CCDC40

Chr 17AR

coiled-coil domain 40 molecular ruler complex subunit

Also known as: CFAP172, CILD15, FAP172

NCBI Gene: 55036 ENSG00000141519 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.841 OMIM phenotype

Clinical Summary— CCDC40

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Gene-Disease Validity (ClinGen)

primary ciliary dyskinesia 15 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

115 unique Pathogenic / Likely Pathogenic· 465 VUS of 1202 total submissions

Explore recent and relevant literature in Research Assistant →

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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 OE?0.64 (0.49–0.84)

0≤0.351.4

Missense OE?1.02 (0.96–1.09)

0≤0.61.4

Synonymous OE?0.98

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

This gene — mechanism propensity

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

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

1202 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic74

Likely Pathogenic41

VUS465

Likely Benign392

Benign131

Conflicting80

Pathogenic

Likely Pathogenic

465

VUS

392

Likely Benign

131

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	66	5	3	0	74
Likely Pathogenic	39	0	2	0	41
VUS	6	408	42	9	465
Likely Benign	7	35	139	211	392
Benign	1	15	100	15	131
Conflicting	—				80
Total	119	463	286	235	1,183

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap CCDC40 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →