# CCDC78

## Overview
CCDC78 is a gene that encodes the coiled-coil domain containing 78 protein, which plays a crucial role in cellular structural organization, particularly in the formation and maintenance of cilia and flagella. This protein is categorized as a structural protein due to its involvement in intracellular transport and signal transduction, essential for normal cellular and organismal function. In skeletal muscle, CCDC78 is localized to the sarcolemma, perinuclear region, and the triad, indicating its importance in maintaining the structural integrity of muscle cells and facilitating excitation-contraction coupling. Mutations in the CCDC78 gene have been linked to congenital myopathies, where they disrupt calcium homeostasis and muscle function, often through interactions with other proteins such as RyR1. These mutations can lead to muscle diseases characterized by structural abnormalities, highlighting the gene's clinical significance in muscle pathology (Mohar2024The; Ayvat2013P.10.3).

## Function
CCDC78 is a gene that encodes a protein involved in the structural organization of cells, particularly in the formation and maintenance of cilia and flagella, which are essential for cell motility and signaling. The protein is primarily active in the cytoplasm and plays a role in intracellular transport and signal transduction, contributing to normal cellular and organismal function. In skeletal muscle, CCDC78 localizes to the sarcolemma, perinuclear region, and the triad, which is the structural interface between the T-tubule and portions of the sarcoplasmic reticulum. This localization suggests that CCDC78 is necessary for the structural integrity of the triad and may play a role in the oligomerization of large protein complexes (Mohar2024The).

In the context of congenital myopathy, CCDC78 is involved in the regulation of excitation-contraction coupling and autophagy, processes critical for muscle function and maintenance (Ayvat2013P.10.3). The protein's role in excitation-contraction coupling is particularly significant, as it is associated with the proper localization of RyR1, a calcium channel protein, which is crucial for calcium homeostasis and muscle contraction (Mohar2024The).

## Clinical Significance
Mutations in the CCDC78 gene have been implicated in various muscle diseases, particularly those involving structural abnormalities in muscle fibers. A notable condition associated with CCDC78 mutations is centronuclear myopathy, which is characterized by muscle weakness and the presence of muscle cores, or regions with disrupted sarcomeric structure and reduced mitochondria (Mohar2024The). The CCDC78 variant c.712A>C (p.Lys238Gln) has been identified as a contributor to muscle pathology, especially when present alongside mutations in the LMNA gene. This combination can lead to a distinct muscle disease phenotype, including limb-girdle muscular dystrophy Type 1B (LGMD1B) and core myopathy, which are not typically associated with LMNA mutations alone (Mohar2024The).

The presence of the CCDC78 variant can exacerbate the effects of LMNA mutations, resulting in more severe skeletal muscle disease and the formation of muscle cores, a feature atypical for LMNA-associated conditions (Mohar2024The). This suggests that the CCDC78 variant may interact with other genetic factors to influence the severity and presentation of muscle diseases, highlighting the complexity of genetic interactions in these conditions (Mohar2024The).

## Interactions
CCDC78 is involved in several protein interactions that are crucial for its function in cellular processes. It is a component of the deuterosome, where it interacts with other proteins such as Cep70 and Deup1. These interactions are significant in the context of centriole biogenesis in multiciliated cells (MCCs). CCDC78 localizes to both centrioles and deuterosomes, and its interaction with Cep70 has been confirmed through co-immunoprecipitation assays. Cep70, a centriolar protein, also interacts with Deup1, suggesting that CCDC78, Cep70, and Deup1 form a complex that plays a role in regulating centriole amplification (Kim2021A).

In the context of skeletal muscle, CCDC78 interacts with RyR1, a protein of the terminal sarcoplasmic reticulum involved in excitation-contraction coupling. This interaction is particularly relevant in congenital myopathies, where mutations in CCDC78 lead to its aggregation with RyR1 in muscle cores. This mislocalization is associated with disruptions in calcium homeostasis and muscle pathology (Mohar2024The; Majczenko2012Dominant). The presence of CCDC78 aggregates in muscle biopsies, co-staining with proteins like desmin and actin, further underscores its role in muscle structure and function (Majczenko2012Dominant).


## References


[1. (Kim2021A) Sun K. Kim, Eva Brotslaw, Virginie Thome, Jen Mitchell, Rosa Ventrella, Caitlin Collins, and Brian Mitchell. A role for cep70 in centriole amplification in multiciliated cells. Developmental Biology, 471:10–17, March 2021. URL: http://dx.doi.org/10.1016/j.ydbio.2020.11.011, doi:10.1016/j.ydbio.2020.11.011. This article has 7 citations and is from a peer-reviewed journal.](https://doi.org/10.1016/j.ydbio.2020.11.011)

[2. (Mohar2024The) Nathaniel P. Mohar, Efrem M. Cox, Emily Adelizzi, Steven A. Moore, Katherine D. Mathews, Benjamin W. Darbro, and Lori L. Wallrath. The influence of a genetic variant in ccdc78 on lmna-associated skeletal muscle disease. International Journal of Molecular Sciences, 25(9):4930, April 2024. URL: http://dx.doi.org/10.3390/ijms25094930, doi:10.3390/ijms25094930. This article has 0 citations and is from a peer-reviewed journal.](https://doi.org/10.3390/ijms25094930)

[3. (Ayvat2013P.10.3) E. Ayvat, M. Kilinc, Y. Parlak Demir, S.A. Yildirim, and E. Tan. P.10.3 the characteristics of low back pain and its effects on quality of life in patients with neuromuscular diseases. Neuromuscular Disorders, 23(9–10):789–790, October 2013. URL: http://dx.doi.org/10.1016/j.nmd.2013.06.533, doi:10.1016/j.nmd.2013.06.533. This article has 0 citations and is from a peer-reviewed journal.](https://doi.org/10.1016/j.nmd.2013.06.533)

[4. (Majczenko2012Dominant) Karen Majczenko, Ann E. Davidson, Sandra Camelo-Piragua, Pankaj B. Agrawal, Richard A. Manfready, Xingli Li, Sucheta Joshi, Jishu Xu, Weiping Peng, Alan H. Beggs, Jun Z. Li, Margit Burmeister, and James J. Dowling. Dominant mutation of ccdc78 in a unique congenital myopathy with prominent internal nuclei and atypical cores. The American Journal of Human Genetics, 91(2):365–371, August 2012. URL: http://dx.doi.org/10.1016/j.ajhg.2012.06.012, doi:10.1016/j.ajhg.2012.06.012. This article has 78 citations.](https://doi.org/10.1016/j.ajhg.2012.06.012)