CHAT

Chr 10AR

choline O-acetyltransferase

Also known as: CHOACTASE, CMS1A, CMS1A2, CMS6

NCBI Gene: 1103ENSG00000070748UniProt: P28329

This gene encodes choline acetyltransferase, the enzyme that catalyzes acetylcholine biosynthesis in cholinergic neurons. Mutations cause congenital myasthenic syndrome type 6 with episodic apnea through autosomal recessive inheritance. The pathogenic mechanism involves presynaptic dysfunction due to impaired acetylcholine synthesis at the neuromuscular junction.

Summary from RefSeq, OMIM, Mechanism
Research Assistant →

Primary Disease Associations & Inheritance

Myasthenic syndrome, congenital, 6, presynapticMIM #254210
AR
6
Active trials
1067
Pubs (1 yr)
46
P/LP submissions
10%
P/LP missense
0.88
LOEUF
DN
Mechanism· predicted
Clinical Summary— CHAT
🧬
Gene-Disease Validity (ClinGen)
congenital myasthenic syndrome 6 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 126 VUS of 400 total submissions
💊
Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — CHAT
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.000
Z-score 2.11
OE 0.62 (0.44–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.30Z-score
OE missense 0.96 (0.89–1.04)
414 obs / 431.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.44–0.88)
0≤0.351.4
Missense OE0.96 (0.89–1.04)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 22 / 35.6Missense obs/exp: 414 / 431.3Syn Z: -1.44
DN
0.6939th %ile
GOF
0.5464th %ile
LOF
0.3066th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic25
VUS126
Likely Benign230
Benign2
Conflicting1
16
Pathogenic
25
Likely Pathogenic
126
VUS
230
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
10
0
16
Likely Pathogenic
16
4
5
0
25
VUS
2
114
6
4
126
Likely Benign
0
5
79
146
230
Benign
0
1
1
0
2
Conflicting
—1
Total24124101150400

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CHAT · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
CTNNB1 Neurodevelopmental Syndrome

Gene Replacement Therapy for Treatment of Paediatric Patients With CTNNB1 Neurodevelopmental Syndrome

RECRUITING
NCT07270549Phase PHASE1, PHASE2CTNNB1 FoundationStarted 2025-11-01
Urbagen gene addition therapySirolimusMethylprednisolone (Corticosteroid)
Autism

A Strength-Based Employment Maintenance Program for Individuals on the Autism Spectrum

RECRUITING
NCT06255925Phase NAKessler FoundationStarted 2023-01-01
KF-STRIDE® Into Work!
Open Angle Glaucoma (OAG)NAION( Non-arteritic Anterior Ischemic Optic Neuropathy)

Evaluating ER-100 for Safety in People With Glaucoma or Non-Arteritic Anterior Ischemic Optic Neuropathy (Optic Nerve Conditions)

RECRUITING
NCT07290244Phase PHASE1Life Biosciences Inc.Started 2026-03-02
ER-100 epigenetic therapy
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10
Gene Mutation-Related CancerGenetic Predisposition

Genetic Information Assistant in Telegenetics

RECRUITING
NCT06089421Phase NAUniversity of VirginiaStarted 2025-04-01
Genetic Information AssistantTelegenetics with UVA genetic counselor
CTNNB1 Neurodevelopmental Syndrome

CTNNB1 Neurodevelopmental Syndrome - Natural History Study

RECRUITING
NCT07167732University Medical Centre LjubljanaStarted 2024-06-14
A General Medical and Neurological AssessmentWorld Health Organisation (WHO) Motor MilestonesBurke-Fahn-Marsden Dystonia Rating Scale
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Appeler un chat un chat
Ranque B·Rev Med Interne
2021
Let's chat.
Hancocks Obe S·Br Dent J
2023
To chat or bot to chat: Ethical issues with using chatbots in mental health
Coghlan S et al.·Digit Health
2023
Let's chat.
·Nat Methods
2021
A Chat About Peer Review.
Smith JR et al.·Clin Exp Ophthalmol
2025Review
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients