Parkinsonism with polyneuropathy

disease

On this page

Summary

Parkinsonism with polyneuropathy (MONDO:0036193) is a disease with 1 cohort gene.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Cohort genes: 1
ClinVar variants: 12

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	parkinsonism with polyneuropathy
Mondo ID	MONDO:0036193
OMIM	619279
Orphanet	611237
UMLS	C5543299
MedGen	1783451
GARD	0018028
Is cancer (heuristic)	no

Data availability: 12 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.

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 › parkinsonism with polyneuropathy

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

12 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1064665	NM_003365.3(UQCRC1):c.[70-1G>A;73dup]		Pathogenic	no assertion criteria provided
1064663	NM_003365.3(UQCRC1):c.941A>C (p.Tyr314Ser)	UQCRC1	Pathogenic	no assertion criteria provided
1064664	NM_003365.3(UQCRC1):c.931A>C (p.Ile311Leu)	UQCRC1	Pathogenic	no assertion criteria provided
2506569	NM_003365.3(UQCRC1):c.359T>C (p.Leu120Pro)	UQCRC1	Likely pathogenic	no assertion criteria provided
2469062	NM_003365.3(UQCRC1):c.83G>T (p.Arg28Leu)	LOC129936713	Uncertain significance	criteria provided, multiple submitters, no conflicts
4076294	NM_003365.3(UQCRC1):c.65G>T (p.Arg22Leu)	LOC129936714	Uncertain significance	criteria provided, single submitter
2441752	NM_003365.3(UQCRC1):c.279G>C (p.Leu93Phe)	UQCRC1	Uncertain significance	criteria provided, single submitter
3024091	NM_003365.3(UQCRC1):c.964G>A (p.Val322Met)	UQCRC1	Uncertain significance	criteria provided, single submitter
3242192	NM_003365.3(UQCRC1):c.736G>A (p.Ala246Thr)	UQCRC1	Uncertain significance	criteria provided, single submitter
3366876	NM_003365.3(UQCRC1):c.239G>A (p.Arg80His)	UQCRC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3898003	NM_003365.3(UQCRC1):c.91_108dup (p.Ala36_Thr37insAlaLeuArgSerThrAla)	UQCRC1	Uncertain significance	criteria provided, single submitter
4086146	NM_003365.3(UQCRC1):c.953A>C (p.Tyr318Ser)	UQCRC1	Uncertain significance	criteria provided, single submitter

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
UQCRC1	Limited	Autosomal dominant	parkinsonism with polyneuropathy	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
UQCRC1	HGNC:12585	ENSG00000010256	P31930	Cytochrome b-c1 complex subunit 1, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UQCRC1	Cytochrome b-c1 complex subunit 1, mitochondrial	Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UQCRC1	Protease	yes		Peptidase_M16_C, Metalloenz_LuxS/M16, Pept_M16_N

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
apex of heart	1
heart left ventricle	1
heart right ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UQCRC1	296	ubiquitous	marker	apex of heart, heart left ventricle, heart right ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UQCRC1	4,109

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UQCRC1	P31930	5

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
Complex III assembly	1	439.2×	0.005	UQCRC1
Respiratory electron transport	1	95.2×	0.011	UQCRC1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to alkaloid	1	1532.0×	0.002	UQCRC1
oxidative phosphorylation	1	1404.3×	0.002	UQCRC1
mitochondrial electron transport, ubiquinol to cytochrome c	1	1296.3×	0.002	UQCRC1
cellular respiration	1	432.1×	0.003	UQCRC1
response to activity	1	324.1×	0.004	UQCRC1
aerobic respiration	1	247.8×	0.004	UQCRC1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UQCRC1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
UQCRC1	1	Binding:1

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	1	UQCRC1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
UQCRC1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: UQCRC1