CCDC40

Chr 17AR

coiled-coil domain 40 molecular ruler complex subunit

Also known as: CFAP172, CILD15, FAP172

NCBI Gene: 55036ENSG00000141519UniProt: Q4G0X9

This gene encodes a protein that is necessary for motile cilia function. It functions in correct left-right axis formation by regulating the assembly of the inner dynein arm and the dynein regulatory complexes, which control ciliary beat. Mutations in this gene cause ciliary dyskinesia type 15, a disorder due to defects in cilia motility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 15MIM #613808
AR
0
Active trials
51
Pathogenic / LP
481
ClinVar variants
6
Pubs (1 yr)
-0.2
Missense Z
0.84
LOEUF
Clinical Summary— CCDC40
🧬
Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia 15 · 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
51 Pathogenic / Likely Pathogenic· 211 VUS of 481 total submissions
📖
GeneReview available — CCDC40
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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.
0.84LOEUF
pLI 0.000
Z-score 2.49
OE 0.64 (0.49–0.84)
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.
-0.18Z-score
OE missense 1.02 (0.96–1.09)
680 obs / 666.9 exp
Tolerant

Tolerant to missense variation

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.0.64 (0.49–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.96–1.09)
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: 35 / 54.9Missense obs/exp: 680 / 666.9Syn Z: 0.28

ClinVar Variant Classifications

481 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic17
VUS211
Likely Benign177
Benign12
Conflicting30
34
Pathogenic
17
Likely Pathogenic
211
VUS
177
Likely Benign
12
Benign
30
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
1
17
0
34
Likely Pathogenic
10
0
7
0
17
VUS
3
180
24
4
211
Likely Benign
1
10
72
94
177
Benign
0
2
10
0
12
Conflicting
—30
Total3019313098481

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

View in ClinVar →

Protein Context — Lollipop Plot

CCDC40 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CCDC40-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, 15

MIM #613808

Molecular basis of disorder known

Autosomal recessive

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
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
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
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
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
Genetics of 67 patients of suspected primary ciliary dyskinesia from India.
Jat KR et al.·Clin Genet
2024Cohort
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
Malignancy in Adults with Inborn Errors of Immunity: A Retrospective Single-Center Study.
Gumusburun R et al.·J Clin Immunol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Genomic Complexity of ccdc40 in Xenopus : Implications for CRISPR Targeting and Disease Modeling.
Nakayama T et al.·MicroPubl Biol
2025Open AccessFunctional
Novel rare variation of CCDC40 plays a role in the development of idiopathic scoliosis possibly via dysfunction of cilia motility.
Xu L et al.·Spine J
2025
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
2024Open Access
Identification of a Homozygous Mutation of CCDC40 in a Chinese Infertile Man with MMAF and PCD-like Phenotypes.
Liu Z et al.·Genet Test Mol Biomarkers
2024
Pathogenic gene variants in CCDC39, CCDC40, RSPH1, RSPH9, HYDIN, and SPEF2 cause defects of sperm flagella composition and male infertility.
Aprea I et al.·Front Genet
2023Open Access
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients