Details for: MEGF8

Gene ID: 1954

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: MEGF8

Ensembl ID: ENSG00000105429

Description: multiple EGF like domains 8

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • interneuron CL0000099
    CSI 3.04
    rCSI 6.1%
    PRS 63.3
  • endothelial cell of vascular tree CL0002139
    CSI 2.8
    rCSI 15.3%
    PRS 71.06
  • choroid plexus epithelial cell CL0000706
    CSI 2.76
    rCSI 4.51%
    PRS 62.99
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.38
    rCSI 2.85%
    PRS 55.08
  • cerebral cortex endothelial cell CL1001602
    CSI 2.35
    rCSI 4.06%
    PRS 64.56
  • vascular leptomeningeal cell CL4023051
    CSI 2.28
    rCSI 4%
    PRS 66.61
  • neural crest cell CL0011012
    CSI 2.28
    rCSI 1.8%
    PRS 61.43
  • multi-ciliated epithelial cell CL0005012
    CSI 2.24
    rCSI 2.23%
    PRS 67.42
  • cerebral cortex neuron CL0010012
    CSI 2.15
    rCSI 8.78%
    PRS 66.28
  • epithelial cell of proximal tubule CL0002306
    CSI 2.12
    rCSI 5.18%
    PRS 66.64
  • transit amplifying cell of colon CL0009011
    CSI 2.1
    rCSI 2.47%
    PRS 75.8
  • stem cell CL0000034
    CSI 1.97
    rCSI 1.9%
    PRS 66.05
  • amacrine cell CL0000561
    CSI 1.91
    rCSI 5.55%
    PRS 62.9
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.86
    rCSI 4.16%
    PRS 55.75
  • inhibitory interneuron CL0000498
    CSI 1.73
    rCSI 3.99%
    PRS 61.72
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.71
    rCSI 2.2%
    PRS 56.5
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 1.69
    rCSI 3.67%
    PRS 61.18
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.68
    rCSI 2.09%
    PRS 53.17
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.57
    rCSI 2.78%
    PRS 54.28
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.45
    rCSI 3.67%
    PRS 63.71
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.39
    rCSI 2.34%
    PRS 55.15
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.36
    rCSI 2.18%
    PRS 56.87
  • glutamatergic neuron CL0000679
    CSI 1.33
    rCSI 2.74%
    PRS 61.85
  • basal cell of epidermis CL0002187
    CSI 1.3
    rCSI 2.31%
    PRS 44.2
  • retinal ganglion cell CL0000740
    CSI 1.27
    rCSI 2.81%
    PRS 59.48
  • peripheral nervous system neuron CL2000032
    CSI 1.21
    rCSI 1.65%
    PRS 65.14
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1
    rCSI 1.21%
    PRS 56.22
  • GABAergic neuron CL0000617
    CSI 0.95
    rCSI 3.18%
    PRS 57.91
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.88
    rCSI 2.14%
    PRS 53.37
  • melanocyte of skin CL1000458
    CSI 0.85
    rCSI 1.15%
    PRS 41.56
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.83
    rCSI 2.59%
    PRS 59.44
  • retinal cone cell CL0000573
    CSI 0.74
    rCSI 1.19%
    PRS 63.35
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.58
    rCSI 1.83%
    PRS 56.96
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.57
    rCSI 2.06%
    PRS 53.29
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.54
    rCSI 2.03%
    PRS 55.64
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.36
    rCSI 8.79%
    PRS 54.46
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.36
    rCSI 2.09%
    PRS 56.12
  • direct pathway medium spiny neuron CL4023026
    CSI 0.28
    rCSI 6.63%
    PRS 53.85

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [MEGF8](/details-gene/1954) (multiple EGF like domains 8) is a protein-coding gene located on chromosome 19q13.2. It encodes the Multiple epidermal growth factor-like domains protein 8, a large protein implicated in a wide array of fundamental developmental processes. Functionally, [MEGF8](/details-gene/1954) is associated with embryonic morphogenesis, including left/right pattern formation, skeletal and limb development, and neurogenesis. Mutations in this gene are known to cause a subtype of Carpenter syndrome, a rare congenital disorder characterized by craniosynostosis, polysyndactyly, and defects in lateralization [[Link](https://doi.org/10.1016/j.ajhg.2012.08.027)]. Expression data reveals that **Overall**, [MEGF8](/details-gene/1954) is most significant in diverse cell types of the central nervous system, particularly [interneuron](/details-cell/CL0000099)s, as well as in various endothelial and specialized epithelial cells, consistent with its critical role in the development of multiple organ systems. ## Cellular Roles and Expression Landscape The expression profile of [MEGF8](/details-gene/1954) highlights its importance in the nervous and vascular systems. **Overall**, it shows the highest significance in neuronal populations, including [interneuron](/details-cell/CL0000099) (CSI: 3.04), [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 2.38), and [cerebral cortex neuron](/details-cell/CL0010012) (CSI: 2.15). This suggests a key role in neuronal identity, migration, or function. Concurrently, [MEGF8](/details-gene/1954) is a significant marker for vascular and associated cell types, such as [endothelial cell of vascular tree](/details-cell/CL0002139) (CSI: 2.80), [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 2.35), and [vascular leptomeningeal cell](/details-cell/CL4023051) (CSI: 2.28). This dual prominence in both neural and vascular compartments points towards a potential role in the neurovascular unit or in coordinating the development of these two intertwined systems. The gene's significance extends to specialized epithelial cells, including [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 2.76) and [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 2.24), as well as progenitor populations like [neural crest cell](/details-cell/CL0011012) (CSI: 2.28) and [stem cell](/details-cell/CL0000034) (CSI: 1.97), underscoring its broad involvement in embryonic morphogenesis and tissue maintenance. The diverse cellular contexts where [MEGF8](/details-gene/1954) is highly expressed are consistent with the pleiotropic effects observed in Carpenter syndrome. ## Pathways and Molecular Function The functional annotations for [MEGF8](/details-gene/1954) strongly align with its expression profile and known clinical relevance. It is deeply involved in a multitude of developmental biological processes, most notably those governing body patterning and organogenesis. These include '[Left/right pattern formation](/details-go/GO:0060972)', '[Determination of heart left/right asymmetry](/details-go/GO:0061371)', '[Embryonic limb morphogenesis](/details-go/GO:0030326)', and '[Embryonic skeletal system morphogenesis](/details-go/GO:0048704)', which directly relate to the clinical manifestations of Carpenter syndrome. Its high expression in neural and endothelial cells is supported by its annotated roles in '[Embryonic brain development](/details-go/GO:1990403)', '[Aorta development](/details-go/GO:0035904)', '[Coronary vasculature development](/details-go/GO:0060976)', and '[Positive regulation of axon extension involved in axon guidance](/details-go/GO:0048842)'. At the molecular level, [MEGF8](/details-gene/1954) participates in crucial signaling cascades such as the '[Bmp signaling pathway](/details-go/GO:0030509)' and the '[Smoothened signaling pathway](/details-go/GO:0007224)', both of which are fundamental regulators of embryonic development. The protein's predicted molecular functions include '[Calcium ion binding](/details-go/GO:0005509)' and '[Protein binding](/details-go/GO:0005515)', and it is a component of the '[Membrane](/details-go/GO:0016020)' and the '[Ubiquitin ligase complex](/details-go/GO:0000151)', suggesting it may function as a cell surface receptor or a component of a signaling complex that regulates protein turnover. ## Research Directions Given that mutations in [MEGF8](/details-gene/1954) lead to severe developmental disorders, future research should focus on elucidating its precise molecular mechanisms during embryogenesis. ### Proposed Hypotheses 1. **Hypothesis 1:** Based on its high significance in [interneuron](/details-cell/CL0000099)s and its role in '[axon guidance](/details-go/GO:0048842)', [MEGF8](/details-gene/1954) acts as a cell-surface signaling receptor that directs the migration and laminar positioning of cortical interneurons during brain development. Its dysfunction could lead to disorganized cortical circuitry. 2. **Hypothesis 2:** Considering its high expression in both [cerebral cortex endothelial cell](/details-cell/CL1001602)s and [astrocyte of the cerebral cortex](/details-cell/CL0002605), [MEGF8](/details-gene/1954) may mediate critical cell-cell interactions at the neurovascular interface, contributing to the formation and maintenance of the blood-brain barrier. ### Key Experimental Approach To test Hypothesis 1, a cerebral organoid model derived from human induced pluripotent stem cells (iPSCs) could be employed. CRISPR-Cas9-mediated knockout of [MEGF8](/details-gene/1954) in iPSCs would be performed. The resulting organoids could then be compared to isogenic controls. Using immunofluorescence and live-cell imaging with fluorescently labeled interneuron precursors, one could directly assess deficits in interneuron migration, proliferation, and integration into the developing cortical plate. RNA-sequencing of sorted neuronal populations from these organoids would further reveal the downstream transcriptional changes resulting from [MEGF8](/details-gene/1954) loss. ### Therapeutic Potential Due to its fundamental role in embryonic development, [MEGF8](/details-gene/1954) is unlikely to be a viable therapeutic target for inhibition in postnatal life. Its widespread importance in multiple tissues suggests that systemic inhibition would have severe off-target effects. However, for congenital disorders like Carpenter syndrome caused by loss-of-function mutations, future gene therapy strategies that aim to restore [MEGF8](/details-gene/1954) expression in specific progenitor cell populations during early development could be a theoretical long-term goal. Currently, its primary clinical utility lies in genetic diagnostics for developmental syndromes.

Genular Protein ID: 3444886545

Symbol: MEGF8_HUMAN

Name: Multiple epidermal growth factor-like domains protein 8

UniProtKB Accession Codes:

Q7Z7M0 A8KAY0 O75097

Database IDs:

AGR 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 3 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 ExpressionAtlas 1 GO 21 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 12 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 8 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 8 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 2 SMART 5 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9693030

Title: Identification of high-molecular-weight proteins with multiple EGF-like motifs by motif-trap screening.

PubMed ID: 9693030

DOI: 10.1006/geno.1998.5341

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 16335952

Title: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.

PubMed ID: 16335952

DOI: 10.1021/pr0502065

PubMed ID: 23063620

Title: Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization.

PubMed ID: 23063620

DOI: 10.1016/j.ajhg.2012.08.027

Sequence Information:

  • Length: 2845
  • Mass: 303100
  • Checksum: DDBF0EE07511587D
  • Sequence:
    • MALGKVLAMA LVLALAVLGS LSPGARAGDC KGQRQVLREA PGFVTDGAGN YSVNGNCEWL 
IEAPSPQHRI LLDFLFLDTE CTYDYLFVYD GDSPRGPLLA SLSGSTRPPP IEASSGKMLL 
HLFSDANYNL LGFNASFRFS LCPGGCQSHG QCQPPGVCAC EPGWGGPDCG LQECSAYCGS 
HGTCASPLGP CRCEPGFLGR ACDLHLWENQ GAGWWHNVSA RDPAFSARIG AAGAFLSPPG 
LLAVFGGQDL NNALGDLVLY NFSANTWESW DLSPAPAARH SHVAVAWAGS LVLMGGELAD 
GSLTNDVWAF SPLGRGHWEL LAPPASSSSG PPGLAGHAAA LVDDVWLYVS GGRTPHDLFS 
SGLFRFRLDS TSGGYWEQVI PAGGRPPAAT GHSMVFHAPS RALLVHGGHR PSTARFSVRV 
NSTELFHVDR HVWTTLKGRD GLQGPRERAF HTASVLGNYM VVYGGNVHTH YQEEKCYEDG 
IFFYHLGCHQ WVSGAELAPP GTPEGRAAPP SGRYSHVAAV LGGSVLLVAG GYSGRPRGDL 
MAYKVPPFVF QAPAPDYHLD YCSMYTDHSV CSRDPECSWC QGACQAAPPP GTPLGACPAA 
SCLGLGRLLG DCQACLAFSS PTAPPRGPGT LGWCVHNESC LPRPEQARCR GEQISGTVGW 
WGPAPVFVTS LEACVTQSFL PGLHLLTFQQ PPNTSQPDKV SIVRSTTITL TPSAETDVSL 
VYRGFIYPML PGGPGGPGAE DVAVWTRAQR LHVLARMARG PDTENMEEVG RWVAHQEKET 
RRLQRPGSAR LFPLPGRDHK YAVEIQGQLN GSAGPGHSEL TLLWDRTGVP GGSEISFFFL 
EPYRSSSCTS YSSCLGCLAD QGCGWCLTSA TCHLRQGGAH CGDDGAGGSL LVLVPTLCPL 
CEEHRDCHAC TQDPFCEWHQ STSRKGDAAC SRRGRGRGAL KSPEECPPLC SQRLTCEDCL 
ANSSQCAWCQ STHTCFLFAA YLARYPHGGC RGWDDSVHSE PRCRSCDGFL TCHECLQSHE 
CGWCGNEDNP TLGRCLQGDF SGPLGGGNCS LWVGEGLGLP VALPARWAYA RCPDVDECRL 
GLARCHPRAT CLNTPLSYEC HCQRGYQGDG ISHCNRTCLE DCGHGVCSGP PDFTCVCDLG 
WTSDLPPPTP APGPPAPRCS RDCGCSFHSH CRKRGPGFCD ECQDWTWGEH CERCRPGSFG 
NATGSRGCRP CQCNGHGDPR RGHCDNLSGL CFCQDHTEGA HCQLCSPGYY GDPRAGGSCF 
RECGGRALLT NVSSVALGSR RVGGLLPPGG GAARAGPGLS YCVWVVSATE ELQPCAPGTL 
CPPLTLTFSP DSSTPCTLSY VLAFDGFPRF LDTGVVQSDR SLIAAFCGQR RDRPLTVQAL 
SGLLVLHWEA NGSSSWGFNA SVGSARCGSG GPGSCPVPQE CVPQDGAAGA GLCRCPQGWA 
GPHCRMALCP ENCNAHTGAG TCNQSLGVCI CAEGFGGPDC ATKLDGGQLV WETLMDSRLS 
ADTASRFLHR LGHTMVDGPD ATLWMFGGLG LPQGLLGNLY RYSVSERRWT QMLAGAEDGG 
PGPSPRSFHA AAYVPAGRGA MYLLGGLTAG GVTRDFWVLN LTTLQWRQEK APQTVELPAV 
AGHTLTARRG LSLLLVGGYS PENGFNQQLL EYQLATGTWV SGAQSGTPPT GLYGHSAVYH 
EATDSLYVFG GFRFHVELAA PSPELYSLHC PDRTWSLLAP SQGAKRDRMR NVRGSSRGLG 
QVPGEQPGSW GFREVRKKMA LWAALAGTGG FLEEISPHLK EPRPRLFHAS ALLGDTMVVL 
GGRSDPDEFS SDVLLYQVNC NAWLLPDLTR SASVGPPMEE SVAHAVAAVG SRLYISGGFG 
GVALGRLLAL TLPPDPCRLL SSPEACNQSG ACTWCHGACL SGDQAHRLGC GGSPCSPMPR 
SPEECRRLRT CSECLARHPR TLQPGDGEAS TPRCKWCTNC PEGACIGRNG SCTSENDCRI 
NQREVFWAGN CSEAACGAAD CEQCTREGKC MWTRQFKRTG ETRRILSVQP TYDWTCFSHS 
LLNVSPMPVE SSPPLPCPTP CHLLPNCTSC LDSKGADGGW QHCVWSSSLQ QCLSPSYLPL 
RCMAGGCGRL LRGPESCSLG CAQATQCALC LRRPHCGWCA WGGQDGGGRC MEGGLSGPRD 
GLTCGRPGAS WAFLSCPPED ECANGHHDCN ETQNCHDQPH GYECSCKTGY TMDNMTGLCR 
PVCAQGCVNG SCVEPDHCRC HFGFVGRNCS TECRCNRHSE CAGVGARDHC LLCRNHTKGS 
HCEQCLPLFV GSAVGGGTCR PCHAFCRGNS HICISRKELQ MSKGEPKKYS LDPEEIENWV 
TEGPSEDEAV CVNCQNNSYG EKCESCLQGY FLLDGKCTKC QCNGHADTCN EQDGTGCPCQ 
NNTETGTCQG SSPSDRRDCY KYQCAKCRES FHGSPLGGQQ CYRLISVEQE CCLDPTSQTN 
CFHEPKRRAL GPGRTVLFGV QPKFTNVDIR LTLDVTFGAV DLYVSTSYDT FVVRVAPDTG 
VHTVHIQPPP APPPPPPPAD GGPRGAGDPG GAGASSGPGA PAEPRVREVW PRGLITYVTV 
TEPSAVLVVR GVRDRLVITY PHEHHALKSS RFYLLLLGVG DPSGPGANGS ADSQGLLFFR 
QDQAHIDLFV FFSVFFSCFF LFLSLCVLLW KAKQALDQRQ EQRRHLQEMT KMASRPFAKV 
TVCFPPDPTA PASAWKPAGL PPPAFRRSEP FLAPLLLTGA GGPWGPMGGG CCPPAIPATT 
AGLRAGPITL EPTEDGMAGV ATLLLQLPGG PHAPNGACLG SALVTLRHRL HEYCGGGGGA 
GGSGHGTGAG RKGLLSQDNL TSMSL