Congenital myopathy 2b, severe infantile, autosomal recessive

Summary

Congenital myopathy 2b, severe infantile, autosomal recessive (MONDO:0859517) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myopathy 2b, severe infantile, autosomal recessive
Mondo ID	MONDO:0859517
OMIM	620265
DOID	DOID:0081339
UMLS	C5830300
MedGen	1840936
GARD	0026732
Is cancer (heuristic)	no

Data availability: 12 ClinVar variants.

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 › congenital myopathy 2b, severe infantile, autosomal recessive

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, 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 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:

4 pathogenic/likely pathogenic, 4 pathogenic, 2 likely pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1459640	NM_001100.4(ACTA1):c.436del (p.Ala146fs)	ACTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18279	NM_001100.4(ACTA1):c.287T>C (p.Leu96Pro)	ACTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18281	NM_001100.4(ACTA1):c.49G>C (p.Gly17Arg)	ACTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18283	NM_001100.4(ACTA1):c.782A>T (p.Glu261Val)	ACTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2443895	NM_001100.4(ACTA1):c.121C>T (p.Arg41Ter)	ACTA1	Pathogenic	no assertion criteria provided
2443897	NM_001100.4(ACTA1):c.809-1G>T	ACTA1	Pathogenic	no assertion criteria provided
420100	NM_001100.4(ACTA1):c.541del (p.Asp181fs)	ACTA1	Pathogenic	reviewed by expert panel
692271	NM_001100.4(ACTA1):c.739G>A (p.Gly247Arg)	ACTA1	Pathogenic	criteria provided, multiple submitters, no conflicts
224666	NM_001100.4(ACTA1):c.460G>C (p.Val154Leu)	ACTA1	Likely pathogenic	criteria provided, single submitter
4292037	NM_001100.4(ACTA1):c.946del (p.Gln316fs)	ACTA1	Likely pathogenic	criteria provided, single submitter
3341326	NM_001100.4(ACTA1):c.3G>C (p.Met1Ile)	ACTA1	Uncertain significance	criteria provided, single submitter
4293593	NM_001100.4(ACTA1):c.277T>C (p.Tyr93His)	ACTA1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACTA1	Orphanet:171430	Severe congenital nemaline myopathy
ACTA1	Orphanet:171433	Intermediate nemaline myopathy
ACTA1	Orphanet:171436	Typical nemaline myopathy
ACTA1	Orphanet:171439	Childhood-onset nemaline myopathy
ACTA1	Orphanet:2020	Congenital fiber-type disproportion myopathy
ACTA1	Orphanet:447977	Progressive scapulohumeroperoneal distal myopathy
ACTA1	Orphanet:97240	Zebra body myopathy
ACTA1	Orphanet:97244	Rigid spine syndrome
ACTA1	Orphanet:98904	Congenital myopathy with excess of thin filaments

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
ACTA1	HGNC:129	ENSG00000143632	P68133	Actin, alpha skeletal muscle	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACTA1	Actin, alpha skeletal muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

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)
ACTA1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS

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
diaphragm	1
gluteal muscle	1
skeletal muscle tissue of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACTA1	203	broad	marker	gluteal muscle, skeletal muscle tissue of biceps brachii, diaphragm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACTA1	523

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACTA1	P68133	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Regulation of CDH1 Function	1	951.7×	0.007	ACTA1
Striated Muscle Contraction	1	308.6×	0.008	ACTA1
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.008	ACTA1
Activation of STAT3 by cadherin engagement	1	163.1×	0.009	ACTA1
Non-integrin membrane-ECM interactions	1	154.3×	0.009	ACTA1
Muscle contraction	1	77.2×	0.015	ACTA1
Extracellular matrix organization	1	63.1×	0.016	ACTA1

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
mesenchyme migration	1	3370.4×	9e-04	ACTA1
skeletal muscle thin filament assembly	1	2808.7×	9e-04	ACTA1
skeletal muscle fiber development	1	543.6×	0.003	ACTA1
muscle contraction	1	208.1×	0.006	ACTA1
positive regulation of gene expression	1	38.7×	0.026	ACTA1

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
ACTA1	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	ACTA1

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)
ACTA1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.