B3GAT1

Chr 11

beta-1,3-glucuronyltransferase 1

Also known as: CD57, GLCATP, GLCUATP, HNK1, LEU7, NK-1, NK1

The B3GAT1 protein functions as a glucuronyltransferase that catalyzes the biosynthesis of the HNK-1 carbohydrate epitope on glycoproteins and participates in glycosaminoglycan biosynthesis. Mutations cause autosomal recessive multiple congenital anomalies-hypotonia-seizures syndrome, characterized by early-onset developmental delays, hypotonia, seizures, and distinctive facial features. The gene shows moderate constraint against loss-of-function variants, consistent with its role in essential carbohydrate modification pathways.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
88
P/LP submissions
0%
P/LP missense
0.64
LOEUF
DN
Mechanism· predicted
Clinical SummaryB3GAT1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
88 unique Pathogenic / Likely Pathogenic· 43 VUS of 136 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.135
Z-score 2.51
OE 0.28 (0.140.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.42Z-score
OE missense 0.57 (0.490.65)
138 obs / 244.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.28 (0.140.64)
00.351.4
Missense OE0.57 (0.490.65)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 4 / 14.2Missense obs/exp: 138 / 244.2Syn Z: -0.41
DN
0.6550th %ile
GOF
0.6151th %ile
LOF
0.3258th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

Classification Summary

Pathogenic81
Likely Pathogenic7
VUS43
Likely Benign1
Benign1
81
Pathogenic
7
Likely Pathogenic
43
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
81
0
81
Likely Pathogenic
0
0
7
0
7
VUS
0
33
10
0
43
Likely Benign
0
0
1
0
1
Benign
0
0
0
1
1
Total033991133

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

View in ClinVar →

Protein Context — Lollipop Plot

B3GAT1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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