The DMKN gene encodes several different isoforms of the DMKN protein. Of these, the DMKN delta-5 isoform is ubiquitously expressed in cells and is believed to play a role in early endosomal vesicle formation and trafficking. It carries out this function by interacting with endogenous HeLa cell RAB5 and promoting GTP loading onto RAB5. DMKN-beta, a secreted isoform specific to keratinocytes, is believed to play a role in the terminal differentiation of the epidermis and cornified envelope assembly. Recent studies in human keratinocytes have identified DMKN-beta to inhibit the phosphorylation of extracellular-signal-regulated kinase (ERK) and increase caspase activity.
The DMKN gene is located on the long arm of chromosome 19. It spans a length of 15.4 kb of DNA and its coding sequence is spread across 28 exons. The gene encodes a 47 kDa protein product comprised of 476 amino acids. As mentioned above, around 16 different isoforms of the DMKN protein exist due to alternatively spliced transcript variants. These isoforms differ in their cellular distributions and domain components. While the DMKN gene is widely expressed, overexpression is seen in the epidermis of the skin.
Monies et al. (2017) described the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One patient, a 5-year-old male, presented with a ventricular septal defect, speech delay, learning disability, cleft lip/palate, skin laxity and joint laxity. His parents were consanguineous and he had a family history of the phenotype. Using whole exome sequencing, a homozygous mutation (c.850_851insCA, p.G284fs) was identified in exon 5 of the patient’s DMKN gene. This mutation was considered a candidate for pathogenicity due to it being a novel truncating variant located within the autozygome and the expression pattern of the gene being consistent with the phenotype. Further studies are required to independently confirm this association.
View PDF version of Dermokine
To contribute with your findings to the content of this record, please fill the CTGA Database Information Submission Form and email it, along with supportive documents, to email@example.com.