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KLLN Gene

protein-coding   GIFtS: 32
GCID: GC10M089619

Killin, P53-Regulated DNA Replication Inhibitor

  See related diseases
at  

(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
Killin, P53-Regulated DNA Replication Inhibitor1 2
CWS42 5
KILLIN2
killin2

External Ids:    HGNC: 372121   Entrez Gene: 1001447482   Ensembl: ENSG000002272687   OMIM: 6121055   UniProtKB: B2CW773   

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(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 KLLN Gene:
The protein encoded by this intronless gene is found in the nucleus, where it can inhibit DNA synthesis and
promote S phase arrest coupled to apoptosis. The expression of this DNA binding protein is upregulated by
transcription factor p53. (provided by RefSeq, Dec 2012)

GeneCards Summary for KLLN Gene:
KLLN (killin, p53-regulated DNA replication inhibitor) is a protein-coding gene. Diseases associated with KLLN include cowden syndrome 4, and cowden syndrome 1.

UniProtKB/Swiss-Prot: KILIN_HUMAN, B2CW77
Function: DNA-binding protein involved in S phase checkpoint control-coupled apoptosis by mediating
p53/TP53-induced apoptosis. Has the ability to inhibit DNA synthesis and S phase arrest coupled to apoptosis. Has
affinity to both double- and single-stranded DNA




(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_000010.11  NC_018921.2  NT_030059.14  
Regulatory elements:
   Search for regulatory transcription factor binding sites for KLLN
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
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Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat KLLN


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

Entrez Gene cytogenetic band: 10q23   Ensembl cytogenetic band:  10q23.31   HGNC cytogenetic band: 10q23

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

GeneLoc information about chromosome 10         GeneLoc Exon Structure

GeneLoc location for GC10M089619:  view genomic region     (about GC identifiers)

Start:
89,618,918 bp from pter      End:
89,623,194 bp from pter
Size:
4,277 bases      Orientation:
minus 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, 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, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: KILIN_HUMAN, B2CW77 (See protein sequence)
Recommended Name: Killin  
Size: 178 amino acids; 19958 Da

Explore the universe of human proteins at neXtProt for KLLN: NX_B2CW77

Explore proteomics data for KLLN at MOPED


See KLLN Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_001119521.1  
ENSEMBL proteins: 
 ENSP00000392204  

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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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ProtoNet protein and cluster: B2CW77


(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: KILIN_HUMAN, B2CW77
Function: DNA-binding protein involved in S phase checkpoint control-coupled apoptosis by mediating
p53/TP53-induced apoptosis. Has the ability to inhibit DNA synthesis and S phase arrest coupled to apoptosis. Has
affinity to both double- and single-stranded DNA
Induction: By p53/TP53; direct transcription target of p53/TP53

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

GO IDQualified GO termEvidencePubMed IDs
GO:0003677DNA binding IEA--
     
KLLN for ontologies           About GeneDecksing


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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
KILIN_HUMAN, B2CW77: Nucleus

Gene Ontology (GO): 1 cellular component term:    About this table

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

KLLN 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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Interactions:

    Search GeneGlobe Interaction Network for KLLN

Gene Ontology (GO): 2 biological process terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0006915apoptotic process IEA--
GO:0007049cell cycle IEA--

KLLN 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)
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(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, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for KLLN gene: 
NM_001126049.1  

Unigene Cluster for KLLN:

Killin, p53-regulated DNA replication inhibitor
Hs.559820  [show with all ESTs]
Unigene Representative Sequence: EU552092
1 Ensembl transcript including schematic representation, and UCSC links where relevant:
ENST00000445946(uc009xti.3)
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Additional mRNA sequence: EU552092.1 

2 DOTS entries:

DT.107155  DT.75116470 

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

KLLN Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

KLLN Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.559820
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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 chimp.

Orthologs for KLLN gene from 1 species (see representative species )    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
chimpanzee
(Pan troglodytes)
Mammalia KLLN1 killin, p53-regulated DNA replication inhibitor 99.63(n)
99.44(a)
  100610121  XM_003312681.1  XP_003312729.1 


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

(Paralogs according to 1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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  --

(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 KLLN (see all 51)    About this table    
Genomic DataTranscription Related DataAllele Frequencies
SNP IDValidClinical
significance
Chr 10 posSequence#AA
Chg
TypeMore#Allele
freq
PopTotal
sample
More
----------
rs26738301,2
C,H--89618430(-) TAGGCC/AGAAAT 1 -- ds50019Minor allele frequency- A:0.00NA WA CSA 16
rs1817388971,2
--89618524(+) AAACAA/GTGTGC 1 -- ds50010--------
rs1417214141,2
C--89618581(+) GTAGCA/TAGTGT 1 -- ds50010--------
rs1869377511,2
--89618613(+) CAAAGC/TTGTCT 1 -- ds50010--------
rs1462571801,2
--89618623(+) TTGTCA/GTGTTA 1 -- ds50010--------
rs1914087781,2
--89618677(+) CTGAAC/TGCCAC 1 -- ds50010--------
rs1181005711,2
F--89618757(+) AGAATG/AATGAT 1 -- ds50011Minor allele frequency- A:0.01NA 120
rs125717371,2
C,H--89618914(+) AGCGCC/TTTTTG 1 -- ds50014Minor allele frequency- T:0.00NS EA 418
rs766311581,2
C--89618930(+) TGTCTA/TAAAAT 1 -- ut310--------
rs775428001,2
C,F--89619225(+) ACAAAG/CAGCAC 1 -- ut311Minor allele frequency- C:0.04WA 118

HapMap Linkage Disequilibrium report for KLLN (89618918 - 89623194 bp)

Structural Variations
     Database of Genomic Variants (DGV) 1 variation for KLLN:    About this table    
Variant IDTypeSubtypePubMed ID
esv2673693CNV Deletion23128226

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

(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: 612105   
OMIM disorders: 615107  
UniProtKB/Swiss-Prot: KILIN_HUMAN, B2CW77
  • Cowden syndrome 4 (CWS4) [MIM:615107]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with
    age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of
    ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair
    follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several
    types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon
    cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but
    most commonly in the skin, gastrointestinal tract, breast and thyroid. Note=The disease is caused by mutations
    affecting the gene represented in this entry. Germline KLLN methylation is common among patients with Cowden
    syndrome or Cowden-like syndrome and is associated with increased risks of breast and renal cancer over PTEN
    mutation-positive individuals (PubMed:21177507)

  • 8 diseases for KLLN:    
    About MalaCards
    cowden syndrome 4    cowden syndrome 1    breast-ovarian cancer, familial, 2    thyroid cancer
    renal cell carcinoma    thyroiditis    prostatitis    breast cancer


    KLLN for disorders           About GeneDecksing


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

    1. Killin is a p53-regulated nuclear inhibitor of DNA synthesis. (PubMed id 18385383)1, 2, 3 Cho Y.J. and Liang P. (Proc. Natl. Acad. Sci. U.S.A. 2008)
    2. Germline epigenetic regulation of KILLIN in Cowden and Cowden-like syndrome. (PubMed id 21177507)1, 2 Bennett K.L....Eng C. (JAMA 2010)
    3. Androgen receptor-induced tumor suppressor, KLLN, inhibits breast cancer growth and transcriptionally activates p53/p73-mediated apoptosis in breast carcinomas. (PubMed id 23418309)1 Wang Y....Eng C. (Hum. Mol. Genet. 2013)
    4. Transcription factor KLLN inhibits tumor growth by AR suppression, induces apoptosis by TP53/TP73 stimulation in prostate carcinomas, and correlates with cellular differentiation. (PubMed id 23386643)1 Wang Y....Eng C. (J. Clin. Endocrinol. Metab. 2013)
    5. Germline and somatic KLLN alterations in breast cancer dysregulate G2 arrest. (PubMed id 23446638)1 Nizialek E.A....Eng C. (Hum. Mol. Genet. 2013)
    6. Analysis of KLLN as a high-penetrance breast cancer predisposition gene. (PubMed id 22580995)1 Thompson E.R....Campbell I.G. (Breast Cancer Res. Treat. 2012)
    7. Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma. (PubMed id 21584899)1 Bennett K.L....Eng C. (amp 2011)
    8. Incidence and clinical characteristics of thyroid cancer in prospective series of individuals with Cowden and Cowden-like syndrome characterized by germline PTEN, SDH, or KLLN alterations. (PubMed id 21956414)1 Ngeow J....Eng C. (J. Clin. Endocrinol. Metab. 2011)
    9. The DNA sequence and comparative analysis of human chromosome 10. (PubMed id 15164054)2 Deloukas P.... Rogers J. (Nature 2004)
    10. Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. (PubMed id 15146197)1 Brandenberger R.... Stanton L.W. (Nat. Biotechnol. 2004)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    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: 100144748 HGNC: 37212 Ensembl:ENSG00000227268 euGenes: HUgn100144748 ECgene: KLLN
    H-InvDB: KLLN

    (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 KLLN 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 KLLN gene:
    Search GeneIP for patents involving KLLN

    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, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, 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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