Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

KNL1 (cancer susceptibility candidate 5)

Written2000-03Jean-Loup Huret, Christiane Charrin
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH); Service d'Hematologie, Hopital Edouard Herriot, Lyon, France (CC).
Updated2006-09Masato Takimoto
Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
Updated2012-06Masato Takimoto
Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
Updated2016-10Masato Takimoto, Jean-Loup Huret
Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. takimoto@igm.hokudai.ac.jp (MT); Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. jean-loup.huret@chu-poitiers.fr (JLH)

Abstract Review on KNL1, with data on DNA, on the protein encoded, and where the gene is implicated.

Keywords KNL1

(Note : for Links provided by Atlas : click)

Identity

Alias_namesMCPH4
CASC5
microcephaly, primary autosomal recessive 4
cancer susceptibility candidate 5
Alias_symbol (synonym)D40
AF15Q14
CT29
KIAA1570
hKNL-1
hSpc105
PPP1R55
Spc7
Other aliasPPP1R5
AF15q14
HGNC (Hugo) KNL1
LocusID (NCBI) 57082
Atlas_Id 318
Location 15q15.1  [Link to chromosome band 15q15]
Location_base_pair Starts at 40594249 and ends at 40662683 bp from pter ( according to hg19-Feb_2009)  [Mapping KNL1.png]
Fusion genes
(updated 2016)
KNL1 (15q15.1) / ADAMTS9-AS2 (3p14.1)KNL1 (15q15.1) / KMT2A (11q23.3)KMT2A (11q23.3) / KNL1 (15q15.1)

DNA/RNA

Note Whole genomic size is about 70 kbp, but consists of 27 exons.
Transcription KNL1 mRNA expression is dominant in normal human testis and slight expression are observed in other organs, such as placenta. Analysis on cancer cell lines, such as HeLa, gave single band with 8.5 kb. There is another alternative splicing site at the 5' side of this gene that generates a short exon with 78 bp in cDNA. There are potential other alternative splicing at cancer cell lines.
Analysis on testis mRNA shows two bands with size of approximately 6 and 8,5 kb which are probably derived from the two isoforms.

Protein

 
  Figure 1. Domain structure of KNL1 protein. Brown arrows indicate protein interactions, and blue arrows and line with T-shape indicate phosphorylation and dephosphorylation, respectively. MT :microtubules. KT : kinetochore.
Description Encodes 1833 amino acids and 2342 amino acids.
The KLN1 protein contains: conserved motifs, which are the following: a (S/G)ILK motif (aa 25-28), a RRVSF motif (aa 57-61), and, for BUB3 recognition, MELT repeats (aa 140-161, 308-329, 474-494, 562-582, 750-769, 859-882, 902-924, 940-962, 1025-1044, 1073-1096, 1114-1136, 1152-1174). The Bubs recognition KI motifs KI(D/N)XXXF(L/I)XXLK, are KIDTTSFLANLK (aa 202-213) for BUB1, and KIDFNDFIKRLK (aa 238-249) for BUB1B: (BUBR1); a nuclear localization signal (aa 1789-1803); a coiled coil region (aa 1942-2133) and the ZWINT (Zwint-1) binding region (aa 1834 or 19811 for a smaller region -2108); and RWD repeats (aa 2109- 2353) With the NSL1 (hMis14)-binding region (aa 2109-2316), according to Kiyomitsu et al., 2011, VEGA checking, and SwissProt.
Expression KNL1 protein expressions with molecular weight of approximately 250 kDa and 300 kDa are observed in human testicular germ cells and cancer cell lines.
Localisation In germ cell of testis, significant high expressions of KNL1 protein are observed in nucleus of spermatocytes and slightly in spermatogonia. It is noteworthy that round spermatids express significantly high KNL1 protein in their pre-acrosome. As KNL1 protein has no hydrophobic signal peptide in its amino terminus, it probably localizes outer surface of pre-acrosome membrane of spermatids inside of the cells..
In mitosis KNL1 protein is localized in kinetochore in a human cancer cell line.
Function KNL1 is a large of kinetochore protein, constituting KMN (KNL1/ MIS12 complex/ NDC80 complex) network. KMN network is the central hub of outer kinetochore, not only connecting mitotic chromosomes and spindles but also coordinating microtubule-binding, chromosome congression and spindle assembly checkpoint (SAC) signaling. There are two microtubule binding activity in KMN network, one in NDC80 and the other in KNL1. KNL1 protein binds directly microtubule through its far N-terminal region, consisting of 68 amino acids, in vitro, and indirectly through the interactions with MIS12 and NDC80 complexes at its C-terminus. KNL1 depletion affects metaphase chromosome congression. In C. elegans,
The depletion preclude metaphase chromosomal congression, while in yeast, Drosophila and human cells, the depletions show partial alignment phenotypes, in which some chromosomes congress to the equator but many chromosomes remain stranded near the spindle poles. In the N-terminus of KNL1 protein, AURKB (Aurora kinase B) phosphorylates SILK and RVSF motifs, and then disrupts the interaction between KNL1 and protein phosphatase I (PP1), which also binds the motifs. KNL1 augments Aurora B kinase activity that phosphorylates outer kinetochore protein, such as NDC80, resulting in reduction its microtubule-binding activity. Protein phosphatase 2A ( PP2A) is recruited by BUB1B (BubR1), one of SAC protein. Both PP1 and PPA2 are suggested to counteract Aurora B kinase activity. Especially, PP1 was shown to stabilize microtubule attachments to kinetochores probably through KNL1, while Aurora B kinase destabilizes microtubule-binding by NDC80 phosphorylation as described. The destabilized binding of KNL1 to microtubules is presumably important for correcting and eliminating erroneous kinetochore-microtubule attachment during SAC.
It is suggested that the bindings with microtubule and with PP1 also play roles in SAC silencing. Although their binding sites are in close proximity, one of their bindings do not affect the other, and they contribute independently to the silencing of SAC. Two KI motifs, KI1 and KI2, localized in the N-terminus, bind SAC protein, BUB1 and BUB1B, respectively, through tetratricopeptide repeats (TPRs) of the proteins, resulting into folding the motifs into short alpha-helices. Although BUB1 fragment with mutation in KI-binding domain was not able to bind to KNL1 in vitro, BUB1 and BUB1B mutants with KI-binding sites were able to attach to kinetochore. Mutations in the BUB3-binding domain (BUB3-BD) in BUB1 and BUB1B prevent kinetochore localization of the SAC protein. BUB1 fragment consisting only of N-terminus with TPRs does not localize to kinetochore and longer fragments that accommodate BUB3-BD did. Those results suggest that BUB3-BD of BUB1 and BUB1B, rather than TPRs, is critical for their recruitment to kinetochore and that the interaction between TPRs of Bub proteins and KI-motif of KNL1 might play a subsidiary role in the localization of BUB1 and BUB1B to kinetochore. In response to SAC signal, the first step of this response is phosphorylation of MELT motifs of KNL1, located in the N-terminal and central region, by Mps1 kinase, and then the phosphorylated MELT motifs bind BUB3/BUB1complex, mediating SAC signaling. KNL1- BUB3-BUB1(KBB) complex binds MXD1 (MAD1)/ MAD2L1 (MAD2) complex, and then, together with MAD1 phosphorylation by Msp1, the binding leads to CDC20/MAD2 formation, an essential part of Mitotic Checkpoint Complex (MCC) that inhibits Anaphase Promoting Complex/Cyclosome (APC/C).
Recently, it suggested that there are two pathways for recruiting MAD1-MAD2 that results in SAC activation. One is the pathway through KBB, as described above, the other is KNTC1 (ROD)-RW10- ZWILCH, (RZZ) complex, which interacts with KNL1 through ZWINT (Zwint-1 protein). The former is required for SAC activation when kinetochores are misaligned but is not essential when kinetochores are unattached from microtubules. The latter binds SPDL1 (Spindly protein) and MAD1-MAD2, and causes the anaphase-onset delay in response to unattached kinetochore independently of the former.
It was suggested that the binding of KNL1 with microtubules and with PP1 contribute to silencing of SAC, in which motor protein dynein, moving along on microtubules, is suggested to work to strip MAD1-MAD2. The C-terminal region of KNL1 interacts with MIS12 and Zwint-1 protein, through RWD motif and coiled-coiled region, respectively. The binding with the former plays role in connecting inner kinetochore with KNL1 and the latter mediates the interaction of KNL1 with RZZ complex which works in SAC regulation as described above.

Implicated in

Note KNL1 expression was observed in many human cancer cell lines and primary cancers derived from different organs and tissues. In one study, KNL1 mRNA expression was detected in all the cancer cell lines examined and positive in 31 out of 103 primary human cancers (30%). As KNL1 is overexpressed in normal testis, KNL1 is a member of Cancer/Testis gene family. Among the primary cancers examined lung cancer showed the highest positive rate, more than 40%, and its clincopathological characteristics are significantly correlated with KNL1 mRNA expression as described below.
  
Entity Leukemia
Note A small subset of leukemia with a t(11;15)(q23;q14) has been described for long and has often be referred as: t(11;15)(q23;q15) MLL/AF15q14. KMT2A, (previous symbol: mixed leukemia gene (MLL)) is translocated with KNL1 (previous symbol CASC5, originally described as AF15q14), which makes research of published cases often arduous.
  • t(11;15)(q23;q15) and/or KMT2A/KNL1
    t(11;15)(q23;q14-15)
    Data on 16 cases with a t(11;15)(q23;q14-15), according to (Yang et al., 2014) are the following: there was 2 of myelodysplastic syndrome (MDS) cases, 10 acute myeloid leukemia (AML) cases (2 M1, 4 M2, 3 M4, and 1 NOS), and 4 acute lymphoblastic leukemia (ALL) cases. Mean age of the patients was 20.6 years (range 1-54); there were 11 males and 5 females. Abnormalities of chromosome 3 were seen in 10 out of 16 cases. Out of 8 patients for whom clinical data were available, only 3 are in complete remission, whereas 5 patients died with a mean survival period of 10.4 months.
    t(11;15)(q23;q15) and KMT2A/KNL1
    Of 7 cases with a t(11;15)(q23;q15) and KMT2A/KNL1 hybrid gene and fusion protein ((Chinwalla et al., 2003; Kuefer et al., 2003; Meyer et al., 2006; Yang et al., 2014). Diagnosis was: therapy related MDS (t-MDS) in 2 cases, AML in 4 cases (1 M2, 2 AML-M4, 1 AML-NOS), and 1 de novo T-ALL. Sex ratio was 5M:1F; There was 3 children and 4 adult patients. Of three cases with data on survival, patients died at: 8 mths, 8 mths, and 22 mths. Of four cases with documented karyotypes: the karyotype was a complex karyotype with markers in two cases, abnormalities of chromosome 3 were seen in three cases, +21 in two cases. KMT2A (MLL) exon 8, 9, or 10 were fused to exon 10, 11 or 12 of KNL1, the fusion protein contains the 1362 or 1418 first aa from MLL with aa 1796, 1818 or 1819 from KNL1 (according to authors and/or VEGA).
  • A t(3;15;p14;q15) KNL1/ ADAMTS9-AS2 is mentioned, without further data in the ChiTARS database (Gorohovski et al., 2016) as a chimeric EST (dbEST Id:12413828; accession BQ375909).
  •   
      
    Entity Lung cancer
    Note In one study on primary lung cancer, KNL1 mRNA expression was observed in more than 40% of the cases, which is the highest among all the different types of cancers examined. The study also revealed that clinicopathological findings correlates with KNL1 expression. KNL1 mRNA expression is more frequent in the tumors with low differentiation than the ones with moderate and high differentiation. Further, the tumors derived from smoker express higher incidence of KNL1 mRNA than the ones from non-smoker.
      
      
    Entity Spermatogenesis
    Note KNL1 mRNA was highly expressed in normal testis. As KNL1 protein expressions were observed in spermatogonia and spermatocytes in seminiferous tube of human testes, this protein may also play a role in cell division as a kinetochore protein in meiotic cells. It is noteworthy that KNL1 protein is also significantly expressed in pre-acrosome of spermatids, especially from its early stage, suggesting that KNL1 might be playing important role in the formation of acrosome, an essential organelle for fertilization. KNL1 expressions in testes of the patients with infertility were significantly lower than normal ones.
      
      
    Entity Microcephaly
    Disease Autosomal recessive primary microcephaly (MCPH) is a very rare neuro-developmental disorder with brain size reduction, no structural malformation of the brain at birth, mild-to moderate mental retardation and absence of other neurological or somatic disease. There are 12 genetic loci responsible for MCPH, and it was suggested that one of the responsible genetic locus, MCPH4, resides on chromosome 15. Subsequently, the study on the patients with MCPH4 of consanguineous families in Morocco revealed that a homozygous missense mutation was observed in exon 18 of KNL1 gene. This point mutation caused skipping this exon in splicing reaction in the mRNA maturation of KNL1, suggesting that the affected nucleotide is a part of Exonic splicing enhancers. The mutation resulted in frame-shift and truncation of KNL1 protein. As RWD repeats at near its carboxy terminus were deleted by this mutation, the truncated protein is no longer able to bind to Mis12, leading to the defected recruitment of KNL1 protein to kinetochore. One of the patients in the Morroco families has cryptorchidism in addition to microcephaly. The results of studies on MCH4 is a direct demonstration that KNL1 is essential to cell division in vivo.
      

    Bibliography

    Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases
    Blencowe BJ
    Trends Biochem Sci 2000 Mar;25(3):106-10
    PMID 10694877
     
    Kinetochore signalling: the KIss that MELTs Knl1
    Bollen M
    Curr Biol 2014 Jan 20;24(2):R68-70
    PMID 24456977
     
    KNL1: bringing order to the kinetochore
    Caldas GV, DeLuca JG
    Chromosoma 2014 Jun;123(3):169-81
    PMID 24310619
     
    The conserved KMN network constitutes the core microtubule-binding site of the kinetochore.
    Cheeseman IM, Chappie JS, Wilson-Kubalek EM, Desai A.
    Cell. 2006 Dec 1;127(5):983-97.
    PMID 17129783
     
    A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15
    Chinwalla V, Chien A, Odero M, Neilly MB, Zeleznik-Le NJ, Rowley JD
    Oncogene 2003 Mar 6;22(9):1400-10
    PMID 12618766
     
    Microtubule binding by KNL-1 contributes to spindle checkpoint silencing at the kinetochore.
    Espeut J, Cheerambathur DK, Krenning L, Oegema K, Desai A.
    J Cell Biol. 2012 Feb 20;196(4):469-82. Epub 2012 Feb 13.
    PMID 22331849
     
    The (phospho) needle in the (MELT) Haystack
    Faesen AC, Musacchio A
    Mol Cell 2015 Mar 5;57(5):765-6
    PMID 25747656
     
    Kinetochore KMN network gene CASC5 mutated in primary microcephaly
    Genin A, Desir J, Lambert N, Biervliet M, Van Der Aa N, Pierquin G, Killian A, Tosi M, Urbina M, Lefort A, Libert F, Pirson I, Abramowicz M
    Hum Mol Genet 2012 Dec 15;21(24):5306-17
    PMID 22983954
     
    ChiTaRS-3.1-the enhanced chimeric transcripts and RNA-seq database matched with protein-protein interactions.
    Gorohovski A, Tagore S, Palande V, Malka A, Raviv-Shay D, Frenkel-Morgenstern M
    Nucleic Acids Res. 2016 Nov 29. pii: gkw1127. [Epub ahead of print]
    PMID 27899596
     
    AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14).
    Hayette S, Tigaud I, Vanier A, Martel S, Corbo L, Charrin C, Beillard E, Deleage G, Magaud JP, Rimokh R.
    Oncogene. 2000 Sep 7;19(38):4446-50.
    PMID 10980622
     
    Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15
    Jamieson CR, Govaerts C, Abramowicz MJ
    Am J Hum Genet 1999 Nov;65(5):1465-9
    PMID 10521316
     
    The fission yeast kinetochore component Spc7 associates with the EB1 family member Mal3 and is required for kinetochore-spindle association.
    Kerres A, Vietmeier-Decker C, Ortiz J, Karig I, Beuter C, Hegemann J, Lechner J, Fleig U.
    Mol Biol Cell. 2004 Dec;15(12):5255-67. Epub 2004 Sep 15.
    PMID 15371542
     
    Protein interaction domain mapping of human kinetochore protein Blinkin reveals a consensus motif for binding of spindle assembly checkpoint proteins BUB1 and BUB1B.
    Kiyomitsu T, Murakami H, Yanagida M.
    Mol Cell Biol. 2011 Mar;31(5):998-1011. Epub 2011 Jan 3.
    PMID 21199919
     
    Finding the middle ground: how kinetochores power chromosome congression
    Kops GJ, Saurin AT, Meraldi P
    Cell Mol Life Sci 2010 Jul;67(13):2145-61
    PMID 20232224
     
    Structural analysis reveals features of the spindle checkpoint kinase BUB1-kinetochore subunit Knl1 interaction.
    Krenn V, Wehenkel A, Li X, Santaguida S, Musacchio A.
    J Cell Biol. 2012 Feb 20;196(4):451-67. Epub 2012 Feb 13.
    PMID 22331848
     
    Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14)
    Kuefer MU, Chinwalla V, Zeleznik-Le NJ, Behm FG, Naeve CW, Rakestraw KM, Mukatira ST, Raimondi SC, Morris SW
    Oncogene 2003 Mar 6;22(9):1418-24
    PMID 12618768
     
    Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase.
    Liu D, Vleugel M, Backer CB, Hori T, Fukagawa T, Cheeseman IM, Lampson MA.
    J Cell Biol. 2010 Mar 22;188(6):809-20. Epub 2010 Mar 15.
    PMID 20231380
     
    The MLL recombinome of acute leukemias
    Meyer C, Schneider B, Jakob S, Strehl S, Attarbaschi A, Schnittger S, Schoch C, Jansen MW, van Dongen JJ, den Boer ML, Pieters R, Ennas MG, Angelucci E, Koehl U, Greil J, Griesinger F, Zur Stadt U, Eckert C, Szczepański T, Niggli FK, Schäfer BW, Kempski H, Brady HJ, Zuna J, Trka J, Nigro LL, Biondi A, Delabesse E, Macintyre E, Stanulla M, Schrappe M, Haas OA, Burmeister T, Dingermann T, Klingebiel T, Marschalek R
    Leukemia 2006 May;20(5):777-84
    PMID 16511515
     
    A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1.
    Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M.
    Nat Cell Biol. 2004 Nov;6(11):1135-41. Epub 2004 Oct 24.
    PMID 15502821
     
    Molecular analysis of core kinetochore composition and assembly in Drosophila melanogaster.
    Przewloka MR, Zhang W, Costa P, Archambault V, D'Avino PP, Lilley KS, Laue ED, McAinsh AD, Glover DM.
    PLoS One. 2007 May 30;2(5):e478.
    PMID 17534428
     
    The protein encoded by cancer/testis gene D40/AF15q14 is localized in spermatocytes, acrosomes of spermatids and ejaculated spermatozoa.
    Sasao T, Itoh N, Takano H, Watanabe S, Wei G, Tsukamoto T, Kuzumaki N, Takimoto M.
    Reproduction. 2004 Dec;128(6):709-16.
    PMID 15579588
     
    Testis cancer gene D40 expression and its relationship with clinicopathological features in infertile men.
    Sasao T, Takimoto M, Itoh N, Maeda T, Tanaka T, Masumori N, Tsukamoto T.
    Int J Urol. 2011 Feb;18(2):175-9. doi: 10.1111/j.1442-2042.2010.02692.x. Epub 2011 Jan 12.
    PMID 21272090
     
    KNL1-Bubs and RZZ Provide Two Separable Pathways for Checkpoint Activation at Human Kinetochores
    Silió V, McAinsh AD, Millar JB
    Dev Cell 2015 Dec 7;35(5):600-13
    PMID 26651294
     
    Cancer/testis antigens, gametogenesis and cancer.
    Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ.
    Nat Rev Cancer. 2005 Aug;5(8):615-25. (REVIEW)
    PMID 16034368
     
    Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers.
    Takimoto M, Wei G, Dosaka-Akita H, Mao P, Kondo S, Sakuragi N, Chiba I, Miura T, Itoh N, Sasao T, Koya RC, Tsukamoto T, Fujimoto S, Katoh H, Kuzumaki N.
    Br J Cancer. 2002 Jun 5;86(11):1757-62.
    PMID 12087463
     
    Kinetochore localisation and phosphorylation of the mitotic checkpoint components Bub1 and BubR1 are differentially regulated by spindle events in human cells
    Taylor SS, Hussein D, Wang Y, Elderkin S, Morrow CJ
    J Cell Sci 2001 Dec;114(Pt 24):4385-95
    PMID 11792804
     
    Chromosomal assignment of a novel human gene D40.
    Wei G, Takimoto M, Yoshida I, Mao PZ, Koya RC, Miura T, Kuzumaki N.
    Nucleic Acids Symp Ser. 1999;(42):71-2.
    PMID 10780384
     
    Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochore-microtubule interface.
    Welburn JP, Vleugel M, Liu D, Yates JR 3rd, Lampson MA, Fukagawa T, Cheeseman IM.
    Mol Cell. 2010 May 14;38(3):383-92.
    PMID 20471944
     
    Molecular characterization and clinical impact of t(11;15)(q23;q14-15) MLL-CASC5 rearrangement
    Yang JJ, Park TS, Lee ST, Seo JY, Oh SH, Cho EH, Strehl S, Mühlegger N, Dworzak MN, Zuna J, Pospisilova D, Meyer C, Marschalek R, Kim HJ, Kim SH
    Haematologica 2014 Jan;99(1):e11-3
    PMID 24425691
     

    Citation

    This paper should be referenced as such :
    Takimoto M, Huret JL
    KNL1 (cancer susceptibility candidate 5);
    Atlas Genet Cytogenet Oncol Haematol. in press
    On line version : http://AtlasGeneticsOncology.org/Genes/AF15q14ID318.html
    History of this paper:
    Huret, JL ; Charrin, C. AF15q14 (ALL1 fused gene from 15q14). Atlas Genet Cytogenet Oncol Haematol. 2000;4(2):50-50.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37605/03-2000-AF15q14ID318.pdf
    Takimoto, M. CASC5 (cancer sensitibity candidate 5). Atlas Genet Cytogenet Oncol Haematol. 2007;11(1):8-9.
    http://documents.irevues.inist.fr/bitstream/handle/2042/38375/09-2006-AF15q14ID318.pdf
    Takimoto, M. CASC5 (cancer susceptibility candidate 5). Atlas Genet Cytogenet Oncol Haematol. 2013;17(1):1-2.
    http://documents.irevues.inist.fr/bitstream/handle/2042/48462/06-2012-AF15q14ID318.pdf


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
      11q23 rearrangements (KMT2A) in leukaemia
    t(11;15)(q23;q14) KMT2A/CASC5


    External links

    Nomenclature
    HGNC (Hugo)KNL1   24054
    Cards
    AtlasAF15q14ID318
    Entrez_Gene (NCBI)KNL1  57082  kinetochore scaffold 1
    AliasesAF15Q14; CASC5; CT29; D40; 
    MCPH4; PPP1R55; Spc7; hKNL-1; hSpc105
    GeneCards (Weizmann)KNL1
    Ensembl hg19 (Hinxton)ENSG00000137812 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000137812 [Gene_View]  chr15:40594249-40662683 [Contig_View]  KNL1 [Vega]
    ICGC DataPortalENSG00000137812
    TCGA cBioPortalKNL1
    AceView (NCBI)KNL1
    Genatlas (Paris)KNL1
    WikiGenes57082
    SOURCE (Princeton)KNL1
    Genetics Home Reference (NIH)KNL1
    Genomic and cartography
    GoldenPath hg38 (UCSC)KNL1  -     chr15:40594249-40662683 +  15q15.1   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)KNL1  -     15q15.1   [Description]    (hg19-Feb_2009)
    EnsemblKNL1 - 15q15.1 [CytoView hg19]  KNL1 - 15q15.1 [CytoView hg38]
    Mapping of homologs : NCBIKNL1 [Mapview hg19]  KNL1 [Mapview hg38]
    OMIM604321   609173   
    Gene and transcription
    Genbank (Entrez)AB022190 AB046790 AF173994 AF248041 AF461041
    RefSeq transcript (Entrez)NM_144508 NM_170589
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)KNL1
    Cluster EST : UnigeneHs.181855 [ NCBI ]
    CGAP (NCI)Hs.181855
    Alternative Splicing GalleryENSG00000137812
    Gene ExpressionKNL1 [ NCBI-GEO ]   KNL1 [ EBI - ARRAY_EXPRESS ]   KNL1 [ SEEK ]   KNL1 [ MEM ]
    Gene Expression Viewer (FireBrowse)KNL1 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)57082
    GTEX Portal (Tissue expression)KNL1
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ8NG31   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ8NG31  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ8NG31
    Splice isoforms : SwissVarQ8NG31
    PhosPhoSitePlusQ8NG31
    Domain families : Pfam (Sanger)
    Domain families : Pfam (NCBI)
    Conserved Domain (NCBI)KNL1
    DMDM Disease mutations57082
    Blocks (Seattle)KNL1
    PDB (SRS)3SI5    4A1G    4NF9    4NFA   
    PDB (PDBSum)3SI5    4A1G    4NF9    4NFA   
    PDB (IMB)3SI5    4A1G    4NF9    4NFA   
    PDB (RSDB)3SI5    4A1G    4NF9    4NFA   
    Structural Biology KnowledgeBase3SI5    4A1G    4NF9    4NFA   
    SCOP (Structural Classification of Proteins)3SI5    4A1G    4NF9    4NFA   
    CATH (Classification of proteins structures)3SI5    4A1G    4NF9    4NFA   
    SuperfamilyQ8NG31
    Human Protein AtlasENSG00000137812
    Peptide AtlasQ8NG31
    HPRD10634
    IPIIPI00220694   IPI00170766   IPI00163659   IPI00747876   IPI01018189   IPI00794405   IPI00981919   IPI00980608   
    Protein Interaction databases
    DIP (DOE-UCLA)Q8NG31
    IntAct (EBI)Q8NG31
    FunCoupENSG00000137812
    BioGRIDKNL1
    STRING (EMBL)KNL1
    ZODIACKNL1
    Ontologies - Pathways
    QuickGOQ8NG31
    Ontology : AmiGOcondensed chromosome kinetochore  acrosomal vesicle  acrosome assembly  protein binding  nucleus  nucleoplasm  nucleoplasm  cytosol  cytosol  sister chromatid cohesion  attachment of spindle microtubules to kinetochore  negative regulation of phosphatase activity  nuclear body  CENP-A containing nucleosome assembly  protein localization to kinetochore  cell division  extracellular exosome  spindle assembly checkpoint  
    Ontology : EGO-EBIcondensed chromosome kinetochore  acrosomal vesicle  acrosome assembly  protein binding  nucleus  nucleoplasm  nucleoplasm  cytosol  cytosol  sister chromatid cohesion  attachment of spindle microtubules to kinetochore  negative regulation of phosphatase activity  nuclear body  CENP-A containing nucleosome assembly  protein localization to kinetochore  cell division  extracellular exosome  spindle assembly checkpoint  
    NDEx NetworkKNL1
    Atlas of Cancer Signalling NetworkKNL1
    Wikipedia pathwaysKNL1
    Orthology - Evolution
    OrthoDB57082
    GeneTree (enSembl)ENSG00000137812
    Phylogenetic Trees/Animal Genes : TreeFamKNL1
    HOVERGENQ8NG31
    HOGENOMQ8NG31
    Homologs : HomoloGeneKNL1
    Homology/Alignments : Family Browser (UCSC)KNL1
    Gene fusions - Rearrangements
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerKNL1 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)KNL1
    dbVarKNL1
    ClinVarKNL1
    1000_GenomesKNL1 
    Exome Variant ServerKNL1
    ExAC (Exome Aggregation Consortium)KNL1 (select the gene name)
    Genetic variants : HAPMAP57082
    Genomic Variants (DGV)KNL1 [DGVbeta]
    DECIPHERKNL1 [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisKNL1 
    Mutations
    ICGC Data PortalKNL1 
    TCGA Data PortalKNL1 
    Broad Tumor PortalKNL1
    OASIS PortalKNL1 [ Somatic mutations - Copy number]
    Mutations and Diseases : HGMDKNL1
    BioMutasearch KNL1
    DgiDB (Drug Gene Interaction Database)KNL1
    DoCM (Curated mutations)KNL1 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)KNL1 (select a term)
    intoGenKNL1
    NCG5 (London)KNL1
    Cancer3DKNL1(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM604321    609173   
    Orphanet732   
    MedgenKNL1
    Genetic Testing Registry KNL1
    NextProtQ8NG31 [Medical]
    TSGene57082
    GENETestsKNL1
    Target ValidationKNL1
    Huge Navigator KNL1 [HugePedia]
    snp3D : Map Gene to Disease57082
    BioCentury BCIQKNL1
    ClinGenKNL1
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD57082
    Chemical/Pharm GKB GenePA142672201
    Clinical trialKNL1
    Miscellaneous
    canSAR (ICR)KNL1 (select the gene name)
    Probes
    Litterature
    PubMed54 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineKNL1
    EVEXKNL1
    GoPubMedKNL1
    iHOPKNL1
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Wed Jun 7 11:55:33 CEST 2017

    Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.