UGT1A8
Chr 2UDP glucuronosyltransferase family 1 member A8
Also known as: UDPGT, UDPGT 1-8, UGT-1H, UGT1-08, UGT1.8, UGT1A8S, UGT1H
UGT1A8 encodes a UDP-glucuronosyltransferase that conjugates lipophilic substrates with glucuronic acid to facilitate their excretion, playing an essential role in drug metabolism and detoxification of endogenous compounds including steroid hormones. The gene shows low constraint to loss-of-function variation (pLI near 0, LOEUF 1.08), and no Mendelian diseases have been definitively associated with UGT1A8 mutations in pediatric patients. This enzyme is part of a complex gene family where different isoforms have distinct substrate specificities for various drugs, xenobiotics, and endogenous molecules.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
UGT1A8 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools