B3GAT3

Chr 11AR

beta-1,3-glucuronyltransferase 3

Also known as: GLCATI, JDSCD, glcUAT-I

NCBI Gene: 26229ENSG00000149541UniProt: O94766

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]

Primary Disease Associations & Inheritance

Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defectsMIM #245600
AR
319
ClinVar variants
42
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— B3GAT3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 141 VUS of 319 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.69Z-score
OE missense 0.86 (0.76–0.98)
178 obs / 205.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.84 (0.54–1.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.76–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 13 / 15.5Missense obs/exp: 178 / 205.9Syn Z: -0.23

ClinVar Variant Classifications

319 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic20
VUS141
Likely Benign118
Benign10
Conflicting8
22
Pathogenic
20
Likely Pathogenic
141
VUS
118
Likely Benign
10
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
5
11
0
22
Likely Pathogenic
4
6
10
0
20
VUS
2
124
13
2
141
Likely Benign
2
2
43
71
118
Benign
0
1
9
0
10
Conflicting
—8
Total141388673319

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

View in ClinVar →

Protein Context — Lollipop Plot

B3GAT3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

B3GAT3-related multiple joint dislocations, short stature, and craniofacial dysmorphism with or without congenital heart defects

limited
ARUndeterminedAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects

MIM #245600

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
The clinical and mutational spectrum of B3GAT3 linkeropathy: two case reports and literature review.
Colman M et al.·Orphanet J Rare Dis
2019Review
Further Defining the Phenotypic Spectrum of B3GAT3 Mutations and Literature Review on Linkeropathy Syndromes.
Ritelli M et al.·Genes (Basel)
2019Review
Severe phenotypes of B3GAT3-related disorder caused by two heterozygous variants: a case report and literature review.
Li Y et al.·BMC Med Genomics
2022Review
B3GAT3-related linkeropathy and an in-frame homozygous deletion in an adult patient.
Bolund ACS et al.·Eur J Med Genet
2021Review
Pseudodiastrophic dysplasia expands the known phenotypic spectrum of defects in proteoglycan biosynthesis.
Byrne AB et al.·J Med Genet
2020
Prenatal and neonatal phenotype of Larsen of La Réunion Island syndrome (B4GALT7-linkeropathy).
Alessandri JL et al.·Eur J Med Genet
2024
Functional validation of novel compound heterozygous variants in B3GAT3 resulting in severe osteopenia and fractures: expanding the disease phenotype.
Job F et al.·BMC Med Genet
2016Case report
Skeletal dysplasia, global developmental delay, and multiple congenital anomalies in a 5-year-old boy-report of the second family with B3GAT3 mutation and expansion of the phenotype.
von Oettingen JE et al.·Am J Med Genet A
2014Case report
Investigation of Copy Number Variation in South African Patients With Congenital Heart Defects.
Saacks NA et al.·Circ Genom Precis Med
2022Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools