Human Gene MEGF10 (uc003kui.4) Description and Page Index
  Description: Homo sapiens multiple EGF-like-domains 10 (MEGF10), transcript variant 2, mRNA.
RefSeq Summary (NM_001256545): 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].
Transcript (Including UTRs)
   Position: hg19 chr5:126,626,456-126,796,910 Size: 170,455 Total Exon Count: 25 Strand: +
Coding Region
   Position: hg19 chr5:126,667,001-126,793,010 Size: 126,010 Coding Exon Count: 24 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr5:126,626,456-126,796,910)mRNA (may differ from genome)Protein (1140 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
OMIMPubMedStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Multiple epidermal growth factor-like domains protein 10; Short=Multiple EGF-like domains protein 10; Flags: Precursor;
FUNCTION: Membrane receptor involved in phagocytosis by macrophages of apoptotic cells. 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. 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. May play role in cell adhesion and motility. Is also an essential factor in the regulation of myogenesis. Controls the balance between skeletal muscle satellite cells proliferation and differentiation problably through regulation of the notch signaling pathway.
SUBUNIT: Homopolymer (Probable). Interacts with GULP1 and ABCA1. Interacts with AP2M1. Does not interact with MEGF11.
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Basolateral cell membrane; Single-pass type I membrane protein. Cell projection, phagocytic cup. Note=Enriched at the sites of contact with apoptotic thymocyte cells (By similarity). Forms an irregular, mosaic-like adhesion pattern in region of the cell surface that becomes firmely fixed to the substrate. Expressed at the cell surface in clusters around cell corpses during engulfment. During the engulfment of apoptotic thymocytes, recruited at the bottom of the forming phagocytic cup. Colocalizes with ABCA1 in absence of any phagocytic challenge. Does not localize within lamellipodia. Does not localize with MEGF11.
DOMAIN: The EMI and EGF-like domains work in concert to promote self-assembly.
PTM: Phosphorylated on tyrosine residues.
PTM: Ubiquitinated; mono- and polyubiquitinated forms are detected.
DISEASE: Defects in MEGF10 are the cause of 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 biopsy shows 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.
SIMILARITY: Belongs to the MEGF family.
SIMILARITY: Contains 15 EGF-like domains.
SIMILARITY: Contains 1 EMI domain.
SEQUENCE CAUTION: Sequence=BAB47409.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): MEGF10
CDC HuGE Published Literature: MEGF10
Positive Disease Associations: Body Height , Body Weights and Measures , Cholesterol, HDL , Erythrocyte Indices , Hematocrit , Lipoproteins, VLDL , Platelet Aggregation
Related Studies:
  1. Body Height
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
  2. Body Weights and Measures
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
  3. Cholesterol, HDL
    Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics. [PubMed 17903299]
    Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: MEGF10
Diseases sorted by gene-association score: myopathy, areflexia, respiratory distress, and dysphagia, early-onset* (1650), dysphagia (48), congenital myopathy (22), multiminicore disease (10), scoliosis (9), myopathy (7), schizophrenia (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.79 RPKM in Brain - Spinal cord (cervical c-1)
Total median expression: 59.23 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -97.24311-0.313 Picture PostScript Text
3' UTR -977.543900-0.251 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000742 - EG-like_dom
IPR013032 - EGF-like_CS
IPR002049 - EGF_laminin
IPR011489 - EMI_domain

Pfam Domains:
PF00053 - Laminin EGF domain
PF12661 - Human growth factor-like EGF

SCOP Domains:
57196 - EGF/Laminin

ModBase Predicted Comparative 3D Structure on Q96KG7
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserNo orthologNo ortholog
Gene Details  Gene Details  
Gene Sorter  Gene Sorter  
  Protein SequenceProtein Sequence  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001849 complement component C1q binding
GO:0005044 scavenger receptor activity
GO:0005112 Notch binding

Biological Process:
GO:0006898 receptor-mediated endocytosis
GO:0006909 phagocytosis
GO:0007155 cell adhesion
GO:0007517 muscle organ development
GO:0014719 skeletal muscle satellite cell activation
GO:0014816 skeletal muscle satellite cell differentiation
GO:0014841 skeletal muscle satellite cell proliferation
GO:0033002 muscle cell proliferation
GO:0034109 homotypic cell-cell adhesion
GO:0043652 engulfment of apoptotic cell
GO:0043654 recognition of apoptotic cell
GO:0048641 regulation of skeletal muscle tissue development
GO:0051147 regulation of muscle cell differentiation
GO:0051451 myoblast migration
GO:0055001 muscle cell development
GO:1902742 apoptotic process involved in development

Cellular Component:
GO:0001891 phagocytic cup
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0042995 cell projection

-  Descriptions from all associated GenBank mRNAs
  AK123568 - Homo sapiens cDNA FLJ41574 fis, clone CTONG2010116, weakly similar to Rattus norvegicus mRNA for MEGF6.
CR749437 - Homo sapiens mRNA; cDNA DKFZp781K1852 (from clone DKFZp781K1852).
AK307919 - Homo sapiens cDNA, FLJ97867.
BC020198 - Homo sapiens multiple EGF-like-domains 10, mRNA (cDNA clone IMAGE:4904255), complete cds.
AB058676 - Homo sapiens mRNA for MEGF10 protein, partial cds.
BC152478 - Homo sapiens multiple EGF-like-domains 10, mRNA (cDNA clone MGC:176737 IMAGE:8862616), complete cds.
AB384636 - Synthetic construct DNA, clone: pF1KA1780, Homo sapiens MEGF10 gene for multiple EGF-like-domains 10, complete cds, without stop codon, in Flexi system.
KJ899799 - Synthetic construct Homo sapiens clone ccsbBroadEn_09193 MEGF10 gene, encodes complete protein.
JD038862 - Sequence 19886 from Patent EP1572962.
JD306591 - Sequence 287615 from Patent EP1572962.
JD424371 - Sequence 405395 from Patent EP1572962.
JD501007 - Sequence 482031 from Patent EP1572962.
JD434854 - Sequence 415878 from Patent EP1572962.
JD435378 - Sequence 416402 from Patent EP1572962.
JD435379 - Sequence 416403 from Patent EP1572962.
JD325027 - Sequence 306051 from Patent EP1572962.
JD416645 - Sequence 397669 from Patent EP1572962.
JD519466 - Sequence 500490 from Patent EP1572962.
JD391977 - Sequence 373001 from Patent EP1572962.
JD152051 - Sequence 133075 from Patent EP1572962.
JD350597 - Sequence 331621 from Patent EP1572962.
JD203902 - Sequence 184926 from Patent EP1572962.
JD506854 - Sequence 487878 from Patent EP1572962.
JD074701 - Sequence 55725 from Patent EP1572962.
JD358446 - Sequence 339470 from Patent EP1572962.
JD060565 - Sequence 41589 from Patent EP1572962.
JD149820 - Sequence 130844 from Patent EP1572962.
JD502403 - Sequence 483427 from Patent EP1572962.
JD048456 - Sequence 29480 from Patent EP1572962.
JD040866 - Sequence 21890 from Patent EP1572962.
JD328846 - Sequence 309870 from Patent EP1572962.
JD234494 - Sequence 215518 from Patent EP1572962.
JD186095 - Sequence 167119 from Patent EP1572962.
JD061525 - Sequence 42549 from Patent EP1572962.
JD039760 - Sequence 20784 from Patent EP1572962.
JD357481 - Sequence 338505 from Patent EP1572962.
JD438684 - Sequence 419708 from Patent EP1572962.
JD082692 - Sequence 63716 from Patent EP1572962.
JD378996 - Sequence 360020 from Patent EP1572962.
JD502654 - Sequence 483678 from Patent EP1572962.
AK021631 - Homo sapiens cDNA FLJ11569 fis, clone HEMBA1003304.
JD434141 - Sequence 415165 from Patent EP1572962.
JD450629 - Sequence 431653 from Patent EP1572962.
JD551568 - Sequence 532592 from Patent EP1572962.
JD435857 - Sequence 416881 from Patent EP1572962.
JD281004 - Sequence 262028 from Patent EP1572962.
JD053528 - Sequence 34552 from Patent EP1572962.
JD499399 - Sequence 480423 from Patent EP1572962.
JD094335 - Sequence 75359 from Patent EP1572962.
JD370776 - Sequence 351800 from Patent EP1572962.

-  Other Names for This Gene
  Alternate Gene Symbols: KIAA1780, MEG10_HUMAN, NM_001256545, NP_115822, Q68DE5, Q8WUL3, Q96KG7
UCSC ID: uc003kui.4
RefSeq Accession: NM_001256545
Protein: Q96KG7 (aka MEG10_HUMAN)
CCDS: CCDS4142.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_001256545.1
exon count: 25CDS single in 3' UTR: no RNA size: 7638
ORF size: 3423CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 7037.00frame shift in genome: no % Coverage: 99.95
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.