Zebra body myopathy

Summary

Zebra body myopathy (MONDO:0019949) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 22

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0000467	Neck muscle weakness	Very frequent (80-99%)
HP:0000473	Torticollis	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001319	Neonatal hypotonia	Very frequent (80-99%)
HP:0001558	Decreased fetal movement	Very frequent (80-99%)
HP:0002460	Distal muscle weakness	Very frequent (80-99%)
HP:0002515	Waddling gait	Very frequent (80-99%)
HP:0003236	Elevated circulating creatine kinase concentration	Very frequent (80-99%)
HP:0003327	Axial muscle weakness	Very frequent (80-99%)
HP:0003391	Gowers sign	Very frequent (80-99%)
HP:0003458	EMG: myopathic abnormalities	Very frequent (80-99%)
HP:0003551	Difficulty climbing stairs	Very frequent (80-99%)
HP:0003555	Muscle fiber splitting	Very frequent (80-99%)
HP:0003701	Proximal muscle weakness	Very frequent (80-99%)
HP:0003715	Myofibrillar myopathy	Very frequent (80-99%)
HP:0003736	Autophagic vacuoles	Very frequent (80-99%)
HP:0003798	Nemaline bodies	Very frequent (80-99%)
HP:0003805	Rimmed vacuoles	Very frequent (80-99%)
HP:0006785	Limb-girdle muscular dystrophy	Very frequent (80-99%)
HP:0010628	Facial palsy	Very frequent (80-99%)
HP:0012899	Handgrip myotonia	Very frequent (80-99%)
HP:0003713	Muscle fiber necrosis	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	zebra body myopathy
Mondo ID	MONDO:0019949
Orphanet	97240
ICD-11	1699813614
SNOMED CT	34513009
UMLS	C0270969
MedGen	543080
GARD	0019354
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › alpha-actinopathy › zebra body myopathy

Related subtypes (3): congenital myopathy 2a, typical, autosomal dominant, progressive scapulohumeroperoneal distal myopathy, cap myopathy

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 9 · 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
ACTA1	Definitive	Semidominant	congenital myopathy 2a, typical, autosomal dominant	15

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	gencc

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.