Mutated CCDC51 Coding for a Mitochondrial Protein, MITOK Is a Candidate Gene Defect for Autosomal Recessive Rod-Cone Dystrophy

Abstract

The purpose of this work was to identify the gene defect underlying a relatively mild rod-cone dystrophy (RCD), lacking disease-causing variants in known genes implicated in inherited retinal disorders (IRD), and provide transcriptomic and immunolocalization data to highlight the best candidate. The DNA of the female patient originating from a consanguineous family revealed no large duplication or deletion, but several large homozygous regions. In one of these, a homozygous frameshift variant, c.244_246delins17 p.(Trp82Valfs*4); predicted to lead to a nonfunctional protein, was identified in CCDC51. CCDC51 encodes the mitochondrial coiled-coil domain containing 51 protein, also called MITOK. MITOK ablation causes mitochondrial dysfunction. Here we show for the first time that CCDC51/MITOK localizes in the retina and more specifically in the inner segments of the photoreceptors, well known to contain mitochondria. Mitochondrial proteins have previously been implicated in IRD, although usually in association with syndromic disease, unlike our present case. Together, our findings add another ultra-rare mutation implicated in non-syndromic IRD, whose pathogenic mechanism in the retina needs to be further elucidated.

Exploring the Role of Surface and Mitochondrial ATP-Sensitive Potassium Channels in Cancer: From Cellular Functions to Therapeutic Potentials

“…Further detailed examination through immunofluorescence assays has shed light on the spatial expression pattern of the CCDC51 protein within cells. These assays revealed a precise localization, with the protein consistently present on the inner mitochondrial membrane [23,88]. This finding is notable as it underscores the specificity of CCDC51's role in mitochondrial function.…”

Pan-Cancer Analysis Identifies CCDC51 as a Potential Biomarker for Liver Hepatocellular Carcinoma

“…Pan cancer analysis is critical to compare heterogeneity between different tumors for identifying novel cancer biomarkers and therapeutic targets [21]. CCDC51 has been demonstrated to be involved in retinal disease [5]. Currently, no studies have tested whether CCDC51 is associated with cancer prognosis.…”

“…Coiled coil domain containing protein 51 (CCDC51), presents the pore-forming subunit of a mitoK (ATP) channel, alias MITOK [5]. It has been reported CCDC51 related to retinal disease [5].…”

“…Coiled coil domain containing protein 51 (CCDC51), presents the pore-forming subunit of a mitoK (ATP) channel, alias MITOK [5]. It has been reported CCDC51 related to retinal disease [5]. However, the CCDC51 role in pan-cancer diagnosis, prognosis, RNA modification, and immune regulation remains unclear.…”