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

TONSL Gene

protein-coding   GIFtS: 47
GCID: GC08M145656

tonsoku-like, DNA repair protein

(Previous name: nuclear factor of kappa light polypeptide gene enhancer...)
(Previous symbol: NFKBIL2)
 Explore 6 diseases affiliated with
TONSL via our new
 Human Malady Compendium 
Biological research products
for TONSL
    

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

Aliases
Tonsoku-Like, DNA Repair Protein1 2     I-Kappa-B-Related Protein2 3
IKBR1 2 3 5     NF-Kappa-B Inhibitor-Like Protein 22 3
NFKBIL21 2 3 5     IkappaBR3
Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells
Inhibitor-Like 21 2 3
     Tonsoku-Like Protein2
Inhibitor Of Kappa B-Related Protein2 3     IkappaBR3

External Ids:    HGNC: 78011   Entrez Gene: 47962   Ensembl: ENSG000001609497   OMIM: 6045465   UniProtKB: Q96HA73   

Export aliases for TONSL gene to outside databases

Previous GC identifer: GC08M145655


(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 TONSL:
The protein encoded by this gene is thought to be a negative regulator of NF-kappa-B mediated transcription. The
encoded protein may bind NF-kappa-B complexes and trap them in the cytoplasm, preventing them from entering the
nucleus and interacting with the DNA. Phosphorylation of this protein targets it for degradation by the ubiquitination
pathway, which frees the NF-kappa-B complexes to enter the nucleus. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: TONSL_HUMAN, Q96HA7
Function: Component of the MMS22L-TONSL complex, a complex that stimulates the recombination-dependent repair of
stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA
replication by promoting homologous recombination-mediated repair of replication fork-associated double-strand breaks.
It may act by mediating the assembly of RAD51 filaments on ssDNA. Within the complex, may act as a scaffold




(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_037704.5  
Regulatory elements:
   Search SABiosciences Regulatory transcription factor binding sites for TONSL
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidTONSL promoter sequence
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Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TONSL


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

Entrez Gene cytogenetic band: 8q24.3   Ensembl cytogenetic band:  8q24.3   HGNC cytogenetic band: 8q24.3

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

GeneLoc information about chromosome 8         GeneLoc Exon Structure

GeneLoc location for GC08M145656:  view genomic region     (about GC identifiers)

Start:
145,654,163 bp from pter      End:
145,669,827 bp from pter
Size:
15,665 bases      Orientation:
minus strand

1 alternative location:
Chr8-,PATCHES 145,568,923-145,574,425     

(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: TONSL_HUMAN, Q96HA7 (See protein sequence)
Recommended Name: Tonsoku-like protein  
Size: 1378 amino acids; 150929 Da
Subunit: Component of the MMS22L-TONSL complex, a complex at least composed of MMS22L and TONSL/NFKBIL2. Interacts with
the MCM complex, the FACT complex and the RPA complex. Binds histones
Subcellular location: Cytoplasm. Nucleus. Note=Mainly nuclear. Localizes to DNA damage sites, accumulates at stressed
replication forks
Caution: Was reported to share sequence similarities with IKBKB and therefore named 'NF-kappa-B inhibitor-like protein
2' (PubMed:7738005). However, the sequence similarity is remote and effects as regulator of NF-kappa-B are probably
indirect and require additional evidence (PubMed:9242696)
Sequence caution: Sequence=AAA85819.1; Type=Frameshift; Positions=Several; Sequence=AAH08782.1; Type=Erroneous
initiation; Note=Translation N-terminally extended; Sequence=CAB63467.1; Type=Erroneous gene model prediction;
Secondary accessions: B5MDP0 C9JKB1 C9JNV8 Q13006 Q9UGJ2
Alternative splicing: 2 isoforms:  Q96HA7-1   Q96HA7-2   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for TONSL: NX_Q96HA7

Post-translational modifications:

  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q96HA7

  • TONSL Protein expression data from MOPED and PaxDb:    About this image 
    TONSL Protein Expression
    REFSEQ proteins: NP_038460.4  
    ENSEMBL proteins: 
     ENSP00000386239  

    Human Recombinant Protein Products for TONSL: 
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    Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005662colocalizes with DNA replication factor A complex IDA--
    GO:0005730NOT nucleolus IDA--
    GO:0005737cytoplasm IEA--
    GO:0035101colocalizes with FACT complex IDA--

    TONSL 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

    TONSL for domains           About GeneDecksing

    5 InterPro domains/families:
     IPR011990 TPR-like_helical
     IPR020683 Ankyrin_rpt-contain_dom
     IPR013026 TPR-contain_dom
     IPR019734 TPR_repeat
     IPR002110 Ankyrin_rpt

    Graphical View of Domain Structure for InterPro Entry Q96HA7

    ProtoNet protein and cluster: Q96HA7

    2 Blocks protein families:
    IPB001611 Leucine-rich repeat signature
    IPB002110 Ankyrin repeat signature


    UniProtKB/Swiss-Prot: TONSL_HUMAN, Q96HA7
    Domain: The ANK repeats mediate the interaction with the MCM complex and histones, while the LRR repeats mediate the
    interaction with MMS22L
    Similarity: Belongs to the Tonsoku family
    Similarity: Contains 3 ANK repeats
    Similarity: Contains 7 LRR (leucine-rich) repeats
    Similarity: Contains 8 TPR repeats


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

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TONSL_HUMAN, Q96HA7
    Function: Component of the MMS22L-TONSL complex, a complex that stimulates the recombination-dependent repair of
    stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA
    replication by promoting homologous recombination-mediated repair of replication fork-associated double-strand breaks.
    It may act by mediating the assembly of RAD51 filaments on ssDNA. Within the complex, may act as a scaffold

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003714transcription corepressor activity TAS7738005
    GO:0005515protein binding IPI--
    GO:0042393histone binding IDA--
         
    TONSL for ontologies           About GeneDecksing


    Phenotypes:
         3 GenomeRNAi human phenotypes for TONSL:
     Decreased nuclei size in G2M  Decreased viability of wild-ty  Large cells 

    Animal Models:
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    (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 TONSL

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

    5/29 Interacting proteins for TONSL (Q96HA72, 3 ENSP000003862394) via UniProtKB, MINT, STRING, and/or I2D (see all 29)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MMS22LQ6ZRQ52, 3, ENSP000002750534MINT-8089662 MINT-8089673 MINT-8089726 MINT-8089667 MINT-8089790 I2D: score=2 STRING: ENSP00000275053
    MCM4P339912, 3, ENSP000002621054MINT-8089790 I2D: score=1 STRING: ENSP00000262105
    SSRP1Q089452, 3, ENSP000002784124MINT-8089790 I2D: score=1 STRING: ENSP00000278412
    GSK3BP498412, 3MINT-8257526 I2D: score=2 
    MCM2P497362, 3, ENSP000002650564MINT-8089673 MINT-8089739 MINT-8089790 I2D: score=1 STRING: ENSP00000265056
    About this table

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000724double-strand break repair via homologous recombination IMP--
    GO:0031297replication fork processing IMP--
    GO:0042994cytoplasmic sequestering of transcription factor TAS7738005

    TONSL 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
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    (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,
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    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 TONSL gene: 
    NM_013432.4  

    Unigene Cluster for TONSL:

    Tonsoku-like, DNA repair protein
    Hs.675285  [show with all ESTs]
    Unigene Representative Sequence: NM_013432
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000497613 ENST00000409379(uc011llg.2)

    miRNA
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    Inhib. RNA
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    Additional cDNA sequence: BC008782.2 

    4 DOTS entries:

    DT.91749069  DT.100684369  DT.95290589  DT.97806224 

    24/51 AceView cDNA sequences (see all 51):

    BQ944722 BE871368 BQ960372 BU190662 BM918035 BC008782 NM_013432 BM463971 
    AK097406 BM903924 BQ230076 BM799907 BU597311 BG390892 BM048623 BU173679 
    BI117416 BU190557 BG284976 BI092283 BG819532 BU154566 BU145350 BM479763 

    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

    TONSL expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: GAGCCTGTAT
    TONSL Expression
    About this image

    TONSL expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table

    3 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    BrainHypothalamusBrain
    Neural TubeDiencephalic Ventricular ZoneNeural Tube
    Neural TubeMesencephalic Ventricular ZoneNeural Tube
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

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

    SOURCE GeneReport for Unigene cluster: Hs.675285

    UniProtKB/Swiss-Prot: TONSL_HUMAN, Q96HA7
    Tissue specificity: Expressed in heart, skeletal muscle and tracheal epithelial cells

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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)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for TONSL gene from 4/17 species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    lizard
    (Anolis carolinensis)
    Reptilia TONSL6
    --
    51(a)
    1 ↔ 1
    GL343892.1(43424-98001)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.150102 Xenopus laevis transcribed sequence with weak similarity more 74.51(n)    CA792151.1 
    zebrafish
    (Danio rerio)
    Actinopterygii BI875764.12   -- 74.2(n)    BI875764.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG74571 CG7457 41.35(n)
    30.89(a)
      38865  NM_139893.3  NP_648150.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for TONSL gene
    ANKRD112  BARD12  ANKRD322  ANKRD122  ANKRD312  
    3 SIMAP similar genes for TONSL using alignment to 1 protein entry:     TONSL_HUMAN:
    IkBa    DKFZp761E1322    MTPN

    TONSL 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

    10/439 NCBI SNPs in TONSL are shown (see all 439    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 8 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs175536001,2
    C--140767208(-) GGGGG-/GTCGCC 2 -- us2k10--------
    rs576451331,2
    C--140767208(+) CCCCGC/-CCCCT 2 -- us2k11Minor allele frequency- -:0.00NA 2
    rs1126995771,2
    F--140768885(+) CCCCTG/TCTGCC 2 -- us2k12Minor allele frequency- T:0.50CSA 4
    rs125431881,2
    C,F,H--140771979(+) gtgagC/Acactg 1 -- us2k13Minor allele frequency- A:0.50NA 6
    rs38021631,2
    C,H--140773778(+) AGAGTG/AGGTGT 1 -- us2k1 ese35Minor allele frequency- A:0.00NS EA NA 420
    rs125420481,2
    C,F,H--140773817(+) CTGCTG/ACCTGC 1 -- nc-transcript-variant1Minor allele frequency- A:0.33NA 6
    rs793798361,2
    C,F--140775406(+) CCCCCC/G/TGTTCA 2 -- nc-transcript-variant2NA 4470
    rs1113938581,2
    C,F--140775456(+) GCATCG/ATGGAG 1 -- nc-transcript-variant3Minor allele frequency- A:0.00CSA NA 4398
    rs1151195821,2
    C,F--140776997(+) ATGAGG/AAAGTT 1 -- int11Minor allele frequency- A:0.03WA 118
    rs1113982041,2
    F--140777055(+) TGCTAG/CGCAGC 1 -- int12Minor allele frequency- C:0.50CSA 6

    HapMap Linkage Disequilibrium report for TONSL (145654163 - 145669827 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for TONSL: --

    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

    TONSL for disorders           About GeneDecksing

    OMIM gene information: 604546    OMIM disorders: --

    6 diseases for TONSL:    About MalaCards
    t-cell leukemia    psoriasis    breast cancer    atherosclerosis
    leukemia    immunodeficiency

    2 Novoseek disease relationships for TONSL gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    necrosis 2.41 1 7796813 (1)
    tumors 0 1 7796813 (1)


    Export disorders for TONSL 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 TONSL gene, integrated from 9 sources (see all 46):
    (articles sorted by number of sources associating them with TONSL)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Isolation, sequence, and chromosomal localisation of the human IkappaBR gene (NFKBIL2). (PubMed id 11246458)1, 2, 3 Norman D.A. and Barton P.J. (2000)
    2. Cloning of a differentially expressed I kappa B-related protein. (PubMed id 7738005)1, 2, 3 Ray P.... Ray A. (1995)
    3. The MMS22L-TONSL complex mediates recovery from repli cation stress and homologous recombination. (PubMed id 21055983)1, 2 O'Donnell L....Durocher D. (2010)
    4. A genome-wide camptothecin sensitivity screen identifies a mammalian MMS22L-NFKBIL2 complex required for genomic stability. (PubMed id 21055985)1, 2 O'Connell B.C.... Harper J.W. (2010)
    5. Identification of the MMS22L-TONSL complex that promo tes homologous recombination. (PubMed id 21055984)1, 2 Duro E....Rouse J. (2010)
    6. A census of human soluble protein complexes. (PubMed id 22939629)1 Havugimana P.C....Emili A. (2012)
    7. Codanin-1, mutated in the anaemic disease CDAI, regula tes Asf1 function in S-phase histone supply. (PubMed id 22407294)1 Ask K....Groth A. (2012)
    8. Initial characterization of the human central proteome. (PubMed id 21269460)2 Burkard T.R.... Colinge J. (2011)
    9. A directed protein interaction network for investigat ing intracellular signal transduction. (PubMed id 21900206)1 Vinayagam A....Wanker E.E. (2011)
    10. Systematic and quantitative assessment of the ubiquiti n-modified proteome. (PubMed id 21906983)1 Kim W....Gygi S.P. (2011)

    (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: 4796 HGNC: 7801 AceView: NFKBIL2 Ensembl:ENSG00000160949 euGenes: HUgn4796
    ECgene: TONSL H-InvDB: TONSL

    (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 TONSL 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 TONSL gene:
    Search GeneIP for patents involving TONSL

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



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