The CCDC40 gene provides instructions for making a protein that is involved in the assembly of a larger group of proteins (a complex) called dynein. Dynein functions within cell structures called cilia and flagella. Cilia are microscopic, finger-like projections that stick out from the surface of cells. Coordinated back and forth movement of cilia can move the cell or the fluid surrounding the cell. Flagella are similar to cilia, but flagella are found only in sperm cells. Dynein makes up the structures (arms) that produce the force needed for cilia and flagella to move. 

Dynein forms structures known as inner dynein arms (IDAs) and outer dynein arms (ODAs) within the core of cilia and flagella (the axoneme). Coordinated movement of the dynein arms causes the entire axoneme to bend back and forth. The CCDC40 protein is necessary for the proper assembly of the IDAs, which play a central role in the coordinated movement of cilia and flagella. 

Researchers suspect that the CCDC40 protein is also involved in the proper assembly of the nexin-dynein regulatory complex, which helps regulate and coordinate the activity of the inner and outer dynein arms. By helping with the assembly of both the IDAs and the nexin-dynein regulatory complex, the CCDC40 protein plays a central role in the coordinated movement of cilia and flagella. 

Tests Listed in the Genetic Testing Registry

• Tests of CCDC40

Scientific Articles on PubMed

• PubMed

Catalog of Genes and Diseases from OMIM

• COILED-COIL DOMAIN-CONTAINING PROTEIN 40; CCDC40

Gene and Variant Databases

• NCBI Gene
• ClinVar

• Antony D, Becker-Heck A, Zariwala MA, Schmidts M, Onoufriadis A, Forouhan M, Wilson R, Taylor-Cox T, Dewar A, Jackson C, Goggin P, Loges NT, Olbrich H, Jaspers M, Jorissen M, Leigh MW, Wolf WE, Daniels ML, Noone PG, Ferkol TW, Sagel SD, Rosenfeld M, Rutman A, Dixit A, O'Callaghan C, Lucas JS, Hogg C, Scambler PJ, Emes RD; Uk10k; Chung EM, Shoemark A, Knowles MR, Omran H, Mitchison HM. Mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms. Hum Mutat. 2013 Mar;34(3):462-72. doi: 10.1002/humu.22261. Epub 2013 Feb 11. Citation on PubMed
• Antony D, Brunner HG, Schmidts M. Ciliary Dyneins and Dynein Related Ciliopathies. Cells. 2021 Jul 25;10(8):1885. doi: 10.3390/cells10081885. Citation on PubMed
• Becker-Heck A, Zohn IE, Okabe N, Pollock A, Lenhart KB, Sullivan-Brown J, McSheene J, Loges NT, Olbrich H, Haeffner K, Fliegauf M, Horvath J, Reinhardt R, Nielsen KG, Marthin JK, Baktai G, Anderson KV, Geisler R, Niswander L, Omran H, Burdine RD. The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nat Genet. 2011 Jan;43(1):79-84. doi: 10.1038/ng.727. Epub 2010 Dec 5. Citation on PubMed
• Blanchon S, Legendre M, Copin B, Duquesnoy P, Montantin G, Kott E, Dastot F, Jeanson L, Cachanado M, Rousseau A, Papon JF, Beydon N, Brouard J, Crestani B, Deschildre A, Desir J, Dollfus H, Leheup B, Tamalet A, Thumerelle C, Vojtek AM, Escalier D, Coste A, de Blic J, Clement A, Escudier E, Amselem S. Delineation of CCDC39/CCDC40 mutation spectrum and associated phenotypes in primary ciliary dyskinesia. J Med Genet. 2012 Jun;49(6):410-6. doi: 10.1136/jmedgenet-2012-100867. Citation on PubMed
• Davis SD, Ferkol TW, Rosenfeld M, Lee HS, Dell SD, Sagel SD, Milla C, Zariwala MA, Pittman JE, Shapiro AJ, Carson JL, Krischer JP, Hazucha MJ, Cooper ML, Knowles MR, Leigh MW. Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype. Am J Respir Crit Care Med. 2015 Feb 1;191(3):316-24. doi: 10.1164/rccm.201409-1672OC. Citation on PubMed
• Despotes KA, Zariwala MA, Davis SD, Ferkol TW. Primary Ciliary Dyskinesia: A Clinical Review. Cells. 2024 Jun 4;13(11):974. doi: 10.3390/cells13110974. Citation on PubMed
• Raidt J, Riepenhausen S, Pennekamp P, Olbrich H, Amirav I, Athanazio RA, Aviram M, Balinotti JE, Bar-On O, Bode SFN, Boon M, Borrelli M, Carr SB, Crowley S, Dehlink E, Diepenhorst S, Durdik P, Dworniczak B, Emiralioglu N, Erdem E, Fonnesu R, Gracci S, Grosse-Onnebrink J, Gwozdziewicz K, Haarman EG, Hansen CR, Hogg C, Holgersen MG, Kerem E, Korner RW, Kotz K, Kouis P, Loebinger MR, Lorent N, Lucas JS, Maj D, Mall MA, Marthin JK, Martinu V, Mazurek H, Mitchison HM, Nothe-Menchen T, Ozcelik U, Pifferi M, Pogorzelski A, Ringshausen FC, Roehmel JF, Rovira-Amigo S, Rumman N, Schlegtendal A, Shoemark A, Sperstad Kennelly S, Staar BO, Sutharsan S, Thomas S, Ullmann N, Varghese J, von Hardenberg S, Walker WT, Wetzke M, Witt M, Yiallouros P, Zschocke A, Zietkiewicz E, Nielsen KG, Omran H. Analyses of 1236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype-phenotype correlations. Eur Respir J. 2024 Aug 8;64(2):2301769. doi: 10.1183/13993003.01769-2023. Print 2024 Aug. Citation on PubMed
• Wee WB, Kinghorn B, Davis SD, Ferkol TW, Shapiro AJ. Primary Ciliary Dyskinesia. Pediatrics. 2024 Jun 1;153(6):e2023063064. doi: 10.1542/peds.2023-063064. Citation on PubMed
• Xu Y, Yang B, Lei C, Yang D, Ding S, Lu C, Wang L, Guo T, Wang R, Luo H. Novel Compound Heterozygous Variants in CCDC40 Associated with Primary Ciliary Dyskinesia and Multiple Morphological Abnormalities of the Sperm Flagella. Pharmgenomics Pers Med. 2022 Apr 15;15:341-350. doi: 10.2147/PGPM.S359821. eCollection 2022. Citation on PubMed
• Zariwala MA, Despotes KA, Davis SD. Primary Ciliary Dyskinesia. 2007 Jan 24 [updated 2025 May 22]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1122/ Citation on PubMed