DNAJC19: A Key Mitochondrial Chaperone in Cardiomyopathy and Neurological Disorders
Comprehensive genomic and proteomic analysis of DNAJC19, a DnaJ/Hsp40 family member implicated in dilated cardiomyopathy with ataxia (DCMA) and 3-methylglutaconic aciduria.
Gene Information Card
| Symbol | DNAJC19 |
|---|---|
| Full Name | DnaJ heat shock protein family (Hsp40) member C19 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q26.33 |
| NCBI Gene ID | 131118 ncbi.nlm.nih.gov/gene/131118 |
| Ensembl ID | ENSG00000163874 |
| UniProt ID | Q8N5I2 |
| OMIM ID | 608977 |
| HGNC ID | 30528 |
| Aliases | TIM14, DCMA, PAM18, SDR5C1 |
Description
DNAJC19 encodes a mitochondrial inner membrane protein belonging to the DnaJ/Hsp40 family. It functions as a co-chaperone for the mitochondrial import motor complex, specifically as a component of the presequence translocase-associated motor (PAM) complex. The protein is essential for protein import into the mitochondrial matrix. Mutations in DNAJC19 cause dilated cardiomyopathy with ataxia (DCMA) syndrome, also known as 3-methylglutaconic aciduria type V, characterized by early-onset cardiomyopathy, cerebellar ataxia, and elevated urinary 3-methylglutaconic acid.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated cardiomyopathy with ataxia (DCMA) syndrome | Loss-of-function mutations impair mitochondrial protein import, leading to mitochondrial dysfunction and energy deficiency in cardiac and neural tissues. | OMIM #610198; ClinVar; multiple case reports |
| 3-Methylglutaconic aciduria type V | Defective mitochondrial chaperone activity disrupts metabolism, causing accumulation of 3-methylglutaconic acid. | OMIM #610198; NCBI GeneReviews |
| Cardiomyopathy, infantile hypertrophic | Mitochondrial import defects compromise cardiac energy production, contributing to hypertrophic remodeling. | ClinVar; limited case studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | High |
| Skeletal muscle | 8.3 | Medium |
| Brain | 6.1 | Medium |
| Liver | 4.7 | Low |
| Kidney | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPSC-derived) | 15.0 | High expression; relevant to disease model |
| SH-SY5Y (neuroblastoma) | 7.8 | Moderate; used in neurological studies |
| HeLa (cervical carcinoma) | 5.3 | Low baseline expression |
| HEK293 (embryonic kidney) | 6.9 | Moderate; common overexpression system |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.130C>T (p.Arg44*) | Nonsense | Rare | Premature stop; loss of protein function; associated with DCMA |
| c.238G>A (p.Gly80Arg) | Missense | Rare | Impaired chaperone activity; reduced mitochondrial import |
| c.1A>G (p.Met1?) | Start loss | Rare | No protein translation; complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations (nonsense, frameshift, start loss) lead to loss of functional protein, impairing mitochondrial protein import and causing DCMA syndrome.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DNAJC19.
Dominant Negative (DN)
No dominant-negative mutations have been characterized; the disease follows an autosomal recessive inheritance pattern.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrion (GO:0005739) | • mitochondrial inner membrane (GO:0005743) |
| • protein folding (GO:0006457) | • protein import into mitochondrial matrix (GO:0030150) |
| • unfolded protein binding (GO:0051082) | • ATPase activator activity (GO:0001671) |
Pathways
• Mitochondrial protein import (REACT_21300)
• PAM complex (presequence translocase-associated motor) (Reactome: R-HSA-1268020)
• Hsp40/DnaJ chaperone system (KEGG: map04141)
Protein Summary
DNAJC19 encodes a 16 kDa mitochondrial inner membrane protein (TIM14) that acts as a co-chaperone for the mitochondrial import motor. It contains a conserved J-domain that stimulates the ATPase activity of mitochondrial Hsp70 (mtHsp70), facilitating protein translocation into the matrix. The protein is anchored to the inner membrane via a transmembrane domain and interacts with other PAM complex components (e.g., PAM16, mtHsp70). Loss of DNAJC19 function disrupts mitochondrial protein import, leading to organellar dysfunction, energy depletion, and tissue-specific pathology in heart and brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DNAJC19 Knockout HEK293 Cell Line | EDJ-KQ1935 | Human | 131118 | Details Get a Quote |
| DNAJC19 Knockout A-549 Cell Line | EDJ-KQ23233 | Human | 131118 | Details Get a Quote |
| DNAJC19 Knockout HCT 116 Cell Line | EDJ-KQ23235 | Human | 131118 | Details Get a Quote |
| DNAJC19 Knockout HeLa Cell Line | EDJ-KQ23236 | Human | 131118 | Details Get a Quote |
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