B4GALNT1

Chr 12AR

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

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

NCBI Gene: 2583ENSG00000135454UniProt: Q00973

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]

Primary Disease Associations & Inheritance

Spastic paraplegia 26, autosomal recessiveMIM #609195
AR
94
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— B4GALNT1
🧬
Gene-Disease Validity (ClinGen)
complex hereditary spastic paraplegia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 48 VUS of 94 total submissions

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.
0.79LOEUF
pLI 0.000
Z-score 2.31
OE 0.48 (0.30–0.79)
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.
0.92Z-score
OE missense 0.85 (0.77–0.94)
267 obs / 313.0 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.0.48 (0.30–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.77–0.94)
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.0.98
0≤1.21.6
LoF obs/exp: 11 / 23.0Missense obs/exp: 267 / 313.0Syn Z: 0.15

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic4
VUS48
Likely Benign35
7
Pathogenic
4
Likely Pathogenic
48
VUS
35
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
2
0
7
Likely Pathogenic
2
1
1
0
4
VUS
0
44
4
0
48
Likely Benign
0
1
12
22
35
Benign
0
0
0
0
0
Total746192294

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

View in ClinVar →

Protein Context — Lollipop Plot

B4GALNT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spastic paraplegia 26, autosomal recessive

MIM #609195

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — B4GALNT1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
B4GALNT1 promotes progression and metastasis in lung adenocarcinoma through JNK/c-Jun/Slug pathway.
Jiang T et al.·Carcinogenesis
2021
B4GALNT1 promotes carcinogenesis by regulating epithelial-mesenchymal transition in hepatocellular carcinoma based on pan-cancer analysis.
Liu W et al.·J Gene Med
2023
Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma.
Paret C et al.·Int J Mol Sci
2025
Pan-Cancer Analysis of B4GALNT1 as a Potential Prognostic and Immunological Biomarker.
Yi H et al.·J Immunol Res
2022
Glycosyltransferase B4GALNT1 and type 1 diabetes in Croatian population: clinical investigation.
Boraska V et al.·Clin Biochem
2009
Downregulation of B4GALNT1 inhibits proliferation and metastasis of osteosarcoma cells.
Li S et al.·Zhong Nan Da Xue Xue Bao Yi Xue Ban
2024
Functional validation of novel variants in B4GALNT1 associated with early-onset complex hereditary spastic paraplegia with impaired ganglioside synthesis.
Alecu JE et al.·Am J Med Genet A
2022Case report
Gangliosides, α-Synuclein, and Parkinson's Disease.
Ledeen RW et al.·Prog Mol Biol Transl Sci
2018Review
Diseases of ganglioside biosynthesis: An expanding group of congenital disorders of glycosylation.
Trinchera M et al.·Mol Genet Metab
2018Review
Characterization of Human Recombinant β1,4-GalNAc-Transferase B4GALNT1 and Inhibition by Selected Compounds.
Abidi I et al.·Molecules
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools