MEGF10 (multiple EGF like domains 10)

Gene

• Entrez ID: 84466
• Gene name: Multiple EGF like domains 10
• Gene symbol: MEGF10
• Synonyms: EMARDD, SR-F3
• Chromosome: 5
• Chromosome location: 5q23.2
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs35591368	C>G,T	Conflicting-interpretations-of-pathogenicity, benign	Coding sequence variant, synonymous variant, genic downstream transcript variant, missense variant
rs115184652	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Intron variant
rs199750143	A>C,G	Conflicting-interpretations-of-pathogenicity	Splice acceptor variant, genic downstream transcript variant
rs200174116	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant, stop gained
rs372378202	T>C	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Intron variant, genic downstream transcript variant
rs387907071	C>A,T	Pathogenic	Genic downstream transcript variant, coding sequence variant, synonymous variant, stop gained
rs387907072	T>C	Pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant
rs387907073	T>C	Pathogenic	Coding sequence variant, missense variant, 5 prime UTR variant
rs387907074	C>T	Pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs762560221	->T	Likely-pathogenic	Splice donor variant, genic downstream transcript variant
rs794726677	G>A	Pathogenic	Coding sequence variant, stop gained
rs794726678	T>G	Pathogenic	Coding sequence variant, genic downstream transcript variant, stop gained
rs794726679	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs931073338	G>A,C	Likely-pathogenic	Genic upstream transcript variant, splice donor variant
rs989552169	C>T	Pathogenic	Genic downstream transcript variant, stop gained, coding sequence variant
rs1057518682	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1057519152	G>A	Likely-pathogenic	Genic downstream transcript variant, splice acceptor variant
rs1057523896	G>A	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs1064793831	G>T	Pathogenic	Stop gained, coding sequence variant, genic upstream transcript variant
rs1064795948	G>-	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, frameshift variant
rs1291487750	->A	Likely-pathogenic	Coding sequence variant, genic upstream transcript variant, frameshift variant
rs1298663120	G>A	Likely-pathogenic	Genic downstream transcript variant, splice donor variant
rs1454219963	C>T	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, stop gained
rs1561599823	T>C	Likely-pathogenic	Splice donor variant, genic upstream transcript variant
rs1580733016	G>ACATTC	Pathogenic	Stop gained, coding sequence variant, genic upstream transcript variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001849	Function	Complement component C1q complex binding	IDA	27170117
GO:0001891	Component	Phagocytic cup	IDA	17205124
GO:0005044	Function	Scavenger receptor activity	IDA	27170117
GO:0005112	Function	Notch binding	IBA	21873635
GO:0005112	Function	Notch binding	IPI	28498977
GO:0005886	Component	Plasma membrane	IDA	27170117
GO:0014719	Process	Skeletal muscle satellite cell activation	ISS
GO:0014816	Process	Skeletal muscle satellite cell differentiation	IMP	22101682
GO:0014841	Process	Skeletal muscle satellite cell proliferation	ISS
GO:0016021	Component	Integral component of membrane	IEA
GO:0022409	Process	Positive regulation of cell-cell adhesion	IMP
GO:0033002	Process	Muscle cell proliferation	IMP	28498977
GO:0034109	Process	Homotypic cell-cell adhesion	IDA	22407321
GO:0042995	Component	Cell projection	IEA
GO:0043277	Process	Apoptotic cell clearance	IBA	21873635
GO:0043652	Process	Engulfment of apoptotic cell	ISS
GO:0043654	Process	Recognition of apoptotic cell	IEA
GO:0048627	Process	Myoblast development	IEA
GO:0048641	Process	Regulation of skeletal muscle tissue development	IMP	22101682
GO:0051147	Process	Regulation of muscle cell differentiation	IMP	22101682
GO:0051451	Process	Myoblast migration	IMP	28498977
GO:0055001	Process	Muscle cell development	IMP	22101682
GO:1902742	Process	Apoptotic process involved in development	ISS
GO:2000288	Process	Positive regulation of myoblast proliferation	IMP

Other IDs

• MIM: 612453
• HGNC: 29634
• e!Ensembl: ENSG00000145794

Protein

• UniProt ID: Q96KG7
• Protein name: Multiple epidermal growth factor-like domains protein 10 (Multiple EGF-like domains protein 10)
• Protein 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, Ref.14). 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).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF12661	hEGF	197 → 216	Human growth factor-like EGF	Domain
  PF12661	hEGF	240 → 259	Human growth factor-like EGF	Domain
  PF00053	Laminin_EGF	281 → 326	Laminin EGF domain	Domain
  PF00053	Laminin_EGF	367 → 415	Laminin EGF domain	Domain
  PF12661	hEGF	415 → 434	Human growth factor-like EGF	Domain
  PF12661	hEGF	501 → 520	Human growth factor-like EGF	Domain
  PF12661	hEGF	587 → 606	Human growth factor-like EGF	Domain
  PF12661	hEGF	718 → 737	Human growth factor-like EGF	Domain
  PF00053	Laminin_EGF	759 → 804	Laminin EGF domain	Domain
  PF00053	Laminin_EGF	802 → 838	Laminin EGF domain	Domain

• Sequence:

  MVISLNSCLSFICLLLCHWIGTASPLNLEDPNVCSHWESYSVTVQESYPHPFDQIYYTSC
  TDILNWFKCTRHRVSYRTAYRHGEKTMYRRKSQCCPGFYESGEMCVPHCADKCVHGRCIA
  PNTCQCEPGWGGTNCSSACDGDHWGPHCTSRCQCKNGALCNPITGACHCAAGFRGWRCED
  RCEQGTYGNDCHQRCQCQNGATCDHVTGECRCPPGYTGAFCEDLCPPGKHGPQCEQRCPC
  QNGGVCHHVTGECSCPSGWMGTVCGQPCPEGRFGKNCSQECQCHNGGTCDAATGQCHCSP
  GYTGERCQDECPVGTYGVLCAETCQCVNGGKCYHVSGACLCEAGFAGERCEARLCPEGLY
  GIKCDKRCPCHLENTHSCHPMSGECACKPGWSGLYCNETCSPGFYGEACQQICSCQNGAD
  CDSVTGKCTCAPGFKGIDCSTPCPLGTYGINCSSRCGCKNDAVCSPVDGSCTCKAGWHGV
  DCSIRCPSGTWGFGCNLTCQCLNGGACNTLDGTCTCAPGWRGEKCELPCQDGTYGLNCAE
  RCDCSHADGCHPTTGHCRCLPGWSGVHCDSVCAEGRWGPNCSLPCYCKNGASCSPDDGIC
  ECAPGFRGTTCQRICSPGFYGHRCSQTCPQCVHSSGPCHHITGLCDCLPGFTGALCNEVC
  PSGRFGKNCAGICTCTNNGTCNPIDRSCQCYPGWIGSDCSQPCPPAHWGPNCIHTCNCHN
  GAFCSAYDGECKCTPGWTGLYCTQRCPLGFYGKDCALICQCQNGADCDHISGQCTCRTGF
  MGRHCEQKCPSGTYGYGCRQICDCLNNSTCDHITGTCYCSPGWKGARCDQAGVIIVGNLN
  SLSRTSTALPADSYQIGAIAGIIILVLVVLFLLALFIIYRHKQKGKESSMPAVTYTPAMR
  VVNADYTISGTLPHSNGGNANSHYFTNPSYHTLTQCATSPHVNNRDRMTVTKSKNNQLFV
  NLKNVNPGKRGPVGDCTGTLPADWKHGGYLNELGAFGLDRSYMGKSLKDLGKNSEYNSSN
  CSLSSSENPYATIKDPPVLIPKSSECGYVEMKSPARRDSPYAEINNSTSANRNVYEVEPT
  VSVVQGVFSNNGRLSQDPYDLPKNSHIPCHYDLLPVRDSSSSPKQEDSGGSSSNSSSSSE
  

• Sequence length: 1140

Associated diseases

Disease name	Disease term	References
	Alzheimer`s Disease	23535033
	Respiratory Distress Syndrome, Newborn	22101682
	Congenital clubfoot
	Congenital pectus excavatum
	Deglutition Disorders	22101682
	Esophageal Dysphagia	22101682
	Facial paralysis
	Byzanthine arch palate
	Clumsiness - motor delay
	Myopathy	22101682
	MYOPATHY, AREFLEXIA, RESPIRATORY DISTRESS, AND DYSPHAGIA, EARLY-ONSET	22371254, 27460346, 22101682, 23453856, 23954233, 28498977, 27170117, 18056409
	MYOPATHY, AREFLEXIA, RESPIRATORY DISTRESS, AND DYSPHAGIA, EARLY-ONSET, MILD VARIANT	22101682, 23453856
	Early-onset myopathy-areflexia-respiratory distress-dysphagia syndrome
	Neonatal Hypotonia
	Oropharyngeal Dysphagia	22101682
	Respiratory Failure
	Schizophrenia	29503163, 18179784
	Scoliosis, unspecified