Parkinson disease 12

Summary

Parkinson disease 12 (MONDO:0010360) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Parkinson disease 12
Mondo ID	MONDO:0010360
MeSH	C564486
OMIM	300557
UMLS	C1845165
MedGen	337173
GARD	0018604
Is cancer (heuristic)	no

Also known as: PARK12 · Parkinson disease 12

Data availability: 2 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 › young-onset Parkinson disease › Parkinson disease 12

Related subtypes (8): juvenile-onset Parkinson disease, autosomal recessive juvenile Parkinson disease 2, Parkinson disease 3, autosomal dominant, autosomal recessive early-onset Parkinson disease 6, autosomal recessive early-onset Parkinson disease 7, Parkinson disease 10, early-onset Parkinson disease 20, autosomal recessive early-onset Parkinson disease 23

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

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
7050	NM_004562.3(PRKN):c.823C>T (p.Arg275Trp)	PRKN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
283504	NM_004562.3(PRKN):c.1310C>T (p.Pro437Leu)	PRKN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRKN	Orphanet:2828	Young-onset Parkinson disease

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
PRKN	HGNC:8607	ENSG00000185345	O60260	E3 ubiquitin-protein ligase parkin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRKN	E3 ubiquitin-protein ligase parkin	Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRKN	Transcription factor	no	2.3.2.27	Ubiquitin-like_dom, IBR_dom, Parkin

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
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRKN	174	ubiquitous	marker	sural nerve, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKN	10,281

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRKN	O60260	21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Josephin domain DUBs	1	951.7×	0.006	PRKN
Regulation of necroptotic cell death	1	439.2×	0.006	PRKN
PINK1-PRKN Mediated Mitophagy	1	356.9×	0.006	PRKN
Aggrephagy	1	248.3×	0.006	PRKN
Amyloid fiber formation	1	102.9×	0.012	PRKN
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.027	PRKN

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
positive regulation of neurotransmitter uptake	1	16852.0×	0.002	PRKN
negative regulation of spontaneous neurotransmitter secretion	1	16852.0×	0.002	PRKN
positive regulation of protein linear polyubiquitination	1	8426.0×	0.002	PRKN
negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway	1	8426.0×	0.002	PRKN
response to curcumin	1	8426.0×	0.002	PRKN
positive regulation of retrograde transport, endosome to Golgi	1	8426.0×	0.002	PRKN
negative regulation of intralumenal vesicle formation	1	8426.0×	0.002	PRKN
negative regulation of glucokinase activity	1	5617.3×	0.002	PRKN
mitochondrion to lysosome vesicle-mediated transport	1	5617.3×	0.002	PRKN
regulation protein catabolic process at presynapse	1	5617.3×	0.002	PRKN
regulation of synaptic vesicle transport	1	5617.3×	0.002	PRKN
cellular response to hydrogen sulfide	1	5617.3×	0.002	PRKN
regulation of lipid transport	1	4213.0×	0.002	PRKN
negative regulation of exosomal secretion	1	4213.0×	0.002	PRKN
cellular response to L-glutamine	1	4213.0×	0.002	PRKN
positive regulation of mitochondrial fusion	1	3370.4×	0.002	PRKN
type 2 mitophagy	1	3370.4×	0.002	PRKN
negative regulation of mitochondrial fission	1	3370.4×	0.002	PRKN
negative regulation of actin filament bundle assembly	1	2808.7×	0.002	PRKN
aggresome assembly	1	2808.7×	0.002	PRKN
free ubiquitin chain polymerization	1	2407.4×	0.002	PRKN
cellular response to manganese ion	1	2407.4×	0.002	PRKN
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	2407.4×	0.002	PRKN
cellular response to dopamine	1	2407.4×	0.002	PRKN
negative regulation of mitochondrial fusion	1	2106.5×	0.002	PRKN
positive regulation of mitochondrial membrane potential	1	2106.5×	0.002	PRKN
obsolete regulation of protein targeting to mitochondrion	1	2106.5×	0.002	PRKN
dopamine uptake involved in synaptic transmission	1	1872.4×	0.002	PRKN
regulation of necroptotic process	1	1872.4×	0.002	PRKN
regulation of dopamine metabolic process	1	1685.2×	0.002	PRKN

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
PRKN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRKN	2.3.2.27, 2.3.2.31	RING-type E3 ubiquitin transferase, RBR-type E3 ubiquitin transferase

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	PRKN

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)
PRKN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.