CHAT (Choline O-Acetyltransferase)
Key enzyme in acetylcholine biosynthesis, critical for cholinergic neurotransmission.
Gene Information Card
| Symbol | CHAT |
|---|---|
| Full Name | Choline O-Acetyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 10q11.23 |
| NCBI Gene ID | 1103 ncbi.nlm.nih.gov/gene/1103 |
| Ensembl ID | ENSG00000170776 |
| UniProt ID | P28329 |
| OMIM ID | 118490 |
| HGNC ID | 1912 |
| Aliases | CMS1A, CMS1A2, CHOACTASE, ChAT |
Description
The CHAT gene encodes choline O-acetyltransferase, the enzyme responsible for catalyzing the biosynthesis of acetylcholine from choline and acetyl-CoA. This enzyme is expressed in cholinergic neurons of the central and peripheral nervous systems and plays a fundamental role in neuromuscular transmission and autonomic nervous system function. Mutations in CHAT are associated with congenital myasthenic syndromes, particularly presynaptic defects.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital Myasthenic Syndrome 1A (CMS1A) | Loss-of-function mutations reduce acetylcholine synthesis, impairing neuromuscular transmission. | ClinVar, OMIM |
| Congenital Myasthenic Syndrome 1B (CMS1B) | Similar mechanism; episodic apnea and respiratory failure. | OMIM |
| Cholinergic Dysfunction in Alzheimer Disease | Reduced CHAT activity correlates with cognitive decline; not a direct genetic cause. | NCBI, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 3.2 | Low |
| Spinal cord | 8.7 | Medium |
| Skeletal muscle | 0.1 | Not detected |
| Heart | 0.3 | Not detected |
| Placenta | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 5.1 | Cholinergic-like phenotype |
| IMR-32 (neuroblastoma) | 4.8 | Moderate expression |
| HepG2 (liver) | 0.0 | Not detected |
| A549 (lung) | 0.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.914T>C (p.Leu305Pro) | Missense | Rare | Reduced enzyme activity; CMS1A |
| c.1205G>A (p.Arg402His) | Missense | Rare | Impaired catalytic function; CMS1A |
| c.1492C>T (p.Arg498*) | Nonsense | Rare | Premature truncation; loss of function |
| c.1882G>A (p.Gly628Arg) | Missense | Rare | Dominant-negative effect in some families |
Mutation functional classification
Loss of Function (LOF)
Most CHAT mutations are loss-of-function, leading to reduced acetylcholine synthesis and impaired neuromuscular transmission.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Rare missense mutations (e.g., p.Gly628Arg) may exert dominant-negative effects by interfering with enzyme dimerization.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Acetylcholine synthesis (Reactome: R-HSA-264642)
• Neurotransmitter release cycle (Reactome: R-HSA-112310)
• Cholinergic synapse (KEGG: hsa04725)
Protein Summary
Choline O-acetyltransferase (ChAT) is a 748-amino acid protein that catalyzes the formation of acetylcholine. It is localized in the cytoplasm of cholinergic nerve terminals. The enzyme exists as multiple isoforms due to alternative splicing. ChAT activity is essential for cholinergic neurotransmission, and its deficiency leads to presynaptic congenital myasthenic syndromes. The protein is also a marker for cholinergic neurons in development and disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHAT Knockout HEK293 Cell Line | EDJ-KQ3782 | Human | 1103 | Details Get a Quote |
| CHAT Knockout HeLa Cell Line | EDJ-KQ52886 | Human | 1103 | Details Get a Quote |
| CHAT Knockout A-549 Cell Line | EDJ-KQ61357 | Human | 1103 | Details Get a Quote |
| CHAT Knockout HCT 116 Cell Line | EDJ-KQ69851 | Human | 1103 | Details Get a Quote |
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