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KRIT1 Gene

protein-coding   GIFtS: 65
GCID: GC07M091828

KRIT1, Ankyrin Repeat Containing

(Previous name: cerebral cavernous malformations 1)
(Previous symbol: CCM1)
Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
KRIT1, Ankyrin Repeat Containing1 2     CAM2 5
CCM11 2 3 5     Cerebral Cavernous Malformations 11
Cerebral Cavernous Malformations 1 Protein2 3     Ankyrin Repeat-Containing Protein Krit12
Krev Interaction Trapped 12 3     Krev Interaction Trapped Protein 12

External Ids:    HGNC: 15731   Entrez Gene: 8892   Ensembl: ENSG000000016317   OMIM: 6042145   UniProtKB: O005223   

Export aliases for KRIT1 gene to outside databases

Previous GC identifers: GC07M091473 GC07M091666 GC07M086435


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for KRIT1 Gene:
This gene encodes a protein containing four ankyrin repeats, a band 4.1/ezrin/radixin/moesin (FERM) domain, and
multiple NPXY sequences. The encoded protein is localized in the nucleus and cytoplasm. It binds to integrin
cytoplasmic domain-associated protein-1 alpha (ICAP1alpha), and plays a critical role in beta1-integrin-mediated
cell proliferation. It associates with junction proteins and RAS-related protein 1A (Rap1A), which requires the
encoded protein for maintaining the integrity of endothelial junctions. It is also a microtubule-associated
protein and may play a role in microtubule targeting. Mutations in this gene result in cerebral cavernous
malformations. Multiple alternatively spliced transcript variants have been found for this gene. (provided by
RefSeq, Sep 2009)

GeneCards Summary for KRIT1 Gene:
KRIT1 (KRIT1, ankyrin repeat containing) is a protein-coding gene. Diseases associated with KRIT1 include cavernous malformations of cns and retina, and retinal cavernous hemangioma. GO annotations related to this gene include microtubule binding and phosphatidylinositol-4,5-bisphosphate binding. An important paralog of this gene is FRMD8.

UniProtKB/Swiss-Prot: KRIT1_HUMAN, O00522
Function: Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and
integrity (By similarity). Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis,
migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation
in a NOTCH-dependent and independent manner, and inhibits ERK1/2 phosphorylation indirectly through activation of
the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity
and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and
RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and
cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents
the interaction between ITGB1 and ITGB1BP1. Microtubule-associated protein that binds to phosphatidylinositol
4,5-bisphosphate (PIP2)-containing membranes in a GTP-bound RAP1-dependent manner. Plays an important role in the
maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage.
Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2.
Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative
growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2
levels

Gene Wiki entry for KRIT1 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000007.14  NT_007933.16  NC_018918.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the KRIT1 gene promoter:
         CREB   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): KRIT1 promoter sequence
   Search Chromatin IP Primers for KRIT1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat KRIT1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7q21.2   Ensembl cytogenetic band:  7q21.2   HGNC cytogenetic band: 7q21.2

KRIT1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
KRIT1 gene location

GeneLoc information about chromosome 7         GeneLoc Exon Structure

GeneLoc location for GC07M091828:  view genomic region     (about GC identifiers)

Start:
91,828,283 bp from pter      End:
91,875,480 bp from pter
Size:
47,198 bases      Orientation:
minus strand

1 alternative location:
Chr7-,CRA_TCAG 91,157,516-91,204,647     

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: KRIT1_HUMAN, O00522 (See protein sequence)
Recommended Name: Krev interaction trapped protein 1  
Size: 736 amino acids; 84348 Da
Subunit: Interacts with CDH5 (By similarity). Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A.
Interacts (via C-terminus FERM domain) with RAP1A (active GTP-bound form preferentially); the interaction does
not induce the opening conformation of KRIT1. Interacts (via FERM domain) with RAP1B. Interacts (via N-terminus
NPXY motif) with ITGB1BP1; the interaction induces the opening conformation of KRIT1 and competes with ITGB1 for
ITGB1BP1 interaction. Interacts with HEG1 and CCM2; greatly facilitates CCM2-binding to HEG1. Associates (via
N-terminus and C-terminus regions) with microtubules; the interaction is inhibited in presence of ITGB1BP1 and
active GTP-bound RAP1A
6 PDB 3D structures from and Proteopedia for KRIT1:
3U7D (3D)        4DX8 (3D)        4DXA (3D)        4HDO (3D)        4HDQ (3D)        4JIF (3D)    
Secondary accessions: A6NNU0 O43894 Q506L6 Q6U276 Q75N19 Q9H180 Q9H264 Q9HAX5
Alternative splicing: 3 isoforms:  O00522-1   O00522-2   O00522-3   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for KRIT1: NX_O00522

