MEGF8

Protein identityUniProt · HPA

UniProt accession

Q7Z7M0

Gene

MEGF8

Ensembl

ENSG00000105429

Chromosome

19

Canonical length

2845 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

The protein encoded by this gene is a single-pass type I membrane protein of unknown function that contains several EGF-like domains, Kelch repeats, and PSI domains. Defects in this gene are a cause of Carpenter syndrome 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

Canonical amino-acid sequenceUniProt

2845 residues, UniProt reviewed canonical sequence.

>Q7Z7M0|MEGF8
     1  MALGKVLAMA LVLALAVLGS LSPGARAGDC KGQRQVLREA PGFVTDGAGN YSVNGNCEWL
    61  IEAPSPQHRI LLDFLFLDTE CTYDYLFVYD GDSPRGPLLA SLSGSTRPPP IEASSGKMLL
   121  HLFSDANYNL LGFNASFRFS LCPGGCQSHG QCQPPGVCAC EPGWGGPDCG LQECSAYCGS
   181  HGTCASPLGP CRCEPGFLGR ACDLHLWENQ GAGWWHNVSA RDPAFSARIG AAGAFLSPPG
   241  LLAVFGGQDL NNALGDLVLY NFSANTWESW DLSPAPAARH SHVAVAWAGS LVLMGGELAD
   301  GSLTNDVWAF SPLGRGHWEL LAPPASSSSG PPGLAGHAAA LVDDVWLYVS GGRTPHDLFS
   361  SGLFRFRLDS TSGGYWEQVI PAGGRPPAAT GHSMVFHAPS RALLVHGGHR PSTARFSVRV
   421  NSTELFHVDR HVWTTLKGRD GLQGPRERAF HTASVLGNYM VVYGGNVHTH YQEEKCYEDG
   481  IFFYHLGCHQ WVSGAELAPP GTPEGRAAPP SGRYSHVAAV LGGSVLLVAG GYSGRPRGDL
   541  MAYKVPPFVF QAPAPDYHLD YCSMYTDHSV CSRDPECSWC QGACQAAPPP GTPLGACPAA
   601  SCLGLGRLLG DCQACLAFSS PTAPPRGPGT LGWCVHNESC LPRPEQARCR GEQISGTVGW
   661  WGPAPVFVTS LEACVTQSFL PGLHLLTFQQ PPNTSQPDKV SIVRSTTITL TPSAETDVSL
   721  VYRGFIYPML PGGPGGPGAE DVAVWTRAQR LHVLARMARG PDTENMEEVG RWVAHQEKET
   781  RRLQRPGSAR LFPLPGRDHK YAVEIQGQLN GSAGPGHSEL TLLWDRTGVP GGSEISFFFL
   841  EPYRSSSCTS YSSCLGCLAD QGCGWCLTSA TCHLRQGGAH CGDDGAGGSL LVLVPTLCPL
   901  CEEHRDCHAC TQDPFCEWHQ STSRKGDAAC SRRGRGRGAL KSPEECPPLC SQRLTCEDCL
   961  ANSSQCAWCQ STHTCFLFAA YLARYPHGGC RGWDDSVHSE PRCRSCDGFL TCHECLQSHE
  1021  CGWCGNEDNP TLGRCLQGDF SGPLGGGNCS LWVGEGLGLP VALPARWAYA RCPDVDECRL
  1081  GLARCHPRAT CLNTPLSYEC HCQRGYQGDG ISHCNRTCLE DCGHGVCSGP PDFTCVCDLG
  1141  WTSDLPPPTP APGPPAPRCS RDCGCSFHSH CRKRGPGFCD ECQDWTWGEH CERCRPGSFG
  1201  NATGSRGCRP CQCNGHGDPR RGHCDNLSGL CFCQDHTEGA HCQLCSPGYY GDPRAGGSCF
  1261  RECGGRALLT NVSSVALGSR RVGGLLPPGG GAARAGPGLS YCVWVVSATE ELQPCAPGTL
  1321  CPPLTLTFSP DSSTPCTLSY VLAFDGFPRF LDTGVVQSDR SLIAAFCGQR RDRPLTVQAL
  1381  SGLLVLHWEA NGSSSWGFNA SVGSARCGSG GPGSCPVPQE CVPQDGAAGA GLCRCPQGWA
  1441  GPHCRMALCP ENCNAHTGAG TCNQSLGVCI CAEGFGGPDC ATKLDGGQLV WETLMDSRLS
  1501  ADTASRFLHR LGHTMVDGPD ATLWMFGGLG LPQGLLGNLY RYSVSERRWT QMLAGAEDGG
  1561  PGPSPRSFHA AAYVPAGRGA MYLLGGLTAG GVTRDFWVLN LTTLQWRQEK APQTVELPAV
  1621  AGHTLTARRG LSLLLVGGYS PENGFNQQLL EYQLATGTWV SGAQSGTPPT GLYGHSAVYH
  1681  EATDSLYVFG GFRFHVELAA PSPELYSLHC PDRTWSLLAP SQGAKRDRMR NVRGSSRGLG
  1741  QVPGEQPGSW GFREVRKKMA LWAALAGTGG FLEEISPHLK EPRPRLFHAS ALLGDTMVVL
  1801  GGRSDPDEFS SDVLLYQVNC NAWLLPDLTR SASVGPPMEE SVAHAVAAVG SRLYISGGFG
  1861  GVALGRLLAL TLPPDPCRLL SSPEACNQSG ACTWCHGACL SGDQAHRLGC GGSPCSPMPR
  1921  SPEECRRLRT CSECLARHPR TLQPGDGEAS TPRCKWCTNC PEGACIGRNG SCTSENDCRI
  1981  NQREVFWAGN CSEAACGAAD CEQCTREGKC MWTRQFKRTG ETRRILSVQP TYDWTCFSHS
  2041  LLNVSPMPVE SSPPLPCPTP CHLLPNCTSC LDSKGADGGW QHCVWSSSLQ QCLSPSYLPL
  2101  RCMAGGCGRL LRGPESCSLG CAQATQCALC LRRPHCGWCA WGGQDGGGRC MEGGLSGPRD
  2161  GLTCGRPGAS WAFLSCPPED ECANGHHDCN ETQNCHDQPH GYECSCKTGY TMDNMTGLCR
  2221  PVCAQGCVNG SCVEPDHCRC HFGFVGRNCS TECRCNRHSE CAGVGARDHC LLCRNHTKGS
  2281  HCEQCLPLFV GSAVGGGTCR PCHAFCRGNS HICISRKELQ MSKGEPKKYS LDPEEIENWV
  2341  TEGPSEDEAV CVNCQNNSYG EKCESCLQGY FLLDGKCTKC QCNGHADTCN EQDGTGCPCQ
  2401  NNTETGTCQG SSPSDRRDCY KYQCAKCRES FHGSPLGGQQ CYRLISVEQE CCLDPTSQTN
  2461  CFHEPKRRAL GPGRTVLFGV QPKFTNVDIR LTLDVTFGAV DLYVSTSYDT FVVRVAPDTG
  2521  VHTVHIQPPP APPPPPPPAD GGPRGAGDPG GAGASSGPGA PAEPRVREVW PRGLITYVTV
  2581  TEPSAVLVVR GVRDRLVITY PHEHHALKSS RFYLLLLGVG DPSGPGANGS ADSQGLLFFR
  2641  QDQAHIDLFV FFSVFFSCFF LFLSLCVLLW KAKQALDQRQ EQRRHLQEMT KMASRPFAKV
  2701  TVCFPPDPTA PASAWKPAGL PPPAFRRSEP FLAPLLLTGA GGPWGPMGGG CCPPAIPATT
  2761  AGLRAGPITL EPTEDGMAGV ATLLLQLPGG PHAPNGACLG SALVTLRHRL HEYCGGGGGA
  2821  GGSGHGTGAG RKGLLSQDNL TSMSL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MEGF8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0

Highest tissue expression

40 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MEGF8.

Disease | AllUniProt

Conditions MEGF8 is implicated in, by any mechanism.

• Carpenter syndrome 2 (CRPT2) MIM:614976

Disease | GeneticClinVar

44 pathogenic / likely-pathogenic of 1,263 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• MEGF8-related Carpenter syndrome
• Carpenter syndrome
• Craniosynostosis syndrome
• Polydactyly
• MEGF8-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.37

gnomAD pLI

0

gnomAD missense Z

3.48

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aorta development
• BMP signaling pathway
• cell migration involved in gastrulation
• coronary vasculature development
• craniofacial suture morphogenesis
• determination of digestive tract left/right asymmetry
• determination of heart left/right asymmetry
• embryonic brain development
• embryonic digit morphogenesis
• embryonic heart tube left/right pattern formation
• embryonic heart tube morphogenesis
• embryonic limb morphogenesis
• embryonic skeletal system morphogenesis
• fasciculation of sensory neuron axon
• left/right pattern formation
• limb morphogenesis
• negative regulation of smoothened signaling pathway
• pharyngeal arch artery morphogenesis
• positive regulation of axon extension involved in axon guidance
• protein ubiquitination
• protein-containing complex assembly
• regulation of gene expression
• smoothened signaling pathway
• epiboly involved in gastrulation with mouth forming second

Molecular functions

• calcium ion binding

Cellular components

• extracellular exosome
• membrane
• nucleus
• ubiquitin ligase complex

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• CUB domain
• EGF-like calcium-binding domain
• Laminin-type EGF domain
• Plexin repeat
• Kelch-type beta-propeller
• PSI domain
• EGF-like calcium-binding, conserved site
• NELL2-like, EGF domain
• Spermadhesin, CUB domain superfamily
• NOTCH1, EGF-like calcium-binding domain
• Attractin/MKLN-like, beta-propeller domain
• Laminin/attractin/netrin-like, EGF domain
• Laminin EGF domain
• CUB domain
• Plexin repeat
• Calcium-binding EGF domain
• EGF domain
• Laminin/attractin EGF domain
• Attractin/LZTR1 beta-propeller

KeywordsUniProt

• Calcium
• Craniosynostosis
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Kelch repeat
• Laminin EGF-like domain
• Membrane
• Phosphoprotein
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of MEGF8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RNF157
• ATXN7