GALNT3 Gene: Polypeptide N-Acetylgalactosaminyltransferase 3
Key regulator of FGF23 O-glycosylation and phosphate metabolism
Gene Information Card
| Symbol | GALNT3 |
|---|---|
| Full Name | Polypeptide N-acetylgalactosaminyltransferase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q24.3 |
| NCBI Gene ID | 2591 ncbi.nlm.nih.gov/gene/2591 |
| Ensembl ID | ENSG00000115339 |
| UniProt ID | Q14435 |
| OMIM ID | 601756 |
| HGNC ID | 4125 |
| Aliases | GalNAc-T3, GalNAc transferase 3, pp-GalNAc-T3 |
Description
GALNT3 encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family, which initiates O-linked glycosylation of mucin-type glycoproteins. The enzyme catalyzes the transfer of N-acetylgalactosamine (GalNAc) to serine and threonine residues. GALNT3 is critical for the O-glycosylation and stability of fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate homeostasis. Loss-of-function mutations in GALNT3 cause hyperphosphatemic familial tumoral calcinosis (HFTC) due to impaired FGF23 secretion.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperphosphatemic familial tumoral calcinosis (HFTC) | Loss-of-function mutations in GALNT3 prevent O-glycosylation of FGF23, leading to its intracellular degradation and reduced secretion, resulting in elevated serum phosphate and ectopic calcifications. | OMIM #211900; multiple case reports |
| Hyperostosis-hyperphosphatemia syndrome (HHS) | Same molecular mechanism as HFTC; GALNT3 mutations cause defective FGF23 processing, leading to hyperphosphatemia and bone overgrowth. | OMIM #610233; clinical studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Salivary gland | 10.8 | Medium |
| Stomach | 9.2 | Medium |
| Pancreas | 7.1 | Low |
| Liver | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in recombinant systems |
| HepG2 | 8.5 | Moderate expression |
| MCF7 | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1524C>G (p.Tyr508*) | Nonsense | Rare | Loss of function; truncated protein |
| c.1312C>T (p.Arg438Cys) | Missense | Rare | Loss of function; reduced enzymatic activity |
| c.485G>A (p.Arg162His) | Missense | Rare | Loss of function; impaired FGF23 glycosylation |
Mutation functional classification
Loss of Function (LOF)
Most reported GALNT3 mutations are loss-of-function, leading to reduced or absent GalNAc transferase activity and defective FGF23 O-glycosylation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for GALNT3.
Dominant Negative (DN)
No dominant-negative mutations have been described; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • polypeptide N-acetylgalactosaminyltransferase activity (GO:0004653) | • protein O-linked glycosylation (GO:0006493) |
| • Golgi apparatus (GO:0005794) | • protein O-linked mannosylation (GO:0035269) |
Pathways
• O-linked glycosylation of mucins (Reactome: R-HSA-913709)
• FGF23 processing and phosphate homeostasis (Reactome: R-HSA-8851805)
Protein Summary
GALNT3 (GalNAc-T3) is a 633-amino acid type II transmembrane protein localized to the Golgi apparatus. It contains a catalytic domain with a GT-A fold and a lectin domain that binds GalNAc. The enzyme initiates mucin-type O-glycosylation by transferring GalNAc to serine/threonine residues. Its most well-characterized substrate is FGF23; O-glycosylation at Thr178 protects FGF23 from furin-mediated cleavage, ensuring secretion of intact, active hormone. Loss of GALNT3 function leads to FGF23 deficiency, hyperphosphatemia, and ectopic calcification.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GALNT3 Knockout HEK293 Cell Line | EDJ-KQ4675 | Human | 2591 | Details Get a Quote |
| B4GALNT3 Knockout HEK293 Cell Line | EDJ-KQ12508 | Human | 283358 | Details Get a Quote |
| B4GALNT3 Knockout HCT 116 Cell Line | EDJ-KQ41488 | Human | 283358 | Details Get a Quote |
| GALNT3 Knockout HCT 116 Cell Line | EDJ-KQ27368 | Human | 2591 | Details Get a Quote |
| GALNT3 Knockout HeLa Cell Line | EDJ-KQ27369 | Human | 2591 | Details Get a Quote |
| B4GALNT3 Knockout HeLa Cell Line | EDJ-KQ59389 | Human | 283358 | Details Get a Quote |
| GALNT3 Knockout A-549 Cell Line | EDJ-KQ61786 | Human | 2591 | Details Get a Quote |
| B4GALNT3 Knockout A-549 Cell Line | EDJ-KQ67855 | Human | 283358 | Details Get a Quote |
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