B3GAT1

Chr 11

beta-1,3-glucuronyltransferase 1

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

NCBI Gene: 27087 ENSG00000109956 UniProt: Q9P2W7 OMIM: 151290

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the glucuronyltransferase gene family. These enzymes exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product functions as the key enzyme in a glucuronyl transfer reaction during the biosynthesis of the carbohydrate epitope HNK-1 (human natural killer-1, also known as CD57 and LEU7). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.135

Z-score 2.51

OE 0.28 (0.14–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.42Z-score

OE missense 0.57 (0.49–0.65)

138 obs / 244.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.28 (0.14–0.64)

0≤0.351.4

Missense OE?0.57 (0.49–0.65)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 14.2Missense obs/exp: 138 / 244.2Syn Z: -0.41

Background carrier burden — how many people carry a rare variant somewhere in B3GAT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

408 rare PASS variants

Rare truncating (LoF)

1 in 12,000

32 rare PASS variants

Rare synonymous (reference)

1 in 270

269 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for B3GAT1. 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 190	1 in 9,000
South Asian	~43k	1 in 180	none seen
Remaining (unassigned)	~30k	1 in 230	≈ 1 in 15,000
European (Finnish)	~27k	1 in 770	1 in 4,300
Admixed American	~22k	1 in 330	≈ 1 in 11,000
African / African American	~21k	1 in 210	≈ 1 in 16,000
East Asian	~20k	1 in 240	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 1,600	none seen
Middle Eastern	~2,884	1 in 190	none seen

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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