Congenital myopathy with internal nuclei and atypical cores
diseaseOn this page
Also known as centronuclear myopathy type 4CNM4myopathy, centronuclear, 4myopathy, centronuclear, type 4
Summary
Congenital myopathy with internal nuclei and atypical cores (MONDO:0013890) is a disease with 1 cohort gene.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Cohort genes: 1
- ClinVar variants: 611
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 5 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | congenital myopathy with internal nuclei and atypical cores |
| Mondo ID | MONDO:0013890 |
| OMIM | 614807 |
| Orphanet | 319160 |
| DOID | DOID:0111224 |
| SNOMED CT | 764945007 |
| UMLS | C4707232 |
| MedGen | 1642424 |
| GARD | 0017443 |
| Is cancer (heuristic) | no |
Also known as: centronuclear myopathy type 4 · CNM4 · myopathy, centronuclear, 4 · myopathy, centronuclear, type 4
Data availability: 611 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › congenital myopathy › centronuclear myopathy › congenital myopathy with internal nuclei and atypical cores
Related subtypes (4): autosomal dominant centronuclear myopathy, X-linked myotubular myopathy, autosomal recessive centronuclear myopathy, myopathy, centronuclear, 6, with fiber-type disproportion
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
600 retrieved; paginated sample, class counts are floors:
286 uncertain significance, 237 likely benign, 37 conflicting classifications of pathogenicity, 22 benign, 17 benign/likely benign, 1 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 4280670 | CCDC78, TRP402TER (rs752371476) | CCDC78 | Pathogenic | no assertion criteria provided |
| 1001979 | NM_001378030.1(CCDC78):c.109G>A (p.Ala37Thr) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1033221 | NM_001378030.1(CCDC78):c.1134-19C>T | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1035436 | NM_001378030.1(CCDC78):c.432C>G (p.Phe144Leu) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1051473 | NM_001378030.1(CCDC78):c.593G>A (p.Arg198Gln) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1107562 | NM_001378030.1(CCDC78):c.1220G>A (p.Arg407Gln) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 128634 | NM_001378030.1(CCDC78):c.966C>A (p.Asn322Lys) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1349222 | NM_001378030.1(CCDC78):c.1057G>A (p.Gly353Ser) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1392443 | NM_001378030.1(CCDC78):c.893G>C (p.Ser298Thr) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1398368 | NM_001378030.1(CCDC78):c.692G>T (p.Arg231Leu) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1622968 | NM_001378030.1(CCDC78):c.28A>G (p.Arg10Gly) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2019648 | NM_001378030.1(CCDC78):c.592C>G (p.Arg198Gly) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2073227 | NM_001378030.1(CCDC78):c.477C>G (p.His159Gln) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2185072 | NM_001378030.1(CCDC78):c.1311C>G (p.His437Gln) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 383732 | NM_001378030.1(CCDC78):c.267+3G>A | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 425081 | NM_001378030.1(CCDC78):c.1241C>A (p.Ala414Asp) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 434621 | NM_001378030.1(CCDC78):c.730G>A (p.Val244Ile) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 447008 | NM_001378030.1(CCDC78):c.384G>T (p.Glu128Asp) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 447011 | NM_001378030.1(CCDC78):c.973G>C (p.Ala325Pro) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 473249 | NM_001378030.1(CCDC78):c.1103G>A (p.Gly368Glu) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 473250 | NM_001378030.1(CCDC78):c.1214G>A (p.Arg405Gln) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 473252 | NM_001378030.1(CCDC78):c.1275G>A (p.Gln425=) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 473257 | NM_001378030.1(CCDC78):c.365C>T (p.Pro122Leu) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 473258 | NM_001378030.1(CCDC78):c.368G>A (p.Arg123Gln) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 473259 | NM_001378030.1(CCDC78):c.468T>G (p.Asn156Lys) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 473260 | NM_001378030.1(CCDC78):c.472C>T (p.Gln158Ter) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 540468 | NM_001378030.1(CCDC78):c.536G>A (p.Arg179Gln) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 540470 | NM_001378030.1(CCDC78):c.554C>T (p.Thr185Met) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 566102 | NM_001378030.1(CCDC78):c.683A>C (p.Glu228Ala) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 573114 | NM_001378030.1(CCDC78):c.1281C>T (p.Tyr427=) | CCDC78 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| CCDC78 | Supportive | Autosomal dominant | congenital myopathy with internal nuclei and atypical cores | 3 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CCDC78 | Orphanet:319160 | Congenital myopathy with internal nuclei and atypical cores |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| CCDC78 | HGNC:14153 | ENSG00000162004 | A2IDD5 | Coiled-coil domain-containing protein 78 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CCDC78 | Coiled-coil domain-containing protein 78 | Component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells that can generate more than 100 centrioles. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| CCDC78 | Other/Unknown | no | DUF4472, CCDC78 |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| bronchial epithelial cell | 1 |
| bronchus | 1 |
| right uterine tube | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CCDC78 | 176 | broad | marker | right uterine tube, bronchial epithelial cell, bronchus |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| CCDC78 | 1,019 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| CCDC78 | A2IDD5 | 66.65 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| de novo centriole assembly involved in multi-ciliated epithelial cell differentiation | 1 | 3370.4× | 9e-04 | CCDC78 |
| skeletal muscle contraction | 1 | 510.7× | 0.003 | CCDC78 |
| cell projection organization | 1 | 374.5× | 0.003 | CCDC78 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| CCDC78 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | CCDC78 |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| CCDC78 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: CCDC78