UGT1A5

Chr 2

UDP glucuronosyltransferase family 1 member A5

Also known as: UDPGT, UDPGT 1-5, UGT1E

This enzyme catalyzes glucuronidation reactions that conjugate lipophilic substrates with glucuronic acid to facilitate their excretion, playing an essential role in drug metabolism and detoxification of xenobiotics and endogenous compounds. The gene shows very low constraint against loss-of-function variants (pLI near 0, LOEUF 1.29), and no definitive Mendelian diseases have been established from mutations in this gene. Based on current evidence, UGT1A5 variants are not considered a cause of pediatric neurological disorders.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
229
P/LP submissions
19%
P/LP missense
1.29
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryUGT1A5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
117 unique Pathogenic / Likely Pathogenic· 304 VUS of 565 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.29LOEUF
pLI 0.000
Z-score 0.68
OE 0.82 (0.541.29)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.30Z-score
OE missense 1.05 (0.951.15)
314 obs / 299.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.82 (0.541.29)
00.351.4
Missense OE1.05 (0.951.15)
00.61.4
Synonymous OE1.25
01.21.6
LoF obs/exp: 14 / 17.0Missense obs/exp: 314 / 299.6Syn Z: -2.19
DN
0.77top 25%
GOF
0.73top 25%
LOF
0.1993th %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

565 submitted variants in ClinVar

Classification Summary

Pathogenic75
Likely Pathogenic42
VUS304
Likely Benign84
Benign19
Conflicting39
75
Pathogenic
42
Likely Pathogenic
304
VUS
84
Likely Benign
19
Benign
39
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
5
46
0
75
Likely Pathogenic
18
17
7
0
42
VUS
0
264
33
7
304
Likely Benign
1
18
16
49
84
Benign
0
3
14
2
19
Conflicting
39
Total4330711658563

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

View in ClinVar →

Protein Context — Lollipop Plot

UGT1A5 · 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

No active trials found for this gene.

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

No open access results found