Ccdc15-KO Mouse

CCDC15, whose full name is Coiled-Coil Domain Containing 15, localizes to the centriole inner scaffold and is crucial for centriole length and integrity. Centrioles are essential for forming centrosomes and cilia, involved in microtubule-organizing, signaling, and motility functions. The proper biogenesis and maintenance of centrioles rely on CCDC15, and it may also be associated with pathways related to ciliary motility and Hedgehog signaling [1].

Using ultrastructure expansion microscopy and loss-of-function experiments, it was found that CCDC15 depletion affects centriole length and integrity, leading to defective cilium formation, maintenance, and response to Hedgehog signaling. It also plays a role in recruiting both the inner scaffold protein POC1B and the distal SFI1/Centrin-2 complex to centrioles [1]. In human spermatozoa, CCDC15 colocalizes with centrin in both the proximal centriole and distal centriole, furthering our understanding of spermatozoan centrosome composition [2]. In pregnant women with Systemic lupus erythematosus (SLE), CCDC15 was upregulated in T cells of the SLE-C group (pregnant women with active SLE), showing potential links to the disease [3]. In mantle cell lymphoma, somatic mutations in CCDC15 were identified, although its functional role in this cancer was not previously suspected [4]. In Non-small cell lung cancer (NSCLC), CCDC15 was found to be prognostically relevant among a set of discovered biomarkers [5]. In Indian adolescents, rare variants in CCDC15 were highlighted by SKATO analysis in relation to CRP levels, suggesting a role in inflammatory and cardiometabolic pathways [6]. In stomach adenocarcinoma, a nine-gene signature prognostic model including CCDC15 was constructed, which was significantly related to overall survival, clinical characteristics, and the tumor microenvironment [7].

In conclusion, CCDC15 is essential for centriole-related functions such as centriole length, integrity, and cilium-associated processes. Its study through various models has also revealed potential associations with multiple diseases including SLE, mantle cell lymphoma, NSCLC, and conditions related to inflammation and cardiometabolic pathways in adolescents, as well as in stomach adenocarcinoma. These findings contribute to a better understanding of the biological functions related to centrioles and disease mechanisms associated with CCDC15.

References:

1. Arslanhan, Melis D, Cengiz-Emek, Seyma, Odabasi, Ezgi, Guichard, Paul, Firat-Karalar, Elif Nur. 2023. CCDC15 localizes to the centriole inner scaffold and controls centriole length and integrity. In The Journal of cell biology, 222, . doi:10.1083/jcb.202305009. https://pubmed.ncbi.nlm.nih.gov/37934472/

2. Achinger, Luke, Hehl, Briggs, Suh, Jason, Sindhwani, Puneet, Avidor-Reiss, Tomer. 2025. CEP44 and CCDC15 label the spermatozoa proximal and atypical distal centrioles. In microPublication biology, 2025, . doi:10.17912/micropub.biology.001393. https://pubmed.ncbi.nlm.nih.gov/39845269/

3. Liu, Congcong, Yu, Zeyang, Song, Yijun, Li, Yuezhen, Liu, Juntao. 2024. Single-cell RNA sequencing of peripheral blood mononuclear cells from pregnant women with Systemic lupus erythematosus. In International reviews of immunology, 43, 381-393. doi:10.1080/08830185.2024.2376649. https://pubmed.ncbi.nlm.nih.gov/39066603/

4. Yang, Ping, Zhang, Weilong, Wang, Jing, An, Ran, Jing, Hongmei. 2018. Genomic landscape and prognostic analysis of mantle cell lymphoma. In Cancer gene therapy, 25, 129-140. doi:10.1038/s41417-018-0022-5. https://pubmed.ncbi.nlm.nih.gov/29755111/

5. Dwivedi, Kountay, Rajpal, Ankit, Rajpal, Sheetal, Agarwal, Manoj, Kumar, Naveen. 2023. Enlightening the path to NSCLC biomarkers: Utilizing the power of XAI-guided deep learning. In Computer methods and programs in biomedicine, 243, 107864. doi:10.1016/j.cmpb.2023.107864. https://pubmed.ncbi.nlm.nih.gov/37866126/

6. Nair, Janaki M, Bandesh, Khushdeep, Giri, Anil K, Tandon, Nikhil, Bharadwaj, Dwaipayan. 2025. Genetic insights into CRP levels in Indian adolescents: confirming adult genetic associations. In Molecular genetics and genomics : MGG, 300, 17. doi:10.1007/s00438-024-02213-7. https://pubmed.ncbi.nlm.nih.gov/39843866/

7. Ye, Zaisheng, Zheng, Miao, Zeng, Yi, Zheng, Qiuhong, Chen, Luchuan. 2020. Bioinformatics Analysis Reveals an Association Between Cancer Cell Stemness, Gene Mutations, and the Immune Microenvironment in Stomach Adenocarcinoma. In Frontiers in genetics, 11, 595477. doi:10.3389/fgene.2020.595477. https://pubmed.ncbi.nlm.nih.gov/33362856/