UGT2A1

Chr 4

UDP glucuronosyltransferase family 2 member A1 complex locus

Also known as: UDPGT2A1

This UDP-glucuronosyltransferase conjugates lipophilic substrates with glucuronic acid to facilitate their excretion, with particular importance in detoxifying drugs, xenobiotics, steroid hormones, and bile acids, especially in olfactory tissue. The gene shows very low constraint to loss-of-function mutations (LOEUF 1.533), and while polymorphisms may be associated with taste and smell alterations during SARS-CoV-2 infection, no established Mendelian pediatric neurogenetic disorders have been definitively linked to UGT2A1 mutations.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.53
Clinical SummaryUGT2A1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 5 VUS of 21 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.53LOEUF
pLI 0.000
Z-score -0.40
OE 1.09 (0.791.53)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.40Z-score
OE missense 1.24 (1.131.35)
340 obs / 274.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.09 (0.791.53)
00.351.4
Missense OE1.24 (1.131.35)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 24 / 22.0Missense obs/exp: 340 / 274.7Syn Z: -0.80
DN
0.7327th %ile
GOF
0.6833th %ile
LOF
0.2483th %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

21 submitted variants in ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS5
Likely Benign3
Benign1
11
Pathogenic
1
Likely Pathogenic
5
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
Likely Pathogenic
1
VUS
5
Likely Benign
3
Benign
1
Total21

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

UGT2A1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC