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Center for Computational Systems Medicine
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FusionGeneSummary

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FusionProtFeature

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FusionGeneSequence

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FusionGenePPI

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RelatedDrugs

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RelatedDiseases

Fusion gene ID: 6550

FusionGeneSummary for CDK2_ALK

check button Fusion gene summary
Fusion gene informationFusion gene name: CDK2_ALK
Fusion gene ID: 6550
HgeneTgene
Gene symbol

CDK2

ALK

Gene ID

1017

238

Gene namecyclin dependent kinase 2ALK receptor tyrosine kinase
SynonymsCDKN2|p33(CDK2)CD246|NBLST3
Cytomap

12q13.2

2p23.2-p23.1

Type of geneprotein-codingprotein-coding
Descriptioncyclin-dependent kinase 2cdc2-related protein kinasecell division protein kinase 2p33 protein kinaseALK tyrosine kinase receptorCD246 antigenanaplastic lymphoma receptor tyrosine kinasemutant anaplastic lymphoma kinase
Modification date2018052720180527
UniProtAcc

P24941

Q9UM73

Ensembl transtripts involved in fusion geneENST00000266970, ENST00000553376, 
ENST00000440311, ENST00000354056, 
ENST00000556656, 
ENST00000389048, 
ENST00000431873, ENST00000498037, 
Fusion gene scores* DoF score4 X 4 X 2=3224 X 23 X 10=5520
# samples 446
** MAII scorelog2(4/32*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(46/5520*10)=-3.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: CDK2 [Title/Abstract] AND ALK [Title/Abstract] AND fusion [Title/Abstract]

Functional or gene categories assigned by FusionGDB annotationTumor suppressor gene involved fusion gene, retained protein feature but frameshift.
DDR (DNA damage repair) gene involved fusion gene, in-frame but not retained their domain.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneCDK2

GO:0006468

protein phosphorylation

12944431|28666995

HgeneCDK2

GO:0008284

positive regulation of cell proliferation

10767298

HgeneCDK2

GO:0016572

histone phosphorylation

11746698

HgeneCDK2

GO:0018105

peptidyl-serine phosphorylation

23184662

HgeneCDK2

GO:0060968

regulation of gene silencing

20935635

TgeneALK

GO:0016310

phosphorylation

9174053

TgeneALK

GO:0046777

protein autophosphorylation

9174053


check button Fusion gene information from three resources
(ChiTars (NAR, 2018), tumorfusions (NAR, 2018), Gao et al. (Cell, 2018))
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
Data typeSourceCancer typeSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
TCGALDSKCMTCGA-WE-A8K4-01ACDK2chr12

56365031

+ALKchr2

29448431

-
* LD: Li Ding group's fusion gene list
  RV: Roel Verhaak group's fusion gene list
  ChiTaRs fusion database

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
Frame-shiftENST00000266970ENST00000389048CDK2chr12

56365031

+ALKchr2

29448431

-
5CDS-intronENST00000266970ENST00000431873CDK2chr12

56365031

+ALKchr2

29448431

-
5CDS-intronENST00000266970ENST00000498037CDK2chr12

56365031

+ALKchr2

29448431

-
Frame-shiftENST00000553376ENST00000389048CDK2chr12

56365031

+ALKchr2

29448431

-
5CDS-intronENST00000553376ENST00000431873CDK2chr12

56365031

+ALKchr2

29448431

-
5CDS-intronENST00000553376ENST00000498037CDK2chr12

56365031

+ALKchr2

29448431

-
Frame-shiftENST00000440311ENST00000389048CDK2chr12

56365031

+ALKchr2

29448431

-
5CDS-intronENST00000440311ENST00000431873CDK2chr12

56365031

+ALKchr2

29448431

-
5CDS-intronENST00000440311ENST00000498037CDK2chr12

56365031

+ALKchr2

29448431

-
Frame-shiftENST00000354056ENST00000389048CDK2chr12

56365031

+ALKchr2

29448431

-
5CDS-intronENST00000354056ENST00000431873CDK2chr12

56365031

+ALKchr2

29448431

-
5CDS-intronENST00000354056ENST00000498037CDK2chr12

56365031

+ALKchr2

29448431

-
3UTR-3CDSENST00000556656ENST00000389048CDK2chr12

56365031

+ALKchr2

29448431

-
3UTR-intronENST00000556656ENST00000431873CDK2chr12

56365031

+ALKchr2

29448431

-
3UTR-intronENST00000556656ENST00000498037CDK2chr12

56365031

+ALKchr2

29448431

-

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FusionProtFeatures for CDK2_ALK


check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
CDK2

P24941

ALK

Q9UM73

Serine/threonine-protein kinase involved in the controlof the cell cycle; essential for meiosis, but dispensable formitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1,BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes andDNA. Acts at the G1-S transition to promote the E2Ftranscriptional program and the initiation of DNA synthesis, andmodulates G2 progression; controls the timing of entry intomitosis/meiosis by controlling the subsequent activation of cyclinB/CDK1 by phosphorylation, and coordinates the activation ofcyclin B/CDK1 at the centrosome and in the nucleus. Crucial rolein orchestrating a fine balance between cellular proliferation,cell death, and DNA repair in human embryonic stem cells (hESCs).Activity of CDK2 is maximal during S phase and G2; activated byinteraction with cyclin E during the early stages of DNA synthesisto permit G1-S transition, and subsequently activated by cyclin A2(cyclin A1 in germ cells) during the late stages of DNAreplication to drive the transition from S phase to mitosis, theG2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance andepigenetic gene silencing. Phosphorylates CABLES1 (By similarity).Cyclin E/CDK2 prevents oxidative stress-mediated Ras-inducedsenescence by phosphorylating MYC. Involved in G1-S phase DNAdamage checkpoint that prevents cells with damaged DNA frominitiating mitosis; regulates homologous recombination-dependentrepair by phosphorylating BRCA2, this phosphorylation is low in Sphase when recombination is active, but increases as cellsprogress towards mitosis. In response to DNA damage, double-strandbreak repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbsits interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2promotes its dissociates from unduplicated centrosomes, thusinitiating centrosome duplication. Cyclin E/CDK2-mediatedphosphorylation of NPAT at G1-S transition and until prophasestimulates the NPAT-mediated activation of histone genetranscription during S phase. Required for vitamin D-mediatedgrowth inhibition by being itself inactivated. Involved in thenitric oxide- (NO) mediated signaling in anitrosylation/activation-dependent manner. USP37 is activated byphosphorylation and thus triggers G1-S transition. CTNNB1phosphorylation regulates insulin internalization. PhosphorylatesFOXP3 and negatively regulates its transcriptional activity andprotein stability (By similarity). Phosphorylates CDK2AP2(PubMed:12944431). {ECO:0000250|UniProtKB:P97377,ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347,ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387,ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:11113184,ECO:0000269|PubMed:12944431, ECO:0000269|PubMed:15800615,ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:18372919,ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20079829,ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20195506,ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:21262353,ECO:0000269|PubMed:21319273, ECO:0000269|PubMed:21596315,ECO:0000269|PubMed:28666995}. Neuronal receptor tyrosine kinase that is essentiallyand transiently expressed in specific regions of the central andperipheral nervous systems and plays an important role in thegenesis and differentiation of the nervous system. Transducessignals from ligands at the cell surface, through specificactivation of the mitogen-activated protein kinase (MAPK) pathway.Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK inducestyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well asof the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptorfor ligands pleiotrophin (PTN), a secreted growth factor, andmidkine (MDK), a PTN-related factor, thus participating in PTN andMDK signal transduction. PTN-binding induces MAPK pathwayactivation, which is important for the anti-apoptotic signaling ofPTN and regulation of cell proliferation. MDK-binding inducesphosphorylation of the ALK target insulin receptor substrate(IRS1), activates mitogen-activated protein kinases (MAPKs) andPI3-kinase, resulting also in cell proliferation induction. DrivesNF-kappa-B activation, probably through IRS1 and the activation ofthe AKT serine/threonine kinase. Recruitment of IRS1 to activatedALK and the activation of NF-kappa-B are essential for theautocrine growth and survival signaling of MDK.{ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720,ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760,ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009,ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:15908427,ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150,ECO:0000269|PubMed:17274988}.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

.

* Minus value of BPloci means that the break pointn is located before the CDS.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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FusionGeneSequence for CDK2_ALK


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences.
(nt: nucleotides, aa: amino acids)

* Fusion amino acid sequences.

* Fusion transcript sequences (only coding sequence (CDS) region).

* Fusion transcript sequences (Full-length transcript).

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FusionGenePPI for CDK2_ALK


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page

.

check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors
CDK2CDKN3, CDKN1B, EPB41, UBE2M, VHL, SORT1, RADIL, NEDD8, TSC22D1, WRAP73, OGT, CASP4, FBL, PTP4A3, CDK15, NAA25, PCED1A, BRCA1, CDKN1A, BCCIP, INCA1, XRCC6, RBM4, SPDYA, FEN1, CCNA2, CCNE1, CDK2AP1, RB1, POLA1, RBL2, RBL1, CCNB1, CCNA1, PPP2CA, PPM1B, CDK6, CDC25A, CNOT7, E2F1, TP53, CDC6, RRN3, NPDC1, CCNB3, REL, MYBL2, ORC1, ORC2, SKP2, CEBPA, CCNE2, CKS1B, BIRC5, MCM4, CDC25B, MS4A3, PCNA, LYN, PRKCH, CDC5L, UBE2A, IKBKG, CHAF1A, CDT1, MGMT, NOV, SP1, TSPYL2, FOXM1, HIST1H1A, EZH2, ARID4A, CDK7, UHRF2, EP300, NPM1, CEBPG, PIN1, KAT2B, KAT2A, MCM3, HIST1H1D, CDC7, HIST1H1B, CDK2, H1F0, MCM2, CDC25C, CDC45, TUBG1, MITF, PGR, PSMD9, FZR1, NPAT, CDK5R1, CCNH, MARCKS, MYC, PSMA6, CCND3, CCND1, CCND2, RPA1, ACTL6A, KIF26B, SKP1, PPP1CA, PPP1CC, CCNG1, DSP, ACTB, HSP90AB1, FLNA, EEF1A1, HSPA8, HSP90AA1, ACTA1, HRNR, GAPDH, VCL, TUBB4B, S100A8, TUBB2A, MYH9, JUP, DCD, HSPD1, DSG1, EEF2, ENO1, TUBA1C, DYNC1H1, PRDX1, ANXA2, HSP90B1, PPIA, FASN, CLTC, HSPA5, PDE4D, FLG2, ATP5B, PRKDC, EIF4A1, HIST2H2BE, HIST1H2AH, SERPINH1, RPS18, KPRP, LDHB, NASP, RPS3, RAB15, TLN1, PKM, DSC1, FLNC, DPYSL3, LRPPRC, RPL35, GRN, PDIA3, AHNAK, ALDOA, RPL36, HNRNPK, PDIA4, YWHAE, DHX9, TPI1, CCT8, RPL23A, HMGB1, CCT3, DPYSL2, XRCC5, TPM3, AZGP1, RPL7, PRDX2, RPL26, LYZ, UBA1, ATP5A1, GANAB, HNRNPA1, TUFM, RPL8, PCBP2, CFL1, PHGDH, HYOU1, HNRNPU, PCMT1, MYH10, COPA, RPS16, LDHA, RPS4X, PFN1, CCT6A, SEMG1, PCBP1, TPM4, HSPA9, EEF1G, GNB2L1, TALDO1, PARP1, RPL32, TARS, CCT4, PODXL, PA2G4, TCP1, FLNB, PGD, MSN, ARF1, RPS19, RPS27A, RPS14, RPL12, HNRNPF, TKT, RPL11, CCT2, YWHAG, RPL27, MTHFD1, ARF4, CAND1, GTF2I, CSTA, GPI, RPS11, SLC25A4, VCP, CSE1L, YWHAZ, RPS2, EPRS, RPS20, SFPQ, HSPA4, GARS, HBB, RAN, RPS3A, RPL10A, SMARCA5, RPS15A, RPS13, CRABP1, GSTP1, ILF3, LGALS7, RPL22, FSCN1, PHB2, RPL19, TTN, DEK, CCT7, PSMD2, AHCY, P4HB, EIF4A3, IGF2BP3, TAGLN2, ARGLU1, CYCS, TRIM28, DHX15, MYL6, MCM7, RPS17, SARS, RPL30, FKBP4, ENO2, LARS, PUF60, HNRNPD, SUPT16H, MFAP1, SLC25A3, GOT2, PHB, PLEC, PSMD3, CCT5, RPL23, RPLP0, APOD, SPTBN1, PSAT1, KPNB1, PSMB6, DDX17, IARS, STMN1, RPL13, ANXA5, UGP2, CAD, SF3B3, PDIA6, SUB1, HMGB2, PTBP1, HMGA1, PGK1, SND1, RPL14, ST13, MCM6, EIF3A, QARS, RPL31, ESYT1, LMNA, MYOF, CALR, TRIM21, PRMT1, HK1, ACTN1, GDI1, IQGAP1, RPS5, ATP5O, YARS, SART3, SRSF7, VARS, PNN, RPS28, PPIB, RPL3, RPL27A, GLG1, CDK1, NOMO1, SMC4, EIF2S3, CASP3, PSMA5, IMPDH2, CTPS1, ATIC, FUS, RPS9, PRDX6, CBS, RPL34, RPS23, PAICS, RPS8, YWHAH, VDAC1, DDX3X, RBM17, HNRNPM, CYP2S1, PSMD11, SET, RPL10L, MYL12B, HADHA, RPS24, ATP5F1, RHOC, IDH1, PAFAH1B2, NPEPPS, PRDX3, VDAC2, NAP1L1, CKB, HADHB, OAT, HDLBP, PSMC6, YWHAQ, SNRPD2, PNP, RPS21, EIF3C, DDX21, SARNP, RPS12, RPS7, EIF3I, IDH2, CLIC1, TPT1, ATP1A1, ILF2, UBE2N, CLIC4, SPTAN1, WDR1, EIF3H, DDX39B, MARCKSL1, ASNS, KHSRP, RCC2, VIM, TOP1, FUBP1, RPL6, CYB5R3, AP1B1, FH, COPB1, DDX1, MIF, SMC1A, SMC3, ANXA1, PAFAH1B1, HNRNPC, CRABP2, RPL18, RPL28, BZW1, CUL4B, COG7, VAT1, DHRS1, MAGOHB, UPF1, COQ6, NCBP2-AS2, SERPINB9, SSBP1, ERH, TMED10, S100A6, ATP5L, AARS, CAPZB, PSMC5, EEF1D, RAB11B, TPP2, HCFC1, VPS35, UCHL1, MAPRE1, COX2, SEC23A, MSH2, MATR3, RAB5C, RRM1, EIF3E, RRAS2, SAP18, ACOT7, RAC1, PSMD8, DAD1, G3BP2, SSB, ALDH18A1, RPLP2, RPS10, NACA2, IPO7, NUMA1, ARPC2, USP7, ARHGDIA, GNB2, KPNA2, GCN1L1, DSTN, RPS27, AURKAIP1, VPS39, MDH2, SNRPF, HSPE1, ACP1, HMGN2, TXN, APOO, UBE2I, ELAVL2, SNRPE, NHP2L1, ATP5D, RBM3, ACOT13, SSR4, SNRPA, IFITM2, EIF5A2, ATP2A3, CUL1, COPS5, COPS6, TMEM54, LATS2, TTK, CDK20, ID2, ID3, TFDP1, CDX2, PRC1, UBTF, POLD1, CCP110, DBF4, FBXW7, STOML1, SMAD3, SMAD2, BRCA2, PML, HIST1H4A, CCNB2, TP73, PRKAR1A, NFYA, NFYB, NFYC, CTNNB1, PTMA, C12orf65, IL15RA, MAPRE2, PHLDA3, ACKR4, BTBD2, GOLGA2, CREBBP, CDK13, CDKN1C, CKS2, GMNN, MNAT1, CDK3, CDC20, TCOF1, CCNJ, MAPK15, SAMHD1, MAPT, ESR1, SCN5A, HIST1H2AB, HIST1H2BB, BARD1, CAPRIN1, CNBP, YBX3, DDX5, DST, E2F4, FAM133B, LIN37, MT1E, RPL37, SHROOM3, SRRM2, ALYREF, WDR77, LOC100419906, USP37, CTSA, POLR3H, GORASP1, C2CD5, GATA3, LATS1, ARF6, ALDOC, NOP2, RPE, POLR2A, NTRK1, OFD1, ACTG1, BUB1, ELMSAN1, CNTROB, CLTA, DAPK3, DBN1, DNMT1, FLII, GSN, ABLIM1, LMO7, MYO1B, MYO1C, MYO5A, MYO6, PPP1R12A, CDK16, PPP1CB, RAP1GDS1, ROBO1, S100A4, SVIL, TAF7, TMOD1, TPM1, TPM2, LUZP1, AKR7A2, LRRFIP2, BCLAF1, SEC16A, ARPC1B, RBM7, SYNCRIP, ZMYND11, SYNPO, LIMCH1, UHRF1BP1L, MPRIP, SPECC1L, CORO1C, RAI14, TES, ASTE1, TMOD3, TRA2A, RMDN1, MRPL27, LIMA1, BMP2K, YEATS2, CARKD, THAP11, AFAP1, ARPC5L, PARP10, DOCK7, TOP1MT, PGAM5, MYO18A, KLF10, KMT2E, POLL, UBE2T, UBE2H, SLBP, SIRT2, PLA2G4A, SMTNL2, GLB1, RNF157ALKPTN, SHC1, PLCG1, JAK3, SHC3, RAB35, HSPD1, MAP3K4, GRB2, SOCS1, PIK3CB, RAD17, IRF7, EPHB2, EIF4B, MAPK8IP3, CENPF, PLCB2, PDX1, STAT3, MAP2K7, JAK2, MAP3K5, MEP1B, GAK, EPHA1, UBASH3A, MTIF2, MYLK, MAP3K1, MAPK1, SOCS5, CDK13, SMC6, IRS4, KRT18, KRT74, IRS1, IKBKG, ZC3HC1, TNK2, ERRFI1, PIK3R1, HSP90AA1, BCAR1, ACTB, PDLIM3, VIM, TUBB4B, MYO6, MYH10, MYH9, TUBGCP2, ACTN4, CORO1C, FLII, BICD2, GNB2L1, SRC, PXN, PRKCQ, MYBPC2, CDK9, PPM1A, DUSP19


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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RelatedDrugs for CDK2_ALK


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.0 2018-04-02)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
HgeneCDK2P24941DB06616BosutinibCyclin-dependent kinase 2small moleculeapproved
TgeneALKQ9UM73DB08865CrizotinibALK tyrosine kinase receptorsmall moleculeapproved
TgeneALKQ9UM73DB09063CeritinibALK tyrosine kinase receptorsmall moleculeapproved

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RelatedDiseases for CDK2_ALK


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneCDK2C0025202melanoma1CTD_human
TgeneALKC0007131Non-Small Cell Lung Carcinoma28CTD_human
TgeneALKC0027819Neuroblastoma12CTD_human;ORPHANET
TgeneALKC0152013Adenocarcinoma of lung (disorder)8CTD_human
TgeneALKC0206180Ki-1+ Anaplastic Large Cell Lymphoma6CTD_human
TgeneALKC2751681NEUROBLASTOMA, SUSCEPTIBILITY TO, 34UNIPROT
TgeneALKC0018199Granuloma, Plasma Cell3CTD_human
TgeneALKC0007621Neoplastic Cell Transformation2CTD_human
TgeneALKC0027627Neoplasm Metastasis2CTD_human
TgeneALKC0001973Alcoholic Intoxication, Chronic1PSYGENET
TgeneALKC0006118Brain Neoplasms1CTD_human
TgeneALKC0007134Renal Cell Carcinoma1CTD_human
TgeneALKC0011570Mental Depression1PSYGENET
TgeneALKC0011581Depressive disorder1PSYGENET
TgeneALKC0027643Neoplasm Recurrence, Local1CTD_human
TgeneALKC0036341Schizophrenia1PSYGENET
TgeneALKC0079744Diffuse Large B-Cell Lymphoma1CTD_human
TgeneALKC0085269Plasma Cell Granuloma, Pulmonary1CTD_human
TgeneALKC0278601Inflammatory Breast Carcinoma1CTD_human