A4GALT (Alpha-1,4-Galactosyltransferase)
Key enzyme in P1PK blood group system and globoside biosynthesis
Gene Information Card
| Symbol | A4GALT |
|---|---|
| Full Name | Alpha-1,4-Galactosyltransferase (P blood group) |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.2 |
| NCBI Gene ID | 53947 ncbi.nlm.nih.gov/gene/53947 |
| Ensembl ID | ENSG00000128274 |
| UniProt ID | Q9NPC4 |
| OMIM ID | 607922 |
| HGNC ID | 18149 |
| Aliases | A14GALT, Gb3S, P(k) synthase, P1/P(k) synthase |
Description
The A4GALT gene encodes alpha-1,4-galactosyltransferase, an enzyme that catalyzes the transfer of galactose to lactosylceramide to form globotriaosylceramide (Gb3), the P(k) antigen, and subsequently globoside (P antigen). This enzyme is essential for the biosynthesis of P1PK blood group antigens and plays a role in cellular adhesion, infection susceptibility, and glycosphingolipid metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| P1PK blood group system (P1, P(k), p phenotypes) | Loss-of-function mutations in A4GALT abolish Gb3 and globoside synthesis, leading to the rare p phenotype; altered expression determines P1 vs P(k) phenotypes. | OMIM #607922; ClinVar |
| Urinary tract infection susceptibility | Absence of globoside (P antigen) on uroepithelial cells reduces binding of uropathogenic E. coli, conferring resistance to recurrent UTIs. | PMID: 10958655; NCBI Gene |
| Fabry disease (modifier) | A4GALT variants may influence globotriaosylceramide (Gb3) accumulation in Fabry disease, potentially modulating disease severity. | PMID: 23352160; OMIM #301500 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Liver | 8.3 | Low |
| Small intestine | 15.2 | Medium |
| Colon | 10.1 | Medium |
| Lung | 6.7 | Low |
| Spleen | 9.4 | Low |
| Testis | 7.8 | Low |
| Brain | 4.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.5 | High expression |
| HeLa | 12.3 | Medium expression |
| K-562 | 9.8 | Low expression |
| HepG2 | 7.1 | Low expression |
| A549 | 5.6 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.548G>A (p.Trp183*) | Nonsense | Rare | Loss of function; associated with p phenotype |
| c.802C>T (p.Arg268Cys) | Missense | Rare | Reduced enzyme activity; linked to P(k) phenotype |
| c.1006A>G (p.Thr336Ala) | Missense | Polymorphic | Alters P1/P2 antigen expression |
| c.987G>A (p.Met329Ile) | Missense | Polymorphic | Associated with P1 antigen expression |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Trp183*) abolish enzyme activity, leading to the p phenotype with absence of P, P1, and P(k) antigens.
Gain of Function (GOF)
Not reported for A4GALT.
Dominant Negative (DN)
Not reported for A4GALT.
View complete mutation data：
Gene Ontology (GO)
| • GO:0008378 (galactosyltransferase activity) | • GO:0006689 (lactosylceramide alpha-1 |
| • 4-galactosyltransferase activity) | • GO:0005794 (Golgi apparatus) |
| • GO:0016021 (integral component of membrane) | • GO:0006688 (glycosphingolipid biosynthetic process) |
| • GO:0005886 (plasma membrane) |
Pathways
• Glycosphingolipid biosynthesis - globo series (KEGG: hsa00603)
• P1PK blood group biosynthesis (Reactome: R-HSA-9033807)
• Sphingolipid metabolism (KEGG: hsa00600)
Protein Summary
Alpha-1,4-galactosyltransferase (A4GALT) is a 353-amino acid type II transmembrane protein localized to the Golgi apparatus. It catalyzes the addition of galactose in an alpha-1,4 linkage to lactosylceramide to form globotriaosylceramide (Gb3, P(k) antigen). Gb3 is further elongated to globoside (P antigen) by the B3GALNT1 enzyme. A4GALT also synthesizes the P1 antigen by adding galactose to paragloboside. The enzyme is critical for the P1PK blood group system and influences susceptibility to bacterial infections and lysosomal storage disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| A4GALT Knockout HEK293 Cell Line | EDJ-KQ10691 | Human | 53947 | Details Get a Quote |
| A4GALT Knockout A-549 Cell Line | EDJ-KQ39564 | Human | 53947 | Details Get a Quote |
| A4GALT Knockout HCT 116 Cell Line | EDJ-KQ39566 | Human | 53947 | Details Get a Quote |
| A4GALT Knockout HeLa Cell Line | EDJ-KQ39567 | Human | 53947 | Details Get a Quote |
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