UGT1A9
Chr 2UDP glucuronosyltransferase family 1 member A9
Also known as: HLUGP4, LUGP4, UDPGT, UDPGT 1-9, UGT-1I, UGT1-09, UGT1-9, UGT1.9
This gene encodes UDP-glucuronosyltransferase 1A9, an enzyme that conjugates lipophilic substrates with glucuronic acid to facilitate their excretion, playing a critical role in drug metabolism and detoxification of endogenous compounds like estrogen hormones and eicosanoids. Mutations cause Crigler-Najjar syndrome and Gilbert syndrome, autosomal recessive disorders of bilirubin metabolism that can present in the neonatal period with severe hyperbilirubinemia or later with milder jaundice. The gene shows tolerance to loss-of-function variants (LOEUF 1.112), suggesting that complete loss may be compatible with survival but can still cause clinically significant bilirubin metabolism defects.
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
497 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 13 | 3 | 13 | 0 | 29 |
Likely Pathogenic | 13 | 7 | 2 | 0 | 22 |
VUS | 4 | 301 | 18 | 1 | 324 |
Likely Benign | 0 | 30 | 11 | 47 | 88 |
Benign | 0 | 5 | 14 | 4 | 23 |
Conflicting | — | 9 | |||
| Total | 30 | 346 | 58 | 52 | 495 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
UGT1A9 · 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
External Resources
Links to major genomics databases and tools