juvenile-onset Parkinson disease

Summary

juvenile-onset Parkinson disease (MONDO:0000828) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile-onset Parkinson disease
Mondo ID	MONDO:0000828
DOID	DOID:0060893
UMLS	C0752105
MedGen	155699
GARD	0022833
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 3 Mondo subtypes.

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 › juvenile-onset Parkinson disease

Related subtypes (8): Parkinson disease 12, 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

Subtypes (3): Kufor-Rakeb syndrome, juvenile onset Parkinson disease 19A, Parkinson disease 19B, early-onset

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 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1098717	Single allele	TNFRSF9	Pathogenic	no assertion criteria provided
1334461	NM_007262.5(PARK7):c.377A>G (p.His126Arg)	PARK7	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 5 · 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
PODXL	Supportive	Autosomal recessive	young-onset Parkinson disease	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PODXL	Orphanet:2828	Young-onset Parkinson disease
PODXL	Orphanet:391411	Atypical juvenile parkinsonism
TNFRSF9	Orphanet:664726	EBV-induced lymphoproliferative disease due to CD137 deficiency
PARK7	Orphanet:2828	Young-onset Parkinson disease
PARK7	Orphanet:90020	Parkinson-dementia complex of Guam

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PODXL	HGNC:9171	ENSG00000128567	O00592	Podocalyxin	gencc
TNFRSF9	HGNC:11924	ENSG00000049249	Q07011	Tumor necrosis factor receptor superfamily member 9	clinvar
PARK7	HGNC:16369	ENSG00000116288	Q99497	Parkinson disease protein 7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PODXL	Podocalyxin	Involved in the regulation of both adhesion and cell morphology and cancer progression.
TNFRSF9	Tumor necrosis factor receptor superfamily member 9	Receptor for TNFSF9/4-1BBL.
PARK7	Parkinson disease protein 7	Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PODXL	Other/Unknown	no		CD34/Podocalyxin, PODXL
TNFRSF9	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, Growth_fac_rcpt_cys_sf, TNFR_9
PARK7	Enzyme (other)	yes	3.5.1.124	DJ-1/PfpI, DJ-1, Class_I_gatase-like

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
germinal epithelium of ovary	1
metanephric glomerulus	1
renal glomerulus	1
buccal mucosa cell	1
cartilage tissue	1
lymph node	1
adult organism	1
deltoid	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PODXL	276	ubiquitous	marker	renal glomerulus, metanephric glomerulus, germinal epithelium of ovary
TNFRSF9	133	broad	marker	buccal mucosa cell, lymph node, cartilage tissue
PARK7	294	ubiquitous	marker	adult organism, tibia, deltoid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PARK7	5,722
PODXL	2,741
TNFRSF9	2,245

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PARK7	Q99497	88
TNFRSF9	Q07011	14

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PODXL	O00592	53.66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 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
Chaperone Mediated Autophagy	1	248.3×	0.008	PARK7
TNFs bind their physiological receptors	1	196.9×	0.008	TNFRSF9
Late endosomal microautophagy	1	163.1×	0.008	PARK7
Aggrephagy	1	124.1×	0.008	PARK7
SUMOylation of transcription cofactors	1	121.5×	0.008	PARK7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 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 acute inflammatory response to antigenic stimulus	1	5617.3×	1e-03	PARK7
regulation of immature T cell proliferation in thymus	1	5617.3×	1e-03	TNFRSF9
cellular response to glyoxal	1	5617.3×	1e-03	PARK7
glycolate biosynthetic process	1	5617.3×	1e-03	PARK7
detoxification of mercury ion	1	5617.3×	1e-03	PARK7
detoxification of hydrogen peroxide	1	5617.3×	1e-03	PARK7
obsolete methylglyoxal catabolic process to lactate	1	5617.3×	1e-03	PARK7
guanine deglycation	1	5617.3×	1e-03	PARK7
obsolete guanine deglycation, methylglyoxal removal	1	5617.3×	1e-03	PARK7
guanine deglycation, glyoxal removal	1	5617.3×	1e-03	PARK7
cellular detoxification of methylglyoxal	1	5617.3×	1e-03	PARK7
regulation of supramolecular fiber organization	1	5617.3×	1e-03	PARK7
negative regulation of death-inducing signaling complex assembly	1	5617.3×	1e-03	PARK7
negative regulation of TRAIL-activated apoptotic signaling pathway	1	5617.3×	1e-03	PARK7
glyoxal metabolic process	1	5617.3×	1e-03	PARK7
obsolete positive regulation of L-dopa biosynthetic process	1	5617.3×	1e-03	PARK7
methylglyoxal metabolic process	1	2808.7×	0.001	PARK7
detection of oxidative stress	1	2808.7×	0.001	PARK7
epithelial tube formation	1	2808.7×	0.001	PODXL
negative regulation of protein K48-linked deubiquitination	1	2808.7×	0.001	PARK7
positive regulation of dopamine biosynthetic process	1	2808.7×	0.001	PARK7
negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway	1	2808.7×	0.001	PARK7
lactate biosynthetic process	1	1872.4×	0.002	PARK7
positive regulation of mitochondrial electron transport, NADH to ubiquinone	1	1872.4×	0.002	PARK7
negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway	1	1872.4×	0.002	PARK7
hydrogen peroxide metabolic process	1	1404.3×	0.002	PARK7
positive regulation of autophagy of mitochondrion	1	1404.3×	0.002	PARK7
positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1	1123.5×	0.003	PARK7
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	1	1123.5×	0.003	PARK7
negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide	1	1123.5×	0.003	PARK7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PARK7	1	2
PODXL	0	0
TNFRSF9	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	PARK7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PARK7	62	Binding:62
TNFRSF9	11	Binding:11

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PARK7	3.5.1.124, 4.2.1.130	protein deglycase, D-lactate dehydratase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	PARK7

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	1	PARK7
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PODXL, TNFRSF9

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PODXL	0	—
TNFRSF9	11	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.