B3GAT3

Chr 11AR

beta-1,3-glucuronyltransferase 3

Also known as: GLCATI, JDSCD, glcUAT-I

NCBI Gene: 26229 ENSG00000149541 UniProt: O94766 OMIM: 606374

This glucuronosyltransferase catalyzes the final step in forming the glycosaminoglycan-protein linkage region essential for proteoglycan biosynthesis by transferring glucuronic acid to the linkage tetrasaccharide in heparan sulfate and chondroitin sulfate. Biallelic mutations cause autosomal recessive multiple joint dislocations with short stature, craniofacial dysmorphism, and variable congenital heart defects. The gene shows very low constraint against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the glucuronyltransferase gene family, enzymes that exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product catalyzes the formation of the glycosaminoglycan-protein linkage by way of a glucuronyl transfer reaction in the final step of the biosynthesis of the linkage region of proteoglycans. A pseudogene of this gene has been identified on chromosome 3. [provided by RefSeq, Dec 2013]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defectsMIM #245600

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.33

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.33LOEUF

pLI 0.000

Z-score 0.59

OE 0.84 (0.54–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.69Z-score

OE missense 0.86 (0.76–0.98)

178 obs / 205.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.54–1.33)

0≤0.351.4

Missense OE?0.86 (0.76–0.98)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 13 / 15.5Missense obs/exp: 178 / 205.9Syn Z: -0.23

Background carrier burden — how many people carry a rare variant somewhere in B3GAT3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 99

409 rare PASS variants

Rare truncating (LoF)

1 in 650

55 rare PASS variants

Rare synonymous (reference)

1 in 200

185 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for B3GAT3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 850
South Asian	~43k	1 in 160	1 in 1,600
Remaining (unassigned)	~30k	1 in 100	1 in 620
European (Finnish)	~27k	1 in 220	≈ 1 in 5,600
Admixed American	~22k	1 in 110	1 in 560
African / African American	~21k	1 in 93	1 in 230
East Asian	~20k	1 in 150	≈ 1 in 13,000
Ashkenazi Jewish	~13k	1 in 1,500	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 170	≈ 1 in 650

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