CCDC78

Chr 16AD

coiled-coil domain containing 78

Also known as: C16orf25, CNM4, JFP10, hsCCDC78

The CCDC78 protein is a component of the deuterosome that promotes de novo centriole amplification in multiciliated cells and is essential for centriole assembly during multiciliated epithelial cell differentiation. Mutations cause centronuclear myopathy 4, a muscle disorder affecting skeletal muscle function. The gene shows tolerance to loss-of-function variants (low constraint), and inheritance pattern information is not provided in the available data.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismADLOEUF 1.791 OMIM phenotype
Clinical SummaryCCDC78
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Gene-Disease Validity (ClinGen)
centronuclear myopathy · ADLimited

Limited evidence — not for standalone diagnostic reporting

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.79LOEUF
pLI 0.000
Z-score -1.94
OE 1.39 (1.081.79)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.86Z-score
OE missense 1.15 (1.041.26)
313 obs / 273.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.39 (1.081.79)
00.351.4
Missense OE1.15 (1.041.26)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 40 / 28.8Missense obs/exp: 313 / 273.0Syn Z: -0.36
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCCDC78-related congenital myopathyLOFAD
DN
0.7230th %ile
GOF
0.6736th %ile
LOF
0.3647th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CCDC78 · 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

No active trials found for this gene.

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Clinical Literature
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