OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardAll1OMIMdbSNP0OMIMUniSTS0*138700LinksAPOLIPOPROTEINHAPOHAlternativetitlessymbolsGLYCOPROTEINBETA2GLYCOPROTEINIB2G1BGGenemaplocus17q23qterTEXTHauptetal(1968)describedafamilyinwhich2brothershadcompleteabsenceofwhattheytermedbeta2glycoproteinIintheserumBothparentsasisterandbothchildrenof1ofthebrothershadhalfnormallevelsoftheproteinCleveandRittner(1969)found9familiesoutof88inwhich1parentandabouthalfthechildrenhadintermediateconcentrationsofbeta2glycoproteinIandwerepresumedtobeheterozygousforadeficiency('null')geneIrregularitiesinotherfamilieslimittheuseofthetraitingeneticstudiesThelocuswassymbolizedBgBg(N)allelehasafrequencyvaryingfrom082to094inseveralpopulationsstudied(Koppeetal1970Rahimietal1977)LinkagedatanoneestablishinglinkagewerepresentedbyEibergetal(1984)AsreviewedbyLozieretal(1984)whodetermineditsfullaminoacidsequencethephysiologicfunctionofbeta2glycoproteinIhasnotbeenestablishedwithcertaintyInman35%oftheproteinisassociatedwiththelipoproteinswith16%inchylomicronsandverylowdensitylipoproteins2%inlowdensitylipoproteinsand17%inhighdensitylipoproteinsNakayaetal(1980)demonstratedbeta2glycoproteinIactivationoflipoproteinlipaseanddesignatedthisglycoproteinasapolipoproteinHHoegetal(1985)identified5personswithnodetectablecirculatingapoHTheauthorswereimpressedbythelackofconsistenteffectsonplasmalipoproteinsandconcludedthatthelackofapolipoproteinHdoesnotresultinasignificantperturbationofnormallipoproteinmetabolismItmaybethatthisshouldbeconsidereda'nondisease'UsingthinlayerpolyacrylamideisoelectricfocusinggelsandimmunologicidentificationKambohetal(1988)demonstratedgeneticallydeterminedpolymorphismofapolipoproteinHThreecommonalleleswereidentifiedinUSwhitesandblacksAfourthallelewasobservedinblackindividualsFamilydataconfirmedautosomalcodominantinheritanceof4allelesatasingleAPOHlocusRichterandCleve(1988)demonstratedgeneticvariationsbymeansofisoelectricfocusingSepehrniaetal(1988)provideddataonthedistributionofapolipoproteinpolymorphismsinNigeriaincludingpolymorphismofAPOHTheobservationssupportedtheconclusionthattheAPOH*4isamarkeralleleuniquetoblacksandonethatmaybewidelydistributedamongAfricanpopulationswhereastheAPOH*1allelemaybeauniqueCaucasianallelethatwasintroducedintotheblackpopulationoftheUSbyadmixtureEibergetal(1989)reportedlinkagedatasuggestingthatthestructuralandquantitativepolymorphismsassociatedwithserumbeta2glycoproteinIareverytightlylinked(maximumlodscore=328attheta=00maleandfemaledatacombined)TheypresentedexclusiondataforthelocalizationofAPOHSepehrniaetal(1989)foundspecificassociationsbetweenparticularAPOHallelesandtheleveloftriglyceridesinfemalesDataongenefrequenciesofallelicvariantsweretabulatedbyRoychoudhuryandNei(1988)Haagerupetal(1991)demonstratedRFLPsintheAPOHgeneandusedtheseinCEPHfamilystudiestolocatethegeneon17qThemarkerthatshowedclosestlinkagewasHOX2(142960)locatedat17q21q22lodscore=883attheta=005LinkagetoCOL1A1(120150)wasindicatedbyalodscoreof618attheta=012ByhybridizingacDNAprobeforAPOHtoapanelofsomaticcellhybridsSteinkassereretal(1992)showedthatthestructurallocusmapsto17q23qterNorthernblotanalysisestablishedthatAPOHissynthesizedintheliverwhereatranscriptofapproximately15kbwasidentifiedMehdietal(1991)clonedandsequencedAPOHcDNAsfromhumanliverandfromahumanhepatomacelllineBothcDNAspredictedaproteinof345aminoacidsincludinga19aminoacidhydrophobicNterminalsignalsequencethatisnotpresentinthematureproteinThelevelofAPOHmRNAexpressedbythehepatomacellswasdownregulatedbyincubationwithinflammatorymediatorsimplyingthatAPOHisanegativeacutephaseproteinNonakaetal(1992)mappedthemouseApohgenetochromosome11Theycommentedthattheproteiniscomposedof5repeatingunitscalledshortconsensusrepeats(SCR)whicharefoundmostlyintheregulatoryproteinsofthecomplementsystemmostofthegenesfortheseproteinsmaptochromosome1(egC4BPA120830)Shengetal(1997)foundthatthemouseApohgenecontains8exonsandspansapproximately18kbApoHhasbeenimplicatedinavarietyofphysiologicpathwaysincludinglipoproteinmetabolismcoagulationandtheproductionofantiphospholipidautoantibodiesSangheraetal(1997)citedreportssupportingtheconclusionthatApoHisarequiredcofactorforanionicphospholipidbindingbytheantiphospholipidautoantibodiesfoundinseraofmanypatientswithlupus(152700)andprimaryantiphospholipidsyndrome(107320)butitdoesnotseemtoberequiredforthereactivityofantiphospholipidautoantibodiesassociatedwithinfectionsThesestudiessuggestedthattheapoHphospholipidcomplexformstheantigentowhichtheautoantibodiesaredirectedGeneticallydeterminedstructuralabnormalitiesinthelipidbindingdomain(s)ofapoHcanaffectitsabilitytobindlipidandconsequentlytheproductionoftheautoantibodiesSangheraetal(1997)identified2commonstructuralmutationsatcodons316and306inthefifthdomainofapoHwhichrenderapoHunabletobindtonegativelychargedphosphatidylserineThemissensemutationatcodon316(TGGtoTCG)replacedtrp316withser316anddisruptedthesequenceof4highlyconservedhydrophobicaminoacidsatpositions313to316whichisapotentialproteinlipidhydrophobicinteractionsiteThemissensemutationatcodon306(TGCtoGGC)involvedasubstitutionofcys306bygly306whichcausedthedisruptionofadisulfidebondbetweencys281andcys306andaffectedthenormalconfigurationofthefifthdomainofapoHthatappearstobecriticalforclusteringpositivelychargedaminoacidsalongwiththe4hydrophobicaminoacidsequenceApoHfrom2ser316homozygotesandall7ser316/gly306compoundheterozygotesfailedtobindtophosphatidylserineallheterozygotesatoneortheothersitesandwildtypeshowednormalphosphatidylserinebindingThesedataindicatedtoSangheraetal(1997)thatthefifthdomainofapoHharborsthelipidbindingregionAnestimated2millionCaucasiansintheUnitedStateswhoarecompoundheterozygotesforthe2mutationsmaybeprecludedfromproducingapoHdependentantiphospholipidautoantibodiesSangheraetal(2001)foundthatthechimpanzeeAPOHgenelikethehumangeneconsistsof8exonsandencodesadeduced326aminoacidproteinasinhumansThehumanandchimpanzeeAPOHproteinsshare994%sequencesimilarityUsingisoelectricfocusing(IEF)andimmunoblottingSangheraetal(2001)screened155chimpanzees(128unrelatedcapturedparentsand27captivebornoffspring)fortheapoHproteinpolymorphismThemostcommonIEFpatterninchimpanzeeswasidenticaltoapreviouslydescribedAPOH*3alleleinhumansInadditiontheyidentifiedinchimpanzeesanalleledesignatedAPOH*4resultingfromalys210toglumissensechangeinexon6TheyfoundthattheprevalenceofantiapoHantibodiesinchimpanzees(64%)wasunusuallyhighcomparedtothatinhumansNoassociationwasfoundbetweenthelys210toglumutationandtheoccurrenceofantiapoHantibodiesTheauthorssuggestedthatthechimpanzeemayserveasausefulanimalmodelforhumanantiphospholipidsyndrome(107320)(selectedexamples)0001APOHPOLYMORPHISM[APOHVAL247LEU]Steinkassereretal(1993)describeda2alleleRsaIrestrictionfragmentlengthpolymorphism(RFLP)anddemonstratedthatitledtoaval247toleuaminoacidexchangeInstudiesof34unrelatedparentsintheCEPHfamilypanelallelefrequencieswerefoundtobe076forvalineand023forleucineThevalleupolymorphismdidnotcorrelatewiththe4isoelectricfocusingallelespreviouslydescribedSEEALSOCleve(1968)Walteretal(1979)REFERENCES1CleveHGeneticstudiesonthedeficiencyofbeta2glycoproteinIofhumanserumHumangenetik52943041968PubMedID56706082CleveHRittnerCFurtherfamilystudiesonthegeneticcontrolofbeta2glycoproteinIconcentrationinhumanserumHumangenetik793971969PubMedID57994983EibergHMohrJNielsenLSThebeta2glycoproteinI(BG)allelefrequenciesandlinkagerelationships(Abstract)CytogenetCellGenet37462only19844EibergHNielsenLSMohrJExclusionmappingofapolipoproteinH(APOH)andrelationshipbetweenelectrophoreticandquantitativepolymorphism(Abstract)CytogenetCellGenet51994only19895HaagerupAKristensenTKruseTAPolymorphismandgeneticmappingofthegeneencodinghumanbeta2glycoproteinItochromosome17(Abstract)CytogenetCellGenet582005only19916HauptHSchwickHGStorikoKUebereinenerblichenbeta2GlykoproteinIMangelHumangenetik52912931968PubMedID56706077HoegJMSegalPGreggREChangYSLindgrenFTAdamsonGLFrankMBrickmanCBrewerHBJrCharacterizationofplasmalipidsandlipoproteinsinpatientswithbeta2glycoproteinI(apolipoproteinH)deficiencyAtherosclerosis5525341985PubMedID39240648KambohMIFerrellRESepehrniaBGeneticstudiesofhumanapolipoproteinsIVStructuralheterogeneityofapolipoproteinH(beta2glycoproteinI)AmJHumGenet424524571988PubMedID33482139KoppeALWalterHChopraVPBajatzadehMInvestigationsonthegeneticsandpopulationgeneticsofthebeta2glycoproteinIpolymorphismHumangenetik91641711970PubMedID542392910LozierJTakahashiNPutnamFWCompleteaminoacidsequenceofhumanplasmabeta2glycoproteinIProcNatAcadSci81364036441984PubMedID658737811MehdiHNunnMSteelDMWhiteheadASPerezMWalkerLPeeplesMENucleotidesequenceandexpressionofthehumangeneencodingapolipoproteinH(beta2glycoproteinI)Gene1082932981991PubMedID174831412NakayaYSchaeferEJBrewerHBActivationofhumanpostheparinlipasebyapolipoproteinH(beta2glycoproteinI)BiochemBiophysResCommun95116811721980PubMedID741730713NonakaMMatsudaYShiroishiTMoriwakiKNonakaMNatsuumeSakaiSMolecularcloningofmousebeta2glycoproteinIandmappingofthegenetochromosome11Genomics13108210871992PubMedID133938714RahimiAGGoeddeHWFlatzGKaifieSBenkmannHGDelbruckHSerumproteinpolymorphismsinfourpopulationsofAfghanistanAmJHumGenet293563601977PubMedID6940015RichterACleveHGeneticvariationsofhumanserumbeta2glycoproteinIdemonstratedbyisoelectricfocusingElectrophoresis93173221988PubMedID314846316RoychoudhuryAKNeiMHumanPolymorphicGenesWorldDistributionNewYorkOxfordUnivPress(pub)198817SangheraDKNestlerodeCSFerrellREKambohMIChimpanzeeapolipoproteinH(beta2glycoproteinI)reportonthegenestructureacommonpolymorphismandahighprevalenceofantiphospholipidantibodiesHumGenet10963722001PubMedID1147973718SangheraDKWagenknechtDRMcIntyreJAKambohMIIdentificationofstructuralmutationsinthefifthdomainofapolipoproteinH(beta2glycoproteinI)whichaffectphospholipidbindingHumMolecGenet63113161997PubMedID906375219SepehrniaBKambohMIAdamsCampbellLLBunkerCHNwankwoMMajumderPPFerrellREGeneticstudiesofhumanapolipoproteinsVIIIRoleoftheapolipoproteinHpolymorphisminrelationtoserumlipoproteinconcentrationsHumGenet821181221989PubMedID272218620SepehrniaBKambohMIAdamsCampbellLLNwankwoMFerrellREGeneticstudiesofhumanapolipoproteinsVIIPopulationdistributionofpolymorphismsofapolipoproteinsAIAIIAIVCIIEandHinNigeriaAmJHumGenet438478531988PubMedID314326321ShengYHerzogHKrilisSACloningandcharacterizationofthegeneencodingthemousebeta2glycoproteinIGenomics411281301997PubMedID912649422SteinkassererACockburnDJBlackDMBoydYSolomonESimRBAssignmentofapolipoproteinH(APOHbeta2glycoproteinI)tohumanchromosome17q23qterdeterminationofthemajorexpressionsiteCytogenetCellGenet6031331992PubMedID158225423SteinkassererADornerCWurznerRSimRBHumanbeta2glycoproteinImolecularanalysisofDNAandaminoacidpolymorphismHumGenet914014021993PubMedID809906124WalterHHillingMBrachtelRHitzerothHWOnthepopulationgeneticsofbeta2glycoproteinIHumHered292362411979PubMedID478560CONTRIBUTORSRebekahSRasoolyupdated5/7/1998VictorAMcKusickupdated4/21/1997VictorAMcKusickupdated4/15/1997CREATIONDATEVictorAMcKusick6/4/1986EDITHISTORYcarol3/1/2002mcapotos9/17/2001mcapotos8/24/2001psherman5/7/1998jenny4/21/1997jenny4/15/1997terry4/9/1997terry1/10/1997pfoster2/18/1994carol7/12/1993carol8/31/1992carol8/13/1992carol6/23/1992supermim3/16/1992Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH