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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CBR1
carbonyl reductase 1
Chromosome 21 · 21q22.12
NCBI Gene: 873Ensembl: ENSG00000159228.13HGNC: HGNC:1548UniProt: A0A384NL53
164PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
carbonyl reductase (NADPH) activityprotein bindingxenobiotic metabolic processglucocorticoid metabolic processneurodegenerative diseasemitral valve prolapseLeft bundle branch blockalcohol drinking
✦AI Summary

CBR1 (carbonyl reductase 1) is an NADPH-dependent oxidoreductase with broad substrate specificity that catalyzes the reduction of diverse carbonyl compounds 1. Physiologically, CBR1 metabolizes endogenous substrates including prostaglandins, converting prostaglandin E2 to prostaglandin F2α 2, and participates in glucocorticoid metabolism by reducing cortisol to 20β-dihydrocortisol [UniProt data supported by metabolic pathway literature]. Pharmacologically, CBR1 metabolizes anthracycline anticancer drugs (doxorubicin, daunorubicin) to their cardiotoxic alcohol metabolites (doxorubicinol, daunorubicinol) 3. CBR1 expression is transcriptionally regulated by the antioxidant-responsive transcription factor Nrf2 through antioxidant response elements in its promoter 4. Functionally, genetic variants like CBR1 V88I affect catalytic activity and NADPH binding affinity, influencing both prostaglandin and anthracycline metabolism 2. In brown adipose tissue, CBR1-mediated prostaglandin F2α production improves systemic insulin sensitivity through m6A-dependent mRNA decay regulation 56. CBR1 knockout increases doxorubicin-induced cardiotoxicity in cardiomyocytes 3, while CBR1 protein levels are retained after resistance training, suggesting a role in skeletal muscle adaptation 7. CBR1 overexpression associates with aggressive hepatocellular carcinoma 8.

Sources cited
1
CBR1 is an NADPH-dependent carbonyl reductase belonging to the short-chain dehydrogenase/reductase superfamily with broad substrate specificity
PMID: 20942781
2
CBR1 metabolizes prostaglandin E2 and daunorubicin; V88I polymorphism affects catalytic velocity and NADPH binding affinity
PMID: 17344335
3
CBR1 knockout increases susceptibility to doxorubicin-induced cardiotoxicity in hiPSC-derived cardiomyocytes
PMID: 38510289
4
CBR1 gene transcription is regulated by Nrf2 transcription factor through antioxidant response elements
PMID: 23247010
5
CBR1 in brown adipocytes produces prostaglandin F2α; METTL14-mediated m6A regulates CBR1 mRNA decay, affecting insulin sensitivity
PMID: 39255799
6
CBR1 expression in brown adipocytes is regulated by m6A-dependent mRNA decay through YTHDF2/3 machinery; relevant to metabolic disease pathophysiology
PMID: 39788955
7
CBR1 protein levels are retained in skeletal muscle after detraining, suggesting a proteomic memory of resistance training
PMID: 40183698
8
CBR1 is overexpressed as a drugable target in aggressive hepatocellular carcinoma
PMID: 39348425
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
mitral valve prolapseOpen Targets
0.26Weak
Left bundle branch blockOpen Targets
0.14Weak
alcohol drinkingOpen Targets
0.11Weak
femoral neck fractureOpen Targets
0.11Weak
facial morphologyOpen Targets
0.10Suggestive
Burkitts lymphomaOpen Targets
0.10Suggestive
osteoporosisOpen Targets
0.09Suggestive
head and neck squamous cell carcinomaOpen Targets
0.09Suggestive
stomach diseaseOpen Targets
0.09Suggestive
migraine disorderOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
COVID-19Open Targets
0.08Suggestive
major depressive disorderOpen Targets
0.08Suggestive
prostate cancerOpen Targets
0.07Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.07Suggestive
oral squamous cell carcinomaOpen Targets
0.07Suggestive
joint diseaseOpen Targets
0.07Suggestive
musculoskeletal system diseaseOpen Targets
0.07Suggestive
spondylolisthesisOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DHFR2Protein interaction99%PTSProtein interaction99%DHFRProtein interaction98%CYP3A4Protein interaction98%AKR1B1Protein interaction97%SPRProtein interaction97%
Tissue Expression6 tissues
Liver
100%
Brain
86%
Lung
21%
Heart
19%
Ovary
17%
Bone Marrow
11%
Gene Interaction Network
Click a node to explore
CBR1DHFR2PTSDHFRCYP3A4AKR1B1SPR
PROTEIN STRUCTURE
Preparing viewer…
PDB1WMA · 1.24 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.42LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.89 [0.58–1.42]
RankingsWhere CBR1 stands among ~20K protein-coding genes
  • #2,725of 20,598
    Most Researched164 · top quartile
  • #14,634of 17,882
    Most Constrained (LOEUF)1.42
Genes detectedCBR1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Integrated ubiquitomics characterization of hepatocellular carcinomas.
PMID: 39348425
Hepatology · 2025
1.00
2
m
PMID: 39255799
Cell Metab · 2024
0.90
3
Functional Validation of Doxorubicin-Induced Cardiotoxicity-Related Genes.
PMID: 38510289
JACC CardioOncol · 2024
0.80
4
Human skeletal muscle possesses both reversible proteomic signatures and a retained proteomic memory after repeated resistance training.
PMID: 40183698
J Physiol · 2025
0.70
5
Lactylation modulation identifies key biomarkers and therapeutic targets in KMT2A-rearranged AML.
PMID: 39789150
Sci Rep · 2025
0.64