juvenile onset Parkinson disease 19A

Summary

juvenile onset Parkinson disease 19A (MONDO:0014231) is a disease caused by DNAJC6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DNAJC6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 230

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile onset Parkinson disease 19A
Mondo ID	MONDO:0014231
OMIM	615528
DOID	DOID:0060891
UMLS	C3809811
MedGen	816141
GARD	0018461
Is cancer (heuristic)	no

Also known as: DNAJC6 Parkinson disease · juvenile onset Parkinson disease 19A · juvenile onset Parkinson disease type 19A · PARK19 · PARK19A · Parkinson disease 19, juvenile-onset · Parkinson disease caused by mutation in DNAJC6

Data availability: 230 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: 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 › juvenile onset Parkinson disease 19A

Related subtypes (2): Kufor-Rakeb syndrome, 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

230 retrieved; paginated sample, class counts are floors:

92 likely benign, 91 uncertain significance, 18 benign, 9 benign/likely benign, 8 pathogenic, 4 not provided, 4 conflicting classifications of pathogenicity, 4 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1399200	NM_001256864.2(DNAJC6):c.677_678dup (p.Ala227fs)	DNAJC6	Pathogenic	criteria provided, single submitter
1451316	NM_001256864.2(DNAJC6):c.2456dup (p.Gln820fs)	DNAJC6	Pathogenic	criteria provided, single submitter
219301	NM_001256864.2(DNAJC6):c.454C>T (p.Arg152Ter)	DNAJC6	Pathogenic	criteria provided, single submitter
253094	NM_001256864.2(DNAJC6):c.2779A>G (p.Arg927Gly)	DNAJC6	Pathogenic	no assertion criteria provided
265964	NM_001256864.2(DNAJC6):c.2536C>T (p.Gln846Ter)	DNAJC6	Pathogenic	no assertion criteria provided
88854	NM_001256864.2(DNAJC6):c.801-2A>G	DNAJC6	Pathogenic	no assertion criteria provided
88855	NM_001256864.2(DNAJC6):c.2410C>T (p.Gln804Ter)	DNAJC6	Pathogenic	no assertion criteria provided
976692	NM_001256864.2(DNAJC6):c.988C>T (p.Arg330Ter)	DNAJC6	Pathogenic	criteria provided, multiple submitters, no conflicts
1676536	NM_001256864.2(DNAJC6):c.49G>T (p.Glu17Ter)	DNAJC6	Likely pathogenic	criteria provided, single submitter
2096560	NM_001256864.2(DNAJC6):c.666+1G>A	DNAJC6	Likely pathogenic	criteria provided, single submitter
2505345	NM_001256864.2(DNAJC6):c.2570del (p.Pro857fs)	DNAJC6	Likely pathogenic	criteria provided, single submitter
3646343	NM_001256864.2(DNAJC6):c.194-1G>A	DNAJC6	Likely pathogenic	criteria provided, single submitter
1378591	NM_001256864.2(DNAJC6):c.1715C>T (p.Ala572Val)	DNAJC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1484761	NM_001256864.2(DNAJC6):c.344+4C>T	DNAJC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1974816	NM_001256864.2(DNAJC6):c.344+6C>T	DNAJC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
703945	NM_001256864.2(DNAJC6):c.1492T>A (p.Cys498Ser)	DNAJC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1004818	NM_001256864.2(DNAJC6):c.101G>C (p.Gly34Ala)	DNAJC6	Uncertain significance	criteria provided, single submitter
1024855	NM_001256864.2(DNAJC6):c.1831G>A (p.Ala611Thr)	DNAJC6	Uncertain significance	criteria provided, single submitter
1098746	NM_001256864.2(DNAJC6):c.2038+3A>G	DNAJC6	Uncertain significance	criteria provided, single submitter
1176504	NM_001256864.2(DNAJC6):c.1070T>C (p.Met357Thr)	DNAJC6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1298426	NM_001256864.2(DNAJC6):c.829G>A (p.Ala277Thr)	DNAJC6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1345716	NM_001256864.2(DNAJC6):c.844C>T (p.Arg282Cys)	DNAJC6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1358065	NM_001256864.2(DNAJC6):c.1113G>A (p.Lys371=)	DNAJC6	Uncertain significance	criteria provided, single submitter
1363460	NM_001256864.2(DNAJC6):c.154C>G (p.Arg52Gly)	DNAJC6	Uncertain significance	criteria provided, single submitter
1364685	NM_001256864.2(DNAJC6):c.224A>G (p.Tyr75Cys)	DNAJC6	Uncertain significance	criteria provided, single submitter
1374469	NM_001256864.2(DNAJC6):c.1348T>G (p.Ser450Ala)	DNAJC6	Uncertain significance	criteria provided, single submitter
1374640	NM_001256864.2(DNAJC6):c.1651C>A (p.Pro551Thr)	DNAJC6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1376516	NM_001256864.2(DNAJC6):c.2072A>G (p.Asp691Gly)	DNAJC6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1379214	NM_001256864.2(DNAJC6):c.1607A>G (p.Lys536Arg)	DNAJC6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1380743	NM_001256864.2(DNAJC6):c.1856G>A (p.Arg619His)	DNAJC6	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
DNAJC6	Strong	Autosomal recessive	juvenile onset Parkinson disease 19A	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAJC6	Orphanet:2828	Young-onset Parkinson disease
DNAJC6	Orphanet:391411	Atypical juvenile parkinsonism

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
DNAJC6	HGNC:15469	ENSG00000116675	O75061	Auxilin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAJC6	Auxilin	May act as a protein phosphatase and/or a lipid phosphatase.

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAJC6	Phosphatase	yes		Tyr_Pase_dom, DnaJ_domain, Tensin_C2-dom

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
Brodmann (1909) area 23	1
endothelial cell	1
substantia nigra pars compacta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAJC6	227	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, substantia nigra pars compacta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNAJC6	3,784

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNAJC6	O75061	64.29

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
Lysosome Vesicle Biogenesis	1	326.3×	0.010	DNAJC6
trans-Golgi Network Vesicle Budding	1	253.8×	0.010	DNAJC6
Golgi Associated Vesicle Biogenesis	1	200.3×	0.010	DNAJC6
Clathrin-mediated endocytosis	1	85.2×	0.018	DNAJC6
Membrane Trafficking	1	37.1×	0.029	DNAJC6
Vesicle-mediated transport	1	34.8×	0.029	DNAJC6

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
regulation of clathrin coat assembly	1	8426.0×	6e-04	DNAJC6
synaptic vesicle uncoating	1	5617.3×	6e-04	DNAJC6
clathrin coat disassembly	1	4213.0×	6e-04	DNAJC6
regulation of clathrin-dependent endocytosis	1	1685.2×	9e-04	DNAJC6
intracellular transport	1	1532.0×	9e-04	DNAJC6
synaptic vesicle recycling	1	1203.7×	1e-03	DNAJC6
clathrin-dependent endocytosis	1	581.1×	0.002	DNAJC6

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
DNAJC6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	1	DNAJC6
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)
DNAJC6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.