NAT8L (N-Acetyltransferase 8 Like): A Key Enzyme in Neuronal N-Acetylaspartate Synthesis
Explore the gene NAT8L, its role in N-acetylaspartate metabolism, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | NAT8L |
|---|---|
| Full Name | N-acetyltransferase 8 like |
| Gene Type | protein coding |
| Chromosomal Location | 4q26 |
| NCBI Gene ID | 339983 ncbi.nlm.nih.gov/gene/339983 |
| Ensembl ID | ENSG00000151413 |
| UniProt ID | Q8NBF2 |
| OMIM ID | 614044 |
| HGNC ID | 30432 |
| Aliases | CML2, NAT8-like, aspartate N-acetyltransferase |
Description
NAT8L encodes N-acetyltransferase 8 like, an enzyme that catalyzes the synthesis of N-acetylaspartate (NAA) from acetyl-CoA and aspartate. NAA is one of the most abundant amino acid derivatives in the brain, primarily synthesized in neurons. NAT8L is critical for neuronal and brain function, and its deficiency leads to reduced NAA levels, which is associated with various neurological conditions. The gene is located on chromosome 4q26 and is expressed predominantly in the brain, especially in neurons.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Canavan disease | Mutations in NAT8L are not the primary cause; however, reduced NAA synthesis due to NAT8L dysfunction may modulate the phenotype. Canavan disease is caused by ASPA mutations leading to NAA accumulation. | OMIM 614044; literature reports |
| Neuropsychiatric disorders | Altered NAA levels, regulated by NAT8L, are observed in schizophrenia, bipolar disorder, and major depression, suggesting a role in disease pathology. | Case-control studies; MRS imaging |
| Brain injury and ischemia | NAT8L expression and NAA levels change after brain injury, indicating a role in neuronal stress response. | Experimental models |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Spinal cord | Medium | Medium |
| Testis | Low | Low |
| Kidney | Low | Low |
| Liver | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal cell line |
| U-87 MG (glioblastoma) | Medium | Glial cell line |
| HeLa (cervical carcinoma) | Low | Non-neuronal |
| HEK293 (embryonic kidney) | Low | Non-neuronal |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.244C>T (p.Arg82Trp) | Missense | Rare | Reduced enzyme activity |
| c.545G>A (p.Arg182His) | Missense | Rare | Impaired NAA synthesis |
| c.1A>G (p.Met1Val) | Start codon loss | Very rare | Loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish NAT8L enzymatic activity lead to decreased NAA synthesis, as observed in some individuals with neurological symptoms.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NAT8L.
Dominant Negative (DN)
No dominant-negative effects have been described; NAT8L likely functions as a monomer or homodimer, and haploinsufficiency may be relevant.
View complete mutation data：
Gene Ontology (GO)
| • acetyltransferase activity | • aspartate N-acetyltransferase activity |
| • neuron projection | • cytoplasm |
| • acetyl-CoA metabolic process | • N-acetylaspartate biosynthetic process |
Pathways
• NAA metabolism
• Aspartate metabolism
• Acetyl-CoA metabolism
Protein Summary
NAT8L is a 329-amino acid protein localized in the cytoplasm and mitochondria of neurons. It catalyzes the transfer of an acetyl group from acetyl-CoA to aspartate, producing N-acetylaspartate (NAA). NAA is involved in neuronal osmoregulation, lipid synthesis in oligodendrocytes, and energy metabolism. NAT8L expression is highest in the brain, and its activity is essential for maintaining NAA levels. Deficiencies in NAT8L lead to reduced NAA, which is associated with neurological dysfunction, although the full clinical spectrum is still under investigation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NAT8L Knockout HEK293 Cell Line | EDJ-KQ14374 | Human | 339983 | Details Get a Quote |
| NAT8L Knockout A-549 Cell Line | EDJ-KQ44519 | Human | 339983 | Details Get a Quote |
| NAT8L Knockout HeLa Cell Line | EDJ-KQ44520 | Human | 339983 | Details Get a Quote |
| NAT8L Knockout HCT 116 Cell Line | EDJ-KQ43278 | Human | 339983 | Details Get a Quote |
