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.

• Parkinson disease 22, autosomal dominant (1 variants)
• not provided (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8		8
missense	1		34	2		37
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			1	6	11	18
Total	1	0	37	16	11

Variants in CHCHD2

This is a list of pathogenic ClinVar variants found in the CHCHD2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-56101726-C-T			Benign (Mar 28, 2021)
7-56101805-T-TA		CHCHD2-related disorder	Benign (Apr 02, 2021)
7-56101870-A-T			Uncertain significance (Oct 01, 2022)
7-56101877-A-G			Likely benign (Jul 08, 2022)
7-56101980-G-GT			Likely benign (Apr 05, 2021)
7-56102754-A-G			Benign (May 11, 2021)
7-56102850-T-C			Likely benign (Dec 02, 2023)
7-56102853-G-A			Benign (Nov 11, 2023)
7-56102878-C-T		Parkinson disease 22, autosomal dominant	Uncertain significance (Sep 08, 2023)
7-56102894-C-T		Amelogenesis imperfecta	Benign (Apr 04, 2019)
7-56102907-C-A			Uncertain significance (Sep 24, 2023)
7-56102913-G-A		CHCHD2-related disorder	Likely benign (Aug 12, 2021)
7-56102918-T-G		not specified	Uncertain significance (Mar 20, 2024)
7-56102921-T-C		not specified	Uncertain significance (Sep 16, 2021)
7-56102936-G-A			Uncertain significance (Nov 19, 2023)
7-56102939-C-T			Uncertain significance (Jun 13, 2022)
7-56102951-A-C			Uncertain significance (Dec 27, 2021)
7-56102953-T-C			Uncertain significance (Jun 27, 2022)
7-56102992-G-C			Uncertain significance (Feb 08, 2018)
7-56103000-T-TC			Uncertain significance (Jul 07, 2023)
7-56104067-A-C			Benign (Apr 05, 2021)
7-56104219-T-G			Likely benign (Jul 23, 2021)
7-56104221-C-T		Parkinson disease 22, autosomal dominant	Pathogenic (Jul 01, 2015)
7-56104230-T-C			Uncertain significance (Jan 06, 2024)
7-56104233-G-A			Uncertain significance (Dec 23, 2019)

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

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