MEGF10-related myopathy

Summary

MEGF10-related myopathy (MONDO:0013731) is a disease caused by MEGF10 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MEGF10 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 926

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		13	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	MEGF10-related myopathy
Mondo ID	MONDO:0013731
OMIM	614399
Orphanet	439212
DOID	DOID:0111333
UMLS	C3280679
MedGen	482309
GARD	0012199
Is cancer (heuristic)	no

Also known as: congenital myopathy 10A, severe variant · early-onset myopathy, areflexia, respiratory distress and dysphagia · early-onset myopathy-areflexia-respiratory distress-dysphagia syndrome · EMARDD · MEGF10 myopathy · MEGF10-related myopathy · myopathy, areflexia, respiratory distress, and dysphagia, early-onset

Data availability: 926 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 › MEGF10-related 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, Compton-North congenital 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

600 retrieved; paginated sample, class counts are floors:

280 uncertain significance, 232 likely benign, 30 conflicting classifications of pathogenicity, 22 pathogenic, 18 benign, 9 likely pathogenic, 8 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070845	NM_001256545.2(MEGF10):c.240T>G (p.Tyr80Ter)	MEGF10	Pathogenic	criteria provided, single submitter
1073582	NM_001256545.2(MEGF10):c.3169A>T (p.Arg1057Ter)	MEGF10	Pathogenic	criteria provided, single submitter
1351978	NM_001256545.2(MEGF10):c.1518_1528del (p.Cys507fs)	MEGF10	Pathogenic	criteria provided, single submitter
1452067	NM_001256545.2(MEGF10):c.815del (p.Arg272fs)	MEGF10	Pathogenic	criteria provided, single submitter
1457177	NM_001256545.2(MEGF10):c.3094del (p.Thr1032fs)	MEGF10	Pathogenic	criteria provided, single submitter
1906386	NM_001256545.2(MEGF10):c.480C>A (p.Cys160Ter)	MEGF10	Pathogenic	criteria provided, single submitter
2088364	NM_001256545.2(MEGF10):c.2663C>G (p.Ser888Ter)	MEGF10	Pathogenic	criteria provided, single submitter
2114793	NM_001256545.2(MEGF10):c.1169del (p.Gly390fs)	MEGF10	Pathogenic	criteria provided, single submitter
2131505	NM_001256545.2(MEGF10):c.702T>A (p.Cys234Ter)	MEGF10	Pathogenic	criteria provided, single submitter
2173107	NM_001256545.2(MEGF10):c.241C>T (p.Arg81Ter)	MEGF10	Pathogenic	criteria provided, single submitter
2443927	NM_001256545.2(MEGF10):c.413_659del247 (p.Cys139fs)	MEGF10	Pathogenic	no assertion criteria provided
2443928	NM_001256545.2(MEGF10):c.131_132del (p.Val44fs)	MEGF10	Pathogenic	no assertion criteria provided
2860403	NM_001256545.2(MEGF10):c.721C>T (p.Gln241Ter)	MEGF10	Pathogenic	criteria provided, single submitter
30960	NM_001256545.2(MEGF10):c.2288_2297dup (p.Asp766delinsGluArgSerTer)	MEGF10	Pathogenic	no assertion criteria provided
30961	NM_001256545.2(MEGF10):c.1559G>A (p.Trp520Ter)	MEGF10	Pathogenic	no assertion criteria provided
30962	NM_001256545.2(MEGF10):c.2301C>A (p.Cys767Ter)	MEGF10	Pathogenic	criteria provided, single submitter
30963	NM_001256545.2(MEGF10):c.3144T>G (p.Tyr1048Ter)	MEGF10	Pathogenic	no assertion criteria provided
30964	NM_001256545.2(MEGF10):c.1325del (p.Pro442fs)	MEGF10	Pathogenic	no assertion criteria provided
30965	NM_001256545.2(MEGF10):c.2320T>C (p.Cys774Arg)	MEGF10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30966	NM_001256545.2(MEGF10):c.976T>C (p.Cys326Arg)	MEGF10	Pathogenic	criteria provided, single submitter
3605001	NM_001256545.2(MEGF10):c.44T>A (p.Leu15Ter)	MEGF10	Pathogenic	criteria provided, single submitter
3655800	NM_001256545.2(MEGF10):c.3158C>A (p.Ser1053Ter)	MEGF10	Pathogenic	criteria provided, single submitter
3707639	NM_001256545.2(MEGF10):c.24C>A (p.Cys8Ter)	MEGF10	Pathogenic	criteria provided, single submitter
1466583	NM_001256545.2(MEGF10):c.1694-2A>G	MEGF10	Likely pathogenic	criteria provided, single submitter
1512926	NM_001256545.2(MEGF10):c.2980+1G>T	MEGF10	Likely pathogenic	criteria provided, single submitter
1709157	NM_001256545.2(MEGF10):c.2230C>T (p.Gln744Ter)	MEGF10	Likely pathogenic	criteria provided, single submitter
1953122	NM_001256545.2(MEGF10):c.2857-2A>C	MEGF10	Likely pathogenic	criteria provided, single submitter
2073629	NM_001256545.2(MEGF10):c.781-1G>A	MEGF10	Likely pathogenic	criteria provided, single submitter
2103866	NM_001256545.2(MEGF10):c.412+1G>T	MEGF10	Likely pathogenic	criteria provided, single submitter
2195238	NM_001256545.2(MEGF10):c.319+1G>A	MEGF10	Likely pathogenic	criteria provided, single submitter

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
MEGF10	Definitive	Autosomal recessive	MEGF10-related myopathy	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MEGF10	Orphanet:439212	Early-onset myopathy-areflexia-respiratory distress-dysphagia syndrome

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
MEGF10	HGNC:29634	ENSG00000145794	Q96KG7	Multiple epidermal growth factor-like domains protein 10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MEGF10	Multiple epidermal growth factor-like domains protein 10	Membrane receptor involved in phagocytosis by macrophages and astrocytes of apoptotic 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)
MEGF10	Other/Unknown	no		EGF, LE_dom, EMI_domain

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
corpus callosum	1
lateral globus pallidus	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MEGF10	207	broad	marker	corpus callosum, ventricular zone, lateral globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEGF10	1,257

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MEGF10	Q96KG7	70.73

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
muscle cell proliferation	1	16852.0×	8e-04	MEGF10
regulation of skeletal muscle tissue development	1	8426.0×	8e-04	MEGF10
skeletal muscle satellite cell activation	1	5617.3×	8e-04	MEGF10
myoblast development	1	4213.0×	8e-04	MEGF10
skeletal muscle satellite cell proliferation	1	3370.4×	8e-04	MEGF10
recognition of apoptotic cell	1	2407.4×	8e-04	MEGF10
skeletal muscle satellite cell differentiation	1	2106.5×	8e-04	MEGF10
regulation of muscle cell differentiation	1	2106.5×	8e-04	MEGF10
engulfment of apoptotic cell	1	1872.4×	8e-04	MEGF10
myoblast migration	1	1872.4×	8e-04	MEGF10
homotypic cell-cell adhesion	1	1685.2×	8e-04	MEGF10
apoptotic process involved in development	1	1685.2×	8e-04	MEGF10
positive regulation of myoblast proliferation	1	1404.3×	9e-04	MEGF10
muscle cell development	1	936.2×	0.001	MEGF10
apoptotic cell clearance	1	887.0×	0.001	MEGF10
positive regulation of cell-cell adhesion	1	766.0×	0.001	MEGF10

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
MEGF10	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	MEGF10

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)
MEGF10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.