Compton-North congenital myopathy

Summary

Compton-North congenital myopathy (MONDO:0012929) is a disease caused by CNTN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CNTN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 558

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Compton-North congenital myopathy
Mondo ID	MONDO:0012929
MeSH	C567261
OMIM	612540
Orphanet	210163
DOID	DOID:0080101
UMLS	C2675527
MedGen	393406
GARD	0017111
Is cancer (heuristic)	no

Also known as: Compton-North congenital myopathy · myopathy, congenital, Compton-NORTH · MYPCN

Data availability: 558 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 › Compton-North congenital myopathy

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, 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, progressive, with scoliosis, 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

558 retrieved; paginated sample, class counts are floors:

270 likely benign, 223 uncertain significance, 18 benign, 18 pathogenic, 12 benign/likely benign, 12 conflicting classifications of pathogenicity, 5 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1432053	NM_001843.4(CNTN1):c.62del (p.Glu21fs)	CNTN1	Pathogenic	criteria provided, single submitter
1445514	NM_001843.4(CNTN1):c.1615del (p.Val539fs)	CNTN1	Pathogenic	criteria provided, single submitter
1455215	NM_001843.4(CNTN1):c.2632_2636del (p.Phe878fs)	CNTN1	Pathogenic	criteria provided, single submitter
2071790	NM_001843.4(CNTN1):c.2273_2274del (p.Thr758fs)	CNTN1	Pathogenic	criteria provided, single submitter
2082836	NM_001843.4(CNTN1):c.1470_1471del (p.Gly491fs)	CNTN1	Pathogenic	criteria provided, single submitter
2126618	NM_001843.4(CNTN1):c.268C>T (p.Arg90Ter)	CNTN1	Pathogenic	criteria provided, single submitter
2910519	NM_001843.4(CNTN1):c.1711C>T (p.Arg571Ter)	CNTN1	Pathogenic	criteria provided, single submitter
2995467	NM_001843.4(CNTN1):c.482dup (p.Tyr162fs)	CNTN1	Pathogenic	criteria provided, single submitter
2997007	NM_001843.4(CNTN1):c.739C>T (p.Gln247Ter)	CNTN1	Pathogenic	criteria provided, single submitter
3069138	CNTN1, EX2-15DEL and EX18-19DEL	CNTN1	Pathogenic	no assertion criteria provided
3662140	NM_001843.4(CNTN1):c.1362G>A (p.Trp454Ter)	CNTN1	Pathogenic	criteria provided, single submitter
3716597	NM_001843.4(CNTN1):c.2512G>T (p.Glu838Ter)	CNTN1	Pathogenic	criteria provided, single submitter
469421	NM_001843.4(CNTN1):c.2795C>A (p.Ser932Ter)	CNTN1	Pathogenic	criteria provided, single submitter
537192	NM_001843.4(CNTN1):c.2923G>T (p.Glu975Ter)	CNTN1	Pathogenic	criteria provided, single submitter
568623	NM_001843.4(CNTN1):c.215dup (p.Val74fs)	CNTN1	Pathogenic	criteria provided, single submitter
651866	NM_001843.4(CNTN1):c.2506del (p.Lys835_Ile836insTer)	CNTN1	Pathogenic	criteria provided, single submitter
655024	NM_001843.4(CNTN1):c.1074del (p.Ile359fs)	CNTN1	Pathogenic	criteria provided, single submitter
9539	NM_001843.4(CNTN1):c.871dup (p.Ser291fs)	CNTN1	Pathogenic	no assertion criteria provided
1348320	NM_001843.4(CNTN1):c.2597_2710+7delinsTT	CNTN1	Likely pathogenic	criteria provided, single submitter
2875068	NM_001843.4(CNTN1):c.94+2T>C	CNTN1	Likely pathogenic	criteria provided, single submitter
2886308	NM_001843.4(CNTN1):c.704-1G>A	CNTN1	Likely pathogenic	criteria provided, single submitter
3722051	NM_001843.4(CNTN1):c.2711-1G>A	CNTN1	Likely pathogenic	criteria provided, single submitter
469412	NM_001843.4(CNTN1):c.1683+1G>A	CNTN1	Likely pathogenic	criteria provided, single submitter
1463616	NM_001843.4(CNTN1):c.771A>G (p.Gln257=)	CNTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1622916	NM_001843.4(CNTN1):c.827G>A (p.Arg276Gln)	CNTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1980582	NM_001843.4(CNTN1):c.2146G>A (p.Gly716Arg)	CNTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2055648	NM_001843.4(CNTN1):c.2297G>T (p.Arg766Leu)	CNTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
421523	NM_001843.4(CNTN1):c.2644G>A (p.Gly882Arg)	CNTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
423311	NM_001843.4(CNTN1):c.278T>C (p.Met93Thr)	CNTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
434796	NM_001843.4(CNTN1):c.1749C>T (p.Cys583=)	CNTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
CNTN1	Strong	Autosomal recessive	Compton-North congenital myopathy	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNTN1	Orphanet:210163	Congenital lethal myopathy, Compton-North type

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
CNTN1	HGNC:2171	ENSG00000018236	Q12860	Contactin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CNTN1	Contactin-1	Contactins mediate cell surface interactions during nervous system development.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CNTN1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_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
Brodmann (1909) area 23	1
cortical plate	1
endothelial cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CNTN1	228	broad	marker	cortical plate, Brodmann (1909) area 23, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CNTN1	2,717

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNTN1	Q12860	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Neurofascin interactions	1	1427.5×	0.003	CNTN1
NOTCH2 Activation and Transmission of Signal to the Nucleus	1	439.2×	0.004	CNTN1
Activated NOTCH1 Transmits Signal to the Nucleus	1	356.9×	0.004	CNTN1
L1CAM interactions	1	120.2×	0.008	CNTN1

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
central nervous system myelin formation	1	2407.4×	0.005	CNTN1
positive regulation of sodium ion transport	1	842.6×	0.007	CNTN1
cerebellum development	1	358.6×	0.011	CNTN1
locomotory behavior	1	179.3×	0.015	CNTN1
Notch signaling pathway	1	141.6×	0.015	CNTN1
positive regulation of neuron projection development	1	137.0×	0.015	CNTN1
cell-cell adhesion	1	101.5×	0.015	CNTN1
axon guidance	1	90.6×	0.015	CNTN1
gene expression	1	79.9×	0.015	CNTN1
brain development	1	79.5×	0.015	CNTN1
positive regulation of gene expression	1	38.7×	0.027	CNTN1
cell adhesion	1	37.5×	0.027	CNTN1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CNTN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CNTN1	1	Binding:1

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	1	CNTN1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
CNTN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.