Parkinson disease, mitochondrial

Summary

Parkinson disease, mitochondrial (MONDO:0010796) is a disease with 5 cohort genes and 1 clinical trial.

At a glance

• Cohort genes: 5
• ClinVar variants: 5
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Parkinson disease, mitochondrial
Mondo ID	MONDO:0010796
MeSH	C564015
OMIM	556500
UMLS	C1838867
MedGen	333199
Is cancer (heuristic)	no

Also known as: Parkinson disease, mitochondrial

Data availability: 5 ClinVar variants.

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 › Parkinson disease, mitochondrial

Related subtypes (5): late-onset Parkinson disease, parkinsonian-pyramidal syndrome, Parkinson disease 16, young-onset Parkinson disease, Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development

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:

2 benign, 1 risk factor, 1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
9579	NC_012920.1(MT-TK):m.8344A>G	MT-TK	Pathogenic	reviewed by expert panel
18181	NM_000669.5(ADH1C):c.232G>T (p.Gly78Ter)	ADH1C	risk factor	no assertion criteria provided
9559	NC_012920.1(MT-TT):m.15950G>A	MT-TT	Uncertain significance	criteria provided, single submitter
9571	NC_012920.1(MT-TP):m.15965A>G	MT-TP	Benign	criteria provided, single submitter
9054	NM_021074.5(NDUFV2):c.86T>C (p.Val29Ala)	NDUFV2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MT-TK	Orphanet:1349	Mitochondrial DNA-related cardiomyopathy and hearing loss
MT-TK	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-TK	Orphanet:551	MERRF
MT-TP	Orphanet:551	MERRF
MT-TT	Orphanet:254857	Lethal infantile mitochondrial myopathy
NDUFV2	Orphanet:139447	Progressive cavitating leukoencephalopathy
NDUFV2	Orphanet:2609	Isolated complex I deficiency

Cohort genes → proteins

5 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADH1C	HGNC:251	ENSG00000248144	P00326	Alcohol dehydrogenase 1C	clinvar
MT-TK	HGNC:7489	ENSG00000210156		mitochondrially encoded tRNA-Lys (AAA/G)	clinvar
MT-TP	HGNC:7494	ENSG00000210196		mitochondrially encoded tRNA-Pro (CCN)	clinvar
MT-TT	HGNC:7499	ENSG00000210195		mitochondrially encoded tRNA-Thr (ACN)	clinvar
NDUFV2	HGNC:7717	ENSG00000178127	P19404	NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADH1C	Alcohol dehydrogenase 1C	Alcohol dehydrogenase.
NDUFV2	NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial	Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.2

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
Enzyme (other)	1	2.4×	0.353
Other/Unknown	4	1.4×	0.353

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADH1C	Enzyme (other)	yes	1.1.1.1	ADH_Zn_CS, GroES-like_sf, ADH-like_C
MT-TK	Other/Unknown	no
MT-TP	Other/Unknown	no
MT-TT	Other/Unknown	no
NDUFV2	Other/Unknown	no		NuoE-like, Thioredoxin-like_sf, NuoE_N

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skeletal muscle tissue	2
sural nerve	2
jejunal mucosa	1
mucosa of transverse colon	1
nasal cavity epithelium	1
caudate nucleus	1
mucosa of stomach	1
rectum	1
smooth muscle tissue	1
substantia nigra	1
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADH1C	199	tissue_specific	marker	mucosa of transverse colon, jejunal mucosa, nasal cavity epithelium
MT-TK	118		yes	sural nerve, skeletal muscle tissue, caudate nucleus
MT-TP	118	broad	marker	rectum, smooth muscle tissue, mucosa of stomach
MT-TT	118	broad	yes	skeletal muscle tissue, sural nerve, substantia nigra
NDUFV2	137	ubiquitous	marker	apex of heart, gastrocnemius, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDUFV2	3,918
ADH1C	1,955
MT-TK	0
MT-TP	0
MT-TT	0

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDUFV2	P19404	7
ADH1C	P00326	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 5 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Ethanol oxidation	1	475.8×	0.018	ADH1C
RA biosynthesis pathway	1	237.9×	0.018	ADH1C
Signaling by Retinoic Acid	1	203.9×	0.018	ADH1C
Phase I - Functionalization of compounds	1	109.8×	0.020	ADH1C
Metabolism	2	11.6×	0.020	ADH1C, NDUFV2
Complex I biogenesis	1	82.8×	0.022	NDUFV2
Biological oxidations	1	64.9×	0.024	ADH1C
Signaling by Nuclear Receptors	1	51.0×	0.025	ADH1C
Respiratory electron transport	1	47.6×	0.025	NDUFV2
Aerobic respiration and respiratory electron transport	1	44.3×	0.025	NDUFV2
Signal Transduction	1	5.1×	0.187	ADH1C

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cardiac muscle tissue development	1	443.5×	0.009	NDUFV2
retinoic acid metabolic process	1	401.2×	0.009	ADH1C
retinol metabolic process	1	247.8×	0.009	ADH1C
mitochondrial electron transport, NADH to ubiquinone	1	179.3×	0.009	NDUFV2
proton motive force-driven mitochondrial ATP synthesis	1	131.7×	0.009	NDUFV2
aerobic respiration	1	123.9×	0.009	NDUFV2
nervous system development	1	23.0×	0.043	NDUFV2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 2 of 5 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADH1C	0	0
MT-TK	0	0
MT-TP	0	0
MT-TT	0	0
NDUFV2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ADH1C	12	Binding:12
NDUFV2	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADH1C	1.1.1.1	alcohol dehydrogenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	1	ADH1C
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	MT-TK, MT-TP, MT-TT, NDUFV2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ADH1C	12	—
MT-TK	0	—
MT-TP	0	—
MT-TT	0	—
NDUFV2	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04300608	Not specified	UNKNOWN	Measures of Mitochondria Dysfunction in PD