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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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A4GALT
alpha 1,4-galactosyltransferase (P1PK blood group)
Chromosome 22 · 22q13.2
NCBI Gene: 53947Ensembl: ENSG00000128274.18HGNC: HGNC:18149UniProt: A0A0S2Z5J1
56PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membrane organizationgalactosyltransferase activitymembraneglycosphingolipid biosynthetic processdeep vein thrombosischronic kidney diseaseThromboembolismkidney failure
✦AI Summary

A4GALT encodes α1,4-galactosyltransferase, a Golgi membrane-resident enzyme that catalyzes the synthesis of globotriaosylceramide (Gb3) glycosphingolipids and P1 antigens on glycoproteins 1. The enzyme exhibits dual acceptor specificity, synthesizing both glycosphingolipids and modifying glycoproteins through homodimerization and heterodimerization with other galactosyltransferases 1. A4GALT expression levels determine P1/P2 blood group phenotypes, with single nucleotide polymorphisms in the 5' untranslated region affecting transcript levels and enzyme activity 23. The enzyme's products serve as cellular receptors for Shiga toxins, facilitating toxin entry and subsequent cellular damage. In Fabry disease, where α-galactosidase A is deficient, A4GALT contributes to pathological Gb3 accumulation. CRISPR/Cas9-mediated A4GALT suppression effectively rescues Fabry disease phenotypes in kidney organoids and endothelial cells by reducing Gb3 deposition and restoring cellular function 45. Additionally, siRNA-mediated A4GALT knockdown shows therapeutic promise for Fabry disease treatment 6. These findings establish A4GALT as both a critical determinant of blood group antigens and a potential therapeutic target for glycosphingolipid storage disorders.

Sources cited
1
A4GALT encodes a Golgi-resident enzyme that synthesizes Gb3 and P1 antigens, and forms homo/heterodimers affecting acceptor specificity
PMID: 39111055
2
SNPs in A4GALT 5' UTR are associated with P1/P2 blood group phenotypes
PMID: 16507021
3
A4GALT polymorphisms underlie P1PK blood group system variation
PMID: 29709005
4
CRISPR/Cas9-mediated A4GALT suppression rescues Fabry disease endothelial dysfunction
PMID: 39141976
5
A4GALT suppression rescues Fabry disease phenotypes in kidney organoid models
PMID: 36805562
6
siRNA-mediated A4GALT knockdown shows therapeutic potential for Fabry disease
PMID: 40520362
Disease Associationsⓘ20
deep vein thrombosisOpen Targets
0.45Moderate
chronic kidney diseaseOpen Targets
0.43Moderate
ThromboembolismOpen Targets
0.43Moderate
kidney failureOpen Targets
0.43Moderate
breast carcinomaOpen Targets
0.35Weak
Caffey diseaseOpen Targets
0.33Weak
myeloproliferative disorderOpen Targets
0.27Weak
mixed connective tissue diseaseOpen Targets
0.26Weak
neoplasmOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.10Weak
fracture of pelvisOpen Targets
0.10Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
Schnyder corneal dystrophyOpen Targets
0.08Suggestive
Townes-Brocks syndromeOpen Targets
0.08Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.08Suggestive
anemiaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
cancerOpen Targets
0.07Suggestive
tetrasomy 12pOpen Targets
0.07Suggestive
glomerulonephritisOpen Targets
0.06Suggestive
Pathogenic Variants1
NM_017436.7(A4GALT):c.631C>G (p.Gln211Glu)Pathogenic
NOR polyagglutination syndrome
☆☆☆☆2012→ Residue 211
View on ClinVar ↗
Related Genes
GLAProtein interaction95%GLB1Protein interaction95%HEXAProtein interaction95%HEXBProtein interaction95%B4GALT6Protein interaction95%UGCGProtein interaction94%
Tissue Expression6 tissues
Heart
100%
Lung
48%
Bone Marrow
15%
Ovary
12%
Liver
5%
Brain
4%
Gene Interaction Network
Click a node to explore
A4GALTGLAGLB1HEXAHEXBB4GALT6UGCG
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q5D079
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.39LoF Tolerant
pLIⓘ
0.08Tolerant
Observed/Expected LoF0.62 [0.30–1.39]
RankingsWhere A4GALT stands among ~20K protein-coding genes
  • #8,035of 20,598
    Most Researched56
  • #5,062of 5,498
    Most Pathogenic Variants1
  • #14,439of 17,882
    Most Constrained (LOEUF)1.39
Genes detectedA4GALT
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Fabry Disease: Molecular Basis, Pathophysiology, Diagnostics and Potential Therapeutic Directions.
PMID: 33673160
Biomolecules · 2021
1.00
2
CRISPR/Cas9-mediated suppression of A4GALT rescues endothelial cell dysfunction in a fabry disease vasculopathy model derived from human induced pluripotent stem cells.
PMID: 39141976
Atherosclerosis · 2024
0.90
3
CRISPR/Cas9-mediated A4GALT suppression rescues Fabry disease phenotypes in a kidney organoid model.
PMID: 36805562
Transl Res · 2023
0.80
4
Application of a simplified PCR-SSP method to detect A4GALT*01 and A4GALT*02 typing among Thai blood donors.
PMID: 37673392
Transfus Clin Biol · 2023
0.70
5
Sequence variation in the 5' untranslated region of the human A4GALT gene is associated with, but does not define, the P1 blood-group polymorphism.
PMID: 16507021
Vox Sang · 2006
0.60