CCDC50

CCDC50, also known as Ymer, is a gene located on chromosome 3 that encodes a protein involved in epidermal growth factor (EGF)-mediated cell signaling. This protein plays a crucial role in cellular processes such as immune regulation, lysosomal maintenance, and tumor progression. 

At the same time, mutations in CCDC50, particularly in exon 11, are linked to autosomal dominant nonsyndromic sensorineural hearing loss (DFNA44) and various cancers, highlighting its significance in both normal physiology and disease pathology.

What is CCDC50?

CCDC50 (Coiled-Coil Domain-Containing Protein 50) is a gene located on chromosome 3 that encodes the protein Ymer, which is involved in epidermal growth factor (EGF)-mediated cell signaling.

The Ymer protein is involved in several critical cellular processes, though its full biological function is still under investigation. The CCDC50 protein Ymer is expressed in various tissues, including the brain, heart, liver, and pancreas, and is associated with important functions in cellular maintenance and regulation.

Mutations in CCDC50, particularly in exon 11, lead to autosomal dominant nonsyndromic sensorineural hearing loss (DFNA44). This mutation disrupts the protein's function, causing progressive hearing loss by affecting the microtubule structure in the inner ear. 

Despite its widespread expression, the mutation primarily impacts auditory function, highlighting the gene's specific role in cochlear development and epidermal growth factor (EGF) signaling.

Functions of the CCDC50 Protein

CCDC50 plays various roles in cellular processes, influencing cell survival, immunity, and disease progression.

Lysophagy and Tumor Growth

CCDC50 acts as a receptor that helps break down damaged lysosomes. This process helps keep lysosomes healthy, lowers harmful reactive oxygen species (ROS), and helps tumor cells survive. 

When CCDC50 is missing, damaged lysosomes build up, autophagy (the cell's way of cleaning out waste) doesn't work correctly, and ROS levels rise, leading to cell death and preventing tumor growth. 

In melanoma, higher levels of CCDC50 are linked to a worse outlook, suggesting it could be a useful target for cancer treatment.

Immune Regulation

CCDC50 regulates the immune response during viral infections. It interacts with critical components of the antiviral immune response and helps prevent excessive type I interferon (IFN) responses, thereby reducing the risk of autoimmune tissue damage. 

CCDC50 also regulates inflammation by inhibiting the NLRP3 inflammasome, a key mediator of proinflammatory cytokine production. By targeting NLRP3 for autophagic degradation, CCDC50 helps prevent excessive inflammatory responses, and its deficiency leads to heightened inflammation.

Regulation of Cellular Homeostasis

CCDC50 has been implicated in regulating cell growth and proliferation, DNA damage response, and apoptosis (programmed cell death). 

It may help protect cells from DNA damage, initiate repair mechanisms, and eliminate damaged cells, all of which are vital for maintaining cellular homeostasis, although more research is needed to fully understand the importance of CCDC50.

Conditions Associated with CCDC50

The following conditions have been associated with CCDC50 mutations:

CCDC50 and Hearing Loss

Mutations in the CCDC50 gene are linked to autosomal dominant progressive hearing loss (DFNA44). This mutation alters the CCDC50 protein, leading to protein aggregation.

Research in a Spanish family and mouse models show that these mutations affect hearing by disrupting the inner ear's microtubule network, particularly in cells of the cochlea. 

This tissue-specific dysfunction highlights the importance of CCDC50 in maintaining inner ear structure, suggesting that targeting these mutations could offer potential therapeutic strategies for DFNA44 hearing loss.

CCDC50 in Cancer Research

CCDC50 is emerging as a significant driver in various cancers, including colorectal cancer (CRC), Diffuse Large B Cell Lymphoma (DLBCL), and hepatocellular carcinoma (HCC). 

In CRC, high expression of CCDC50 correlates with poor prognosis and promotes tumor growth and metastasis, suggesting its potential as a prognostic marker and therapeutic target. 

In DLBCL, particularly the aggressive ABC subtype, CCDC50 enhances tumor proliferation and serves as a potential biomarker for disease severity. 

In HCC, CCDC50’s upregulation, driven by DNA hypomethylation, is linked to poor prognosis, tumor cell proliferation, and immune microenvironment modulation, reinforcing its role as an oncogene. 

Overall, CCDC50’s involvement in tumor progression and immune modulation indicates that it may be a potential target for cancer diagnosis and therapy.

Who Should Get CCDC50 Expression or Genetic Variation Assessed?

Currently, CCDC50 expression or genetic variation analysis is primarily used in research settings rather than clinical practice. It has not been adopted as a routine diagnostic or prognostic test for cancer or other diseases.

 However, certain cancer types have been studied for their association with CCDC50 expression. Researchers investigating the genetic and molecular mechanisms of cancer often assess CCDC50 as a potential factor, but this is not a standard clinical tool at this time.

Test Procedure and Interpretation

The following section outlines the testing procedures and interpretation.

Testing Procedure and Preparation

Genetic testing involves blood, saliva, or cheek swab samples, although specialized laboratories may recommend different sample types. 

A cheek swab or saliva sample is easily obtained from the comfort of home, while blood samples typically require a blood draw.

Normal Reference Ranges

Normal reference ranges for CCDC50 genetic testing are considered to be without mutations that can alter the activity of the CCDC50 proteins.

Clinical Implications of Positive CCDC50 Mutations

The clinical implications of a positive CCDC50 mutation test result will vary by individual, although CCDC50 mutations in symptomatic patients may signal a need for further assessment and possibly treatment, especially in the setting of cancer and/or progressive hearing loss. 

Patients or practitioners with questions about the clinical implications of CCDC50 mutations should seek further assessment with a genetic counselor or expert. 

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