B4GALT1

Chr 9AR

beta-1,4-galactosyltransferase 1

Also known as: B4GAL-T1, CDG2D, CLDLFIB, GGTB2, GT1, GTB, beta4Gal-T1

NCBI Gene: 2683 ENSG00000086062 UniProt: P15291 OMIM: 137060

The protein is a galactosyltransferase that transfers galactose residues to N-acetylglucosamine on glycoproteins and glycolipids in the Golgi apparatus, and also forms part of the lactose synthase complex in mammary tissue. Biallelic mutations cause congenital disorder of glycosylation type IId and a condition with combined low LDL and fibrinogen, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants (pLI 0.04, LOEUF 0.70), suggesting that complete loss of function may be compatible with survival but causes clinically significant glycosylation defects.

OMIM ResearchSummary from RefSeq, OMIM, 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. This gene is unique among the beta4GalT genes because it encodes an enzyme that participates both in glycoconjugate and lactose biosynthesis. For the first activity, the enzyme adds galactose to N-acetylglucosamine residues that are either monosaccharides or the nonreducing ends of glycoprotein carbohydrate chains. The second activity is restricted to lactating mammary tissues where the enzyme forms a heterodimer with alpha-lactalbumin to catalyze UDP-galactose + D-glucose <=> UDP + lactose. The two enzymatic forms result from alternate transcription initiation sites and post-translational processing. Two transcripts, which differ only at the 5' end, with approximate lengths of 4.1 kb and 3.9 kb encode the same protein. The longer transcript encodes the type II membrane-bound, trans-Golgi resident protein involved in glycoconjugate biosynthesis. The shorter transcript encodes a protein which is cleaved to form the soluble lactose synthase. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.702 OMIM phenotypes

Clinical Summary— B4GALT1

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Gene-Disease Validity (ClinGen)

B4GALT1-congenital disorder of glycosylation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 77 VUS of 158 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.70LOEUF

pLI 0.037

Z-score 2.38

OE 0.33 (0.17–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.98Z-score

OE missense 0.82 (0.72–0.92)

184 obs / 225.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.17–0.70)

0≤0.351.4

Missense OE?0.82 (0.72–0.92)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 5 / 14.9Missense obs/exp: 184 / 225.2Syn Z: -0.47

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongB4GALT1-related congenital disorder of glycosylationLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6648th %ile

GOF

0.6444th %ile

LOF

0.3550th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

158 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS77

Likely Benign46

Benign17

Conflicting4

Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	1	0	0	3
Likely Pathogenic	0	0	0	0	0
VUS	1	66	7	3	77
Likely Benign	0	5	22	19	46
Benign	0	0	15	2	17
Conflicting	—				4
Total	3	72	44	24	147

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

View in ClinVar →

68 pathogenic / likely-pathogenic (of 80) ClinVar copy-number / structural variants overlap B4GALT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →