UGT2B28

Chr 4

UDP glucuronosyltransferase family 2 member B28

NCBI Gene: 54490 ENSG00000135226 UniProt: Q9BY64 OMIM: 606497

The protein is a UDP-glucuronosyltransferase that catalyzes glucuronidation reactions, conjugating lipophilic substrates including steroid hormones, bile acids, and xenobiotics with glucuronic acid to facilitate their excretion and detoxification. This gene is not well-constrained against loss-of-function variants and no established Mendelian diseases have been associated with UGT2B28 mutations in the pediatric population. Clinical significance of variants in this gene remains unclear in the context of pediatric neurogenetic disorders.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the uridine diphosphoglucuronosyltransferase protein family. The encoded enzyme catalyzes the transfer of glucuronic acid from uridine diphosphoglucuronic acid to a diverse array of substrates including steroid hormones and lipid-soluble drugs. This process, known as glucuronidation, is an intermediate step in the metabolism of steroids. Two transcript variants encoding different isoforms have been found for this gene. While both isoforms are targeted to the endoplasmic reticulum, only the longer isoform appears to be active. [provided by RefSeq, May 2011]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.69

Clinical Summary— UGT2B28

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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

87 VUS of 113 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.69LOEUF

pLI 0.000

Z-score -0.88

OE 1.21 (0.88–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.18Z-score

OE missense 1.37 (1.26–1.50)

373 obs / 271.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.21 (0.88–1.69)

0≤0.351.4

Missense OE?1.37 (1.26–1.50)

0≤0.61.4

Synonymous OE?1.34

0≤1.21.6

LoF obs/exp: 24 / 19.8Missense obs/exp: 373 / 271.9Syn Z: -2.55

This gene — mechanism propensity

0.79top 25%

GOF

0.6931th %ile

LOF

0.2190th %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

113 submitted variants in ClinVar

ClinVar

Classification Summary

VUS87

Likely Benign18

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	87	0	0	87
Likely Benign	13	1	4	18
Benign	2	0	1	3
Total	102	1	5	108

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap UGT2B28 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →