OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardAll1OMIMdbSNP0OMIMUniSTS0*604741LinksALDOKETOREDUCTASEFAMILY1MEMBERD1AKR1D1AlternativetitlessymbolsDELTA(4)3OXOSTEROID5BETAREDUCTASESTEROID5BETAREDUCTASESRD5B15@BETAREDUCTASETEXTDESCRIPTIONHumandelta(4)3oxosteroid5betareductase(steroid5betareductase)catalyzes5betareductionofbileacidintermediatesandsteroidhormonescarryingadelta(4)3onestructureCLONINGKondoetal(1994)screenedahumanlivercDNAlibrarywitharat5betareductasecDNAtoisolatethecDNAencodinghuman5betareductaseThefulllengthcDNAencodesapeptideof326aminoacidswitharelativemassof37380DaNorthernblotanalysisofhumanliverRNAidentifieda27kbtranscriptTheauthorsinsertedthe5betareductasecDNAintoanexpressionvectorandtransfecteditintoCOScellsTherecombinantproteinwasdetectedbyimmunoblotanalysisusingamonoclonalantibodyagainstrat5betareductaseRecombinant5betareductaseshowed5betareductaseactivityagainstseveralsubstratesasdetectedbyhighperformanceliquidchromatographyMAPPINGCharbonneauandLuuThe(1999)usedFISHanalysistomapSRD5B1thegeneencodinghuman5betareductasetochromosome7q32q33andapseudogene(SRD5BP1)to1q23q25MOLECULARGENETICSIn3unrelatedpatientswithneonatalcholestasisduetodelta(4)3oxosteroid5betareductasedeficiency(CBAS2235555)Lemondeetal(2003)identified3differenthomozygousmutationsintheAKR1D1gene(60474100016047410003)Urinaryprofileofall3patientsshowedalmostcompleteabsenceofchenodeoxycholicandcholicacids(selectedexamples)0001BILEACIDSYNTHESISDEFECTCONGENITAL2[AKR1D1PRO198LEU]Inapatientwithintrahepaticcholestasisduetodelta(4)3oxosteroid5betareductasedeficiency(235555)firstreportedbyClaytonetal(1996)Lemondeetal(2003)identifiedahomozygous662CTmutationintheAKR1D1generesultinginapro198toleu(P198L)substitutionThemutationwasnotidentifiedin100controlchromosomesThemutationispredictedtointerferewithnormalNADPHbindingrenderingthemutantenzymeinactive0002BILEACIDSYNTHESISDEFECTCONGENITAL2[AKR1D11BPDEL511T]InaPakistanipatientwithCBAS2(235555)bornofconsanguineousparentsLemondeetal(2003)identifiedahomozygous1bpdeletion(511delT)intheAKR1D1generesultinginaframeshiftandprematuretruncationoftheproteininexon5Themutationwasnotidentifiedin100controlchromosomes0003BILEACIDSYNTHESISDEFECTCONGENITAL2[AKR1D1LEU106PHE]InapatientfromSriLankawithCBAS2(235555)whoseparentswereconsanguineousLemondeetal(2003)identifiedahomozygous385CTtransitionintheAKR1D1generesultinginaleu106tophe(L106F)substitutionwithinthealpha3helixoftheenzymeThemutationwasnotidentifiedin100controlchromosomesREFERENCES1CharbonneauALuuTheVAssignmentofsteroid5betareductase(SRD5B1)anditspseudogene(SRD5BP1)tohumanchromosomebands7q32q33and1q23q25respectivelybyinsituhybridizationCytogenetCellGenet841051061999PubMedID103431192ClaytonPTMillsKAJohnsonAWBarabinoAMarazziMGDelta43oxosteroid5betareductasedeficiencyfailureofursodeoxycholicacidtreatmentandresponsetochenodeoxycholicacidpluscholicacidGut386236281996PubMedID87071003KondoKHKaiMHSetoguchiYEggertsenGSjoblomPSetoguchiTOkudaKIBjorkhemICloningandexpressionofcDNAofhumandelta(4)3oxosteroid5betareductaseandsubstratespecificityoftheexpressedenzymeEuropJBiochem2193573631994PubMedID75083854LemondeHACustardEJBouquetJDuranMOvermarsHScamblerPJClaytonPTMutationsinSRD5B1(AKR1D1)thegeneencodingdelta43oxosteroid5betareductaseinhepatitisandliverfailureininfancyGut52149414992003PubMedID12970144CONTRIBUTORSCassandraLKniffinupdated6/6/2006CREATIONDATEStefanieANelson3/24/2000EDITHISTORYcarol6/14/2006ckniffin6/6/2006alopez3/24/2000alopez3/24/2000Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH