HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CHAT
choline O-acetyltransferase
Chromosome 10 Β· 10q11.23
NCBI Gene: 1103Ensembl: ENSG00000070748.19HGNC: HGNC:1912UniProt: P28329
110PubMed Papers
21Diseases
0Drugs
108Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
choline O-acetyltransferase activityneuromuscular synaptic transmissionacetylcholine biosynthetic processcytoplasmCongenital myasthenic syndromesPresynaptic congenital myasthenic syndromescongenital myasthenic syndromeRespiratory insufficiency
✦AI Summary

CHAT (choline O-acetyltransferase) is the biosynthetic enzyme catalyzing the synthesis of acetylcholine (ACh) from acetyl-CoA and choline at cholinergic synapses 1. This enzyme is essential for neurotransmission in both central and peripheral nervous systems, with particularly high expression in brainstem regions like the dorsal motor nucleus of the vagus 2. In the myenteric plexus, ChAT-positive neurons comprise 38-52% of neurons depending on intestinal region, often co-existing or co-absent with nitric oxide synthase in distinct neuronal populations 3. ChAT dysfunction is associated with congenital myasthenic syndrome type 6, a presynaptic disorder 4. Clinically, ChAT has emerged as a therapeutic target in Alzheimer's disease, where cholinergic system degeneration contributes to cognitive decline 4. Neural stem cells overexpressing ChAT improved learning and memory in AD model mice by increasing acetylcholine levels, reducing amyloid-Ξ² deposits, and promoting neuroregeneration 4. Additionally, CHAT genetic variants (rs1258267) show population-specific associations with primary angle-closure glaucoma risk, with decreased risk in Asian populations 5. Altered cholinergic regulation involving ChAT has also been implicated in sudden infant death syndrome neuropathology, with reduced ChAT expression observed in vulnerable brainstem regions 2.

Sources cited
1
CHAT is the biosynthetic enzyme for acetylcholine in CNS and PNS
PMID: 1339386
2
ChAT expression in dorsal motor nucleus of vagus and alterations in SIDS; relationship to cigarette smoke exposure
PMID: 37813167
3
ChAT-positive neurons comprise 38-52% of myenteric neurons with variable co-expression patterns
PMID: 19711100
4
ChAT overexpression in neural stem cells improves cognitive function and reduces amyloid-Ξ² in AD models
PMID: 32486466
5
CHAT rs1258267 polymorphism associated with decreased primary angle-closure glaucoma risk in Asians
PMID: 36727317
Disease Associationsβ“˜21
Congenital myasthenic syndromesOpen Targets
0.80Strong
Presynaptic congenital myasthenic syndromesOpen Targets
0.68Moderate
congenital myasthenic syndromeOpen Targets
0.54Moderate
Respiratory insufficiencyOpen Targets
0.43Moderate
lactic acidosisOpen Targets
0.43Moderate
central sleep apnea syndromeOpen Targets
0.43Moderate
Decreased activity of the pyruvate dehydrogenase complexOpen Targets
0.43Moderate
External ophthalmoplegiaOpen Targets
0.43Moderate
Febrile seizure (within the age range of 3 months to 6 years)Open Targets
0.43Moderate
flatfootOpen Targets
0.43Moderate
gastroesophageal reflux diseaseOpen Targets
0.43Moderate
Pneumonia, AspirationOpen Targets
0.43Moderate
Progressive muscle weaknessOpen Targets
0.43Moderate
Progressive ptosisOpen Targets
0.43Moderate
presynaptic congenital myasthenic syndromeOpen Targets
0.37Weak
Abnormality of the musculatureOpen Targets
0.27Weak
ovarian neoplasmOpen Targets
0.24Weak
genetic disorderOpen Targets
0.20Weak
Gait disturbanceOpen Targets
0.12Weak
RigidityOpen Targets
0.12Weak
Myasthenic syndrome, congenital, 6, presynapticUniProt
Pathogenic Variants108
NM_020549.5(CHAT):c.1669G>A (p.Ala557Thr)Pathogenic
Familial infantile myasthenia|not provided|Congenital myasthenic syndrome
β˜…β˜…β˜†β˜†2026β†’ Residue 557
NM_020549.5(CHAT):c.605T>G (p.Met202Arg)Pathogenic
not provided|Familial infantile myasthenia|Congenital myasthenic syndrome
β˜…β˜…β˜†β˜†2026β†’ Residue 202
NM_020549.5(CHAT):c.472C>T (p.Gln158Ter)Pathogenic
Familial infantile myasthenia
β˜…β˜…β˜†β˜†2026β†’ Residue 158
NM_020549.5(CHAT):c.1231G>T (p.Gly411Ter)Pathogenic
Familial infantile myasthenia
β˜…β˜…β˜†β˜†2026β†’ Residue 411
NM_020549.5(CHAT):c.1061C>T (p.Thr354Met)Pathogenic
11 conditions|Familial infantile myasthenia
β˜…β˜…β˜†β˜†2025β†’ Residue 354
NM_020549.5(CHAT):c.1387C>T (p.Gln463Ter)Pathogenic
Familial infantile myasthenia
β˜…β˜…β˜†β˜†2025β†’ Residue 463
NM_020549.5(CHAT):c.1249G>A (p.Gly417Arg)Likely pathogenic
Familial infantile myasthenia|Congenital myasthenic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 417
NM_020549.5(CHAT):c.1321G>A (p.Glu441Lys)Pathogenic
Familial infantile myasthenia|Congenital myasthenic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 441
NM_020549.5(CHAT):c.1492T>C (p.Ser498Pro)Likely pathogenic
Familial infantile myasthenia|Congenital myasthenic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 498
NM_020549.5(CHAT):c.982del (p.Asp328fs)Pathogenic
Congenital myasthenic syndrome 4C|Familial infantile myasthenia
β˜…β˜…β˜†β˜†2025β†’ Residue 328
NM_020549.5(CHAT):c.1642C>T (p.Arg548Ter)Pathogenic
Familial infantile myasthenia|Congenital myasthenic syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 548
NM_020549.5(CHAT):c.1663G>T (p.Glu555Ter)Pathogenic
Familial infantile myasthenia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 555
NM_020549.5(CHAT):c.1679G>A (p.Arg560His)Pathogenic
Familial infantile myasthenia|not provided|Congenital myasthenic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 560
NM_020549.5(CHAT):c.1681C>T (p.Arg561Ter)Pathogenic
Familial infantile myasthenia
β˜…β˜…β˜†β˜†2025β†’ Residue 561
NM_020549.5(CHAT):c.1840-9A>GPathogenic
not provided|Familial infantile myasthenia|Congenital myasthenic syndrome
β˜…β˜…β˜†β˜†2025
NM_020549.5(CHAT):c.620G>A (p.Arg207His)Pathogenic
Familial infantile myasthenia|not provided|Congenital myasthenic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 207
NM_020549.5(CHAT):c.1715C>G (p.Ser572Trp)Pathogenic
Familial infantile myasthenia|Congenital myasthenic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 572
NM_020549.5(CHAT):c.1687C>T (p.Gln563Ter)Pathogenic
Familial infantile myasthenia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 563
NM_020549.5(CHAT):c.1359_1363del (p.Cys453_Glu455delinsTer)Pathogenic
Familial infantile myasthenia
β˜…β˜…β˜†β˜†2025β†’ Residue 453
NM_020549.5(CHAT):c.1408C>T (p.Arg470Ter)Pathogenic
Familial infantile myasthenia
β˜…β˜…β˜†β˜†2024β†’ Residue 470
View on ClinVar β†—
Related Genes
GAD1Protein interaction97%GPCPD1Protein interaction95%TAC1Protein interaction95%CHRNA9Protein interaction93%ACHEProtein interaction92%CHKAProtein interaction92%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
0%
Ovary
0%
Lung
0%
Heart
0%
Brain
0%
Gene Interaction Network
Click a node to explore
CHATGAD1GPCPD1TAC1CHRNA9ACHECHKA
PROTEIN STRUCTURE
Preparing viewer…
PDB9F85 Β· 1.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.97LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.79 [0.64–0.97]
RankingsWhere CHAT stands among ~20K protein-coding genes
  • #4,310of 20,598
    Most Researched110 Β· top quartile
  • #722of 5,498
    Most Pathogenic Variants108 Β· top quartile
  • #9,248of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedCHAT
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Cri-du-chat.
PMID: 19466618
Dev Neurorehabil Β· 2009
1.00
2
Human Neural Stem Cells Encoding ChAT Gene Restore Cognitive Function via Acetylcholine Synthesis, AΞ² Elimination, and Neuroregeneration in APPswe/PS1dE9 Mice.
PMID: 32486466
Int J Mol Sci Β· 2020
0.90
3
Choline-acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the human infant dorsal motor nucleus of the Vagus (DMNV), and alterations according to sudden infant death syndrome (SIDS) category.
PMID: 37813167
Neurobiol Dis Β· 2023
0.80
4
ChAT and NOS in human myenteric neurons: co-existence and co-absence.
PMID: 19711100
Cell Tissue Res Β· 2009
0.70
5
A Human, Organization, and Technology Perspective on Patients' Experiences of a Chat-Based and Automated Medical History-Taking Service in Primary Health Care: Interview Study Among Primary Care Patients.
PMID: 34661544
J Med Internet Res Β· 2021
0.60