Myopathy, congenital, progressive, with scoliosis

Summary

Myopathy, congenital, progressive, with scoliosis (MONDO:0032821) is a disease caused by PAX7 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PAX7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopathy, congenital, progressive, with scoliosis
Mondo ID	MONDO:0032821
OMIM	618578
DOID	DOID:0081351
UMLS	C5231417
MedGen	1684769
GARD	0025753
Is cancer (heuristic)	no

Also known as: myopathy, congenital, progressive, with scoliosis · MYOSCO

Data availability: 12 ClinVar variants · 4 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 › myopathy, congenital, progressive, with scoliosis

Related subtypes (53): Ullrich congenital muscular dystrophy, congenital structural myopathy, Bethlem myopathy, MYH7-related skeletal myopathy, tubular aggregate myopathy, cylindrical spirals myopathy, congenital myopathy 7A, myosin storage, autosomal dominant, intellectual disability-myopathy-short stature-endocrine defect syndrome, myopathy, myosin storage, autosomal recessive, Bailey-Bloch congenital myopathy, fingerprint body myopathy, myopathy, proximal, and ophthalmoplegia, Compton-North congenital myopathy, MEGF10-related myopathy, fetal akinesia-cerebral and retinal hemorrhage syndrome, Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome, severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome, myopathy with hexagonally cross-linked tubular arrays, benign Samaritan congenital myopathy, congenital generalized hypercontractile muscle stiffness syndrome, hyaline body myopathy, centronuclear myopathy, reducing body myopathy, myopathy, congenital, with tremor, myopathy, congenital, with structured cores and z-line abnormalities, myopathy, congenital, with respiratory insufficiency and bone fractures, myopathy, congenital proximal, with minicore lesions, myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies, congenital myopathy with reduced type 2 muscle fibers, alpha-actinopathy, SELENON-related myopathy, TPM3-related myopathy, SCN4A-related myopathy, autosomal recessive, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, Batten-Turner congenital myopathy, TOR1AIP1-related myopathy, congenital myopathy 11, congenital myopathy 15, congenital myopathy 18, congenital myopathy 10b, mild variant, congenital myopathy 2b, severe infantile, autosomal recessive, congenital myopathy 2c, severe infantile, autosomal dominant, congenital myopathy 20, congenital myopathy 21 with early respiratory failure, congenital myopathy 22A, classic, congenital myopathy 22B, severe fetal, congenital myopathy 25, congenital myopathy 26, congenital myopathy 27, congenital myopathy 28 with rigid spine, congenital myopathy 29 with contractures

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

12 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 4 pathogenic, 1 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3775439	NM_001135254.2(PAX7):c.742G>T (p.Glu248Ter)	PAX7	Pathogenic	criteria provided, single submitter
689506	NM_001135254.2(PAX7):c.433C>T (p.Arg145Ter)	PAX7	Pathogenic	no assertion criteria provided
689507	NM_001135254.2(PAX7):c.86-1G>A	PAX7	Pathogenic	criteria provided, single submitter
689508	NM_001135254.2(PAX7):c.220C>T (p.Arg74Ter)	PAX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
689509	NM_001135254.2(PAX7):c.166C>T (p.Arg56Cys)	PAX7	Pathogenic	no assertion criteria provided
1027713	NM_001135254.2(PAX7):c.398T>C (p.Ile133Thr)	PAX7	Uncertain significance	criteria provided, single submitter
3065455	NM_001135254.2(PAX7):c.739C>T (p.Arg247Cys)	PAX7	Uncertain significance	criteria provided, single submitter
3891909	NM_001135254.2(PAX7):c.304G>A (p.Gly102Ser)	PAX7	Uncertain significance	criteria provided, single submitter
873482	NM_001135254.2(PAX7):c.644G>A (p.Arg215His)	PAX7	Uncertain significance	criteria provided, multiple submitters, no conflicts
873483	NM_001135254.2(PAX7):c.1402+91T>G	PAX7	Uncertain significance	criteria provided, single submitter
998310	NM_001135254.2(PAX7):c.335C>T (p.Pro112Leu)	PAX7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1326989	NM_001135254.2(PAX7):c.879A>G (p.Pro293=)	PAX7	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
PAX7	Strong	Autosomal recessive	myopathy, congenital, progressive, with scoliosis	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PAX7	Orphanet:99756	Alveolar rhabdomyosarcoma

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
PAX7	HGNC:8621	ENSG00000009709	P23759	Paired box protein Pax-7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PAX7	Paired box protein Pax-7	Transcription factor that is involved in the regulation of muscle stem cells proliferation, playing a role in myogenesis and muscle regeneration.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PAX7	Transcription factor	no		HD, Paired_dom, OAR_dom

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
nasal cavity epithelium	1
nasal cavity mucosa	1
olfactory segment of nasal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAX7	61	tissue_specific	marker	olfactory segment of nasal mucosa, nasal cavity epithelium, nasal cavity mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX7	2,847

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PAX7	P23759	63.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Specification of the neural plate border	1	634.4×	0.002	PAX7

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
skeletal muscle satellite cell commitment	1	16852.0×	0.001	PAX7
regulation of cell fate commitment	1	5617.3×	0.002	PAX7
muscle tissue morphogenesis	1	2407.4×	0.002	PAX7
skeletal muscle satellite cell differentiation	1	2106.5×	0.002	PAX7
regulation of chromatin organization	1	1532.0×	0.002	PAX7
positive regulation of myoblast proliferation	1	1404.3×	0.002	PAX7
spinal cord association neuron differentiation	1	1296.3×	0.002	PAX7
skeletal muscle tissue regeneration	1	887.0×	0.002	PAX7
dorsal/ventral neural tube patterning	1	802.5×	0.002	PAX7
neuron fate commitment	1	802.5×	0.002	PAX7
embryonic skeletal system development	1	391.9×	0.004	PAX7
cartilage development	1	251.5×	0.006	PAX7
anatomical structure morphogenesis	1	139.3×	0.010	PAX7
chromatin remodeling	1	73.0×	0.018	PAX7
transcription by RNA polymerase II	1	70.5×	0.018	PAX7
nervous system development	1	45.9×	0.026	PAX7
negative regulation of apoptotic process	1	34.8×	0.032	PAX7
positive regulation of transcription by RNA polymerase II	1	14.9×	0.071	PAX7
regulation of transcription by RNA polymerase II	1	11.7×	0.086	PAX7

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
PAX7	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	PAX7

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)
PAX7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.