CCDC78

Summary

CCDC78 (coiled-coil domain containing 78, HGNC:14153) is a protein-coding gene on chromosome 16p13.3, encoding Coiled-coil domain-containing protein 78 (A2IDD5). Component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells that can generate more than 100 centrioles.

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.

Source: NCBI Gene 124093 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myopathy with internal nuclei and atypical cores (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 691 total — 2 pathogenic
• Phenotypes (HPO): 14
• MANE Select transcript: NM_001378030

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14153
Approved symbol	CCDC78
Name	coiled-coil domain containing 78
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34512
Ensembl gene	ENSG00000162004
Ensembl biotype	protein_coding
OMIM	614666
Entrez	124093

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 14 retained_intron, 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000293889, ENST00000345165, ENST00000423653, ENST00000439619, ENST00000460023, ENST00000463539, ENST00000466708, ENST00000471861, ENST00000474647, ENST00000478979, ENST00000481804, ENST00000482152, ENST00000482878, ENST00000485091, ENST00000538176, ENST00000544996, ENST00000650995, ENST00000682391, ENST00000853031, ENST00000853032, ENST00000853033, ENST00000853034, ENST00000853035, ENST00000853036, ENST00000947032, ENST00000947033

RefSeq mRNA: 4 — MANE Select: NM_001378030 NM_001031737, NM_001378030, NM_001378031, NM_001378033

CCDS: CCDS32353, CCDS92076

Canonical transcript exons

ENST00000345165 — 14 exons

Exon	Start	End
ENSE00003472766	724911	724989
ENSE00003531474	722922	723022
ENSE00003551548	725078	725145
ENSE00003553594	724322	724509
ENSE00003554238	724681	724806
ENSE00003557157	723857	723936
ENSE00003561765	723095	723161
ENSE00003563526	725794	725880
ENSE00003572853	725413	725580
ENSE00003591521	724106	724205
ENSE00003610633	725237	725293
ENSE00003626679	722582	722789
ENSE00003637021	725966	726085
ENSE00003843284	726308	726443

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 99.14.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6005 / max 48.4248, expressed in 267 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155776	0.3025	178
155775	0.2980	105

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.14	gold quality
bronchial epithelial cell	CL:0002328	98.38	gold quality
bronchus	UBERON:0002185	97.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.07	gold quality
oviduct epithelium	UBERON:0004804	91.92	gold quality
nasal cavity epithelium	UBERON:0005384	91.32	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.28	gold quality
fallopian tube	UBERON:0003889	89.22	gold quality
cerebellar hemisphere	UBERON:0002245	89.15	gold quality
cerebellar cortex	UBERON:0002129	88.92	gold quality
caudate nucleus	UBERON:0001873	87.59	gold quality
putamen	UBERON:0001874	87.24	gold quality
cerebellum	UBERON:0002037	86.71	gold quality
nucleus accumbens	UBERON:0001882	83.72	gold quality
pituitary gland	UBERON:0000007	82.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.50	gold quality
adenohypophysis	UBERON:0002196	82.39	gold quality
right lung	UBERON:0002167	81.64	gold quality
left uterine tube	UBERON:0001303	81.59	gold quality
right frontal lobe	UBERON:0002810	80.89	gold quality
hypothalamus	UBERON:0001898	79.32	gold quality
spinal cord	UBERON:0002240	79.08	gold quality
endocervix	UBERON:0000458	77.82	gold quality
trachea	UBERON:0003126	77.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.16	gold quality
anterior cingulate cortex	UBERON:0009835	76.85	gold quality
cortical plate	UBERON:0005343	76.76	gold quality
nasal cavity mucosa	UBERON:0001826	76.74	gold quality
spleen	UBERON:0002106	76.59	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	65.02
E-HCAD-1	yes	29.81
E-MTAB-10287	yes	27.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Dominant mutation of CCDC78 in a unique congenital myopathy with prominent internal nuclei and atypical cores. (PMID:22818856)
• The Influence of a Genetic Variant in CCDC78 on LMNA-Associated Skeletal Muscle Disease. (PMID:38732148)
• CCDC78: Unveiling the Function of a Novel Gene Associated with Hereditary Myopathy. (PMID:39273074)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc78	ENSDARG00000030095
mus_musculus	Ccdc78	ENSMUSG00000071202
rattus_norvegicus	Ccdc78	ENSRNOG00000022331

Protein

Protein identifiers

Coiled-coil domain-containing protein 78 — A2IDD5 (reviewed: A2IDD5)

Alternative names: hsCCDC78

All UniProt accessions (3): A0A494C131, A2IDD5, H3BLT8

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Perinuclear region. Cell membrane. Sarcolemma. Sarcoplasmic reticulum.

Tissue specificity. Expressed primarily in skeletal muscle.

Disease relevance. Myopathy, centronuclear, 4 (CNM4) [MIM:614807] A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Due to intron retention. Due to intron retention. Due to intron retention. Due to intron retention.

Similarity. Belongs to the CCDC78 family.

Isoforms (6)

UniProt ID	Names	Canonical?
A2IDD5-1	1	yes
A2IDD5-2	2
A2IDD5-3	3
A2IDD5-4	4
A2IDD5-5	5
A2IDD5-6	6

RefSeq proteins (4): NP_001026907, NP_001364959, NP_001364960, NP_001364962 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029329	DUF4472	Domain
IPR039873	CCDC78	Family

Pfam: PF14739

UniProt features (14 total): splice variant 7, sequence conflict 2, coiled-coil region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A2IDD5-F1	66.65	0.29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, AREB6_03, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GOBP_SKELETAL_MUSCLE_CONTRACTION, CAGCTG_AP4_Q5, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CENTRIOLE_ASSEMBLY, GOBP_MUSCLE_CONTRACTION, GOBP_ORGANELLE_ASSEMBLY, GOBP_COLUMNAR_CUBOIDAL_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_MUSCLE_SYSTEM_PROCESS, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_NEUROMUSCULAR_PROCESS, GOCC_CENTRIOLE, GOCC_SARCOPLASM

GO Biological Process (3): skeletal muscle contraction (GO:0003009), cell projection organization (GO:0030030), de novo centriole assembly involved in multi-ciliated epithelial cell differentiation (GO:0098535)

GO Molecular Function (0):

GO Cellular Component (9): cytoplasm (GO:0005737), centriole (GO:0005814), sarcoplasmic reticulum (GO:0016529), sarcolemma (GO:0042383), perinuclear region of cytoplasm (GO:0048471), deuterosome (GO:0098536), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membraneless organelle	3
striated muscle contraction	1
musculoskeletal movement	1
cellular component organization	1
de novo centriole assembly	1
multi-ciliated epithelial cell differentiation	1
intracellular anatomical structure	1
microtubule organizing center	1
endoplasmic reticulum	1
sarcoplasm	1
plasma membrane	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

999 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC78	DEUP1	Q05D60	744
CCDC78	MTMR14	Q8NCE2	638
CCDC78	KBTBD13	C9JR72	620
CCDC78	MTM1	Q13496	596
CCDC78	MCIDAS	D6RGH6	593
CCDC78	SELENON	Q9NZV5	593
CCDC78	BICDL2	A1A5D9	589
CCDC78	BBOF1	Q8ND07	559
CCDC78	MEGF10	Q96KG7	544
CCDC78	RYR1	P21817	535
CCDC78	FAM240A	A0A1B0GVK7	509
CCDC78	KLHL40	Q2TBA0	487
CCDC78	CCNO	P22674	450
CCDC78	DNM2	P50570	449
CCDC78	OTOP3	Q7RTS5	435

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CCDC78	CORO1A	psi-mi:“MI:0914”(association)	0.350
CASS4	CCDC78	psi-mi:“MI:0915”(physical association)	0.000
dAK1_1	CCDC78	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): CCDC78 (Affinity Capture-MS), INCA1 (Two-hybrid), BRK1 (Affinity Capture-MS), CORO1A (Affinity Capture-MS), MYH1 (Affinity Capture-MS), ACTN2 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), CASQ1 (Affinity Capture-MS), ACTA1 (Affinity Capture-MS), TPM1 (Affinity Capture-MS), TPM2 (Affinity Capture-MS), ATP2A1 (Affinity Capture-Western), CASQ1 (Affinity Capture-Western), MYH1 (Affinity Capture-Western), ACTN2 (Affinity Capture-Western)

ESM2 similar proteins: A0A8I5KY20, A2A9T0, A2IDD5, B0BNK9, B8ZZ34, C9JI98, C9JLR9, F5GYI3, O18734, P0CG25, P84157, Q0IIA6, Q0PHV7, Q0X0E2, Q13387, Q1RMK9, Q2M3D2, Q2TAM9, Q3ZCQ3, Q4VA45, Q673H1, Q69YZ2, Q6NS60, Q6P6N5, Q6PJ61, Q7Z6J2, Q80ZJ8, Q810I0, Q86SX3, Q86UD0, Q86XT2, Q8BNN1, Q8IUW3, Q8N4Y2, Q8N6N2, Q8QZV0, Q8R4T5, Q8TF61, Q8VCR9, Q8WXF8

Diamond homologs: A2IDD5, D3Z5T1, Q66KE8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

691 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	332
Likely benign	254
Benign	34

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4280670	CCDC78, TRP402TER (rs752371476)	Pathogenic
832709	NC_000016.9:g.(?624055)(2148005_?)del	Pathogenic

SpliceAI

1947 predictions. Top by Δscore:

Variant	Effect	Δscore
16:722944:A:AC	donor_gain	1.0000
16:722944:ACT:A	donor_gain	1.0000
16:722945:C:CC	donor_gain	1.0000
16:722945:CTC:C	donor_gain	1.0000
16:723089:TCCTA:T	donor_loss	1.0000
16:723090:CCTA:C	donor_loss	1.0000
16:723091:CTAC:C	donor_loss	1.0000
16:723092:TACCT:T	donor_loss	1.0000
16:723093:A:AG	donor_loss	1.0000
16:723094:C:CA	donor_loss	1.0000
16:723157:GGCCC:G	acceptor_gain	1.0000
16:723158:GCCC:G	acceptor_gain	1.0000
16:723159:CCC:C	acceptor_gain	1.0000
16:723159:CCCC:C	acceptor_gain	1.0000
16:723160:CC:C	acceptor_gain	1.0000
16:723160:CCCTG:C	acceptor_gain	1.0000
16:723161:CC:C	acceptor_gain	1.0000
16:723162:C:CA	acceptor_loss	1.0000
16:723162:C:CC	acceptor_gain	1.0000
16:723162:C:T	acceptor_gain	1.0000
16:723163:T:C	acceptor_loss	1.0000
16:723164:G:C	acceptor_gain	1.0000
16:723164:G:GC	acceptor_gain	1.0000
16:724338:G:C	donor_gain	1.0000
16:724680:CCA:C	donor_gain	1.0000
16:725236:CGCCG:C	donor_gain	1.0000
16:725790:TCAC:T	donor_loss	1.0000
16:725792:A:AC	donor_gain	1.0000
16:725792:A:AT	donor_loss	1.0000
16:725793:C:CC	donor_gain	1.0000

AlphaMissense

3010 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:725809:G:C	F84L	0.962
16:725809:G:T	F84L	0.962
16:725811:A:G	F84L	0.962
16:725804:A:G	L86P	0.960
16:723110:G:C	F395L	0.948
16:723110:G:T	F395L	0.948
16:723112:A:G	F395L	0.948
16:724739:A:G	L236P	0.942
16:724456:G:C	F273L	0.941
16:724456:G:T	F273L	0.941
16:724458:A:G	F273L	0.941
16:724751:A:G	L232P	0.937
16:725570:A:G	L93P	0.930
16:725561:C:G	R96P	0.921
16:724412:C:G	R288P	0.919
16:725867:A:G	L65P	0.912
16:725820:C:G	A81P	0.896
16:725872:C:A	K63N	0.889
16:725872:C:G	K63N	0.889
16:724730:A:G	L239P	0.887
16:724358:A:G	L306P	0.886
16:724413:G:T	R288S	0.882
16:724400:A:G	L292P	0.881
16:724773:C:G	A225P	0.881
16:724706:A:G	L247P	0.880
16:723132:A:G	I388T	0.878
16:724392:C:G	A295P	0.877
16:725837:A:G	L75P	0.875
16:724389:C:G	A296P	0.874
16:724408:C:A	E289D	0.872

dbSNP variants (sampled 300 via entrez): RS1000549010 (16:725093 G>A), RS1000580272 (16:725314 G>A,C), RS1001573428 (16:727921 G>T), RS1001836787 (16:726753 G>A,T), RS1001939682 (16:727761 G>A,C), RS1002536785 (16:728767 C>A,G,T), RS1002884761 (16:728349 C>T), RS1002917360 (16:728719 G>A,C), RS1004345653 (16:726480 C>A,T), RS1004872968 (16:728280 C>A,T), RS1005404205 (16:723287 A>G), RS1005478564 (16:727266 G>T), RS1006750867 (16:726343 G>A,C), RS1006891646 (16:726086 C>A,T), RS1007080844 (16:722239 G>C)

Disease associations

OMIM: gene MIM:614666 | disease phenotypes: MIM:614807, MIM:160150, MIM:613254

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myopathy with internal nuclei and atypical cores	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
centronuclear myopathy	Limited	AD

Mondo (3): congenital myopathy with internal nuclei and atypical cores (MONDO:0013890), centronuclear myopathy (MONDO:0018947), tuberous sclerosis 2 (MONDO:0013199)

Orphanet (3): Congenital myopathy with internal nuclei and atypical cores (Orphanet:319160), Centronuclear myopathy (Orphanet:595), Tuberous sclerosis complex (Orphanet:805)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001324	Muscle weakness
HP:0002359	Frequent falls
HP:0003326	Myalgia
HP:0003546	Exercise intolerance
HP:0003623	Neonatal onset
HP:0003687	Centrally nucleated skeletal muscle fibers
HP:0003803	Type 1 muscle fiber predominance
HP:0011463	Childhood onset
HP:0040081	Abnormal circulating creatine kinase concentration

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002403_664	Red blood cell count	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566021	Tuberous Sclerosis 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
prothioconazole	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

16 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02201212	PHASE2	COMPLETED	Everolimus for Cancer With TSC1 or TSC2 Mutation
NCT05103358	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)
NCT04033159	PHASE1/PHASE2	TERMINATED	Early Phase Human Drug Trial to Investigate Dynamin 101 (DYN101) in Patients ≥ 16 Years With Centronuclear Myopathies
NCT04743557	PHASE1/PHASE2	WITHDRAWN	Early Phase Human Drug Trial to Investigate DYN101 in Participants 2 to 17 Years With Centronuclear Myopathies
NCT00272883	Not specified	RECRUITING	Molecular and Genetic Studies of Congenital Myopathies
NCT03351270	Not specified	COMPLETED	Prospective Natural History Study of Patients With Myotubular Myopathy and Other CentroNuclear Myopathies
NCT04064307	Not specified	RECRUITING	Myotubular and Centronuclear Myopathy Patient Registry
NCT04977648	Not specified	WITHDRAWN	Natural History Study of Patients With Centronuclear Myopathies
NCT05099107	Not specified	COMPLETED	Changes of Motor Function Tests in Congenital Myopathy Subjects Treated With Oral Salbutamol as Compared to no Treatment
NCT05982119	Not specified	RECRUITING	Assessments in Patients With Muscular Pathology and in Control Subjects : The ActiLiège Next Study
NCT06157268	Not specified	RECRUITING	The Natural History and Muscle Fatigability of Patients With Congenital Myopathies.
NCT06791369	Not specified	NOT_YET_RECRUITING	The Prevalence of RYR1-related Disease
NCT07021820	Not specified	RECRUITING	Multispectral Optoacoustic Tomography for Advanced Imaging of Centronuclear Myopathy
NCT07478172	Not specified	RECRUITING	Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT03817515	Not specified	APPROVED_FOR_MARKETING	Expanded Access for ABI-009 in Patients With Advanced PEComa and Patients With a Malignancy With Relevant Genetic Mutations or mTOR Pathway Activation