CCDC40

Chr 17AR

coiled-coil domain 40 molecular ruler complex subunit

Also known as: CFAP172, CILD15, FAP172

NCBI Gene: 55036ENSG00000141519UniProt: Q4G0X9OMIM: 613799

The protein is required for assembly of dynein regulatory complexes and inner dynein arm complexes that control ciliary beat regulation, playing a central role in motile cilia and flagella function. Mutations cause primary ciliary dyskinesia type 15, a disorder affecting respiratory tract clearance, fertility, and organ lateralization due to defective cilia motility. This condition follows autosomal recessive inheritance and typically presents in early childhood with chronic respiratory symptoms.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.841 OMIM phenotype
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
44 unique Pathogenic / Likely Pathogenic· 215 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
📖
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
0.84LOEUF
pLI 0.000
Z-score 2.49
OE 0.64 (0.49–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.18Z-score
OE missense 1.02 (0.96–1.09)
680 obs / 666.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.64 (0.49–0.84)
0≤0.351.4
Missense OE1.02 (0.96–1.09)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 35 / 54.9Missense obs/exp: 680 / 666.9Syn Z: 0.28
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCCDC40-related primary ciliary dyskinesiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.79top 25%
GOF
0.6345th %ile
LOF
0.2287th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic18
VUS215
Likely Benign208
Benign7
Conflicting7
26
Pathogenic
18
Likely Pathogenic
215
VUS
208
Likely Benign
7
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
1
2
0
26
Likely Pathogenic
17
0
1
0
18
VUS
3
202
8
2
215
Likely Benign
0
10
90
108
208
Benign
0
1
6
0
7
Conflicting
—7
Total43214107110481

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search 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 ↗

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