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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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UGT1A6
UDP glucuronosyltransferase family 1 member A6
Chromosome 2 · 2q37.1
NCBI Gene: 54578Ensembl: ENSG00000167165.19HGNC: HGNC:12538UniProt: P19224
133PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
endoplasmic reticulumglucuronosyltransferase activityxenobiotic metabolic processretinoic acid bindingGilbert syndromeporphyrin metabolism diseaseCrigler-Najjar syndrome type 1Crigler-Najjar syndrome type 2
✦AI Summary

UGT1A6 is a phase II drug-metabolizing enzyme that catalyzes the glucuronidation of various endogenous and xenobiotic compounds. The enzyme demonstrates glucuronosyltransferase activity toward substrates including serotonin, diclofenac, and aspirin metabolites 12. UGT1A6 exhibits complex protein-protein interactions with other UGT1A isoforms (UGT1A1 and UGT1A4), forming both homodimers and heterodimers that can modulate enzymatic activities in substrate- and isoform-specific manners 1. The enzyme is expressed in multiple tissues, including renal proximal tubule epithelial cells and brain microsomes, contributing to extrahepatic drug metabolism 34. Clinically, UGT1A6 genetic polymorphisms significantly impact drug pharmacokinetics, particularly for valproic acid where homozygous variants (541A>G and 552A>C) result in significantly lower concentration-to-dose ratios compared to wild-type 56. These polymorphisms show high frequency in certain populations and may contribute to interindividual variability in drug response 6. Additionally, UGT1A6 plays a role in aspirin metabolism, with genetic variations potentially affecting aspirin intolerance risk 2. The enzyme's tissue-specific expression and genetic variability make it an important consideration for personalized medicine approaches.

Sources cited
1
UGT1A6 catalyzes glucuronidation of serotonin and diclofenac, and forms protein-protein interactions with UGT1A1 and UGT1A4 through heterodimerization
PMID: 17620344
2
UGT1A6 plays a major role in aspirin metabolism and contains polymorphisms associated with aspirin intolerance
PMID: 20214591
3
UGT1A6 is expressed in human renal proximal tubule epithelial cells and contributes to extrahepatic drug metabolism
PMID: 38866474
4
UGT1A6 mRNA is located in brain microsomes and contributes to propofol metabolism
PMID: 11749793
5
UGT1A6 homozygous variants 541A>G and 552A>C result in significantly lower valproic acid concentration-to-dose ratios
PMID: 30686291
6
UGT1A6 genetic polymorphisms significantly affect valproic acid plasma levels and show high variant frequencies in certain populations
PMID: 37820941
Disease Associationsⓘ20
Gilbert syndromeOpen Targets
0.64Moderate
porphyrin metabolism diseaseOpen Targets
0.57Moderate
Crigler-Najjar syndrome type 1Open Targets
0.57Moderate
Crigler-Najjar syndrome type 2Open Targets
0.56Moderate
HyperbilirubinemiaOpen Targets
0.56Moderate
transient familial neonatal hyperbilirubinemiaOpen Targets
0.56Moderate
Crigler-Najjar syndromeOpen Targets
0.55Moderate
bilirubin metabolism diseaseOpen Targets
0.55Moderate
genetic disorderOpen Targets
0.51Moderate
cholelithiasisOpen Targets
0.43Moderate
liver diseaseOpen Targets
0.32Weak
CholecystitisOpen Targets
0.32Weak
JaundiceOpen Targets
0.31Weak
gallstonesOpen Targets
0.30Weak
type 1 diabetes mellitusOpen Targets
0.29Weak
Abnormality of the liverOpen Targets
0.25Weak
insomniaOpen Targets
0.23Weak
agingOpen Targets
0.20Weak
inborn errors of metabolismOpen Targets
0.20Weak
urinary bladder cancerOpen Targets
0.18Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ABCC2Protein interaction98%CYP2A13Protein interaction98%CYP2C19Protein interaction98%CYP3A4Protein interaction98%GSTA1Protein interaction98%ABCB1Protein interaction98%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
0%
Lung
0%
Brain
0%
Heart
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
UGT1A6ABCC2CYP2A13CYP2C19CYP3A4GSTA1ABCB1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P19224
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.92LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.69 [0.52–0.92]
RankingsWhere UGT1A6 stands among ~20K protein-coding genes
  • #3,504of 20,598
    Most Researched133 · top quartile
  • #8,500of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedUGT1A6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Pharmacogenomics and Pharmacokinetics of Aspirin in Preeclampsia Prevention.
PMID: 40329906
Circ Res · 2025
1.00
2
UGT1A6 and UGT2B7 Gene Polymorphism and its Effect in Pediatric Epileptic Patients on Sodium Valproate Monotherapy.
PMID: 33400134
Indian J Pediatr · 2021
0.90
3
Distribution pattern of UGT1A6 and UGT2B7 gene polymorphism and its impact on the pharmacokinetics of valproic acid and carbamazepine: Prospective genetic association study conducted in Pakistani patients with epilepsy.
PMID: 37820941
Gene · 2024
0.80
4
Cytochrome P450 and UDP-Glucuronosyltransferase Expressions, Activities, and Induction Abilities in 3D-Cultured Human Renal Proximal Tubule Epithelial Cells.
PMID: 38866474
Drug Metab Dispos · 2024
0.70
5
Pharmacogenomics in aspirin intolerance.
PMID: 20214591
Curr Drug Metab · 2009
0.60