B4GALT4

Chr 3

beta-1,4-galactosyltransferase 4

Also known as: B4Gal-T4, beta4Gal-T4

NCBI Gene: 8702 ENSG00000121578 UniProt: O60513 OMIM: 604015

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 appears to mainly play a role in glycolipid biosynthesis. Two alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.000

Z-score 1.14

OE 0.70 (0.45–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.19Z-score

OE missense 0.76 (0.66–0.87)

143 obs / 188.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.45–1.14)

0≤0.351.4

Missense OE?0.76 (0.66–0.87)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 12 / 17.1Missense obs/exp: 143 / 188.9Syn Z: 0.33

Background carrier burden — how many people carry a rare variant somewhere in B4GALT4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

397 rare PASS variants

Rare truncating (LoF)

1 in 1,500

66 rare PASS variants

Rare synonymous (reference)

1 in 280

167 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for B4GALT4. 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 300	1 in 1,400
South Asian	~43k	1 in 260	1 in 1,200
Remaining (unassigned)	~30k	1 in 170	1 in 2,500
European (Finnish)	~27k	1 in 390	≈ 1 in 27,000
Admixed American	~22k	1 in 230	≈ 1 in 11,000
African / African American	~21k	1 in 140	1 in 1,600
East Asian	~20k	1 in 400	1 in 2,500
Ashkenazi Jewish	~13k	1 in 2,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 340	≈ 1 in 1,400

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