Parkinson disease 22, autosomal dominant

Summary

Parkinson disease 22, autosomal dominant (MONDO:0014742) is a disease caused by CHCHD2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CHCHD2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Parkinson disease 22, autosomal dominant
Mondo ID	MONDO:0014742
OMIM	616710
DOID	DOID:0080504
UMLS	C4225238
MedGen	907886
GARD	0025012
Is cancer (heuristic)	no

Also known as: CHCHD2 Parkinson disease · PARK22 · Parkinson disease 22, autosomal dominant · Parkinson disease 22, autosomal dominant; PARK22 · Parkinson disease caused by mutation in CHCHD2

Data availability: 5 ClinVar variants · 2 GenCC gene-disease records · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › basal ganglia disorder › parkinsonian disorder › Parkinson disease › late-onset Parkinson disease › Parkinson disease 22, autosomal dominant

Related subtypes (6): autosomal dominant Parkinson disease 1, autosomal dominant Parkinson disease 4, autosomal dominant Parkinson disease 8, autosomal recessive Parkinson disease 14, Parkinson disease 17, Parkinson disease 21

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
218882	NM_016139.4(CHCHD2):c.182C>T (p.Thr61Ile)	CHCHD2	Pathogenic	criteria provided, single submitter
218884	NM_016139.4(CHCHD2):c.300+5G>A	CHCHD2	Pathogenic	no assertion criteria provided
218883	NM_016139.4(CHCHD2):c.434G>A (p.Arg145Gln)	CHCHD2	Uncertain significance	criteria provided, single submitter
3594735	NM_016139.4(CHCHD2):c.156G>T (p.Gln52His)	CHCHD2	Uncertain significance	criteria provided, single submitter
948138	NM_016139.4(CHCHD2):c.101C>T (p.Pro34Leu)	CHCHD2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CHCHD2	Strong	Autosomal dominant	Parkinson disease 22, autosomal dominant	2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CHCHD2	HGNC:21645	ENSG00000106153	Q9Y6H1	Coiled-coil-helix-coiled-coil-helix domain-containing protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHCHD2	Coiled-coil-helix-coiled-coil-helix domain-containing protein 2	Transcription factor.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHCHD2	Other/Unknown	no		CHCH, CHCHD2/10-like

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHCHD2	212	ubiquitous	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHCHD2	2,212

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHCHD2	Q9Y6H1	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitochondrial protein import	1	167.9×	0.009	CHCHD2
Mitochondrial protein degradation	1	114.2×	0.009	CHCHD2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of generation of precursor metabolites and energy	1	5617.3×	7e-04	CHCHD2
positive regulation of mitochondrial ATP synthesis coupled electron transport	1	4213.0×	7e-04	CHCHD2
regulation of cellular response to hypoxia	1	2808.7×	7e-04	CHCHD2
cellular response to oxidative stress	1	154.6×	0.008	CHCHD2
mitochondrion organization	1	151.8×	0.008	CHCHD2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	CHCHD2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHCHD2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CHCHD2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CHCHD2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.