CHCHD10

coiled-coil-helix-coiled-coil-helix domain containing 10, the group of Coiled-coil-helix-coiled-coil-helix domain containing proteins

Basic information

Region (hg38): 22:23765834-23767972

Previous symbols: [ "C22orf16" ]

Links

ENSG00000250479 ∙ NCBI:400916 ∙ OMIM:615903 ∙ HGNC:15559 ∙ Uniprot:Q8WYQ3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant mitochondrial myopathy with exercise intolerance (Strong), mode of inheritance: AD
• lower motor neuron syndrome with late-adult onset (Strong), mode of inheritance: AD
• frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (Strong), mode of inheritance: AD
• amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
• frontotemporal dementia with motor neuron disease (Supportive), mode of inheritance: AD
• lower motor neuron syndrome with late-adult onset (Supportive), mode of inheritance: AD
• autosomal dominant mitochondrial myopathy with exercise intolerance (Supportive), mode of inheritance: AD
• frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (Strong), mode of inheritance: AD
• autosomal dominant mitochondrial myopathy with exercise intolerance (Limited), mode of inheritance: AD
• lower motor neuron syndrome with late-adult onset (Strong), mode of inheritance: AD
• mitochondrial disease (Definitive), mode of inheritance: AD
• frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, isolated mitochondrial, autosomal dominant	AD	Cardiovascular; Musculoskeletal	Individuals have been described with cardiomyopathy, and awareness may allow medical management; Heart transplant has been described; The condition may manifest with muscle weakness, and medical management (with steroids) has been reported as beneficial	Musculoskeletal; Neurologic	9324076; 21715705; 24934289; 25113787; 25193783; 25428574; 35700042

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHCHD10 gene.

• Frontotemporal_dementia_and/or_amyotrophic_lateral_sclerosis_2 (194 variants)
• Autosomal_dominant_mitochondrial_myopathy_with_exercise_intolerance (194 variants)
• Lower_motor_neuron_syndrome_with_late-adult_onset (193 variants)
• not_provided (43 variants)
• Inborn_genetic_diseases (35 variants)
• CHCHD10-related_disorder (26 variants)
• not_specified (10 variants)
• See_cases (1 variants)
• Amyotrophic_lateral_sclerosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHCHD10 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000213720.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	46		49
missense	3	3	101	11	1	119
nonsense		1	7			8
start loss			1			1
frameshift			5			5
splice donor/acceptor (+/-2bp)			2			2
Total	3	4	119	57	1

Highest pathogenic variant AF is 0.0029087

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHCHD10	protein_coding	protein_coding	ENST00000484558	4	2610

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000537	0.143	125343	0	22	125365	0.0000877

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.825	47	65.8	0.714	0.00000309	842
Missense in Polyphen		22	27.018	0.81429		322
Synonymous	-0.414	34	31.1	1.09	0.00000164	303
Loss of Function	-0.746	7	5.17	1.35	2.22e-7	59

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000928	0.000923
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000201	0.0000177
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in the maintenance of mitochondrial organization and mitochondrial cristae structure. {ECO:0000269|PubMed:24934289}.
• Disease: DISEASE: Spinal muscular atrophy, Jokela type (SMAJ) [MIM:615048]: An autosomal dominant, slowly progressive, lower motor neuron disease. SMAJ is characterized by adult-onset of muscle cramps and fasciculations affecting the proximal and distal muscles of the upper and lower limbs. The disorder results in weakness and mild muscle atrophy later in life. {ECO:0000269|PubMed:25428574}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, isolated mitochondrial, autosomal dominant (IMMD) [MIM:616209]: A mitochondrial myopathy presenting with severe exercise intolerance, progressive proximal weakness, and lactic acidemia. The disorder is slowly progressive, with later involvement of facial muscles, muscles of the upper limbs, and distal muscles. {ECO:0000269|PubMed:25193783}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Metabolism of proteins;Mitochondrial protein import (Consensus)

Haploinsufficiency Scores

• pHI: 0.222
• hipred: N
• hipred_score: 0.205
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0876

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chchd10
• 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); cellular phenotype

Gene ontology

• Biological process: oxidative phosphorylation;mitochondrion organization;stabilization of membrane potential;protein-containing complex disassembly;protein localization to nucleus;mitochondrial nucleoid organization;positive regulation of release of cytochrome c from mitochondria;maintenance of synapse structure;positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway;positive regulation of mitochondrial transcription;positive regulation of cristae formation;positive regulation of cytochrome-c oxidase activity
• Cellular component: nucleus;mitochondrion;mitochondrial intermembrane space;MICOS complex
• Molecular function: molecular_function;protein binding