CHAT

choline O-acetyltransferase

Basic information

Region (hg38): 10:49609095-49667942

Links

ENSG00000070748

∙ NCBI:1103 ∙ OMIM:118490 ∙ HGNC:1912 ∙ Uniprot:P28329 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

congenital myasthenic syndrome 6 (Strong), mode of inheritance: AR
congenital myasthenic syndrome 6 (Strong), mode of inheritance: AR
congenital myasthenic syndrome 6 (Strong), mode of inheritance: AR
presynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital 6, presynaptic	AR	Musculoskeletal; Neurologic; Pharmacogenomic	Prophylactic medications (anticholinesterase therapy) in order to prevent apneic episodes/sudden respiratory insufficiency secondary to fever/infections can be effective; Most individuals benefit from AChE inhibitors and/or potassium channel blockers , though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes. Some individuals may be treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency; In severely affected individuals, diagnosis may be difficult due to the presence of failure to thrive, apneic episodes, and aspiration; Certain medications affecting neuromuscular transmission should be avoided	Musculoskeletal; Neurologic	11172068; 12756141; 20301347

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHAT gene.

Familial_infantile_myasthenia (874 variants)
not_provided (116 variants)
Inborn_genetic_diseases (101 variants)
not_specified (47 variants)
CHAT-related_disorder (18 variants)
Congenital_myasthenic_syndrome (15 variants)
Progressive_muscle_weakness (2 variants)
Apnea,_central_sleep (2 variants)
Gastroesophageal_reflux (2 variants)
Progressive_ptosis (2 variants)
Respiratory_insufficiency (2 variants)
Febrile_seizure_(within_the_age_range_of_3_months_to_6_years) (2 variants)
Congenital_myasthenic_syndrome_4C (2 variants)
Decreased_activity_of_the_pyruvate_dehydrogenase_complex (2 variants)
Pes_planus (2 variants)
External_ophthalmoplegia (2 variants)
Aspiration_pneumonia (2 variants)
Lactic_acidosis (2 variants)
See_cases (2 variants)
Rigidity (1 variants)
Sleep_abnormality (1 variants)
Gait_disturbance (1 variants)
Muscle_weakness (1 variants)
Abnormality_of_the_musculature (1 variants)
Gait_ataxia (1 variants)
Gait_imbalance (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHAT gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020549.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	293 clinvar	9 clinvar	304
missense	6 clinvar	26 clinvar	286 clinvar	47 clinvar	5 clinvar	370
nonsense	12 clinvar	15 clinvar	1 clinvar			28
start loss						0
frameshift	16 clinvar	16 clinvar	9 clinvar			41
splice donor/acceptor (+/-2bp)		15 clinvar	2 clinvar			17
Total	34	72	300	340	14

Highest pathogenic variant AF is 0.000080000995

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHAT	protein_coding	protein_coding	ENST00000337653	15	84785

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.63e-11	0.952	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.296	414	431	0.960	0.0000264	4825
Missense in Polyphen		128	162.26	0.78887		1864
Synonymous	-1.44	209	184	1.13	0.0000120	1522
Loss of Function	2.11	22	35.6	0.618	0.00000189	380

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000334	0.000333
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000466	0.0000462
European (Non-Finnish)	0.000221	0.000220
Middle Eastern	0.000109	0.000109
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses. {ECO:0000269|PubMed:17144655}.;
Disease: DISEASE: Myasthenic syndrome, congenital, 6, presynaptic (CMS6) [MIM:254210]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS6 affected individuals have myasthenic symptoms since birth or early infancy, negative tests for anti-AChR antibodies, and abrupt episodic crises with increased weakness, bulbar paralysis, and apnea precipitated by undue exertion, fever, or excitement. CMS6 inheritance is autosomal recessive. {ECO:0000269|PubMed:11172068, ECO:0000269|PubMed:12756141}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Glycerophospholipid metabolism - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Sympathetic Nerve Pathway (Pre- and Post- Ganglionic Junction);Phospholipid Biosynthesis;Acetylcholine Synthesis;Biogenic Amine Synthesis;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Metabolism of lipids;Metabolism;Synthesis of PC;Neuronal System;Glycerophospholipid metabolism;Acetylcholine Neurotransmitter Release Cycle;Neurotransmitter release cycle;Transmission across Chemical Synapses;Glycerophospholipid biosynthesis;Phospholipid metabolism (Consensus)

Recessive Scores

pRec: 0.535

Intolerance Scores

loftool: 0.00620
rvis_EVS: 1.63
rvis_percentile_EVS: 96.05

Haploinsufficiency Scores

pHI: 0.0790
hipred: Y
hipred_score: 0.561
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.876

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Chat
Phenotype: muscle phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; vision/eye phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: chata
Affected structure: motor neuron
Phenotype tag: abnormal
Phenotype quality: decreased length

Gene ontology

Biological process: phosphatidylcholine biosynthetic process;neurotransmitter secretion;neuromuscular synaptic transmission;acetylcholine biosynthetic process
Cellular component: nucleus;cytoplasm;cytosol;neuron projection;presynapse
Molecular function: choline O-acetyltransferase activity