B4GALT1

Chr 9AR

beta-1,4-galactosyltransferase 1

NCBI Gene: 2683 ENSG00000086062 UniProt: P15291

Galactosyltransferase acting in the Golgi stacks. Catalyzes the transfer of galactose (Gal) from UDP-alpha-D-galactose in beta(1->4) linkage to the non-reducing terminal N-acetylglucosamine (GlcNAc) moieties of glycolipids and complex-type N-linked glycans (PubMed:16157350, PubMed:27872474, PubMed:29133956, PubMed:36280670, PubMed:37632720, PubMed:38321209). Adds one Gal residue to both GlcNAc beta(1->2)-linked to the alpha(1->3) and alpha(1->6) mannose antennae of complex-type N-glycans, enabling the formation of mono- and di-galactosylated glycoforms. Galactosylates complex-type N-glycans attached on the fragment crystallizable (Fc) of immunoglobulin-gamma isotypes (IgGs), a prerequisite for antibody glycan sialylation and related anti-inflammatory effector functions (PubMed:27872474, PubMed:29133956, PubMed:36280670, PubMed:37632720). Can also transfer a Gal residue to free GlcNAc to form N-acetyllactosamine (PubMed:16157350). With LALBA/alpha-lactalbumin forms the lactose synthase complex responsible for production of large amounts of lactose in the lactating mammary gland. Interaction with LALBA alters the sugar substrate specificity of the catalytic domain, enabling high affinity binding of glucose and its transformation to lactose (PubMed:16157350)

Primary Disease Associations & Inheritance

Combined low LDL and fibrinogenMIM #620364

Congenital disorder of glycosylation, type IIdMIM #607091

235

ClinVar variants

Pathogenic / LP

0.04

pLI score

Active trials

Clinical Summary— B4GALT1

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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

235 total variants — no pathogenic classifications of 235 total submissions

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Clinical Trials

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.70LOEUF

pLI 0.037

Z-score 2.38

OE 0.33 (0.17–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.98Z-score

OE missense 0.82 (0.72–0.92)

184 obs / 225.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.17–0.70)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.72–0.92)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06

0≤1.21.6

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