UGT1A4
Chr 2UDP glucuronosyltransferase family 1 member A4
Also known as: HUG-BR2, UDPGT 1-4, UGT-1D, UGT1-04, UGT1.4, UGT1A4S, UGT1D
UGT1A4 encodes a UDP-glucuronosyltransferase enzyme that conjugates lipophilic substrates including drugs, steroids, and vitamin D metabolites with glucuronic acid to facilitate their excretion from the body. Mutations cause hyperbilirubinemia due to reduced glucuronidation activity, inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern of associated bilirubin metabolism disorders.
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
UGT1A4 · 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