CCDC39

Chr 3AR

coiled-coil domain 39 molecular ruler complex subunit

Also known as: CFAP59, CILD14, FAP59

NCBI Gene: 339829 ENSG00000284862 UniProt: Q9UFE4 OMIM: 613798

The protein is required for assembly of dynein regulatory and inner dynein arm complexes that regulate ciliary beat, playing a central role in cilia and flagella motility. Mutations cause primary ciliary dyskinesia type 14, an autosomal recessive disorder affecting the respiratory system, fertility, and other ciliated organs. This gene is not highly constrained against loss-of-function variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.751 OMIM phenotype

Clinical Summary— CCDC39

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Gene-Disease Validity (ClinGen)

primary ciliary dyskinesia 14 · 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

186 unique Pathogenic / Likely Pathogenic· 279 VUS of 984 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CCDC39

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?

0.75LOEUF

pLI 0.000

Z-score 2.93

OE 0.54 (0.40–0.75)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.36Z-score

OE missense 0.95 (0.88–1.03)

402 obs / 423.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.40–0.75)

0≤0.351.4

Missense OE?0.95 (0.88–1.03)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 26 / 47.8Missense obs/exp: 402 / 423.0Syn Z: 0.23

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCCDC39-related primary ciliary dyskinesiaLOFAR

This gene — mechanism propensity

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

0.85top 5%

GOF

0.6737th %ile

LOF

0.1796th %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

984 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic129

Likely Pathogenic57

VUS279

Likely Benign402

Benign57

Conflicting53

129

Pathogenic

Likely Pathogenic

279

VUS

402

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	117	0	12	0	129
Likely Pathogenic	48	3	5	1	57
VUS	1	232	44	2	279
Likely Benign	1	10	194	197	402
Benign	0	5	48	4	57
Conflicting	—				53
Total	167	250	303	204	977

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap CCDC39 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →