DNAJC19

Chr 3AR

DnaJ heat shock protein family (Hsp40) member C19

NCBI Gene: 131118ENSG00000205981UniProt: Q96DA6

Mitochondrial co-chaperone which forms a complex with prohibitins to regulate cardiolipin remodeling (By similarity). May be a component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. May act as a co-chaperone that stimulate the ATP-dependent activity (By similarity)

Primary Disease Associations & Inheritance

3-methylglutaconic aciduria, type VMIM #610198
AR
206
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DNAJC19
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
206 total variants — no pathogenic classifications of 206 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.31LOEUF
pLI 0.001
Z-score 0.93
OE 0.66 (0.36–1.31)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.88Z-score
OE missense 0.69 (0.54–0.89)
44 obs / 63.7 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.0.66 (0.36–1.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.54–0.89)
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.0.96
0≤1.21.6
LoF obs/exp: 6 / 9.0Missense obs/exp: 44 / 63.7Syn Z: 0.15

ClinVar Variant Classifications

206 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

DNAJC19 · 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

3-methylglutaconic aciduria, type V

MIM #610198

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic Basis of Severe Childhood-Onset Cardiomyopathies.
Vasilescu C et al.·J Am Coll Cardiol
2018
Progressive Cerebellar Atrophy and a Novel Homozygous Pathogenic DNAJC19 Variant as a Cause of Dilated Cardiomyopathy Ataxia Syndrome.
Al Teneiji A et al.·Pediatr Neurol
2016Review
Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes.
Janz A et al.·Mol Metab
2024
Mitochondrial Protein Homeostasis and Cardiomyopathy.
Wachoski-Dark E et al.·Int J Mol Sci
2022Review
New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies.
Ojala T et al.·Pediatr Res
2012Case report
Novel homozygous pathogenic mitochondrial DNAJC19 variant in a patient with dilated cardiomyopathy and global developmental delay.
Al Tuwaijri A et al.·Mol Genet Genomic Med
2022
Phenotype and pathology of the dilated cardiomyopathy with ataxia syndrome in children.
Machiraju P et al.·J Inherit Metab Dis
2022
Generation of a homozygous DNAJC19 knockout human embryonic stem cell line by CRISPR/Cas9 system.
Chen G et al.·Stem Cell Res
2024
DNAJC19, a mitochondrial cochaperone associated with cardiomyopathy, forms a complex with prohibitins to regulate cardiolipin remodeling.
Richter-Dennerlein R et al.·Cell Metab
2014Functional
Generation of two patient-derived iPSC lines from siblings (LIBUCi001-A and LIBUCi002-A) and a genetically modified iPSC line (JMUi001-A-1) to mimic dilated cardiomyopathy with ataxia (DCMA) caused by a homozygous DNAJC19 mutation.
Janz A et al.·Stem Cell Res
2020
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.

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External Resources

Links to major genomics databases and tools