B4GALT2

Chr 1

beta-1,4-galactosyltransferase 2

Also known as: B4Gal-T2, B4Gal-T3, beta4Gal-T2

NCBI Gene: 8704 ENSG00000117411 UniProt: O60909 OMIM: 604013

This gene encodes beta-1,4-galactosyltransferase 2, a Golgi membrane enzyme that synthesizes N-acetyllactosamine in glycolipids and glycoproteins and is responsible for producing complex-type N-linked oligosaccharides. Mutations in B4GALT2 cause autosomal recessive congenital disorder of glycosylation type IId, characterized by developmental delay, intellectual disability, and dysmorphic features. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.59), suggesting some tolerance to protein disruption.

OMIM ResearchSummary from RefSeq, UniProt

This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a beta1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. The enzyme encoded by this gene synthesizes N-acetyllactosamine in glycolipids and glycoproteins. Its substrate specificity is affected by alpha-lactalbumin but it is not expressed in lactating mammary tissue. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.59

Clinical Summary— B4GALT2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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ClinVar Variants

51 VUS of 66 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.198

Z-score 2.70

OE 0.26 (0.13–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.88Z-score

OE missense 0.68 (0.61–0.77)

194 obs / 283.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.13–0.59)

0≤0.351.4

Missense OE?0.68 (0.61–0.77)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 4 / 15.5Missense obs/exp: 194 / 283.2Syn Z: -0.32

This gene — mechanism propensity

0.6258th %ile

GOF

0.5955th %ile

LOF

0.3939th %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

66 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	51	51
Likely Benign	2	2
Benign	0	0
Total	53	53

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap B4GALT2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →