UGT2B11

Chr 4

UDP glucuronosyltransferase family 2 member B11

NCBI Gene: 10720 ENSG00000213759 UniProt: P06133

The protein catalyzes UDP-glucuronidation of estrogen hormones including estradiol and estriol, facilitating their elimination and detoxification through phase II biotransformation reactions. Mutations cause septo-optic dysplasia, which involves abnormal development of the optic nerve, pituitary gland, and midline brain structures. The condition follows autosomal recessive inheritance and the gene shows low constraint to loss-of-function variation.

ResearchSummary from RefSeq, UniProt

Enables glucuronosyltransferase activity. Involved in estrogen metabolic process. Predicted to be located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.59

Clinical Summary— UGT2B11

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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

120 VUS of 136 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?

1.59LOEUF

pLI 0.000

Z-score -0.48

OE 1.12 (0.80–1.59)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-4.13Z-score

OE missense 1.71 (1.58–1.85)

459 obs / 268.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.12 (0.80–1.59)

0≤0.351.4

Missense OE?1.71 (1.58–1.85)

0≤0.61.4

Synonymous OE?1.54

0≤1.21.6

LoF obs/exp: 22 / 19.7Missense obs/exp: 459 / 268.5Syn Z: -4.13

This gene — mechanism propensity

0.77top 25%

GOF

0.6832th %ile

LOF

0.2287th %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

136 submitted variants in ClinVar

ClinVar

Classification Summary

VUS120

Likely Benign12

120

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	120	0	120
Likely Benign	9	3	12
Benign	0	0	0
Total	129	3	132

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap UGT2B11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →