DNAJC6

Chr 1AR

DnaJ heat shock protein family (Hsp40) member C6

Also known as: DJC6, PARK19

NCBI Gene: 9829ENSG00000116675UniProt: O75061

DNAJC6 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus, a glycine/phenylalanine (G/F)-rich region, and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain (Ohtsuka and Hata, 2000 [PubMed 11147971]).[supplied by OMIM, Mar 2008]

Primary Disease Associations & Inheritance

Parkinson disease 19a, juvenile-onsetMIM #615528
AR
Parkinson disease 19b, early-onsetMIM #615528
AR
419
ClinVar variants
36
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DNAJC6
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 191 VUS of 419 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.22LOEUF
pLI 1.000
Z-score 5.70
OE 0.11 (0.05–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.60Z-score
OE missense 0.80 (0.74–0.87)
424 obs / 527.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.11 (0.05–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.74–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 5 / 47.3Missense obs/exp: 424 / 527.4Syn Z: 0.63

ClinVar Variant Classifications

419 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic7
VUS191
Likely Benign138
Benign50
Conflicting4
29
Pathogenic
7
Likely Pathogenic
191
VUS
138
Likely Benign
50
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
25
0
29
Likely Pathogenic
4
0
3
0
7
VUS
0
168
20
3
191
Likely Benign
0
6
63
69
138
Benign
0
2
39
9
50
Conflicting
—4
Total717715081419

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DNAJC6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Parkinson disease 19a, juvenile-onset

MIM #615528

Molecular basis of disorder known

Autosomal recessive

Parkinson disease 19b, early-onset

MIM #615528

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DNAJC6
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Monogenic Parkinson's Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing.
Jia F et al.·Genes (Basel)
2022Review
Whole-exome Sequencing of Nigerian Prostate Tumors from the Prostate Cancer Transatlantic Consortium (CaPTC) Reveals DNA Repair Genes Associated with African Ancestry.
White JA et al.·Cancer Res Commun
2022
Neurodevelopmental and synaptic defects in DNAJC6 parkinsonism, amenable to gene therapy.
Abela L et al.·Brain
2024
Genotype-Phenotype Relations for the Atypical Parkinsonism Genes: MDSGene Systematic Review.
Wittke C et al.·Mov Disord
2021Review
'Atypical' Parkinson's disease - genetic.
Weissbach A et al.·Int Rev Neurobiol
2019Review
Identification of sixteen novel candidate genes for late onset Parkinson's disease.
Gialluisi A et al.·Mol Neurodegener
2021
The genetic landscape of Parkinson's disease.
Lunati A et al.·Rev Neurol (Paris)
2018Review
Parkinson's Disease Gene Screening in Familial Cases from Central and South America.
Lorenzo-Betancor O et al.·Mov Disord
2024Cohort
New Genes Causing Hereditary Parkinson's Disease or Parkinsonism.
Puschmann A·Curr Neurol Neurosci Rep
2017Review
Haplotype Analysis on the Relationship of the DNAJC6 Gene with Early-Onset Parkinson's Disease Risk in a Chinese Population.
Shen T et al.·J Parkinsons Dis
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools