MEGF10

multiple EGF like domains 10, the group of Scavenger receptors

Basic information

Region (hg38): 5:127290796-127465737

Links

ENSG00000145794 ∙ NCBI:84466 ∙ OMIM:612453 ∙ HGNC:29634 ∙ Uniprot:Q96KG7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MEGF10-related myopathy (Definitive), mode of inheritance: AR
• MEGF10-related myopathy (Strong), mode of inheritance: AR
• MEGF10-related myopathy (Supportive), mode of inheritance: AR
• MEGF10-related myopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital myopathy 10A, severe variant; Congenital myopathy 10B, mild variant	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal	17236770; 22101682; 22371254; 23453856; 27460346; 36349186

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MEGF10 gene.

• MEGF10-related myopathy (16 variants)
• not provided (3 variants)
• Congenital myopathy 10b, mild variant (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MEGF10 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	147	5	159
missense	1	3	402	4	2	412
nonsense	12	4				16
start loss			1			1
frameshift	5	2				7
inframe indel			1			1
splice donor/acceptor (+/-2bp)		13	1			14
splice region			9	24	2	35
non coding			87	156	44	287
Total	18	22	499	307	51

Variants in MEGF10

This is a list of pathogenic ClinVar variants found in the MEGF10 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-127290856-G-T		MEGF10-related myopathy	Uncertain significance (Jan 13, 2018)
5-127290878-T-C		MEGF10-related myopathy	Uncertain significance (Jan 13, 2018)
5-127290923-A-G		MEGF10-related myopathy	Uncertain significance (Mar 02, 2018)
5-127290953-G-A		MEGF10-related myopathy	Benign (Jul 03, 2018)
5-127290979-A-C		MEGF10-related myopathy	Uncertain significance (Jan 13, 2018)
5-127299745-GT-G			Benign (May 29, 2020)
5-127299975-G-C			Benign (Jul 03, 2018)
5-127299983-A-T			Likely benign (Jun 05, 2018)
5-127299989-A-G		not specified	Likely benign (Apr 18, 2016)
5-127299999-A-G		not specified • MEGF10-related myopathy	Benign/Likely benign (Sep 12, 2017)
5-127300033-C-T		not specified	Likely benign (Aug 23, 2016)
5-127300052-T-G		MEGF10-related myopathy	Uncertain significance (Feb 16, 2018)
5-127331112-A-G			Likely benign (Jun 18, 2018)
5-127331273-A-AT			Likely benign (Feb 02, 2021)
5-127331280-C-T		MEGF10-related myopathy	Conflicting classifications of pathogenicity (Apr 15, 2019)
5-127331302-G-A		not specified	Likely benign (Mar 21, 2016)
5-127331311-G-T		MEGF10-related myopathy	Uncertain significance (Apr 23, 2022)
5-127331312-G-A		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
5-127331323-G-A			Likely benign (Mar 29, 2018)
5-127331327-T-C		Inborn genetic diseases	Uncertain significance (Sep 13, 2023)
5-127331350-A-G		MEGF10-related myopathy	Likely benign (Aug 04, 2023)
5-127331358-G-A		MEGF10-related myopathy	Conflicting classifications of pathogenicity (Sep 01, 2023)
5-127331359-C-T		MEGF10-related myopathy	Likely benign (Jul 09, 2022)
5-127331367-T-C		not specified • MEGF10-related myopathy	Conflicting classifications of pathogenicity (Aug 15, 2022)
5-127331374-A-G		MEGF10-related myopathy	Likely benign (Jan 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MEGF10	protein_coding	protein_coding	ENST00000274473	24	174907

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.390	0.610	125674	0	74	125748	0.000294

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	608	685	0.887	0.0000394	7497
Missense in Polyphen		187	259.05	0.72187		2798
Synonymous	0.758	239	254	0.940	0.0000162	2096
Loss of Function	5.85	15	66.5	0.226	0.00000344	766

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000530	0.000530
Ashkenazi Jewish	0.00	0.00
East Asian	0.00114	0.00114
Finnish	0.00	0.00
European (Non-Finnish)	0.000239	0.000237
Middle Eastern	0.00114	0.00114
South Asian	0.000296	0.000294
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Membrane receptor involved in phagocytosis by macrophages and astrocytes of apoptotic cells. Receptor for C1q, an eat-me signal, that binds phosphatidylserine expressed on the surface of apoptotic cells (PubMed:27170117). Cooperates with ABCA1 within the process of engulfment. Promotes the formation of large intracellular vacuoles and may be responsible for the uptake of amyloid-beta peptides (PubMed:20828568, PubMed:17643423). Necessary for astrocyte-dependent apoptotic neuron clearance in the developing cerebellum (PubMed:27170117). Plays role in muscle cell proliferation, adhesion and motility. Is also an essential factor in the regulation of myogenesis. Controls the balance between skeletal muscle satellite cells proliferation and differentiation through regulation of the notch signaling pathway (PubMed:28498977). May also function in the mosaic spacing of specific neuron subtypes in the retina through homotypic retinal neuron repulsion. Mosaics provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements (PubMed:17498693, PubMed:17643423, PubMed:20828568, PubMed:22101682, PubMed:27170117, PubMed:28498977). {ECO:0000269|PubMed:17205124, ECO:0000269|PubMed:17498693, ECO:0000269|PubMed:17643423, ECO:0000269|PubMed:20828568, ECO:0000269|PubMed:22101682, ECO:0000269|PubMed:27170117, ECO:0000269|PubMed:28498977}.
• Disease: DISEASE: Myopathy, early-onset, areflexia, respiratory distress, and dysphagia (EMARDD) [MIM:614399]: An autosomal recessive congenital myopathy characterized by onset at birth, or early in infancy, of respiratory distress caused by diaphragmatic weakness. Additional features are dysphagia resulting in poor feeding, failure to thrive, poor head control, facial weakness, cleft palate, contractures and scoliosis. Affected individuals become ventilator-dependent, and most require feeding by gastrostomy. The disorder results in severe muscle weakness and most patients never achieve walking. Death from respiratory failure in childhood occurs in about half of patients. Muscle biopsies from affected individuals show myopathic changes, replacement of myofibers with fatty tissue, small and incompletely fused muscle fibers, and variation in fiber size. Short regions of sarcomeric disorganization with few or no mitochondria (minicores) have been observed in some cases. {ECO:0000269|PubMed:22101682, ECO:0000269|PubMed:22371254, ECO:0000269|PubMed:23954233, ECO:0000269|PubMed:27170117, ECO:0000269|PubMed:28498977}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.476
• rvis_EVS: -1.21
• rvis_percentile_EVS: 5.72

Haploinsufficiency Scores

• pHI: 0.0906
• hipred: Y
• hipred_score: 0.605
• ghis: 0.598

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.262

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Megf10
• Phenotype: cellular phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: megf10
• Affected structure: muscle
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: receptor-mediated endocytosis;skeletal muscle satellite cell activation;skeletal muscle satellite cell differentiation;skeletal muscle satellite cell proliferation;muscle cell proliferation;homotypic cell-cell adhesion;engulfment of apoptotic cell;recognition of apoptotic cell;regulation of skeletal muscle tissue development;regulation of muscle cell differentiation;myoblast migration;muscle cell development;apoptotic process involved in development
• Cellular component: phagocytic cup;plasma membrane;integral component of membrane;cell projection
• Molecular function: complement component C1q binding;scavenger receptor activity;Notch binding