CCDC39

Chr 3AR

coiled-coil domain 39 molecular ruler complex subunit

Also known as: CFAP59, CILD14, FAP59

NCBI Gene: 339829ENSG00000284862UniProt: Q9UFE4

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]

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 14MIM #613807
AR
499
ClinVar variants
99
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CCDC39
🧬
Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia 14 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
99 Pathogenic / Likely Pathogenic· 133 VUS of 499 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.75LOEUF
pLI 0.000
Z-score 2.93
OE 0.54 (0.40–0.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.36Z-score
OE missense 0.95 (0.88–1.03)
402 obs / 423.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.54 (0.40–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.88–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 26 / 47.8Missense obs/exp: 402 / 423.0Syn Z: 0.23

ClinVar Variant Classifications

499 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic71
Likely Pathogenic28
VUS133
Likely Benign261
Benign4
Conflicting2
71
Pathogenic
28
Likely Pathogenic
133
VUS
261
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
36
0
35
0
71
Likely Pathogenic
20
0
8
0
28
VUS
1
120
11
1
133
Likely Benign
0
2
127
132
261
Benign
0
0
4
0
4
Conflicting
—2
Total57122185133499

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CCDC39 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CCDC39-related primary ciliary dyskinesia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ciliary dyskinesia, primary, 14

MIM #613807

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CCDC39
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Genetic Spectrum of Children With Primary Ciliary Dyskinesia in China.
Guan Y et al.·Chest
2021
Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype.
Davis SD et al.·Am J Respir Crit Care Med
2019Natural history
Undocking of an extensive ciliary network induces proteostasis and cell fate switching resulting in severe primary ciliary dyskinesia.
Brody SL et al.·Sci Transl Med
2025
Analyses of 1236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype-phenotype correlations.
Raidt J et al.·Eur Respir J
2024
Genetics of 67 patients of suspected primary ciliary dyskinesia from India.
Jat KR et al.·Clin Genet
2024Cohort
Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype.
Staar BO et al.·Cells
2023
Primary ciliary dyskinesia phenotypes and correlation with genotype.
Horani A et al.·Curr Opin Pulm Med
2025Review
Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects.
Bolkier Y et al.·J Med Genet
2022
Genotype-Phenotype Correlation in a Group of Italian Patients With Primary Ciliary Dyskinesia.
Petrarca L et al.·Pediatr Pulmonol
2025Cohort
Biallelic Variants in CCDC39 Gene Lead to Primary Ciliary Dyskinesia and Kartagener Syndrome.
Shi X et al.·Biomed Res Int
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CCDC39 Mutation-Related Primary Ciliary Dyskinesia with Congenitally Corrected Transposition of the Great Arteries: A Case Report.
Ghandourah H et al.·Am J Case Rep
2025🔓 Open AccessCase report
[Clinical and genetic analysis of a child with Primary ciliary dyskinesia variants and co-existence of CCDC39 gene variants and 22q11.21 deletion].
Chang J et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025
Chronic Cough, Dyspnea, and a Novel CCDC39 Variant: A Case Report of Heterotaxy Syndrome Without Cardiac Anomalies and Associated Primary Ciliary Dyskinesia.
Juré J et al.·Cureus
2024🔓 Open AccessCase report
Primary Ciliary Dyskinesia Associated Disease-Causing Variants in CCDC39 and CCDC40 Cause Axonemal Absence of Inner Dynein Arm Heavy Chains DNAH1, DNAH6, and DNAH7.
Wilken A et al.·Cells
2024🔓 Open Access
Early postnatal microglial ablation in the Ccdc39 mouse model reveals adverse effects on brain development and in neonatal hydrocephalus.
Brown FN et al.·Fluids Barriers CNS
2023🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools