UGT1A3

Chr 2

UDP glucuronosyltransferase family 1 member A3

Also known as: UDPGT, UDPGT 1-3, UGT-1C, UGT1-03, UGT1.3, UGT1A3S, UGT1C

NCBI Gene: 54659ENSG00000288702UniProt: P35503

This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. Substrates of this enzyme include estrone, 2-hydroxyestrone, and metabolites of benzo alpha-pyrene. [provided by RefSeq, Jul 2008]

Research Assistant →
0
Active trials
15
Pubs (1 yr)
211
P/LP submissions
18%
P/LP missense
1.33
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— UGT1A3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
101 unique Pathogenic / Likely Pathogenic· 178 VUS of 383 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.33LOEUF
pLI 0.000
Z-score 0.52
OE 0.86 (0.58–1.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.35Z-score
OE missense 1.22 (1.12–1.33)
360 obs / 294.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.86 (0.58–1.33)
0≤0.351.4
Missense OE1.22 (1.12–1.33)
0≤0.61.4
Synonymous OE1.33
0≤1.21.6
LoF obs/exp: 15 / 17.4Missense obs/exp: 360 / 294.9Syn Z: -2.82
DN
0.77top 25%
GOF
0.72top 25%
LOF
0.2091th %ile

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.

DNprediction above median
GOFprediction above median

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

383 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic32
VUS178
Likely Benign52
Benign14
Conflicting38
69
Pathogenic
32
Likely Pathogenic
178
VUS
52
Likely Benign
14
Benign
38
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
5
44
0
69
Likely Pathogenic
13
13
6
0
32
VUS
0
141
30
7
178
Likely Benign
0
3
12
37
52
Benign
0
0
14
0
14
Conflicting
—38
Total3316210644383

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

UGT1A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Tetrahydrofurofuranoid Lignans, Eudesmin, Fargesin, Epimagnolin A, Magnolin, and Yangambin Inhibit UDP-Glucuronosyltransferase 1A1 and 1A3 Activities in Human Liver Microsomes
Park R et al.·Pharmaceutics
2021
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.
Wang T et al.·Drug Metab Dispos
2025
Inhibitory effects of quercetin and its major metabolite quercetin-3-O-beta-D-glucoside on human UDP-glucuronosyltransferase 1A isoforms by liquid chromatography-tandem mass spectrometry
Zhang R et al.·Exp Ther Med
2021
In vitro modulatory effects of ginsenoside compound K, 20(S)-protopanaxadiol and 20(S)-protopanaxatriol on uridine 5'-diphospho-glucuronosyltransferase activity and expression.
Jang SN et al.·Xenobiotica
2021
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Uridine 5'-Diphospho-glucuronosyltransferase 1A3 (UGT1A3) Prediction of Hepatic Clearance of Organic Anion Transporting Polypeptide 1B3 (OATP1B3) Substrate Telmisartan by Glucuronidation Using In Vitro-In Vivo Extrapolation (IVIVE).
Gabor-Worwa E et al.·Eur J Drug Metab Pharmacokinet
2024
Retracted: Susceptibility Loci in SLC15A1, UGT1A3, and CWC27 Genes Associated with Bladder Cancer in the Northeast Chinese Population.
International BR.·Biomed Res Int
2023Open Access
Susceptibility Loci in SLC15A1, UGT1A3, and CWC27 Genes Associated with Bladder Cancer in the Northeast Chinese Population.
Wu P et al.·Biomed Res Int
2022Open Access
USF1 Transcriptionally Regulates UGT1A3 and Promotes Lung Adenocarcinoma Progression by Regulating Neurotrophin Signaling Pathway.
Wang Y et al.·Front Mol Biosci
2022Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients