autosomal recessive juvenile Parkinson disease 2

Summary

autosomal recessive juvenile Parkinson disease 2 (MONDO:0010820) is a disease caused by PRKN (GenCC Definitive), with 3 cohort genes and 3 clinical trials.

At a glance

• Causal gene: PRKN (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 204
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive juvenile Parkinson disease 2
Mondo ID	MONDO:0010820
OMIM	600116
DOID	DOID:0060368
UMLS	C1868675
MedGen	401500
GARD	0009642
Is cancer (heuristic)	no

Also known as: autosomal recessive juvenile Parkinson disease · autosomal recessive juvenile Parkinson disease 2 · autosomal recessive juvenile Parkinson disease type 2 · JP · juvenile parkinsonism · PARK2 · Parkinson disease 2 · Parkinson disease 2, autosomal recessive juvenile · Parkinson disease autosomal recessive, early onset · Parkinson disease, juvenile, type 2 · Parkinsonism, early onset, with diurnal fluctuation · PDJ · PRKN young-onset Parkinson disease · young-onset Parkinson disease caused by mutation in PRKN

Data availability: 204 ClinVar variants · 2 GenCC gene-disease records · 99 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 › young-onset Parkinson disease › autosomal recessive juvenile Parkinson disease 2

Related subtypes (8): juvenile-onset Parkinson disease, Parkinson disease 12, 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

204 retrieved; paginated sample, class counts are floors:

80 uncertain significance, 48 pathogenic, 18 conflicting classifications of pathogenicity, 14 likely benign, 12 benign, 11 pathogenic/likely pathogenic, 11 likely pathogenic, 10 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
417459	NC_000006.12:g.(?162201131)(162443473_?)del	LNCR-SMAL	Pathogenic	criteria provided, single submitter
468579	NC_000006.12:g.(?162201111)(162262785_?)del	LNCR-SMAL	Pathogenic	criteria provided, single submitter
7034	NM_004562.2(PRKN):c.172-?_871+?del	LNCR-SMAL	Pathogenic	no assertion criteria provided
1172527	NM_004562.3(PRKN):c.491del (p.Val164fs)	LOC126859871	Pathogenic	no assertion criteria provided
468578	NC_000006.12:g.(?162201111)(162201272_?)del	LOC126859871	Pathogenic	criteria provided, single submitter
7035	NM_004562.2(PRKN):c.413-?_534+?del	LOC126859871	Pathogenic	no assertion criteria provided
7043	NM_004562.3(PRKN):c.483A>T (p.Lys161Asn)	LOC126859871	Pathogenic	no assertion criteria provided
1705255	NC_000006.11:g.(162683798_162864341)_(162864506_163148693)dup	PACRG	Pathogenic	criteria provided, single submitter
3768468	NC_000006.11:g.(162683798_162864341)_(162864506_163148693)del	PACRG	Pathogenic	criteria provided, single submitter
7053	NM_004562.3(PRKN):c.7+1G>T	PACRG	Pathogenic	criteria provided, single submitter
805243	NM_004562.3(PRKN):c.2T>C (p.Met1Thr)	PACRG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1027679	NM_004562.3(PRKN):c.618+7842_618+7934inv	PRKN	Pathogenic	criteria provided, single submitter
1334464	NC_000006.11:g.(?162474785)(162475494_?)del	PRKN	Pathogenic	no assertion criteria provided
1335654	NM_004562.3(PRKN):c.73C>T (p.Gln25Ter)	PRKN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456905	NM_004562.3(PRKN):c.971del (p.Val324fs)	PRKN	Pathogenic	criteria provided, single submitter
1687195	NM_004562.3(PRKN):c.1083+1del	PRKN	Pathogenic	criteria provided, multiple submitters, no conflicts
3385385	NM_004562.3:c.(171+1_172-1)(534+1_535-1)del	PRKN	Pathogenic	criteria provided, single submitter
356016	NM_004562.3(PRKN):c.1289G>A (p.Gly430Asp)	PRKN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3768487	NC_000006.11:g.(162475207_162622162)_(162683798_162864341)del	PRKN	Pathogenic	criteria provided, single submitter
409266	NM_004562.3(PRKN):c.850G>C (p.Gly284Arg)	PRKN	Pathogenic	criteria provided, multiple submitters, no conflicts
417464	NC_000006.12:g.(?162054091)(162054174_?)del	PRKN	Pathogenic	criteria provided, single submitter
425403	NM_004562.3(PRKN):c.101_102del (p.Gln34fs)	PRKN	Pathogenic	criteria provided, multiple submitters, no conflicts
4526575	NM_004562.3(PRKN):c.619-1G>C	PRKN	Pathogenic	criteria provided, single submitter
4526576	NM_004562.3:c.717_832del	PRKN	Pathogenic	criteria provided, single submitter
4526577	NM_004562.3:c.833_1181del	PRKN	Pathogenic	criteria provided, single submitter
4526578	NM_004562.3:c.106_269del	PRKN	Pathogenic	criteria provided, single submitter
4526579	NM_004562.3(PRKN):c.633_716del (p.Lys211_Ile239delinsAsn)	PRKN	Pathogenic	criteria provided, single submitter
4526580	NM_004562.3:c.717_969del	PRKN	Pathogenic	criteria provided, single submitter
4526581	NM_004562.3:c.717_969dup	PRKN	Pathogenic	criteria provided, single submitter
4530572	NM_004562.3:c.(171+1_172-12671)_(534+1_535-1)del	PRKN	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
PRKN	Definitive	Autosomal recessive	Parkinson disease	4

