CHCHD2

coiled-coil-helix-coiled-coil-helix domain containing 2, the group of Coiled-coil-helix-coiled-coil-helix domain containing proteins

Basic information

Region (hg38): 7:56094567-56106479

Previous symbols: [ "C7orf17" ]

Links

ENSG00000106153

∙ NCBI:51142 ∙ OMIM:616244 ∙ HGNC:21645 ∙ Uniprot:Q9Y6H1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Parkinson disease 22, autosomal dominant (Strong), mode of inheritance: AD
Parkinson disease 22, autosomal dominant (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease 22, autosomal dominant	AD	Neurologic	Response to levodopa has been described	Neurologic	25662902

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHCHD2 gene.

not_provided (63 variants)
not_specified (17 variants)
Parkinson_disease_22,_autosomal_dominant (5 variants)
CHCHD2-related_disorder (3 variants)
Amelogenesis_imperfecta (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHCHD2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016139.4. 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				10 clinvar		10
missense	1 clinvar		51 clinvar	3 clinvar	1 clinvar	56
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	1	0	54	13	1

Highest pathogenic variant AF is 0.000008222738

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHCHD2	protein_coding	protein_coding	ENST00000395422	4	5008

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.73e-7	0.0725	125732	0	15	125747	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.121	88	91.3	0.964	0.00000484	950
Missense in Polyphen		14	20.725	0.67553		265
Synonymous	0.468	32	35.5	0.900	0.00000202	329
Loss of Function	-0.855	9	6.63	1.36	2.88e-7	67

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000793	0.0000791
Middle Eastern	0.000163	0.000163
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Transcription factor. Binds to the oxygen responsive element of COX4I2 and activates its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen) (PubMed:23303788). {ECO:0000269|PubMed:23303788}.;
Disease: DISEASE: Parkinson disease 22 (PARK22) [MIM:616710]: An autosomal dominant form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. {ECO:0000269|PubMed:25662902}. Note=The gene represented in this entry may be involved in disease pathogenesis.;
Pathway: Metabolism of proteins;Mitochondrial protein import (Consensus)

Recessive Scores

pRec: 0.100

Intolerance Scores

loftool: 0.686
rvis_EVS: -0.12
rvis_percentile_EVS: 44.54

Haploinsufficiency Scores

pHI: 0.0157
hipred: N
hipred_score: 0.255
ghis: 0.527

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.942

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Chchd2
Phenotype

Gene ontology

Biological process: mitochondrion organization;positive regulation of transcription by RNA polymerase II;regulation of cellular response to hypoxia
Cellular component: nucleus;mitochondrion;mitochondrial intermembrane space
Molecular function: protein binding;transcription factor binding;sequence-specific DNA binding