GeneBe

CCDC78

protein-coding

coiled-coil domain containing 78

Gene summary

Involved in de novo centriole assembly involved in multi-ciliated epithelial cell differentiation and skeletal muscle contraction. Located in several cellular components, including centriole; deuterosome; and sarcolemma. Implicated in centronuclear myopathy 4. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:
  • C16orf25

MANE transcript

NM_001378030.1

Inheritance

AD

ClinVar variants

U:316B:198

Top phenotype

Myopathy, centronuclear, 4

gnomAD constraint

pLI —, LoF o/e 1.39

Max pathogenic AF

—

Genomic locus

chr16:722,582-726,954

External References & Databases

Ensembl (ENSG00000162004)NCBI Gene (124093)OMIM (614666)HGNC:14153GenCCUniProt (A2IDD5)AlphaFoldClinVar (CCDC78)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~4.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital myopathy with internal nuclei and atypical coresSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0013890

Submitter: Orphanet

congenital myopathy with internal nuclei and atypical coresLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013890

Submitter: Labcorp Genetics (formerly Invitae)

centronuclear myopathyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0018947

Submitter: ClinGen

*CCDC78* was reported in relation to autosomal dominant centronuclear myopathy in 2012 (Majczenko et al., PMID: 22818856). At least two unique splicing variants and a missense/nonsense have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 3 probands in 3 publications (PMID: 22818856, 25635128, 39273074). This gene-disease relationship is supported by protein interactions (PMID: 39273074), expression studies and an animal model (PMID: 22818856). In summary, there is Limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This gene-disease pair was originally evaluated by the CM GCEP on 12/09/2019. It was reevaluated on 01/23/25. As a result of this reevaluation new genetic and experimental evidence was identified (PMID: 39273074) and the classification remained Limited.

congenital myopathy with internal nuclei and atypical coresLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013890

Submitter: G2P

Clinical Genomic Database (CGD)

Myopathy, centronuclear, 4AD

Manifestation: Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 22818856Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCDC78 variants in ClinVar

7 Conditions Cataloged
Congenital myopathy with internal nuclei and atypical coresTotal: 600
Inborn genetic diseasesTotal: 102
not providedTotal: 68
not specifiedTotal: 42
CCDC78-related disorderTotal: 26
Centronuclear myopathyTotal: 3
Primary ciliary dyskinesiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001378030.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
15
clinvar
121
clinvar
5
clinvar
 141
missense
245
clinvar
64
clinvar
2
clinvar
 311
nonsense
17
clinvar
3
clinvar
 20
start loss
2
clinvar
 2
frameshift
14
clinvar
 14
splice donor/acceptor (+/-2bp)
23
clinvar
2
clinvar
1
clinvar
 26
Total003161908514
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001378030.1RefSeqNP_001364959.114MANE Select
ENST00000345165.10EnsemblENSP00000316851.514MANE Select
NM_001031737.3RefSeqNP_001026907.214Standard
NM_001378031.1RefSeqNP_001364960.112Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
ccdc78Danio rerio

Structure: skeletal muscle cell

Quality: has extra parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • skeletal muscle contraction
  • cell projection organization
  • de novo centriole assembly involved in multi-ciliated epithelial cell differentiation

Cellular Component

  • centriole
  • sarcoplasmic reticulum
  • sarcolemma
  • perinuclear region of cytoplasm
  • deuterosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000293889
Coding exons
14
Length
4373
Individuals with no LoFs
124787
Homozygous LoFs
0
Heterozygous LoFs
682
Defined
125469
p
0.00272
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.8603132731.150.00001732779
Missense (PolyPhen)8172.3681.1193852
Synonymous-0.3601151101.040.00000672897
Loss of Function-1.944028.81.390.00000159276

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00460.0043notable
Latino/Admixed American0.00380.0038notable
Ashkenazi Jewish0.00140.0014notable
East Asian0.00150.0013notable
Finnish0.00940.0081notable
European (Non-Finnish)0.00210.0021notable
South Asian0.000430.00042rare
Other0.00280.0028notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells that can generate more than 100 centrioles. Deuterosome-mediated centriole amplification occurs in terminally differentiated multiciliated cells (G1/0) and not in S phase. Essential for centriole amplification and is required for CEP152 localization to the deuterosome. {ECO:0000269|PubMed:24075808}.;

Intolerance Scores

LoFtool
0.960
RVIS EVS
1.42
RVIS percentile EVS
94.97

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.0620

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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