Orphanet rare-disease linkage (cohort genes)

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

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRKN	HGNC:8607	ENSG00000185345	O60260	E3 ubiquitin-protein ligase parkin	gencc,clinvar
PACRG	HGNC:19152	ENSG00000112530	Q96M98	Parkin coregulated gene protein	clinvar
LNCR-SMAL	HGNC:58119	ENSG00000303181		lncRNA senescence and mitophagy associated regulator of PRKN	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.
PACRG	Parkin coregulated gene protein	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRKN	Transcription factor	no	2.3.2.27	Ubiquitin-like_dom, IBR_dom, Parkin
PACRG	Other/Unknown	no		Parkin_co-regulated_protein
LNCR-SMAL	Other/Unknown	no

Expression context

Cohort genes with no expression data: 1.

2 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)	2
unknown	1

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1
bronchial epithelial cell	1
epithelium of bronchus	1
right uterine tube	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
PACRG	197	broad	marker	bronchial epithelial cell, right uterine tube, epithelium of bronchus
LNCR-SMAL

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKN	10,281
PACRG	2,520
LNCR-SMAL	0

Intra-cohort edges

A	B	Sources
PACRG	PRKN	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRKN	O60260	21
PACRG	Q96M98	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 3 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to unfolded protein	2	991.3×	1e-04	PRKN, PACRG
positive regulation of neurotransmitter uptake	1	8426.0×	0.003	PRKN
negative regulation of spontaneous neurotransmitter secretion	1	8426.0×	0.003	PRKN
positive regulation of protein linear polyubiquitination	1	4213.0×	0.003	PRKN
negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway	1	4213.0×	0.003	PRKN
response to curcumin	1	4213.0×	0.003	PRKN
positive regulation of retrograde transport, endosome to Golgi	1	4213.0×	0.003	PRKN
negative regulation of intralumenal vesicle formation	1	4213.0×	0.003	PRKN
negative regulation of glucokinase activity	1	2808.7×	0.003	PRKN
mitochondrion to lysosome vesicle-mediated transport	1	2808.7×	0.003	PRKN
regulation protein catabolic process at presynapse	1	2808.7×	0.003	PRKN
regulation of synaptic vesicle transport	1	2808.7×	0.003	PRKN
cellular response to hydrogen sulfide	1	2808.7×	0.003	PRKN
regulation of lipid transport	1	2106.5×	0.004	PRKN
negative regulation of exosomal secretion	1	2106.5×	0.004	PRKN
cellular response to L-glutamine	1	2106.5×	0.004	PRKN
positive regulation of mitochondrial fusion	1	1685.2×	0.004	PRKN
type 2 mitophagy	1	1685.2×	0.004	PRKN
negative regulation of mitochondrial fission	1	1685.2×	0.004	PRKN
negative regulation of actin filament bundle assembly	1	1404.3×	0.004	PRKN
aggresome assembly	1	1404.3×	0.004	PRKN
free ubiquitin chain polymerization	1	1203.7×	0.004	PRKN
cellular response to manganese ion	1	1203.7×	0.004	PRKN
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	1203.7×	0.004	PRKN
cellular response to dopamine	1	1203.7×	0.004	PRKN
negative regulation of mitochondrial fusion	1	1053.2×	0.004	PRKN
positive regulation of mitochondrial membrane potential	1	1053.2×	0.004	PRKN
obsolete regulation of protein targeting to mitochondrion	1	1053.2×	0.004	PRKN
dopamine uptake involved in synaptic transmission	1	936.2×	0.004	PRKN
regulation of necroptotic process	1	936.2×	0.004	PRKN

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
PACRG	0	0
LNCR-SMAL	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: 2; 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	3	PRKN, PACRG, LNCR-SMAL

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PRKN	0	—
PACRG	0	—
LNCR-SMAL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02511015	Not specified	COMPLETED	Hereditary Parkinson s Disease Natural History Protocol
NCT04084509	Not specified	WITHDRAWN	Molecular and Functional Imaging in SNCA, Parkin and PINK1
NCT04148326	Not specified	WITHDRAWN	A Pilot Study to Explore the Role of Gut Flora in Parkinson’s Disease