GNPAT: Glyceronephosphate O-Acyltransferase
Key enzyme in ether lipid biosynthesis and peroxisomal biogenesis disorders
Gene Information Card
| Symbol | GNPAT |
|---|---|
| Full Name | Glyceronephosphate O-Acyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 1q42.2 |
| NCBI Gene ID | 8443 ncbi.nlm.nih.gov/gene/8443 |
| Ensembl ID | ENSG00000116918 |
| UniProt ID | O15228 |
| OMIM ID | 602744 |
| HGNC ID | 4416 |
| Aliases | DHAPAT, DAP-AT, RCDP2 |
Description
GNPAT encodes glyceronephosphate O-acyltransferase, a peroxisomal enzyme that catalyzes the first step of ether phospholipid biosynthesis: the acylation of dihydroxyacetone phosphate (DHAP) with a long-chain fatty acid. This enzyme is essential for the synthesis of plasmalogens, a class of ether lipids abundant in myelin and cell membranes. Mutations in GNPAT cause rhizomelic chondrodysplasia punctata type 2 (RCDP2), a peroxisomal biogenesis disorder characterized by skeletal abnormalities, cataracts, and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rhizomelic chondrodysplasia punctata type 2 (RCDP2) | Loss-of-function mutations in GNPAT impair DHAPAT activity, blocking ether lipid synthesis and leading to peroxisomal dysfunction. | ClinVar, OMIM |
| Peroxisomal biogenesis disorder spectrum | Deficiency in plasmalogen biosynthesis due to GNPAT mutations contributes to peroxisomal assembly defects. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.3 | Medium |
| Brain | 8.7 | Medium |
| Heart | 7.2 | Low |
| Lung | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocyte-derived line |
| HEK293 | 9.8 | Embryonic kidney line |
| SH-SY5Y | 7.5 | Neuroblastoma line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.875G>A (p.Arg292His) | Missense | Rare | Loss of DHAPAT activity; associated with RCDP2 |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein expression; severe RCDP2 phenotype |
| c.1123C>T (p.Arg375*) | Nonsense | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most GNPAT mutations cause loss of DHAPAT enzymatic activity, leading to deficient ether lipid synthesis.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ether lipid metabolism (Reactome: R-HSA-1483206)
• Peroxisomal lipid metabolism (KEGG: hsa04146)
Protein Summary
GNPAT (DHAPAT) is a 680-amino acid peroxisomal membrane protein that catalyzes the acylation of dihydroxyacetone phosphate (DHAP) using long-chain acyl-CoA. This is the committed step in plasmalogen synthesis. The enzyme is anchored to the inner leaflet of the peroxisomal membrane via its N-terminal transmembrane domain. Deficiency leads to accumulation of DHAP and reduced plasmalogen levels, causing RCDP2.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNPAT Knockout HEK293 Cell Line | EDJ-KQ2194 | Human | 8443 | Details Get a Quote |
| GNPAT Knockout A-549 Cell Line | EDJ-KQ23794 | Human | 8443 | Details Get a Quote |
| GNPAT Knockout HCT 116 Cell Line | EDJ-KQ23796 | Human | 8443 | Details Get a Quote |
| GNPAT Knockout HeLa Cell Line | EDJ-KQ23797 | Human | 8443 | Details Get a Quote |
