CCDC39
protein-codingcoiled-coil domain containing 39, the group of Cilia and flagella associated
Gene summary
The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~82.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013434
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0013434
Submitter: ClinGen
The CCDC39 gene was first reported in relation to primary ciliary dyskinesia in 2011 (Merveille et al., PMID: 21131972). The specific disease entity, Primary Ciliary Dyskinesia (PCD) 14, is one of at least 40 different primary ciliary dyskinesias distinguished by a specific monogenic cause. Major phenotypes of primary ciliary dyskinesia include chronic sinusitis, bronchiectasis, rhinitis, rhinorrhea, and chronic cough, largely due to defective mucociliary clearance, as well as laterality defects and, in males, reduced sperm motility (PMID: 19948909). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found the molecular mechanism and autosomal recessive mode of inheritance to be consistent among unrelated patients, while the phenotypic variability among them appeared to represent a spectrum of disease rather than separate disease entities. Therefore, the asserted disease associated with CCDC39 variants, primary ciliary dyskinesia 14 (MONDO:0013434), was curated as a single entity. Thirteen nonsense, frameshift, and splicing variants that have been reported in seven probands (as well as affected family members) in four publications (PMID: 21131972, PMID: 22693285, PMID: 23255504, PMID: 31650533) are included in this curation. Additional evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. The mechanism of pathogenicity is reported to be biallelic loss of function leading to abnormal motile cilia assembly (including absent inner dynein arms) and movement. This gene-disease association is also supported by experimental evidence, including expression in ciliated epithelial tissue relevant to PCD and altered expression in PCD patient tissues, biochemical function and functional alteration in patient cells consistent with a critical role in motile cilia structure/function, and model organisms (Chlamydomonas, zebrafish, dog, and mouse), including phenotypic rescue in the zebrafish model (PMID: 25395538, PMID: 17932292, PMID: 15998802, PMID: 21131972, PMID: 21515572, PMID: 28289722, PMID: 29317443). In summary, CCDC39 is definitively associated with autosomal recessive primary ciliary dyskinesia 14. This has been repeatedly demonstrated in both research and diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Motile Ciliopathy GCEP on October 14, 2021 (SOP Version 8).
Inheritance Pattern: AR
Disease ID:MONDO:0013434
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0016575
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary
Intervention: Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary
Rationale: Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CCDC39 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_181426.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | 213 | 1 | 218 |
| missense | 1 | 3 | 230 | 32 | 5 | 271 |
| nonsense | 40 | 11 | 51 | |||
| start loss | 1 | 1 | ||||
| frameshift | 69 | 22 | 1 | 92 | ||
| splice donor/acceptor (+/-2bp) | 12 | 18 | 3 | 33 | ||
| Total | 123 | 56 | 235 | 246 | 6 | 666 |
Highest pathogenic variant AF is 0.0004661974
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_852091.1 | 20 | MANE Select | |
| Ensembl | ENSP00000417960.2 | 20 | MANE Select | |
| Ensembl | ENSP00000418482.1 | 4 | Standard | |
| Ensembl | ENSP00000420025.1 | 3 | Standard |