylation of isoform 2 of PKM (PKM2) (By similarity). Also acts as a S-nitroso-glutathione reductase by catalyzing the NADPH-dependent reduction of S-nitrosoglutathione (PubMed:31649033). Displays no reductase activity towards retinoids (By similarity)

Subcellular location

Cytoplasm, cytosolApical cell membrane
Domains and Gene Ontology detail (22)

Gene Ontology

  • Capical plasma membrane
  • Ccytosol
  • Cextracellular exosome
  • Cextracellular space
  • Csynapse
  • Falcohol dehydrogenase (NADP+) activity
  • Faldose reductase (NADPH) activity
  • Fallyl-alcohol dehydrogenase activity
  • Fglucuronolactone reductase activity
  • Fglycerol dehydrogenase (NADP+) activity
  • FL-glucuronate reductase activity
  • Fmethylglyoxal reductase (NADPH) (acetol producing) activity

325 aa · 37 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismGO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·lipid metabolic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene AKR1A1

Gene-level evidence surfaced through the gene AKR1A1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neurodegenerative Diseases
0.28Preliminary

Pathway evidence dominant · Open Targets 0.42 · no direct causal or clinical evidence

Heart Failure
0.21Preliminary

Genetic evidence dominant · Open Targets 0.13

Osteogenesis Imperfecta
0.19Preliminary

Animal model evidence dominant · Open Targets 0.06 · no direct causal or clinical evidence

Kallmann syndrome
0.18Preliminary

Animal model evidence dominant · Open Targets 0.06 · no direct causal or clinical evidence

Hypocalcemic vitamin D-resistant rickets
0.18Preliminary

Animal model evidence dominant · Open Targets 0.05 · no direct causal or clinical evidence

View evidence synthesis (5)
Neurodegenerative DiseasesPreliminary
0.28
agreement 0.100.46
Pathway97%Literature3%

Open Targets aggregate 0.42 · 2 independent evidence families · no direct causal or clinical evidence

Heart FailurePreliminary
0.21
agreement 0.070.35
Genetic99%Literature1%

Open Targets aggregate 0.13 · 2 independent evidence families

Osteogenesis ImperfectaPreliminary
0.19
agreement 0.000.42
Animal model100%

Open Targets aggregate 0.06 · 1 independent evidence family · no direct causal or clinical evidence

Kallmann syndromePreliminary
0.18
agreement 0.000.41
Animal model100%

Open Targets aggregate 0.06 · 1 independent evidence family · no direct causal or clinical evidence

Hypocalcemic vitamin D-resistant ricketsPreliminary
0.18
agreement 0.000.41
Animal model100%

Open Targets aggregate 0.05 · 1 independent evidence family · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Neurodegenerative Diseases0.42
Heart Failure0.13
Atrial Fibrillation0.08
Venous Thrombosis0.07
Osteogenesis Imperfecta0.06
Osteoporosis0.06
Kallmann syndrome0.06
Hypocalcemic vitamin D-resistant rickets0.05

Tractability

Small moleculesEmerging

Feasibility evidence (high-quality ligand and high-quality pocket) — no clinical-stage drug of this modality recorded.

AntibodiesEmerging

Feasibility evidence (uniprot loc med conf and go cc med conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc med confAB · GO CC med confPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2011

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Recent

Europe PMC papers linked directly to this protein.