UGT2A1

Chr 4

UDP glucuronosyltransferase family 2 member A1 complex locus

Also known as: UDPGT2A1

NCBI Gene: 10941 ENSG00000173610 UniProt: P0DTE4

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.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the UDP-glycosyltransferase family. Members of this protein family play a role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The encoded enzyme is expressed in the olfactory neuroepithelium, which lines the posterior nasal cavity and is exposed to a wide range of odorants and airborne toxic compounds. Hence, this protein has been suggested to be involved in clearing lipophilic odorant molecules from the sensory epithelium. This gene shares exon structure with the UDP glucuronosyltransferase 2A2 family member, which encodes N-terminally distinct isoforms. Polymorphisms in this gene may be associated with the loss of taste and smell that is reported by some individuals during SARS-CoV-2 infection. [provided by RefSeq, Jan 2022]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.53

Clinical Summary— UGT2A1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

70 VUS of 86 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.53LOEUF

pLI 0.000

Z-score -0.40

OE 1.09 (0.79–1.53)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.40Z-score

OE missense 1.24 (1.13–1.35)

340 obs / 274.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.09 (0.79–1.53)

0≤0.351.4

Missense OE?1.24 (1.13–1.35)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 24 / 22.0Missense obs/exp: 340 / 274.7Syn Z: -0.80

This gene — mechanism propensity

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

86 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

Likely Benign12

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	70	0	0	70
Likely Benign	2	5	3	2	12
Benign	0	1	0	1	2
Total	2	76	3	3	84

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap UGT2A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →