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BLNK (B-cell linker)

Written2012-08Saravanan Yuvaraj, Rudi W Hendriks
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)SLP65
Ly57
SLP-65
BLNK-s
BASH
bca
Other aliasAGM4
BLNK-S
LY57
HGNC (Hugo) BLNK
LocusID (NCBI) 29760
Atlas_Id 804
Location 10q24.1  [Link to chromosome band 10q24]
Location_base_pair Starts at 97951455 and ends at 98031333 bp from pter ( according to hg19-Feb_2009)  [Mapping BLNK.png]
Fusion genes
(updated 2016)
BLNK (10q24.1) / PIK3AP1 (10q24.1)BLNK (10q24.1) / ZNF536 (19q12)UBN1 (16p13.3) / BLNK (10q24.1)
Note BLNK is a cytoplasmic linker or adaptor protein that plays a critical role in B cell development in human and mice.

DNA/RNA

Description The gene spans over 79 kb in human and is encoded in 17 exons on the long arm of chromosome 10.
Transcription The transcript is about 1829 bps in human and about 2097 in mice and UTR regions are present in exons 1, 2 and 17.

Protein

Description BLNK is a 65 kDa protein of 456 amino acids. Translation of the BLNK begins at the ATG site located in exon 2 and ends at exon 17. The amino-terminal region of BLNK is rich in tyrosines and contains a highly conserved leucine zipper that is responsible for the recruitment of BLNK to the plasma membrane. The mid-portion of the molecule contains a proline-rich region that has efficient SH3-domain binding properties. Finally the C-terminus consists of an SH2-domain that allows interaction with other tyrosine phosphorylated proteins. Phosphorylated BLNK provides docking sites for several proteins that induces Ig L chain recombination and differentiation.
Expression BLNK is expressed exclusively in hematopoietic cells, mainly in B cells and myeloid cells.
Localisation It has been shown that the highly conserved N terminus of BLNK comprises a domain for constitutive membrane association, which is essential for its function. Membrane association depends on a leucine zipper motif in the N-terminal domain. The BLNK N-terminus can be functionally replaced by a heterologuous membrane localization signal and can be transferred to other proteins to confer membrane localization. To connect the pre-B cell receptor (pre-BCR) or the BCR with downstream signaling elements, BLNK must be localized at the plasma membrane where these receptors reside. A stimulation-independent and constant association of BLNK with the Cbl-interacting protein of 85 kDa (CIN85) is requisite for BLNK phosphorylation.
Function BLNK lacks intrinsic enzymatic function, but regulates the assembly and localization of signaling complexes. Such molecules are known as adapters or linkers and have the capacity to regulate the availability of a substrate to an enzyme and create a scaffold for bridging signaling cascades. Phosphorylated BLNK (by the spleen tyrosine kinase SYK) provides docking sites for several proteins including the BTK, GRB2, VAV, NCK and PLCγ2 (Figure 1). SYK and its substrate BLNK are proximal signal transducer elements of the BCR. When the in vivo interactome of BLNK in resting and stimulated B cells was determined by mass spectrometry, it was found that BLNK orchestrated a complex signal network of ~30 proteins that was predominantly based on dynamic interactions.
Pre-BCR signaling leads to activation of SYK, which then phosphorylates BLNK and thereby regulates pre-B cell differentiation (Figure 1). BLNK is required for the downregulation of the pre-BCR surrogate light chain component λ-like (λ5 in mice), thereby terminating pre-BCR expression. It has been shown in mice that Blnk-mediated signals induces activation of Ig κ light chain recombination by induction of the expression of the transcription factors Aiolos, Irf-4, Foxo3a and Foxo1. Deficiency of Blnk in mice results in an increased proliferative response of pre-B cells to IL-7 in vitro, indicating that Blnk is crucially involved in the termination of IL-7 driven proliferation. BLNK inhibits IL-7R signaling through direct binding to Jak3 in a Btk-independent manner and also by downregulating IL-7R expression (Figure 1). In the absence of Btk mainly Ig λ L chain germline transcription and recombination is impaired, whereas in Btk/BLNK double-deficient pre-B cells, both κ and λ L chain germline transcripts are severely reduced. These data suggests a dual role of BLNK in the downregulation of surrogate light chain expression and the activation of Igκ germline transcription.
 
  Figure 1. Function of Blnk in pre-BCR signaling in the mouse. A. Pre-BCR activation results in the activation of Syk tyrosine kinase, which together with the Src family kinase Lyn phosphorylates several downstream signaling molecules. This provides signals for proliferation and survival by PI3K-dependent activation of Pkb/Akt and by synergy with the MAP kinase pathway downstream of the IL-7R. In addition, pre-BCR signaling also leads to Blnk-Btk-PLCγ complex formation that is essential for downregulation of proliferative signals. Blnk acts as (1) a negative regulator of Jak3 and (2) through inhibition of Pkb/Akt activation. Activation of FoxO is associated with downregulation of surrogate light chain (SLC) and IL-7R expression and the activation of the Ig kappa locus for gene recombination. B. When in pre-B lymphoma cells Blnk expression is low or absent, proliferative signals are maintained because of (1) ongoing Jak/Stat signaling and (2) Pkb/Akt activation, leading to FoxO phosphorylation and degradation, thereby precluding proper maturation and downregulation of pre-BCR and IL-7R expression, resulting in Syk-dependent pre-B cell proliferation (3).
Homology The SLP76 family of adapters has three members namely SLP76, BLNK (SLP65) and Clnk/MIST.

Implicated in

Note
  
Entity Pre-B cell tumors
Disease Deficiency of BLNK has been found in ~50% of childhood precursor-B cell acute lymphocytic leukemia (ALL) cases. The loss of BLNK protein was found to be due to defective splicing, leading to premature stop codons. Moreover, in precursor-B ALL that where positive for the BCR-ABL translocation the activity of the fusion protein, the BCR-ABL1 kinase, was linked to the expression of the same aberrant BLNK transcripts. Because other expression profiling studies with a large number of patients reported a low frequency it is not clear whether the loss of BLNK is a common leukemogenic event. Nevertheless, the reported findings indicate that loss of BLNK and the accompanying pre-B cell differentiation arrest may be one of the primary causes of precursor-B ALL. In a study of 28 pre-B ALL and 27 B cell lymphomas, BLNK expression was found to be defective in seven and five cases, respectively. BLNK deficiency correlated with RAG1/RAG2 expression and unremitting VH gene rearrangement activity BLNK deficiency resulted in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells.
Blnk-deficient mice spontaneously develop pre-B cell leukemia with a similar phenotype as found in humans. In contrast, mice deficient for Btk, do not develop pre-B cell leukemia. Nevertheless, Btk and Blnk cooperate as tumor suppressors whereby Btk exerts its tumor suppressor function independently of its kinase activity. Combined deficiency of Blnk and Btk result in a more complete arrest at the pre-B cell stage and a higher incidence of pre-B cell leukemia than compared with single deficient mice, suggesting that the developmental block is one of the tumor-promoting factors. In addition, expression of the pre-BCR is also essential for the development of leukemia, because mice which are Rag-deficient or which cannot express the Ig µ H chain on the surface (e.g. because of deficiency of the pre-BCR component λ5 or due to a disruption of the membrane exon of the Ig µ H chain constant region) are arrested at the pro-B cell stage, but do not develop leukemia. Furthermore, Blnk has a specific function that suppresses malignant transformation because in Btk/Plcγ2 and Irf-4/Irf-8 double-deficient mice with a nearly complete arrest at the large pre-B cell stage no leukemias have been reported. The absence of Blnk results in sustained expression of the pre-BCR and the IL-7R in large cycling pre-B cells (Figure 1). Since IL-7R signaling induces c-Myc this results in constitutively high levels of c-Myc. At this stage, Foxo transcription factors that normally suppress c-Myc-driven lymphomagenesis via direct activation of p19Arf are not properly activated because of the absence of BLNK. Furthermore, IL-7R signaling and aberrant pre-BCR signaling represses Bcl6 and thereby induces p19Arf expression. Subsequently, Blnk-deficient pre-B cells acquiring sporadic alterations in the p19Arf-Mdm2-p53 are selected to become malignant. Furthermore, expression of p19Arf in Blnk-deficient leukemias possibly promotes survival under metabolic stress. The Jak3/Stat5 signaling pathway is constitutively activated in pre-B leukemia cells derived from Blnk-deficient mice, mostly due to autocrine production of IL-7. In the leukemia cells, exogenously expressed Blnk inhibited autocrine Jak3/Stat5 signaling, resulting in p27(kip1) induction, cell-cycle arrest, and apoptosis. Blnk-inhibition of Jak3 was dependent on the binding of Blnk to Jak3.
Btk/Slp65 double-deficient mice that carried a functional B cell receptor transgene (3-83µδ), developed B-cell leukemias expressing both the 3-83µδ BCR and the pre-BCR components λ5/VpreB. Interestingly, these leukemias were found at similar frequencies in mice concomitantly deficient for Rag1 or the non-homologous end-joining factor DNA-PKcs. It was therefore concluded that malignant transformation of Btk/Slp65 double-deficient pre-B cells is independent of deregulated V(D)J recombination activity in the mouse.
  
  
Entity Other disease
Note In human, mutations in SLP65 or BTK result in defective pre-B cell proliferation and an almost complete arrest of B cell development at the pro-B to pre-B cell transition, associated with the immunodeficiency disorder agammaglobulinemia. In contrast, mice deficient for Slp65 or Btk show only a partial arrest at the large cycling pre-B cell stage, while a nearly complete block is present in Btk/Slp65 double deficient mice.
  

Bibliography

Mimicry of a constitutively active pre-B cell receptor in acute lymphoblastic leukemia cells.
Feldhahn N, Klein F, Mooster JL, Hadweh P, Sprangers M, Wartenberg M, Bekhite MM, Hofmann WK, Herzog S, Jumaa H, Rowley JD, Muschen M.
J Exp Med. 2005 Jun 6;201(11):1837-52.
PMID 15939795
 
The adaptor protein SLP-65 acts as a tumor suppressor that limits pre-B cell expansion.
Flemming A, Brummer T, Reth M, Jumaa H.
Nat Immunol. 2003 Jan;4(1):38-43. Epub 2002 Nov 18.
PMID 12436112
 
Distinct signaling requirements for Dmu selection, IgH allelic exclusion, pre-B cell transition, and tumor suppression in B cell progenitors.
Hayashi K, Yamamoto M, Nojima T, Goitsuka R, Kitamura D.
Immunity. 2003 Jun;18(6):825-36.
PMID 12818163
 
SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway.
Herzog S, Hug E, Meixlsperger S, Paik JH, DePinho RA, Reth M, Jumaa H.
Nat Immunol. 2008 Jun;9(6):623-31.
PMID 18488031
 
Regulation of B-cell proliferation and differentiation by pre-B-cell receptor signalling.
Herzog S, Reth M, Jumaa H.
Nat Rev Immunol. 2009 Mar;9(3):195-205.
PMID 19240758
 
Expression of the adaptor protein BLNK/SLP-65 in childhood acute lymphoblastic leukemia.
Imai C, Ross ME, Reid G, Coustan-Smith E, Schultz KR, Pui CH, Downing JR, Campana D.
Leukemia. 2004 May;18(5):922-5.
PMID 15029213
 
Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling.
Johnson K, Hashimshony T, Sawai CM, Pongubala JM, Skok JA, Aifantis I, Singh H.
Immunity. 2008 Mar;28(3):335-45. Epub 2008 Feb 14.
PMID 18280186
 
Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukaemia.
Jumaa H, Bossaller L, Portugal K, Storch B, Lotz M, Flemming A, Schrappe M, Postila V, Riikonen P, Pelkonen J, Niemeyer CM, Reth M.
Nature. 2003 May 22;423(6938):452-6.
PMID 12761551
 
B cell signaling and tumorigenesis.
Jumaa H, Hendriks RW, Reth M.
Annu Rev Immunol. 2005;23:415-45.
PMID 15771577
 
The absence of SLP65 and Btk blocks B cell development at the preB cell receptor-positive stage.
Jumaa H, Mitterer M, Reth M, Nielsen PJ.
Eur J Immunol. 2001 Jul;31(7):2164-9.
PMID 11449370
 
Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP-65.
Jumaa H, Wollscheid B, Mitterer M, Wienands J, Reth M, Nielsen PJ.
Immunity. 1999 Nov;11(5):547-54.
PMID 10591180
 
Bruton's tyrosine kinase and SLP-65 regulate pre-B cell differentiation and the induction of Ig light chain gene rearrangement.
Kersseboom R, Ta VB, Zijlstra AJ, Middendorp S, Jumaa H, van Loo PF, Hendriks RW.
J Immunol. 2006 Apr 15;176(8):4543-52.
PMID 16585544
 
The BCR-ABL1 kinase bypasses selection for the expression of a pre-B cell receptor in pre-B acute lymphoblastic leukemia cells.
Klein F, Feldhahn N, Harder L, Wang H, Wartenberg M, Hofmann WK, Wernet P, Siebert R, Muschen M.
J Exp Med. 2004 Mar 1;199(5):673-85.
PMID 14993251
 
A leucine zipper in the N terminus confers membrane association to SLP-65.
Kohler F, Storch B, Kulathu Y, Herzog S, Kuppig S, Reth M, Jumaa H.
Nat Immunol. 2005 Feb;6(2):204-10. Epub 2005 Jan 16.
PMID 15654340
 
IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development.
Lu R, Medina KL, Lancki DW, Singh H.
Genes Dev. 2003 Jul 15;17(14):1703-8. Epub 2003 Jun 27.
PMID 12832394
 
An essential role for BLNK in human B cell development.
Minegishi Y, Rohrer J, Coustan-Smith E, Lederman HM, Pappu R, Campana D, Chan AC, Conley ME.
Science. 1999 Dec 3;286(5446):1954-7.
PMID 10583958
 
BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3.
Nakayama J, Yamamoto M, Hayashi K, Satoh H, Bundo K, Kubo M, Goitsuka R, Farrar MA, Kitamura D.
Blood. 2009 Feb 12;113(7):1483-92. Epub 2008 Dec 1.
PMID 19047679
 
The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85.
Oellerich T, Bremes V, Neumann K, Bohnenberger H, Dittmann K, Hsiao HH, Engelke M, Schnyder T, Batista FD, Urlaub H, Wienands J.
EMBO J. 2011 Aug 5;30(17):3620-34. doi: 10.1038/emboj.2011.251.
PMID 21822214
 
Malignant transformation of Slp65-deficient pre-B cells involves disruption of the Arf-Mdm2-p53 tumor suppressor pathway.
Ta VB, de Bruijn MJ, ter Brugge PJ, van Hamburg JP, Diepstraten HJ, van Loo PF, Kersseboom R, Hendriks RW.
Blood. 2010 Feb 18;115(7):1385-93. Epub 2009 Dec 14.
PMID 20008789
 
Pre-B-cell leukemias in Btk/Slp65-deficient mice arise independently of ongoing V(D)J recombination activity.
Ta VB, de Haan AB, de Bruijn MJ, Dingjan GM, Hendriks RW.
Leukemia. 2011 Jan;25(1):48-56. Epub 2010 Oct 29.
PMID 21030983
 
Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuits.
Thompson EC, Cobb BS, Sabbattini P, Meixlsperger S, Parelho V, Liberg D, Taylor B, Dillon N, Georgopoulos K, Jumaa H, Smale ST, Fisher AG, Merkenschlager M.
Immunity. 2007 Mar;26(3):335-44.
PMID 17363301
 
SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation.
Wienands J, Schweikert J, Wollscheid B, Jumaa H, Nielsen PJ, Reth M.
J Exp Med. 1998 Aug 17;188(4):791-5.
PMID 9705962
 
Combined deficiencies in Bruton tyrosine kinase and phospholipase Cgamma2 arrest B-cell development at a pre-BCR+ stage.
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Blood. 2007 Apr 15;109(8):3377-84. Epub 2006 Dec 12.
PMID 17164342
 

Citation

This paper should be referenced as such :
Yuvaraj, S ; Hendriks, RW
BLNK (B-cell linker)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(2):106-109.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/BLNKID804ch10q24.html


External links

Nomenclature
HGNC (Hugo)BLNK   14211
LRG (Locus Reference Genomic)LRG_21
Cards
AtlasBLNKID804ch10q24
Entrez_Gene (NCBI)BLNK  29760  B-cell linker
AliasesAGM4; BASH; BLNK-S; LY57; 
SLP-65; SLP65; bca
GeneCards (Weizmann)BLNK
Ensembl hg19 (Hinxton)ENSG00000095585 [Gene_View]  chr10:97951455-98031333 [Contig_View]  BLNK [Vega]
Ensembl hg38 (Hinxton)ENSG00000095585 [Gene_View]  chr10:97951455-98031333 [Contig_View]  BLNK [Vega]
ICGC DataPortalENSG00000095585
TCGA cBioPortalBLNK
AceView (NCBI)BLNK
Genatlas (Paris)BLNK
WikiGenes29760
SOURCE (Princeton)BLNK
Genetics Home Reference (NIH)BLNK
Genomic and cartography
GoldenPath hg19 (UCSC)BLNK  -     chr10:97951455-98031333 -  10q23.2-q23.33   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)BLNK  -     10q23.2-q23.33   [Description]    (hg38-Dec_2013)
EnsemblBLNK - 10q23.2-q23.33 [CytoView hg19]  BLNK - 10q23.2-q23.33 [CytoView hg38]
Mapping of homologs : NCBIBLNK [Mapview hg19]  BLNK [Mapview hg38]
OMIM604515   613502   
Gene and transcription
Genbank (Entrez)AF068180 AF068181 AI307343 AK027779 AK225546
RefSeq transcript (Entrez)NM_001114094 NM_001258440 NM_001258441 NM_001258442 NM_013314
RefSeq genomic (Entrez)NC_000010 NC_018921 NG_007575 NT_030059 NW_004929376
Consensus coding sequences : CCDS (NCBI)BLNK
Cluster EST : UnigeneHs.665244 [ NCBI ]
CGAP (NCI)Hs.665244
Alternative Splicing GalleryENSG00000095585
Gene ExpressionBLNK [ NCBI-GEO ]   BLNK [ EBI - ARRAY_EXPRESS ]   BLNK [ SEEK ]   BLNK [ MEM ]
Gene Expression Viewer (FireBrowse)BLNK [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)29760
GTEX Portal (Tissue expression)BLNK
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8WV28   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8WV28  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8WV28
Splice isoforms : SwissVarQ8WV28
PhosPhoSitePlusQ8WV28
Domaine pattern : Prosite (Expaxy)SH2 (PS50001)   
Domains : Interpro (EBI)SH2   
Domain families : Pfam (Sanger)SH2 (PF00017)   
Domain families : Pfam (NCBI)pfam00017   
Domain families : Smart (EMBL)SH2 (SM00252)  
Conserved Domain (NCBI)BLNK
DMDM Disease mutations29760
Blocks (Seattle)BLNK
SuperfamilyQ8WV28
Human Protein AtlasENSG00000095585
Peptide AtlasQ8WV28
HPRD05153
IPIIPI00002434   IPI00004549   IPI00909330   IPI00941993   IPI00854871   IPI00855831   IPI00816180   IPI00981083   IPI00974231   IPI00941158   
Protein Interaction databases
DIP (DOE-UCLA)Q8WV28
IntAct (EBI)Q8WV28
FunCoupENSG00000095585
BioGRIDBLNK
STRING (EMBL)BLNK
ZODIACBLNK
Ontologies - Pathways
QuickGOQ8WV28
Ontology : AmiGOtransmembrane receptor protein tyrosine kinase adaptor activity  SH3/SH2 adaptor activity  protein binding  intracellular  cytoplasm  cytosol  plasma membrane  inflammatory response  humoral immune response  transmembrane receptor protein tyrosine kinase signaling pathway  positive regulation of signal transduction  B cell differentiation  intracellular signal transduction  
Ontology : EGO-EBItransmembrane receptor protein tyrosine kinase adaptor activity  SH3/SH2 adaptor activity  protein binding  intracellular  cytoplasm  cytosol  plasma membrane  inflammatory response  humoral immune response  transmembrane receptor protein tyrosine kinase signaling pathway  positive regulation of signal transduction  B cell differentiation  intracellular signal transduction  
Pathways : KEGGNF-kappa B signaling pathway    Osteoclast differentiation    B cell receptor signaling pathway    Primary immunodeficiency   
REACTOMEQ8WV28 [protein]
REACTOME Pathways912631 [pathway]   983695 [pathway]   
NDEx NetworkBLNK
Atlas of Cancer Signalling NetworkBLNK
Wikipedia pathwaysBLNK
Orthology - Evolution
OrthoDB29760
GeneTree (enSembl)ENSG00000095585
Phylogenetic Trees/Animal Genes : TreeFamBLNK
HOVERGENQ8WV28
HOGENOMQ8WV28
Homologs : HomoloGeneBLNK
Homology/Alignments : Family Browser (UCSC)BLNK
Gene fusions - Rearrangements
Fusion : MitelmanBLNK/PIK3AP1 [10q24.1/10q24.1]  
Fusion : MitelmanBLNK/ZNF536 [10q24.1/19q12]  [t(10;19)(q24;q12)]  
Fusion : MitelmanUBN1/BLNK [16p13.3/10q24.1]  [t(10;16)(q24;p13)]  
Fusion: TCGABLNK 10q24.1 PIK3AP1 10q24.1 BRCA
Fusion: TCGABLNK 10q24.1 ZNF536 19q12 BRCA
Fusion: TCGAUBN1 16p13.3 BLNK 10q24.1 SKCM
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerBLNK [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BLNK
dbVarBLNK
ClinVarBLNK
1000_GenomesBLNK 
Exome Variant ServerBLNK
ExAC (Exome Aggregation Consortium)BLNK (select the gene name)
Genetic variants : HAPMAP29760
Genomic Variants (DGV)BLNK [DGVbeta]
DECIPHER (Syndromes)10:97951455-98031333  ENSG00000095585
CONAN: Copy Number AnalysisBLNK 
Mutations
ICGC Data PortalBLNK 
TCGA Data PortalBLNK 
Broad Tumor PortalBLNK
OASIS PortalBLNK [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICBLNK  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDBLNK
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
BioMutasearch BLNK
DgiDB (Drug Gene Interaction Database)BLNK
DoCM (Curated mutations)BLNK (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)BLNK (select a term)
intoGenBLNK
NCG5 (London)BLNK
Cancer3DBLNK(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604515    613502   
Orphanet10310   
MedgenBLNK
Genetic Testing Registry BLNK
NextProtQ8WV28 [Medical]
TSGene29760
GENETestsBLNK
Huge Navigator BLNK [HugePedia]
snp3D : Map Gene to Disease29760
BioCentury BCIQBLNK
ClinGenBLNK
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD29760
Chemical/Pharm GKB GenePA25371
Clinical trialBLNK
Miscellaneous
canSAR (ICR)BLNK (select the gene name)
Probes
Litterature
PubMed60 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineBLNK
EVEXBLNK
GoPubMedBLNK
iHOPBLNK
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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