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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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UGT1A8
UDP glucuronosyltransferase family 1 member A8
Chromosome 2 · 2q37.1
NCBI Gene: 54576Ensembl: ENSG00000242366.4HGNC: HGNC:12540UniProt: Q5DSZ6
79PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
flavonoid metabolic processenzyme inhibitor activitysteroid bindingxenobiotic metabolic processGilbert syndromeCrigler-Najjar syndrome type 1Crigler-Najjar syndrome type 2transient familial neonatal hyperbilirubinemia
✦AI Summary

UGT1A8 is a UDP-glucuronosyltransferase that catalyzes glucuronidation of diverse substrates including steroid hormones, xenobiotics, and dietary polyphenols. While traditionally considered an extrahepatic enzyme, UGT1A8 mRNA is actually expressed in primary human hepatocytes and can be upregulated by xenobiotic inducers 1. The enzyme exhibits particularly high catalytic activity toward dihydrotestosterone, producing both monoglucuronides and structurally novel diglucuronides 2, and demonstrates robust activity toward troglitazone 3, bavachinin 4, and piceatannol 5. UGT1A8 contains three common allelic variants (UGT1A8*1, *2, and *3), with UGT1A8*3 showing dramatically reduced catalytic activity due to a Y277 substitution 6. The enzyme is subject to allosteric inhibition by erythromycin 7 and aflatoxins 8, with aflatoxins showing 72.79% inhibition potential. In intestinal microsomes, UGT1A8 contributes substantially to first-pass metabolism, particularly for substrates metabolized by extrahepatic UGT isoforms. These findings suggest UGT1A8 plays important roles in both hepatic and intestinal drug metabolism and detoxification.

Sources cited
1
UGT1A8 mRNA is expressed in primary human hepatocytes and can be upregulated by 3-methylcholanthrene and rifampicin
PMID: 17603215
2
UGT1A8 glucuronidates dihydrotestosterone to monoglucuronide and diglucuronide with higher activity in intestinal microsomes
PMID: 16595710
3
UGT1A8 has three common allelic variants with UGT1A8*3 (Y277) showing dramatically reduced catalytic activity
PMID: 12042666
4
UGT1A8 exhibits high catalytic activity toward troglitazone in both liver and intestinal microsomes
PMID: 12433820
5
UGT1A8 is a major enzyme for bavachinin glucuronidation with higher activity in intestinal microsomes
PMID: 26320626
6
UGT1A8 contributes to glucuronidation of piceatannol, a dietary polyphenol
PMID: 20722998
7
Erythromycin selectively inhibits UGT1A8 through mixed-type allosteric inhibition mechanism
PMID: 40347722
8
Aflatoxins inhibit UGT1A8 activity with 72.79% inhibition ratio at 100 μM concentration
PMID: 37164184
Disease Associationsⓘ20
Gilbert syndromeOpen Targets
0.62Moderate
Crigler-Najjar syndrome type 1Open Targets
0.57Moderate
Crigler-Najjar syndrome type 2Open Targets
0.56Moderate
transient familial neonatal hyperbilirubinemiaOpen Targets
0.56Moderate
porphyrin metabolism diseaseOpen Targets
0.55Moderate
Crigler-Najjar syndromeOpen Targets
0.55Moderate
HyperbilirubinemiaOpen Targets
0.53Moderate
genetic disorderOpen Targets
0.51Moderate
bilirubin metabolism diseaseOpen Targets
0.49Moderate
urinary bladder cancerOpen Targets
0.40Weak
cholelithiasisOpen Targets
0.25Weak
Abnormality of skin pigmentationOpen Targets
0.24Weak
neonatal jaundiceOpen Targets
0.21Weak
disorder of metabolite absorption and transportOpen Targets
0.20Weak
CholecystitisOpen Targets
0.11Weak
JaundiceOpen Targets
0.10Weak
psoriasisOpen Targets
0.10Suggestive
insomniaOpen Targets
0.10Suggestive
Abnormality of the liverOpen Targets
0.09Suggestive
gallstonesOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
UGDHProtein interaction100%ABCC2Protein interaction98%CYP1A2Protein interaction98%CYP2A6Protein interaction98%CYP2A13Protein interaction98%CYP2C19Protein interaction98%
Tissue Expression6 tissues
Liver
100%
Lung
0%
Brain
0%
Ovary
0%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
UGT1A8UGDHABCC2CYP1A2CYP2A6CYP2A13CYP2C19
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q5DSZ6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.08LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.83 [0.64–1.08]
RankingsWhere UGT1A8 stands among ~20K protein-coding genes
  • #6,043of 20,598
    Most Researched79
  • #10,995of 17,882
    Most Constrained (LOEUF)1.08
Genes detectedUGT1A8
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human UGT1A8 and UGT1A10 mRNA are expressed in primary human hepatocytes.
PMID: 17603215
Drug Metab Pharmacokinet · 2007
1.00
2
Pharmacogenomics.
PMID: 17631591
Ann Oncol · 2007
0.90
3
Human UDP-glucuronosyltransferase, UGT1A8, glucuronidates dihydrotestosterone to a monoglucuronide and further to a structurally novel diglucuronide.
PMID: 16595710
Drug Metab Dispos · 2006
0.80
4
Identification of selective inhibitors of uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A3 and UGT1A8 and their application in UGT reaction phenotyping studies in human liver and intestinal microsomes.
PMID: 40347722
Drug Metab Dispos · 2025
0.70
5
Inhibition of aflatoxins on UDP-glucuronosyltransferases (UGTs).
PMID: 37164184
Toxicol In Vitro · 2023
0.60