Alternative titles; symbols
HGNC Approved Gene Symbol: DNAJC19
SNOMEDCT: 711412004;
Cytogenetic location: 3q26.33 Genomic coordinates (GRCh38): 3:180,983,709-180,989,838 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 3q26.33 | 3-methylglutaconic aciduria, type V | 610198 | Autosomal recessive | 3 |
By searching for sequences similar to yeast Tim14, Mokranjac et al. (2003) identified human TIM14. The deduced 116-amino acid protein contains an N-terminal transmembrane domain, followed by 3 alpha-helical segments characteristic of the J domain of E. coli DnaJ (see 608375). In yeast, Tim14 is located at the inner mitochondrial membrane and the J domain faces the matrix space.
Using RT-PCR on total RNA isolated from fibroblasts, Davey et al. (2006) detected a dominant full-length 525-bp product as well as a minor 445-bp product lacking exon 4 in all tissues examined. The full-length protein has a predicted molecular mass of 12.5 kD. They identified a single N-terminal transmembrane segment, a predicted mitochondrial targeting sequence, and a C-terminal J domain,
Mokranjac et al. (2003) determined that yeast Tim14 is a component of the mitochondrial protein import motor. They found that Tim14 interacts with Hsp70 (see 140550) in an ATP-dependent manner and has a profound effect on the interaction of Hsp70 with Tim44 (605058).
Sinha et al. (2010) showed that human MAGMAS (PAM16; 614336) is an ortholog of S. cerevisiae Pam16; it has similar functions and is critical for protein translocation across the mitochondrial inner membrane. MAGMAS localized to mitochondria and was peripherally associated with inner mitochondrial membrane in yeast and humans. MAGMAS formed a stable subcomplex with DNAJC19 through its C-terminal region and was tethered to the TIM23 (605034) complex of yeast and humans. Sinha et al. (2010) proposed that mutations resulting in decreased stability of functional MAGMAS:DNAJC19 subcomplex at the human TIM23 channel may lead to impaired protein import and cellular respiration in some patients with dilated cardiomyopathy.
Davey et al. (2006) determined that the DNAJC19 gene contains 6 exons spanning 5.2 kb.
The International Radiation Hybrid Mapping Consortium mapped the DNAJC19 gene to chromosome 3 (SHGC-77577).
Davey et al. (2006) noted that the DNAJC19 gene maps to chromosome 3q26.33.
In 16 patients with dilated cardiomyopathy and ataxia, also called 3-methylglutaconic aciduria type V (MGCA5; 610198), from a Canadian Dariusleut Hutterite population, Davey et al. (2006) identified homozygosity for a splice-site mutation in the DNAJC19 gene (608977.0001).
In 2 Finnish brothers with MGCA5, Ojala et al. (2012) identified a homozygous truncating mutation in the DNAJC19 gene (608977.0002). The unaffected parents were heterozygous for the mutation. Both brothers had noncompaction cardiomyopathy.
In 16 patients with dilated cardiomyopathy and ataxia (MGCA5; 610198) from consanguineous Canadian Dariusleut Hutterite families, Davey et al. (2006) identified homozygosity for a -1G-C transversion in intron 3 of the DNAJC19 gene, predicted to prevent splicing of exon 4 into the DNAJC19 mRNA (delta-ex4). By expression analysis, a dominant full-length 545-bp product and a minor 445-bp product corresponding to delta-ex4 were detected in normal tissues and in a non-Hutterite control subject. In an affected patient, only the 445-bp product was detected. Davey et al. (2006) suggested that alternative splicing is common at this site. Unaffected parents were heterozygous for the mutation; the mutation was not found in 236 controls.
Chong et al. (2012) identified this mutation in heterozygous state in 42 individuals among 1,504 U.S. Schmiedeleut (S-leut) Hutterites screened, for a carrier frequency of 0.028 (1 in 36). No homozygotes for this mutation were identified. This is a private mutation in the Hutterite population.
In 2 Finnish brothers with 3-methylglutaconic aciduria type V (MGCA5; 610198), Ojala et al. (2012) identified a homozygous 1-bp deletion (c.300delA) in exon 6 of the DNAJC19 gene, resulting in a frameshift and premature termination (Ala100fsTer11). The unaffected parents were heterozygous for the mutation, which was not found in a cohort of 22 children with cardiomyopathy. Western blot analysis of patient cells showed no detectable DNAJC19 protein. The brothers had noncompaction cardiomyopathy, which resulted in death in 1 patient at age 13 months.
Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C. A population-based study of autosomal-recessive disease-causing mutations in a founder population. Am. J. Hum. Genet. 91: 608-620, 2012. [PubMed: 22981120] [Full Text: https://doi.org/10.1016/j.ajhg.2012.08.007]
Davey, K. M., Parboosingh, J. S., McLeod, D. R., Chan, A., Casey, R., Ferreira, P., Snyder, F. F., Bridge, P. J., Bernier, F. P. Mutation of DNAJC19, a human homologue of yeast inner mitochondrial co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition. J. Med. Genet. 43: 385-393, 2006. [PubMed: 16055927] [Full Text: https://doi.org/10.1136/jmg.2005.036657]
Mokranjac, D., Sichting, M., Neupert, W., Hell, K. Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria. EMBO J. 22: 4945-4956, 2003. [PubMed: 14517234] [Full Text: https://doi.org/10.1093/emboj/cdg485]
Ojala, T., Polinati, P., Manninen, T., Hiippala, A., Rajantie, J., Karikoski, R., Suomalainen, A., Tyni, T. New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies. Pediat. Res. 72: 432-437, 2012. [PubMed: 22797137] [Full Text: https://doi.org/10.1038/pr.2012.92]
Sinha, D., Joshi, N., Chittoor, B., Samji, P., D'Silva, P. Role of Magmas in protein transport and human mitochondria biogenesis. Hum. Molec. Genet. 19: 1248-1262, 2010. [PubMed: 20053669] [Full Text: https://doi.org/10.1093/hmg/ddq002]