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Center for Computational Systems Medicine
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Kinase Fusion Gene Summary

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Kinase Fusion Gene Sample Information

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Kinase Fusion ORF Analysis

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Kinase Fusion Amino Acid Sequences

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

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Kinase Fusion Protein Structures

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Comparison of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

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pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.

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Ramachandran Plot of Kinase Fusion Protein Structure

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Potential Active Site Information

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Virtual Screening Results

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Kinase-Substrate Information

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Related Drugs with This Kinase Fusion Protein

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Related Disease with This Kinase Fusion Protein

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Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:TMEM104_CDK12

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: TMEM104_CDK12
KinaseFusionDB ID: KFG6604
FusionGDB2.0 ID: KFG6604
HgeneTgene
Gene symbol

TMEM104

CDK12

Gene ID

54868

51755

Gene nametransmembrane protein 104cyclin dependent kinase 12
SynonymsSLC38A12CRK7|CRKR|CRKRS
Cytomap

17q25.1

17q12

Type of geneprotein-codingprotein-coding
Descriptiontransmembrane protein 104cyclin-dependent kinase 12CDC2-related protein kinase 7Cdc2-related kinase, arginine/serine-richcell division cycle 2-related protein kinase 7cell division protein kinase 12
Modification date2024040320240403
UniProtAcc

Q8NE00

Q9NYV4

Ensembl transtripts involved in fusion geneENST idsENST00000335464, ENST00000417024, 
ENST00000582773, ENST00000582330, 
ENST00000584171, 
ENST00000430627, 
ENST00000447079, ENST00000559545, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: TMEM104 [Title/Abstract] AND CDK12 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
TgeneCDK12

GO:0006366

transcription by RNA polymerase II

22988298

TgeneCDK12

GO:0032968

positive regulation of transcription elongation by RNA polymerase II

22988298

TgeneCDK12

GO:0046777

protein autophosphorylation

11683387


check buttonKinase Fusion gene breakpoints across TMEM104 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonKinase Fusion gene breakpoints across CDK12 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.


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Kinase Fusion Gene Sample Information

check buttonKinase Fusion gene information.
check button Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE)
* 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.
SourceSampleHgeneHchrHbpTgeneTchrTbp
CCLEMDA-MB-361TMEM104chr17

72786435

CDK12chr17

37686884

CCLEMDA-MB-361TMEM104chr17

72786435

CDK12chr17

37686857

CCLEMDA-MB-361TMEM104chr17

72786431

CDK12chr17

37686884



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Kinase Fusion ORF Analysis


check buttonKinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(amino acids)
ENST00000335464ENST00000447079TMEM104chr1772786435CDK12chr17376868845023210
ENST00000335464ENST00000447079TMEM104chr1772786431CDK12chr17376868845023210

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Kinase Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq

>ENST00000335464_ENST00000447079_TMEM104_chr17_72786435_CDK12_chr17_37686884_length(amino acids)=210
MVEGDLSSAPQELNPAVTAALLQLLSQPEAEPPGHLPHEHQALRPMEYSTRPRPNRTYGNTDGPETGFSAIDTDERNSGPALTESLVQTL
VKNRTFSGSLSHLGESSSYQGTGSVQFPGDQDLRFARVPLALHPVVGQPFLKAEGSSNSVVHAETKLQNYGELGPGTTGASSSGAGLHWG

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>ENST00000335464_ENST00000447079_TMEM104_chr17_72786431_CDK12_chr17_37686884_length(amino acids)=210
MVEGDLSSAPQELNPAVTAALLQLLSQPEAEPPGHLPHEHQALRPMEYSTRPRPNRTYGNTDGPETGFSAIDTDERNSGPALTESLVQTL
VKNRTFSGSLSHLGESSSYQGTGSVQFPGDQDLRFARVPLALHPVVGQPFLKAEGSSNSVVHAETKLQNYGELGPGTTGASSSGAGLHWG

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Multiple Sequence Alignment of All Fusion Protein Isoforms



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Kinase Fusion Protein Functional Features


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:/chr17:)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
TMEM104

Q8NE00

CDK12

Q9NYV4

FUNCTION: Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}.

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.

check button - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


check button - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote
TgeneTMEM10472786431CDK1237686884ENST00000335464014727_102001491DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneTMEM10472786435CDK1237686884ENST00000335464014727_102001491DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159


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Kinase Fusion Protein Structures

check button CIF files of the predicted kinase fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB)HenstTenstHgeneHchrHbpTgeneTchrTbpAA seqLen(AA seq)
PDB file >>>82_CASC3_CDK12ENST00000335464ENST00000447079TMEM104chr1772786431CDK12chr1737686884
MVEGDLSSAPQELNPAVTAALLQLLSQPEAEPPGHLPHEHQALRPMEYSTRPRPNRTYGNTDGPETGFSAIDTDERNSGPALTESLVQTL
VKNRTFSGSLSHLGESSSYQGTGSVQFPGDQDLRFARVPLALHPVVGQPFLKAEGSSNSVVHAETKLQNYGELGPGTTGASSSGAGLHWG
210
3D view using mol* of 82_CASC3_CDK12
PDB file >>>508_TMEM104_CDK12ENST00000335464ENST00000447079TMEM104chr1772786431CDK12chr1737686884
MVEGDLSSAPQELNPAVTAALLQLLSQPEAEPPGHLPHEHQALRPMEYSTRPRPNRTYGNTDGPETGFSAIDTDERNSGPALTESLVQTL
VKNRTFSGSLSHLGESSSYQGTGSVQFPGDQDLRFARVPLALHPVVGQPFLKAEGSSNSVVHAETKLQNYGELGPGTTGASSSGAGLHWG
210
3D view using mol* of 508_TMEM104_CDK12
PDB file >>>TKFP_861_TMEM104_CDK12ENST00000335464ENST00000447079TMEM104chr1772786435CDK12chr1737686884
MVEGDLSSAPQELNPAVTAALLQLLSQPEAEPPGHLPHEHQALRPMEYSTRPRPNRTYGNTDGPETGFSAIDTDERNSGPALTESLVQTL
VKNRTFSGSLSHLGESSSYQGTGSVQFPGDQDLRFARVPLALHPVVGQPFLKAEGSSNSVVHAETKLQNYGELGPGTTGASSSGAGLHWG
210_TMEM104_CDK12
PDB file >>>TKFP_862_TMEM104_CDK12ENST00000335464ENST00000447079TMEM104chr1772786431CDK12chr1737686884
MVEGDLSSAPQELNPAVTAALLQLLSQPEAEPPGHLPHEHQALRPMEYSTRPRPNRTYGNTDGPETGFSAIDTDERNSGPALTESLVQTL
VKNRTFSGSLSHLGESSSYQGTGSVQFPGDQDLRFARVPLALHPVVGQPFLKAEGSSNSVVHAETKLQNYGELGPGTTGASSSGAGLHWG
210_TMEM104_CDK12


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Comparison of Fusion Protein Isoforms

check button Superimpose the 3D Structures Among All Fusion Protein Isoforms
* Download the pdb file and open it from the molstar online viewer.

check button Comparison of the Secondary Structures of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

TMEM104_CDK12 does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/508_TMEM104_CDK12.png
check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
* The blue color at the bottom marks the best active site residues.
508_TMEM104_CDK12.png
all structure sitemap plddt3 508_TMEM104_CDK12.png
508_TMEM104_CDK12.png
all structure sitemap plddt4 508_TMEM104_CDK12.png


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Potential Active Site Information


check button The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.
Kinase Fusion AA seq ID in KinaseFusionDBSite scoreSizeDscoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues

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Ramachandran Plot of Kinase Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

508_TMEM104_CDK12_ramachandran.png
all structure TMEM104-CDK12

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Virtual Screening Results


check button Distribution of the average docking score across all approved kinase inhibitors.
Distribution of the number of occurrence across all approved kinase inhibitors.
5'-kinase fusion protein case
3'-kinase fusion protein case
all structure TMEM104-CDK12

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check button Drug information from DrugBank of the top 20 interacting small molecules.
* The detailed information of individual kinase inhibitors are available in the download page.
Fusion gene name infoDrugDocking scoreGlide g scoreGlide energy
508_TMEM104_CDK12-DOCK_HTVS_1-001Tofacitinib-2.97077-2.98227-19.9082
508_TMEM104_CDK12-DOCK_HTVS_1-001Tofacitinib-2.97077-2.98227-19.9082
508_TMEM104_CDK12-DOCK_HTVS_1-001Abrocitinib-2.80898-2.82008-21.3597
508_TMEM104_CDK12-DOCK_HTVS_1-001Abrocitinib-2.80898-2.82008-21.3597
508_TMEM104_CDK12-DOCK_HTVS_1-001Upadacitinib-2.56745-2.56845-26.2595
508_TMEM104_CDK12-DOCK_HTVS_1-001Abrocitinib-2.56128-2.57238-23.9034
508_TMEM104_CDK12-DOCK_HTVS_1-001Abrocitinib-2.56128-2.57238-23.9034
508_TMEM104_CDK12-DOCK_HTVS_1-001Ruxolitinib-2.53261-2.53261-20.4245
508_TMEM104_CDK12-DOCK_HTVS_1-001Ruxolitinib-2.40469-2.40469-23.5513
508_TMEM104_CDK12-DOCK_HTVS_1-001Tofacitinib-2.30901-2.32051-19.7795
508_TMEM104_CDK12-DOCK_HTVS_1-001Tofacitinib-2.30901-2.32051-19.7795
508_TMEM104_CDK12-DOCK_HTVS_1-001Upadacitinib-1.8147900000000001-1.8157900000000002-21.3314
508_TMEM104_CDK12-DOCK_HTVS_1-001Tofacitinib-0.697747-3.03865-20.8248
508_TMEM104_CDK12-DOCK_HTVS_1-001Tofacitinib-0.697747-3.03865-20.8248
508_TMEM104_CDK12-DOCK_HTVS_1-001Abrocitinib-0.105939-2.4678400000000003-19.1334
508_TMEM104_CDK12-DOCK_HTVS_1-001Abrocitinib-0.105939-2.4678400000000003-19.1334
508_TMEM104_CDK12-DOCK_HTVS_1-001Tofacitinib0.031103500000000003-2.3098-19.0867
508_TMEM104_CDK12-DOCK_HTVS_1-001Tofacitinib0.031103500000000003-2.3098-19.0867
508_TMEM104_CDK12-DOCK_HTVS_1-001Sirolimus
508_TMEM104_CDK12-DOCK_HTVS_1-001Sirolimus

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Kinase-Substrate Information of TMEM104_CDK12


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
CDK12Q9NYV4humanPAK2Q13177T134LkFyDsNtVkQKyLs
CDK12Q9NYV4humanPOLR2AP24928S1616TPQSPSysPtsPsYSRNA_pol_Rpb1_R
CDK12Q9NYV4humanPAK2Q13177T169TEAPAVVtEEEDDDE
CDK12Q9NYV4humanTP63Q9H3D4-2S68TFDALsPsPAIPSNT
CDK12Q9NYV4humanPOLR2AP24928S1619SPSysPtsPsYSPTSRNA_pol_Rpb1_R
CDK12Q9NYV4humanTP63Q9H3D4-2S66SSTFDALsPsPAIPS
CDK12Q9NYV4humanTP63Q9H3D4-2S301TSIKKRRsPDDELLYP53_tetramer


check button Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

check button Enriched GO biological processes of the phosphorylation target genes of the kinase
KinaseGOIDGO termP.adjust
CDK12IDDescription0.00e+00
CDK12GO:2001235positive regulation of apoptotic signaling pathway2.92e-02
CDK12GO:2001233regulation of apoptotic signaling pathway2.92e-02
CDK12GO:0060525prostate glandular acinus development2.92e-02
CDK12GO:2000271positive regulation of fibroblast apoptotic process2.92e-02
CDK12GO:0060601lateral sprouting from an epithelium2.92e-02
CDK12GO:0060742epithelial cell differentiation involved in prostate gland development2.92e-02
CDK12GO:0035112genitalia morphogenesis2.92e-02
CDK12GO:0043589skin morphogenesis2.92e-02
CDK12GO:1904672regulation of somatic stem cell population maintenance2.92e-02
CDK12GO:0034333adherens junction assembly2.92e-02
CDK12GO:0045605negative regulation of epidermal cell differentiation2.92e-02
CDK12GO:0045683negative regulation of epidermis development2.92e-02
CDK12GO:0010838positive regulation of keratinocyte proliferation2.92e-02
CDK12GO:0033147negative regulation of intracellular estrogen receptor signaling pathway2.92e-02
CDK12GO:0060572morphogenesis of an epithelial bud2.92e-02
CDK12GO:0030540female genitalia development2.92e-02
CDK12GO:0036342post-anal tail morphogenesis2.92e-02
CDK12GO:2000269regulation of fibroblast apoptotic process2.92e-02
CDK12GO:0048485sympathetic nervous system development2.92e-02
CDK12GO:0150105protein localization to cell-cell junction2.92e-02
CDK12GO:1900118negative regulation of execution phase of apoptosis2.92e-02
CDK12GO:0002223stimulatory C-type lectin receptor signaling pathway2.92e-02
CDK12GO:1990840response to lectin2.92e-02
CDK12GO:1990858cellular response to lectin2.92e-02
CDK12GO:0060571morphogenesis of an epithelial fold2.92e-02
CDK12GO:0030859polarized epithelial cell differentiation2.92e-02
CDK12GO:0044346fibroblast apoptotic process2.92e-02
CDK12GO:0060740prostate gland epithelium morphogenesis2.92e-02
CDK12GO:0035116embryonic hindlimb morphogenesis2.92e-02
CDK12GO:0060512prostate gland morphogenesis2.92e-02
CDK12GO:0006353DNA-templated transcription termination2.92e-02
CDK12GO:1900117regulation of execution phase of apoptosis2.92e-02
CDK12GO:0031069hair follicle morphogenesis2.92e-02
CDK12GO:0035115embryonic forelimb morphogenesis2.92e-02
CDK12GO:0051497negative regulation of stress fiber assembly2.92e-02
CDK12GO:0061436establishment of skin barrier2.92e-02
CDK12GO:0009954proximal/distal pattern formation2.92e-02
CDK12GO:0008340determination of adult lifespan2.92e-02
CDK12GO:0033146regulation of intracellular estrogen receptor signaling pathway2.92e-02
CDK12GO:0032232negative regulation of actin filament bundle assembly2.92e-02
CDK12GO:0035137hindlimb morphogenesis2.92e-02
CDK12GO:0033144negative regulation of intracellular steroid hormone receptor signaling pathway2.92e-02
CDK12GO:0048730epidermis morphogenesis2.92e-02
CDK12GO:0045616regulation of keratinocyte differentiation3.09e-02
CDK12GO:0035136forelimb morphogenesis3.09e-02
CDK12GO:0042771intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator3.14e-02
CDK12GO:0033120positive regulation of RNA splicing3.14e-02
CDK12GO:0048483autonomic nervous system development3.14e-02
CDK12GO:0010837regulation of keratinocyte proliferation3.14e-02

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Related Drugs to TMEM104_CDK12


check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

check button Distribution of the number of studies mentioning TMEM104-CDK12 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1Fusion gene - drug pair 2PMIDPublication dateDOIStudy title

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Related Diseases to TMEM104_CDK12


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)
MeSH IDMeSH term

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource


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Clinical Trials of the Found Drugs/Small Molecules


check button Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

check button Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion GeneKinase InhibitorNCT IDStudy StatusPhasesDisease# EnrolmentDate