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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

BHLHE22 Gene

protein-coding   GIFtS: 45
GCID: GC08P065492

basic helix-loop-helix family, member e22

(Previous names: trinucleotide repeat containing 20, basic helix-loop-helix...)
(Previous symbols: TNRC20, BHLHB5)
 Explore 2 diseases affiliated with
BHLHE22 via our new
 Human Malady Compendium 
Biological research products
for BHLHE22
    

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Aliases
Basic Helix-Loop-Helix Family, Member E221 2     BHLHe221
BHLHB51 2 3 5     Class B Basic Helix-Loop-Helix Protein 52 3
TNRC201 2 3     Trinucleotide Repeat-Containing Gene 20 Protein2 3
Beta31 2     Class E Basic Helix-Loop-Helix Protein 222
CAGL851 2     BHLHb51
Basic Helix-Loop-Helix Domain Containing, Class B, 51 2     BETA35
Trinucleotide Repeat Containing 201 2     

External Ids:    HGNC: 119631   Entrez Gene: 273192   Ensembl: ENSG000001808287   OMIM: 6134835   UniProtKB: Q8NFJ83   

Export aliases for BHLHE22 gene to outside databases

Previous GC identifers: GC08P065656 GC08P060983


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for BHLHE22:
BHLHE22 belongs to the basic helix-loop-helix (bHLH) family of transcription factors that regulate cell fate
determination, proliferation, and differentiation. These proteins function as dimers and bind to an E-box DNA sequence
(CANNTG). BHLHE22 is expressed exclusively in the central nervous system and retina (Xu et al., 2002 (PubMed
12213201)).(supplied by OMIM, Jul 2010)

UniProtKB/Swiss-Prot: BHE22_HUMAN, Q8NFJ8
Function: Inhibits DNA binding of TCF3/E47 homodimers and TCF3 (E47)/NEUROD1 heterodimers and acts as a strong
repressor of Neurod1 and Myod-responsive genes, probably by heterodimerization with class a basic helix-loop-helix
factors. Despite the presence of an intact basic domain, does not bind to DNA (By similarity)




(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000008.10  NC_018919.1  NT_008183.19  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the BHLHE22 gene promoter:
         GR   AP-1   GR-beta   ATF-2   Nkx2-5   LCR-F1   SEF-1 (1)   STAT3   c-Jun   GR-alpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidBHLHE22 promoter sequence
   Search SABiosciences Chromatin IP Primers for BHLHE22

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat BHLHE22


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

Entrez Gene cytogenetic band: 8q13   Ensembl cytogenetic band:  8q12.3   HGNC cytogenetic band: 8q12.1

BHLHE22 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
BHLHE22 gene location

GeneLoc information about chromosome 8         GeneLoc Exon Structure

GeneLoc location for GC08P065492:  view genomic region     (about GC identifiers)

Start:
65,492,814 bp from pter      End:
65,496,186 bp from pter
Size:
3,373 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: BHE22_HUMAN, Q8NFJ8 (See protein sequence)
Recommended Name: Class E basic helix-loop-helix protein 22  
Size: 381 amino acids; 36997 Da
Subcellular location: Nucleus (Probable)

Explore the universe of human proteins at neXtProt for BHLHE22: NX_Q8NFJ8

Post-translational modifications:

  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q8NFJ8

  • BHLHE22 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_689627.1  
    ENSEMBL proteins: 
     ENSP00000318799  

    Human Recombinant Protein Products: 
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    Uscn Proteins for BHLHE22

    Gene Ontology (GO): 1 cellular component term (GO ID links to tree view):    About this table

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


    BHLHE22 for ontologies           About GeneDecksing



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    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    BHLHE22 for domains           About GeneDecksing

    1 InterPro domain/family:
     IPR011598 HLH_dom

    Graphical View of Domain Structure for InterPro Entry Q8NFJ8

    ProtoNet protein and cluster: Q8NFJ8

    1 Blocks protein family: IPB001092 Basic helix-loop-helix dimerization domain bHLH

    UniProtKB/Swiss-Prot: BHE22_HUMAN, Q8NFJ8
    Similarity: Contains 1 bHLH (basic helix-loop-helix) domain


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Function Summary:

         UniProtKB/Swiss-Prot: BHE22_HUMAN, Q8NFJ8
    Function: Inhibits DNA binding of TCF3/E47 homodimers and TCF3 (E47)/NEUROD1 heterodimers and acts as a strong
    repressor of Neurod1 and Myod-responsive genes, probably by heterodimerization with class a basic helix-loop-helix
    factors. Despite the presence of an intact basic domain, does not bind to DNA (By similarity)

    miRNA
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    hsa-miR-513a-5p hsa-miR-3653 hsa-miR-624 hsa-miR-192 hsa-miR-3658 hsa-miR-149 hsa-miR-29a* hsa-miR-548e
    SwitchGear 3'UTR luciferase reporter plasmidBHLHE22 3' UTR sequence
    Inhib. RNA
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for BHLHE22

    Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000981sequence-specific DNA binding RNA polymerase II transcription factor activity IEA--
    GO:0003682chromatin binding IEA--
    GO:0042803protein homodimerization activity IEA--


    BHLHE22 for ontologies           About GeneDecksing


    1 GenomeRNAi human phenotype for BHLHE22:
     Lamellipodia and high actin ra 

    Animal Models:
         Mouse knock-out Bhlhe22tm1Meg for BHLHE22
         6 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Bhlhe22):
     behavior/neurological  cellular  growth/size  integument  nervous system 
     vision/eye 

    BHLHE22 for phenotypes           About GeneDecksing


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section



    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for BHLHE22

    Gene Ontology (GO): 5/8 biological process terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006351transcription, DNA-dependent ----
    GO:0021540corpus callosum morphogenesis IEA--
    GO:0021957corticospinal tract morphogenesis IEA--
    GO:0021960anterior commissure morphogenesis IEA--
    GO:0030182neuron differentiation ----


    BHLHE22 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for BHLHE22
    Search CenterWatch for drugs/clinical trials and news about BHLHE22 / BHE22 

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for BHLHE22 gene: 
    NM_152414.4  

    Unigene Clusters for BHLHE22:

    Basic helix-loop-helix family, member e22
    Hs.591870  [show with all ESTs], Hs.743680  [show with all ESTs]
    Unigene Representative Sequences: BC033056, NM_152414
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000321870(uc003xvi.3)

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    8/38 QIAGEN miScript miRNA Assays for microRNAs that regulate BHLHE22 (see all 38):
    hsa-miR-513a-5p hsa-miR-3653 hsa-miR-624 hsa-miR-192 hsa-miR-3658 hsa-miR-149 hsa-miR-29a* hsa-miR-548e
    SwitchGear 3'UTR luciferase reporter plasmidBHLHE22 3' UTR sequence
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      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat BHLHE22
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    Additional cDNA sequence: 

    AK091333.1 AK293979.1 

    1 DOTS entry:

    DT.100019098 

    24/36 AceView cDNA sequences (see all 36):

    AL134707 BM661603 AW665919 M78885 CA392856 BX116391 AA453786 AI498361 
    BM689628 AI380496 NM_152414 AA635141 AI804341 BK000273 BX646197 AW594227 
    BI552771 AA927689 AI968349 AW206610 AA453903 BC045748 AI278054 AI867692 

    GeneLoc Exon Structure


    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    BHLHE22 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: GCTGTTTGAC

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image

    BHLHE22 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    10/12 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 12
    Tissue Anatomical Compartment CellCategory (developmental path)
    EyeGanglion Cell LayerDisplaced Amacrine CellsAmacrine, Retina
    EyeGanglion Cell LayerDopaminergic Amacrine CellsAmacrine, Retina
    EyeInner Nuclear LayerCone Bipolar Precursor CellsBipolar, Retina
    EyeInner Nuclear LayerDopaminergic Amacrine CellsAmacrine, Retina
    EyeInner Nuclear LayerEarly Immature Amacrine CellsAmacrine, Retina
    EyeInner Nuclear LayerGABAergic Amacrine CellsAmacrine, Retina
    EyeInner Nuclear LayerType2 Off Cone Bipolar CellsBipolar, Retina
    BrainBlood Brain BarrierEndothelial CellsBlood Brain Barrier, Endothelium
    KidneyUreteric BudUreteric Bud Tip CellsKidney
    Skeletal MuscleHyoid Arch MusclesMuscle Progenitor CellsSkeletal Muscle
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization
    Stem Cell Differentiation: 1 LifeMap Cell 
    NameCategory
    Definitive endoderm-like cells (A scalable, suspensi...)

    See BHLHE22 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for BHLHE22

    SOURCE GeneReport for Unigene clusters: Hs.591870 Hs.743680

    UniProtKB/Swiss-Prot: BHE22_HUMAN, Q8NFJ8
    Tissue specificity: Brain-specific, with the highest expression in the cerebellum

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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for BHLHE22

    (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

    This gene was present in the common ancestor of eukaryotes.

    Orthologs for BHLHE22 gene from 6/12 species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Bhlhe221 , 5 basic helix-loop-helix family, member e221, 5 87.42(n)1
    93.8(a)1
      3 (4.98 cM)5
    590581  NM_021560.41  NP_067535.31 
     180541745 
    lizard
    (Anolis carolinensis)
    Reptilia BHLHE226
    --
    64(a)
    1 ↔ 1
    4(30018474-30019418)
    zebrafish
    (Danio rerio)
    Actinopterygii zgc642252 similar to basic helix-loop-helix domain containing, more 79.89(n)   393930  BC053312.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Oli6
    Olig family
    37(a)
    1 → many
    2L(17589407-17591267)
    worm
    (Caenorhabditis elegans)
    Secernentea hlh-176
    hlh-326
    (see all 3)
    Helix Loop Helix family member (hlh-32)
    (see all 3)
    50(a)
    49(a)
    (see all 3)
    many ↔ many
    many ↔ many
    (see all 3)
    IV(16254744-16256231)
    IV(16132432-16134245)
    rice
    (Oryza sativa)
    Liliopsida AK100183.12   -- 76.88(n)    AK100183.1 


    ENSEMBL Gene Tree for BHLHE22 (if available)
    TreeFam Gene Tree for BHLHE22 (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for BHLHE22 gene
    OLIG32  BHLHE232  OLIG12  OLIG22  
    2 SIMAP similar genes for BHLHE22 using alignment to 1 protein entry:     BHE22_HUMAN:
    BHLHE23    TWIST1

    BHLHE22 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/80 NCBI SNPs in BHLHE22 are shown (see all 80    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 8 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs799984401,2
    --65490935(+) CCCAAG/AGACTT 2 -- us2k11Minor allele frequency- A:0.01NA 120
    rs745756301,2
    F,--65490947(+) GATAAG/ATTAGT 2 -- us2k11Minor allele frequency- A:0.03WA 118
    rs2022411491,2
    C--65491184(+) CGCTCA/CAGCCT 2 -- us2k10--------
    rs597248101,2
    C,--65491243(+) GCCTGA/GTCTTT 2 -- us2k12Minor allele frequency- G:0.14CSA WA 120
    rs1839630261,2
    --65491484(+) CGAACC/GTCATT 2 -- us2k10--------
    rs1894269301,2
    --65491509(+) AGAGAC/TTAATA 2 -- us2k10--------
    rs1820228551,2
    --65491560(+) TTAACC/TATATG 2 -- us2k10--------
    rs1844393451,2
    --65491668(+) TTAATA/GAAACC 2 -- us2k10--------
    rs1508541691,2
    --65491887(+) CTTCCC/TGAACC 1 -- us2k10--------
    rs347389851,2
    C,--65492053(+) AACCG-/GTTT  
            
    GTTTG
    1 -- us2k11Minor allele frequency- GTTT:0.50CSA 2

    HapMap Linkage Disequilibrium report for BHLHE22 (65492814 - 65496186 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for BHLHE22: --

    SABiosciences Cancer Mutation PCR Assays
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing BHLHE22
    DNA2.0 Custom Variant and Variant Library Synthesis for BHLHE22

    (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.)
    About This Section

    BHLHE22 for disorders           About GeneDecksing

    OMIM gene information: 613483    OMIM disorders: --

    2 diseases for BHLHE22:    About MalaCards
    retinitis    neuronitis


    Export disorders for BHLHE22 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)
    About This Section

    PubMed articles for BHLHE22 gene integrated from 9 sources:
    (articles sorted by number of sources associating them with BHLHE22)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Functional and structural characterization of the human gene BHLHB5, encoding a basic helix-loop-helix transcription factor. (PubMed id 12213201)1, 2, 3, 9 Xu Z.-P....Saunders G.F. (2002)
    2. Phylogenetic and expression analysis of the basic helix-loop-helix transcription factor gene family: genomic approach to cellular differentiation. (PubMed id 18557763)1, 3 Stevens J.D....Skinner M.K. (2008)
    3. Exhaustive identification of human class II basic helix-loop-helix proteins by virtual library screening. (PubMed id 14516699)1, 2 McLellan A.S.... Kealey T. (2002)
    4. cDNAs with long CAG trinucleotide repeats from human brain. (PubMed id 9225980)1, 3 Margolis R.L.... Ross C.A. (1997)
    5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1 Ota T.... Sugano S. (2004)
    6. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)1 Strausberg R.L....Marra M.A. (2002)
    7. Exhaustive identification of human class II basic helix-loop-helix proteins by virtual library screening. (PubMed id 12617822)1 McLellan A.S.... Kealey T. (2002)

    (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)
    About This Section
    Entrez Gene: 27319 HGNC: 11963 AceView: BHLHB5 Ensembl:ENSG00000180828 euGenes: HUgn27319
    ECgene: BHLHE22 H-InvDB: BHLHE22

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for BHLHE22 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for BHLHE22 gene:
    Search GeneIP for patents involving BHLHE22

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



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