UGT2B15

Chr 4

UDP glucuronosyltransferase family 2 member B15

NCBI Gene: 7366 ENSG00000196620 UniProt: P54855 OMIM: 600069

This gene encodes UDP-glucuronosyltransferase 2B15, an enzyme that conjugates glucuronic acid to steroid hormones (testosterone, estradiol) and xenobiotic compounds to facilitate their elimination from the body. The gene shows very low constraint against loss-of-function variants (high LOEUF score), and no definitive disease associations have been established from the provided information. While UGT2B15 is important for detoxification and hormone metabolism, pathogenic variants causing pediatric neurologic disease are not documented in this dataset.

OMIM ResearchSummary from RefSeq, UniProt

UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:16595710, PubMed:18719240, PubMed:23288867, PubMed:7835232, PubMed:9295060). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:7835232). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:16595710, PubMed:18719240, PubMed:23288867, PubMed:7835232, PubMed:9295060). Displays glucuronidation activity toward several classes of xenobiotic substrates, including phenolic compounds (eugenol, 4-nitrophenol, 4-hydroxybiphenyl) and phenylpropanoids (naringenin, coumarins) (PubMed:7835232). Catalyzes the glucuronidation of monoterpenoid alcohols such as borneol, menthol and isomenthol, a class of natural compounds used in essential oils (By similarity)

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.73

Clinical Summary— UGT2B15

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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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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.73LOEUF

pLI 0.000

Z-score -1.20

OE 1.28 (0.94–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.87Z-score

OE missense 1.15 (1.05–1.26)

313 obs / 272.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.28 (0.94–1.73)

0≤0.351.4

Missense OE?1.15 (1.05–1.26)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 28 / 21.9Missense obs/exp: 313 / 272.4Syn Z: -1.55

This gene — mechanism propensity

0.79top 25%

GOF

0.7028th %ile

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.