Explore proteomics data for KRIT1 at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See KRIT1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (5 alternative transcripts): 
    NP_001013424.1  NP_004903.2  NP_919436.1  NP_919437.1  NP_919438.1  

    ENSEMBL proteins: 
     ENSP00000344668   ENSP00000410909   ENSP00000378013   ENSP00000378011   ENSP00000404084  
     ENSP00000391675   ENSP00000410104   ENSP00000405835   ENSP00000396042   ENSP00000391540  
     ENSP00000410467   ENSP00000396352   ENSP00000395346   ENSP00000414694   ENSP00000388076  
     ENSP00000395604   ENSP00000404790   ENSP00000378015  

    KRIT1 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
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    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    Browse OriGene Protein Over-expression Lysates
    OriGene Custom MassSpec
    OriGene Custom Protein Services for KRIT1
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    Novus Biologicals KRIT1 Proteins
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for KRIT1

    KRIT1 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of KRIT1
    Browse R&D Systems for Antibodies
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    OriGene Custom Antibody Services for KRIT1
    Novus Biologicals KRIT1 Antibodies
    Abcam antibodies for KRIT1
    Cloud-Clone Corp. Antibodies for KRIT1
    ThermoFisher Antibodies for KRIT1
    LSBio Antibodies in human, mouse, rat for KRIT1

    KRIT1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for KRIT1
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for KRIT1
    Cloud-Clone Corp. CLIAs for KRIT1


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    ANKRD: Ankyrin repeat domain containing

    Selected InterPro protein domains (see all 6):
     IPR019748 FERM_central
     IPR019749 Band_41_domain
     IPR020683 Ankyrin_rpt-contain_dom
     IPR002110 Ankyrin_rpt
     IPR014352 FERM/acyl-CoA-bd_prot_3-hlx

    Graphical View of Domain Structure for InterPro Entry O00522

    ProtoNet protein and cluster: O00522

    1 Blocks protein domain: IPB002110 Ankyrin repeat signature

    UniProtKB/Swiss-Prot: KRIT1_HUMAN, O00522
    Domain: The FERM domain mediates binding to RAP1A and RAP1B and is necessary for binding to phosphatidylinositol
    4,5-bisphosphate (PIP2)
    Domain: The N-terminal domain has structural similarity to the nudix hydrolase domain, despite the absence of a
    nudix box and low sequence similarity with nudix hydrolase domains. The N-terminus and the C-terminus part
    associate together via the NPAY binding motif and adopt a lose conformation that is disrupted by ITGB1BP1, but
    not by RAP1A
    Similarity: Contains 4 ANK repeats
    Similarity: Contains 1 FERM domain


    KRIT1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: KRIT1_HUMAN, O00522
    Function: Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and
    integrity (By similarity). Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis,
    migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation
    in a NOTCH-dependent and independent manner, and inhibits ERK1/2 phosphorylation indirectly through activation of
    the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity
    and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and
    RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and
    cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents
    the interaction between ITGB1 and ITGB1BP1. Microtubule-associated protein that binds to phosphatidylinositol
    4,5-bisphosphate (PIP2)-containing membranes in a GTP-bound RAP1-dependent manner. Plays an important role in the
    maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage.
    Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2.
    Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative
    growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2
    levels

         Genatlas biochemistry entry for KRIT1:
    KREV (Kirsten transformed cell revertant) interaction trapped 1,associating with KREV1 (RAP1A1)

         Gene Ontology (GO): 5 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005083small GTPase regulator activity TAS9285558
    GO:0005515protein binding IPI16037064
    GO:0005546phosphatidylinositol-4,5-bisphosphate binding IDA17916086
    GO:0008017microtubule binding IDA17916086
    GO:0032403protein complex binding IDA17916086
         
    KRIT1 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for KRIT1:
     Decreased viability after Chla 

         6 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Krit1):
     cardiovascular system  craniofacial  embryogenesis  mortality/aging  nervous system 
     vision/eye 

    KRIT1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Krit1tm1Sfre for KRIT1

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for KRIT1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for KRIT1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for KRIT1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for KRIT1

    miRNA
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    Block miRNA regulation of human, mouse, rat KRIT1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate KRIT1 (see all 55):
    hsa-miR-142-5p hsa-miR-548j hsa-miR-607 hsa-miR-4272 hsa-miR-578 hsa-miR-3653 hsa-miR-218 hsa-miR-371-5p
    SwitchGear 3'UTR luciferase reporter plasmidKRIT1 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for KRIT1
    Predesigned siRNA for gene silencing in human, mouse, rat KRIT1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for KRIT1

    Clone
    Products:
         
    OriGene clones in human, mouse for KRIT1 (see all 30)
    OriGene ORF clones in mouse, rat for KRIT1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 5): KRIT1 (NM_001013406)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for KRIT1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat KRIT1

    Cell Line
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    GenScript Custom overexpressing Cell Line Services for KRIT1
    Browse ESI BIO Cell Lines and PureStem Progenitors for KRIT1 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for KRIT1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    KRIT1_HUMAN, O00522: Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Cell junction.
    Note=KRIT1 and CDH5 reciprocally regulate their localization to endothelial cell-cell junctions. Association with
    RAP1 relocalizes KRIT1 from microtubules to cell junction membranes. Translocates from the cytoplasm along
    microtubules to the cell membrane in a ITGB1BP1-dependent manner
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    plasma membrane5
    cytosol3
    nucleus2
    mitochondrion1

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005615extracellular space IDA--
    GO:0005737cytoplasm IEA--
    GO:0005856cytoskeleton ----
    GO:0005874microtubule IDA17916086
    GO:0005886plasma membrane IDA17916086

    KRIT1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for KRIT1 About    
    See pathways by source

    SuperPathContained pathways About
    1Ras signaling pathway
    Rap1 signaling pathway0.36
    2Hypothetical Network for Drug Addiction
    Hypothetical Network for Drug Addiction
    3G protein signaling Rap1A regulation pathway
    G protein signaling Rap1A regulation pathway

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 GeneGo (Thomson Reuters) Pathway for KRIT1
        G-protein signaling Rap1A regulation pathway

    1 BioSystems Pathway for KRIT1
        Hypothetical Network for Drug Addiction


    1 Kegg Pathway  (Kegg details for KRIT1):
        Rap1 signaling pathway


    KRIT1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Array including KRIT1: 
              Telomeres & Telomerase in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for KRIT1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for KRIT1 (O005221, 3 ENSP000003446684) via UniProtKB, MINT, STRING, and/or I2D (see all 42)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CCM2Q9BSQ51, 3, ENSP000003705034EBI-1573121,EBI-1573056 I2D: score=3 STRING: ENSP00000370503
    RGS4P497983, ENSP000003971814I2D: score=1 STRING: ENSP00000397181
    ITGB1BP1O147133, ENSP000003475044I2D: score=7 STRING: ENSP00000347504
    RAP1AP628343, ENSP000003487864I2D: score=2 STRING: ENSP00000348786
    DAPK1P533553, ENSP000003507854I2D: score=1 STRING: ENSP00000350785
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001525angiogenesis IEA--
    GO:0001937negative regulation of endothelial cell proliferation IMP--
    GO:0007264small GTPase mediated signal transduction TAS9285558
    GO:0010596negative regulation of endothelial cell migration IMP--
    GO:0016525negative regulation of angiogenesis IMP--

    KRIT1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for KRIT1

    Selected Novoseek inferred chemical compound relationships for KRIT1 gene (see all 103)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    calmidazolium 81.3 48 2351670 (3), 12379180 (1), 19081128 (1), 15746192 (1) (see all 26)
    calcium 79.8 1316 9422356 (10), 18076146 (9), 12614169 (8), 19133300 (7) (see all 99)
    n-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide 78.9 18 18803664 (1), 10624566 (1), 20172594 (1), 8964090 (1) (see all 15)
    trifluoperazine 77.6 87 10727421 (4), 11180054 (4), 2167684 (3), 19277699 (3) (see all 41)
    p-mca 76.2 80 15461467 (7), 19000896 (4), 16101291 (4), 15446271 (3) (see all 17)
    mastoparan x 71.1 16 11814356 (7), 16408880 (1)
    rs 20 69.4 2 12829504 (1), 10194305 (1)
    kn 93 68.3 3 16935404 (1), 14578204 (1), 15806159 (1)
    calmodulins 68.2 7 10194305 (2), 17157809 (1)
    kn62 66.1 6 19281832 (1), 7478584 (1), 18227124 (1), 16935404 (1) (see all 5)



    KRIT1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for KRIT1 gene (5 alternative transcripts): 
    NM_001013406.1  NM_004912.3  NM_194454.1  NM_194455.1  NM_194456.1  

    Unigene Cluster for KRIT1:

    KRIT1, ankyrin repeat containing
    Hs.531987  [show with all ESTs]
    Unigene Representative Sequence: AF388384
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 24):
    ENST00000486261(uc010lev.1) ENST00000340022 ENST00000475770 ENST00000412043
    ENST00000394505 ENST00000394503 ENST00000487168 ENST00000445516 ENST00000458177
    ENST00000433016 ENST00000454017 ENST00000440209 ENST00000430102 ENST00000470309
    ENST00000413688 ENST00000458493 ENST00000452773 ENST00000425919
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate KRIT1 (see all 55):
    hsa-miR-142-5p hsa-miR-548j hsa-miR-607 hsa-miR-4272 hsa-miR-578 hsa-miR-3653 hsa-miR-218 hsa-miR-371-5p
    SwitchGear 3'UTR luciferase reporter plasmidKRIT1 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat KRIT1
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    GenScript: all cDNA clones in your preferred vector (see all 5): KRIT1 (NM_001013406)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for KRIT1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat KRIT1
    Primer
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    OriGene qSTAR qPCR primer pairs in human, mouse for KRIT1
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      QuantiTect SYBR Green Assays in human, mouse, rat KRIT1
      QuantiFast Probe-based Assays in human, mouse, rat KRIT1

    Additional mRNA sequence: 

    AF296765.2 AF310133.1 AF388384.1 AJ294850.1 AK055305.1 AK056537.1 AK226131.1 AL049325.1 
    AY380057.1 AY380058.1 AY380059.1 AY380060.1 AY993944.1 BC047343.2 BC094684.1 U90268.1 

    Selected DOTS entries (see all 27):

    DT.311252  DT.40129960  DT.92471341  DT.100789384  DT.121106278  DT.102812  DT.102831016  DT.101962415 
    DT.92471467  DT.121106286  DT.92471464  DT.95286554  DT.121106296  DT.97842545  DT.121106298  DT.97842547 
    DT.99993548  DT.102831013  DT.121106247  DT.95164264  DT.100789388  DT.121106251  DT.121106258  DT.121106263 

    Selected AceView cDNA sequences (see all 138):

    AA780153 AI633769 BQ424644 BX280833 NM_004912 AI738409 BM471073 AF388384 
    AI092627 NM_194454 BM785166 AJ294850 BM720957 CB215990 NM_194456 AW467128 
    AI082872 BQ188499 AW002636 AW068991 BU183752 AA598899 BX280088 AI239706 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for KRIT1 (see all 30)    About this scheme

    ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b · 2c · 2d ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c · 5d ^ 6a · 6b · 6c ^ 7a · 7b · 7c · 7d · 7e · 7f ^ 8a · 8b ·
    SP1:                                                                                      -     -                                                               
    SP2:                                                              -     -     -     -     -                                                                     
    SP3:                                                                                                                                                            
    SP4:                                                              -     -     -     -     -                       -     -     -     -     -     -               
    SP5:                                                                                            -     -     -     -     -     -     -     -     -               

    ExUns: 8c ^ 9a · 9b · 9c · 9d · 9e · 9f ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24a · 24b · 24c
    SP1:                                                                                                                    -                           
    SP2:                                                                                                                    -                           
    SP3:                                                                                                                    -                           
    SP4:                                                                    -                                               -                           
    SP5:                                                                                                                    -                           


    ECgene alternative splicing isoforms for KRIT1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    KRIT1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ATTTGAATAA
    KRIT1 Expression
    About this image


    KRIT1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Neural Tube (Nervous System)
             Telencephalon
     
     Thyroid (Endocrine System)
     
     Testis (Reproductive System)
    KRIT1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    KRIT1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.531987

    UniProtKB/Swiss-Prot: KRIT1_HUMAN, O00522
    Tissue specificity: Low levels in brain. Very weak expression found in heart and muscle

        Pathway & Disease-focused RT2 Profiler PCR Array including KRIT1: 
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of animals.

    Orthologs for KRIT1 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Krit11 , 5 KRIT1, ankyrin repeat containing1, 5 90.17(n)1
    94.57(a)1
      5 (2.26 cM)5
    792641  NM_030675.31  NP_109600.21 
     38031655 
    chicken
    (Gallus gallus)
    Aves KRIT11 KRIT1, ankyrin repeat containing 82.54(n)
    91.84(a)
      420549  NM_001030973.1  NP_001026144.1 
    lizard
    (Anolis carolinensis)
    Reptilia KRIT16
    KRIT1, ankyrin repeat containing
    90(a)
    1 ↔ 1
    6(21117323-21136660)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia krit11 KRIT1, ankyrin repeat containing 76.37(n)
    85.44(a)
      100158531  NM_001127967.1  NP_001121439.1 
    zebrafish
    (Danio rerio)
    Actinopterygii wufb36f072 wufb36f07 73.03(n)   321836  BC055149.1 
    worm
    (Caenorhabditis elegans)
    Secernentea kri-11 kri-1 43.64(n)
    30.91(a)
      191275  NM_001026692.3  NP_001021863.1 


    ENSEMBL Gene Tree for KRIT1 (if available)
    TreeFam Gene Tree for KRIT1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for KRIT1 gene
    FRMD82  
    3 SIMAP similar genes for KRIT1 using alignment to 13 protein entries:     KRIT1_HUMAN (see all proteins):
    CCM1    CASKIN2    ANKRD12

    KRIT1 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for KRIT1 (see all 887)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0235734
    Cerebral cavernous malformations 1 (CCM1)4--see VAR_0235732 F S mis40--------
    VAR_0235744
    Cerebral cavernous malformations 1 (CCM1)4--see VAR_0235742 K E mis40--------
    rs1887410131,2
    --86485410(+) AGAGTA/TGGGTG 2 -- us2k10--------
    rs1391651151,2
    C--86485463(+) AAAATA/GTTGTT 2 -- us2k10--------
    rs711078541,2
    C--91191721(-) GTGTG-/TGTG  
            
    TGTGT
    5 -- int11Minor allele frequency- TGTG:0.00NA 2
    rs349102261,2
    C--91829671(+) TTTTT-/T/TT  
            
    GAGAT
    10 -- ut310--------
    rs356240801,2
    C--91836688(+) AAAAA-/AGCTTT 5 -- int10--------
    rs586505801,2
    C--91838202(+) AAAAAA/-GAAAA 5 -- int11Minor allele frequency- -:0.00NA 2
    rs766242371,2
    C--91841262(+) AAAAA-/AAAGCCAG 5 -- int10--------
    rs2001201191,2
    C--91845542(+) AAAAA-/AGATTT 5 -- int10--------

    HapMap Linkage Disequilibrium report for KRIT1 (91828283 - 91875480 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for KRIT1:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv888735CNV Loss21882294
    nsv888734CNV Loss21882294

    Human Gene Mutation Database (HGMD): KRIT1
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing KRIT1
    DNA2.0 Custom Variant and Variant Library Synthesis for KRIT1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 604214   
    OMIM disorders: 116860  
    UniProtKB/Swiss-Prot: KRIT1_HUMAN, O00522
  • Cerebral cavernous malformations 1 (CCM1) [MIM:116860]: A congenital vascular anomaly of the central
    nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic
    deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of
    endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several
    centimeters. Note=The disease is caused by mutations affecting the gene represented in this entry

  • Selected diseases for KRIT1 (see all 62):    
    About MalaCards
    cavernous malformations of cns and retina    retinal cavernous hemangioma    hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations    intracranial cavernous angioma
    familial cerebral cavernous malformation 1    cerebral cavernous malformations-1    clear cell acanthoma    angiokeratoma corporis diffusum with arteriovenous fistulas
    cerebral angioma    cavernous malformation    cerebral cavernous malformation    cavernous hemangioma
    cerebral cavernous malformation, familial    cerebritis    acanthoma    arteriovenous fistula
    angiokeratoma    klippel-trenaunay syndrome    glomus tumor    hemangioma

    3 diseases from the University of Copenhagen DISEASES database for KRIT1:
    Klippel-Trenaunay syndrome     Cavernous hemangioma     Cerebrovascular accident

    KRIT1 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for KRIT1 gene (see all 40)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cerebral cavernous malformations 95.5 79 11914398 (2), 12140362 (2), 12877753 (2), 11941540 (2) (see all 56)
    vascular anomaly 48.8 1 15905966 (1)
    malformation venous 41.5 2 16379592 (1), 19182478 (1)
    glomus tumors, multiple 41.4 1 16379592 (1)
    intracerebral hemorrhage 22.3 1 12140362 (1)
    klippel-trenaunay syndrome 13.8 1 16379592 (1)
    hepatocellular carcinoma 5.45 2 8762469 (1), 17546603 (1)
    anthrax 4.2 4 12542690 (2)
    heart failure 3.96 2 15350849 (1), 8196073 (1)
    atherosclerosis 3.74 1 11137080 (1)

    GeneTests: KRIT1
    GeneReviews: KRIT1
    Genetic Association Database (GAD): KRIT1
    Human Genome Epidemiology (HuGE) Navigator: KRIT1 (3 documents)

    Export disorders for KRIT1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for KRIT1 gene, integrated from 10 sources (see all 772):
    (articles sorted by number of sources associating them with KRIT1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Identification of eight novel 5`-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1. (PubMed id 11342228)1, 2, 3, 9 Eerola I.... Vikkula M. (Biochim. Biophys. Acta 2001)
    2. Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene. (PubMed id 11161805)1, 2, 9 Sahoo T.... Marchuk D.A. (Genomics 2001)
    3. Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1). (PubMed id 12172908)1, 2, 9 Kehrer-Sawatzki H.... Hameister H. (Acta Neuropathol. 2002)
    4. Interaction between krit1 and icap1alpha infers perturbation of integrin beta1-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation. (PubMed id 11741838)1, 2, 9 Zhang J.... Dietz H.C. (Hum. Mol. Genet. 2001)
    5. KRIT1 association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis. (PubMed id 11854171)1, 2, 9 Zawistowski J.S....Marchuk D.A. (Hum. Mol. Genet. 2002)
    6. Cloning of the murine Krit1 cDNA reveals novel mammalian 5' coding exons. (PubMed id 11161791)1, 2, 9 Zhang J.... Dietz H.C. (Genomics 2000)
    7. CCM1 mutation screen of sporadic cases with cerebral cavernous malformations. (PubMed id 15079030)1, 4, 9 Verlaan D.J....Siegel A.M. (Neurology 2004)
    8. Structural basis for small G protein effector interaction of Ras- related protein 1 (Rap1) and adaptor protein Krev interaction trapped 1 (KRIT1). (PubMed id 22577140)1, 2 Li X.... Boggon T.J. (J. Biol. Chem. 2012)
    9. A mechanism of Rap1-induced stabilization of endothelial cell--cell junctions. (PubMed id 21633110)1, 2 Liu J.J.... Ginsberg M.H. (Mol. Biol. Cell 2011)
    10. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (Mol. Med. 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 889 HGNC: 1573 AceView: CCM1 Ensembl:ENSG00000001631 euGenes: HUgn889
    ECgene: KRIT1 Kegg: 889 H-InvDB: KRIT1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for KRIT1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for KRIT1 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=KRIT1[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for KRIT1 gene:
    Search GeneIP for patents involving KRIT1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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