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HSH2D Gene

protein-coding   GIFtS: 49
GCID: GC19P016244

Hematopoietic SH2 Domain Containing

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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
Hematopoietic SH2 Domain Containing1 2
Adaptor In Lymphocytes Of Unknown Function X2 3
ALX2 3
HSH22
Hematopoietic SH2 Domain-Containing Protein2
Hematopoietic SH2 Protein3

External Ids:    HGNC: 249201   Entrez Gene: 849412   Ensembl: ENSG000001966847   OMIM: 6083495   UniProtKB: Q96JZ23   

Export aliases for HSH2D gene to outside databases

Previous GC identifers: GC19P016106 GC19P016107 GC19P015938 GC19P015815


(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 HSH2D Gene:
T-cell activation requires 2 signals: recognition of antigen by the T-cell receptor (see TCR; MIM 186880) and a
costimulatory signal provided primarily by CD28 (MIM 186760) in naive T cells. HSH2 is a target of both of these
signaling pathways (Greene et al., 2003 (PubMed 12960172)).(supplied by OMIM, Mar 2008)

GeneCards Summary for HSH2D Gene:
HSH2D (hematopoietic SH2 domain containing) is a protein-coding gene.

UniProtKB/Swiss-Prot: HSH2D_HUMAN, Q96JZ2
Function: May be a modulator of the apoptotic response through its ability to affect mitochondrial stability (By
similarity). Adapter protein involved in tyrosine kinase and CD28 signaling. Seems to affect CD28-mediated
activation of the RE/AP element of the interleukin-2 promoter




(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 at NCBI GenBank:
NC_000019.9  NC_018930.2  NT_011295.12  
Regulatory elements:
   Regulatory transcription factor binding sites in the HSH2D gene promoter:
         Sp1   AP-1   Brachyury   ATF-2   NF-kappaB   COMP1   c-Jun   NF-kappaB1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidHSH2D promoter sequence
   Search Chromatin IP Primers for HSH2D

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HSH2D


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

Entrez Gene cytogenetic band: 19p13.12   Ensembl cytogenetic band:  19p13.12   HGNC cytogenetic band: 19p13.12

HSH2D Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HSH2D gene location

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19P016244:  view genomic region     (about GC identifiers)

Start:
16,244,838 bp from pter      End:
16,269,386 bp from pter
Size:
24,549 bases      Orientation:
plus strand

(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, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: HSH2D_HUMAN, Q96JZ2 (See protein sequence)
Recommended Name: Hematopoietic SH2 domain-containing protein  
Size: 352 amino acids; 39002 Da
Subunit: Interacts with FES and TNK2
1 PDB 3D structure from and Proteopedia for HSH2D:
2CS0 (3D)    
Secondary accessions: B5ME72 Q6ZNG7
Alternative splicing: 2 isoforms:  Q96JZ2-1   Q96JZ2-2   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for HSH2D: NX_Q96JZ2

Explore proteomics data for HSH2D at MOPED

Post-translational modifications: 

  • May be phosphorylated by FES and ACK11
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See HSH2D Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_001278203.1  NP_116244.1  

    ENSEMBL proteins: 
     ENSP00000464833   ENSP00000468495   ENSP00000468268   ENSP00000467576   ENSP00000442140  
     ENSP00000465636   ENSP00000467189   ENSP00000468142   ENSP00000380528   ENSP00000253680  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    SH2D: SH2 domain containing

    1 InterPro protein domain:
     IPR000980 SH2

    Graphical View of Domain Structure for InterPro Entry Q96JZ2

    ProtoNet protein and cluster: Q96JZ2

    1 Blocks protein domain: IPB000980 SH2 domain signature

    UniProtKB/Swiss-Prot: HSH2D_HUMAN, Q96JZ2
    Similarity: Contains 1 SH2 domain


    Find genes that share domains with HSH2D           About GenesLikeMe


    (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, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: HSH2D_HUMAN, Q96JZ2
    Function: May be a modulator of the apoptotic response through its ability to affect mitochondrial stability (By
    similarity). Adapter protein involved in tyrosine kinase and CD28 signaling. Seems to affect CD28-mediated
    activation of the RE/AP element of the interleukin-2 promoter

         Gene Ontology (GO): 1 molecular function term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding ----
         
    Find genes that share ontologies with HSH2D           About GenesLikeMe


    Phenotypes:
         2 MGI mutant phenotypes (inferred from 1 allele(MGI details for Hsh2d):
     hematopoietic system  immune system 

    Find genes that share phenotypes with HSH2D           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Hsh2dtm1Viss for HSH2D

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for HSH2D
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    (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
    HSH2D_HUMAN, Q96JZ2: Cytoplasm. Nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol3
    endosome1
    plasma membrane1

    Gene Ontology (GO): 2 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--
    GO:0005737cytoplasm IEA--

    Find genes that share ontologies with HSH2D           About GenesLikeMe


    (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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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for HSH2D
    Interactions:

        GeneGlobe Interaction Network for HSH2D

    STRING Interaction Network Preview (showing 3 interactants - click image to see more details)

    3 Interacting proteins for HSH2D (Q96JZ23 ENSP000002536804) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    FESP073323, ENSP000003315044I2D: score=2 STRING: ENSP00000331504
    TNK2Q079123, ENSP000003713414I2D: score=2 STRING: ENSP00000371341
    MPP3ENSP000003814254STRING: ENSP00000381425
    About this table

    (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)
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    Browse Small Molecules at EMD Millipore
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    Browse Tocris compounds for HSH2D



    (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,
    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, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for HSH2D gene (2 alternative transcripts): 
    NM_001291274.1  NM_032855.3  

    Unigene Cluster for HSH2D:

    Hematopoietic SH2 domain containing
    Hs.631617  [show with all ESTs]
    Unigene Representative Sequence: AK131222
    10 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000593154 ENST00000586872 ENST00000588246 ENST00000589463 ENST00000535834
    ENST00000587963 ENST00000593031 ENST00000591154 ENST00000397372 ENST00000253680(uc002ndp.4 uc002ndr.3 uc010ead.3)

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    Additional mRNA sequence: 

    AK027792.1 AK131222.1 AK298682.1 AK300027.1 AK307563.1 AY319652.1 BC016826.1 BC025237.2 

    9 DOTS entries:

    DT.206653  DT.40120606  DT.100756604  DT.75134736  DT.86852573  DT.121496134  DT.436661  DT.121496119 
    DT.75172695 

    Selected AceView cDNA sequences (see all 536):

    BQ065334 AA328139 BM791355 BP355361 AA322829 AA064715 BM475359 BU166181 
    BX492976 BM978303 BM916405 AU119700 BM923211 BP337883 BM457602 BQ671010 
    BP341634 BU175309 AA654013 AW515871 BG758569 BQ892283 BC002977 BM015854 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for HSH2D (see all 6)    About this scheme

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


    ECgene alternative splicing isoforms for HSH2D

    (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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    HSH2D expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    HSH2D Expression
    About this image


    HSH2D expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     
     Blood (Hematopoietic System)
             Granulocytes Peripheral Blood
    HSH2D Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    HSH2D Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.631617

    UniProtKB/Swiss-Prot: HSH2D_HUMAN, Q96JZ2
    Tissue specificity: Predominantly expressed in spleen and hematopoietic cells such as peripheral blood leukocytes
    and weakly expressed in prostate, thymus, heart, small intestine and placenta

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    In Situ
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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)
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    This gene was present in the common ancestor of human and mouse.

    Orthologs for HSH2D gene from Selected species (see all 5)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Hsh2d1 , 5 hematopoietic SH2 domain containing1, 5 69.87(n)1
    61.26(a)1
      8 (34.87 cM)5
    2094881  NM_197944.11  NP_922935.11 
     721896685 


    ENSEMBL Gene Tree for HSH2D (if available)
    TreeFam Gene Tree for HSH2D (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for HSH2D gene
    2 SIMAP similar genes for HSH2D using alignment to 10 protein entries:     HSH2D_HUMAN (see all proteins):
    GRAP2    CSK

    Find genes that share paralogs with HSH2D           About GenesLikeMe



    (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 HSH2D (see all 621)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1817198481,2
    --15813790(+) GGCTCA/GTTGGT 1 -- us2k10--------
    rs1869573291,2
    --15813806(+) GGTTGG/TTTTGG 1 -- us2k10--------
    rs739287441,2
    C--15813919(+) GAGACG/ATAGTG 1 -- us2k11Minor allele frequency- A:0.50WA 2
    rs3716332951,2
    C--15813948(+) CTCAGA/CAAACC 1 -- us2k10--------
    rs2000051721,2
    --15814042(+) TTTTTC/TCGATG 1 -- us2k10--------
    rs2018825491,2
    C--15814086(+) GCCTCA/GCTCAG 1 -- us2k10--------
    rs1173867531,2
    C--15814099(+) CAGCTG/AACTGT 1 -- us2k11Minor allele frequency- A:0.01NA 120
    rs1913922981,2
    --15814135(+) CAGCCA/GGGGCC 1 -- us2k10--------
    rs1384872361,2
    --15814171(+) GCCGCA/GGCCAC 1 -- us2k10--------
    rs1427345281,2
    --15814313(+) CCACAC/TGTTGT 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for HSH2D (16244838 - 16269386 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for HSH2D:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2718261CNV Deletion23290073
    esv2672837CNV Deletion23128226
    esv2718260CNV Deletion23290073
    nsv833767CNV Loss17160897
    nsv911158CNV Loss21882294

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 608349    OMIM disorders: --


    Find genes that share disorders with HSH2D           About GenesLikeMe

    Genetic Association Database (GAD): HSH2D
    Human Genome Epidemiology (HuGE) Navigator: HSH2D (4 documents)

    Export disorders for HSH2D 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 HSH2D gene, integrated from 10 sources (see all 14):
    (articles sorted by number of sources associating them with HSH2D)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. HSH2: a novel SH2 domain-containing adapter protein involved in tyrosine kinase signaling in hematopoietic cells. (PubMed id 11700021)1, 2, 3, 9 Oda T.... Yamashita T. (Biochem. Biophys. Res. Commun. 2001)
    2. Cloning and characterization of ALX, an adaptor downstream of CD28. (PubMed id 12960172)1, 2, 9 Greene T.A.... Shapiro V.S. (J. Biol. Chem. 2003)
    3. The ALX Src homology 2 domain is both necessary and sufficient to inhibit T cell receptor/CD28-mediated up-regulation of RE/AP. (PubMed id 15284240)1, 2, 9 Shapiro M.J.... Shapiro V.S. (J. Biol. Chem. 2004)
    4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1, 4 Bailey S.D....Anand S. (Diabetes Care 2010)
    5. The carboxyl-terminal segment of the adaptor protein ALX directs its nuclear export during T cell activation. (PubMed id 16169852)1, 2 Shapiro M.J.... Shapiro V.S. (J. Biol. Chem. 2005)
    6. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    7. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (Nat. Genet. 2004)
    8. Toward an understanding of the protein interaction network of the human liver. (PubMed id 21988832)1 Wang J....Yang X. (Mol. Syst. Biol. 2011)
    9. New genetic associations detected in a host response study to hepatitis B vaccine. (PubMed id 20237496)1 Davila S....Seielstad M. (Genes Immun. 2010)
    10. Resolvin D1 binds human phagocytes with evidence for proresolving receptors. (PubMed id 20080636)1 Krishnamoorthy S....Serhan C.N. (Proc. Natl. Acad. Sci. U.S.A. 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 84941 HGNC: 24920 AceView: RAB8AandHSH2D Ensembl:ENSG00000196684 euGenes: HUgn84941
    ECgene: HSH2D H-InvDB: HSH2D

    (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)
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    NameDescription
    PharmGKB entry for HSH2D Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for HSH2D gene:
    Search GeneIP for patents involving HSH2D

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



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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