B4GALNT1

Chr 12AR

beta-1,4-N-acetyl-galactosaminyltransferase 1

Also known as: GALGT, GALNACT, GalNAc-T, SPG26

NCBI Gene: 2583 ENSG00000135454 UniProt: Q00973 OMIM: 601873

The protein catalyzes the transfer of GalNAc to GM3 and GD3 gangliosides via beta-1,4 linkage to synthesize GM2 and GD2 gangliosides, functioning in the Golgi apparatus membrane. Mutations cause spastic paraplegia 26 through autosomal recessive inheritance. The pathogenic mechanism likely involves disrupted ganglioside biosynthesis leading to progressive spasticity of the lower limbs.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids. GalNAc-T is the enzyme involved in the biosynthesis of G(M2) and G(D2) glycosphingolipids. GalNAc-T catalyzes the transfer of GalNAc into G(M3) and G(D3) by a beta-1,4 linkage, resulting in the synthesis of G(M2) and G(D2), respectively. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.791 OMIM phenotype

Clinical Summary— B4GALNT1

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Gene-Disease Validity (ClinGen)

complex hereditary spastic paraplegia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

40 unique Pathogenic / Likely Pathogenic· 178 VUS of 400 total submissions

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GeneReview available — B4GALNT1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.000

Z-score 2.31

OE 0.48 (0.30–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.92Z-score

OE missense 0.85 (0.77–0.94)

267 obs / 313.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.30–0.79)

0≤0.351.4

Missense OE?0.85 (0.77–0.94)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 11 / 23.0Missense obs/exp: 267 / 313.0Syn Z: 0.15

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22

Likely Pathogenic18

VUS178

Likely Benign141

Benign28

Conflicting7

Pathogenic

Likely Pathogenic

178

VUS

141

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	21	1	0	0	22
Likely Pathogenic	14	4	0	0	18
VUS	0	170	6	2	178
Likely Benign	0	8	43	90	141
Benign	0	3	21	4	28
Conflicting	—				7
Total	35	186	70	96	394

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap B4GALNT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →