MEGF10

Chr 5

multiple EGF like domains 10

Also known as: CMYO10A, CMYO10B, CMYP10A, CMYP10B, EMARDD, SR-F3

NCBI Gene: 84466 ENSG00000145794 UniProt: Q96KG7

The encoded protein is a membrane receptor that mediates phagocytosis of apoptotic cells by macrophages and astrocytes, and regulates muscle cell proliferation, adhesion, motility, and myogenesis through the Notch signaling pathway. Mutations cause early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD) as well as congenital myopathy with minicores, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.347), and affected infants typically present with severe muscle weakness and respiratory complications from birth.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the multiple epidermal growth factor-like domains protein family. The encoded protein plays a role in cell adhesion, motility and proliferation, and is a critical mediator of apoptotic cell phagocytosis as well as amyloid-beta peptide uptake in the brain. Expression of this gene may be associated with schizophrenia, and mutations in this gene are a cause of early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD) as well as congenital myopathy with minicores. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Apr 2012]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.35

Clinical Summary— MEGF10

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Gene-Disease Validity (ClinGen)

MEGF10-related myopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

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ClinVar Variants

62 unique Pathogenic / Likely Pathogenic· 579 VUS of 1162 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.390

Z-score 5.85

OE 0.23 (0.15–0.35)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.05Z-score

OE missense 0.89 (0.83–0.95)

608 obs / 685.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.15–0.35)

0≤0.351.4

Missense OE?0.89 (0.83–0.95)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 15 / 66.5Missense obs/exp: 608 / 685.3Syn Z: 0.76

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMEGF10-related myopathy, early-onset, areflexia, respiratory distress, and dysphagiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6258th %ile

GOF

0.6541th %ile

LOF

0.4430th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

1162 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32

Likely Pathogenic30

VUS579

Likely Benign398

Benign53

Conflicting65

Pathogenic

Likely Pathogenic

579

VUS

398

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	29	3	0	0	32
Likely Pathogenic	26	3	1	0	30
VUS	4	470	100	5	579
Likely Benign	0	4	206	188	398
Benign	0	2	46	5	53
Conflicting	—				65
Total	59	482	353	198	1,157

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

18 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap MEGF10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →