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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:STK4-IYD (FusionGDB2 ID:86988)

Fusion Gene Summary for STK4-IYD

check button Fusion gene summary
Fusion gene informationFusion gene name: STK4-IYD
Fusion gene ID: 86988
HgeneTgene
Gene symbol

STK4

IYD

Gene ID

6789

389434

Gene nameserine/threonine kinase 4iodotyrosine deiodinase
SynonymsKRS2|MST1|YSK3C6orf71|DEHAL1|IYD-1|TDH4
Cytomap

20q13.12

6q25.1

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase 4STE20-like kinase MST1kinase responsive to stress 2mammalian STE20-like protein kinase 1mammalian sterile 20-like 1serine/threonine-protein kinase Krs-2iodotyrosine deiodinase 1iodotyrosine dehalogenase 1
Modification date2020031320200313
UniProtAcc

Q13043

Q6PHW0

Ensembl transtripts involved in fusion geneENST00000372806, ENST00000396731, 
ENST00000372801, ENST00000499879, 
ENST00000487587, 		ENST00000229447, 
ENST00000344419, ENST00000392256, 
ENST00000392255, ENST00000500320, 
ENST00000425615, 
Fusion gene scores* DoF score9 X 6 X 7=3784 X 4 X 4=64
# samples 95
** MAII scorelog2(9/378*10)=-2.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(5/64*10)=-0.356143810225275
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: STK4 [Title/Abstract] AND IYD [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointSTK4(43625947)-IYD(150713480), # samples:1
Anticipated loss of major functional domain due to fusion event.STK4-IYD seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
STK4-IYD seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
STK4-IYD seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
STK4-IYD seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
STK4-IYD seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
* 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
HgeneSTK4

GO:0000902

cell morphogenesis

11805089

HgeneSTK4

GO:0001934

positive regulation of protein phosphorylation

19962960

HgeneSTK4

GO:0006468

protein phosphorylation

8566796|11805089

HgeneSTK4

GO:0006915

apoptotic process

21212262

HgeneSTK4

GO:0018105

peptidyl-serine phosphorylation

16751106

HgeneSTK4

GO:0032092

positive regulation of protein binding

22292086

HgeneSTK4

GO:0033138

positive regulation of peptidyl-serine phosphorylation

19962960

HgeneSTK4

GO:0035329

hippo signaling

20412773

HgeneSTK4

GO:0035556

intracellular signal transduction

8566796

HgeneSTK4

GO:0043065

positive regulation of apoptotic process

15109305

HgeneSTK4

GO:0046777

protein autophosphorylation

11805089

HgeneSTK4

GO:0050821

protein stabilization

19962960

TgeneIYD

GO:0006570

tyrosine metabolic process

25395621

TgeneIYD

GO:0042403

thyroid hormone metabolic process

25395621

TgeneIYD

GO:0055114

oxidation-reduction process

25395621


check buttonFusion gene breakpoints across STK4 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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

check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4STADTCGA-D7-A6F2STK4chr20

43625947

+IYDchr6

150713480

+


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Fusion Gene ORF analysis for STK4-IYD

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-shiftENST00000372806ENST00000229447STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372806ENST00000344419STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372806ENST00000392256STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372806ENST00000392255STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372806ENST00000500320STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372806ENST00000425615STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000396731ENST00000229447STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000396731ENST00000344419STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000396731ENST00000392256STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000396731ENST00000392255STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000396731ENST00000500320STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000396731ENST00000425615STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372801ENST00000229447STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372801ENST00000344419STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372801ENST00000392256STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372801ENST00000392255STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372801ENST00000500320STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000372801ENST00000425615STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000499879ENST00000229447STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000499879ENST00000344419STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000499879ENST00000392256STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000499879ENST00000392255STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000499879ENST00000500320STK4chr20

43625947

+IYDchr6

150713480

+
Frame-shiftENST00000499879ENST00000425615STK4chr20

43625947

+IYDchr6

150713480

+
intron-3CDSENST00000487587ENST00000229447STK4chr20

43625947

+IYDchr6

150713480

+
intron-3CDSENST00000487587ENST00000344419STK4chr20

43625947

+IYDchr6

150713480

+
intron-3CDSENST00000487587ENST00000392256STK4chr20

43625947

+IYDchr6

150713480

+
intron-3CDSENST00000487587ENST00000392255STK4chr20

43625947

+IYDchr6

150713480

+
intron-3CDSENST00000487587ENST00000500320STK4chr20

43625947

+IYDchr6

150713480

+
intron-3CDSENST00000487587ENST00000425615STK4chr20

43625947

+IYDchr6

150713480

+

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score

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Fusion Genomic Features for STK4-IYD


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)
STK4chr2043625947+IYDchr6150713480+3.77E-081
STK4chr2043625947+IYDchr6150713480+3.77E-081

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for STK4-IYD


check button Go to

FGviewer for the breakpoints of :-:

.
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
STK4

Q13043

IYD

Q6PHW0

FUNCTION: Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}.FUNCTION: Catalyzes the oxidative NADPH-dependent deiodination of monoiodotyrosine (L-MIT) or diiodotyrosine (L-DIT) (PubMed:15289438, PubMed:25395621, PubMed:18434651). Acts during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways (PubMed:18434651). Acts more efficiently on monoiodotyrosine than on diiodotyrosine (PubMed:15289438). {ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651, ECO:0000269|PubMed:25395621}.

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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Fusion Gene Sequence for STK4-IYD


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for STK4-IYD


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


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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Related Drugs for STK4-IYD


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for STK4-IYD


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneSTK4C3553943T-CELL IMMUNODEFICIENCY, RECURRENT INFECTIONS, AND AUTOIMMUNITY WITH OR WITHOUT CARDIAC MALFORMATIONS2CTD_human;GENOMICS_ENGLAND;ORPHANET
HgeneSTK4C4016913T-CELL IMMUNODEFICIENCY, RECURRENT INFECTIONS, AUTOIMMUNITY, AND CARDIAC MALFORMATIONS2GENOMICS_ENGLAND
HgeneSTK4C0005586Bipolar Disorder1CTD_human
HgeneSTK4C0005587Depression, Bipolar1CTD_human
HgeneSTK4C0024713Manic Disorder1CTD_human
HgeneSTK4C0338831Manic1CTD_human
HgeneSTK4C0494261Combined immunodeficiency1GENOMICS_ENGLAND
TgeneIYDC0342195Thyroid Dyshormonogenesis 42CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneIYDC1848805Thyroid Dyshormonogenesis 12ORPHANET
TgeneIYDC0010308Congenital Hypothyroidism1GENOMICS_ENGLAND
TgeneIYDC0018021Goiter1GENOMICS_ENGLAND
TgeneIYDC0023893Liver Cirrhosis, Experimental1CTD_human