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Fusion Protein:RAPGEF5-STK4 |
Fusion Gene and Fusion Protein Summary |
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Fusion partner gene information | Fusion gene name: RAPGEF5-STK4 | FusionPDB ID: 72253 | FusionGDB2.0 ID: 72253 | Hgene | Tgene | Gene symbol | RAPGEF5 | STK4 | Gene ID | 9771 | 6789 |
Gene name | Rap guanine nucleotide exchange factor 5 | serine/threonine kinase 4 | |
Synonyms | GFR|MR-GEF|REPAC | KRS2|MST1|YSK3 | |
Cytomap | 7p15.3 | 20q13.12 | |
Type of gene | protein-coding | protein-coding | |
Description | rap guanine nucleotide exchange factor 5M-Ras-regulated GEFM-Ras-regulated Rap GEFRap guanine nucleotide exchange factor (GEF) 5guanine nucleotide exchange factor for Rap1related to Epac | serine/threonine-protein kinase 4STE20-like kinase MST1kinase responsive to stress 2mammalian STE20-like protein kinase 1mammalian sterile 20-like 1serine/threonine-protein kinase Krs-2 | |
Modification date | 20200313 | 20200313 | |
UniProtAcc | . | Q13043 Main function of 5'-partner protein: 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}. | |
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000344041, ENST00000405243, ENST00000401957, ENST00000475788, | ENST00000487587, ENST00000372801, ENST00000372806, ENST00000396731, ENST00000499879, |
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 16 X 14 X 10=2240 | 13 X 13 X 7=1183 |
# samples | 21 | 16 | |
** MAII score | log2(21/2240*10)=-3.41503749927884 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(16/1183*10)=-2.88630626345243 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
Fusion gene context | PubMed: RAPGEF5 [Title/Abstract] AND STK4 [Title/Abstract] AND fusion [Title/Abstract] | ||
Fusion neoantigen context | PubMed: RAPGEF5 [Title/Abstract] AND STK4 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | RAPGEF5(22347958)-STK4(43607084), # samples:1 | ||
Anticipated loss of major functional domain due to fusion event. | RAPGEF5-STK4 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. RAPGEF5-STK4 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. RAPGEF5-STK4 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. RAPGEF5-STK4 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. |
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
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Partner | Gene | GO ID | GO term | PubMed ID |
Tgene | STK4 | GO:0000902 | cell morphogenesis | 11805089 |
Tgene | STK4 | GO:0001934 | positive regulation of protein phosphorylation | 19962960 |
Tgene | STK4 | GO:0006468 | protein phosphorylation | 8566796|11805089 |
Tgene | STK4 | GO:0006915 | apoptotic process | 21212262 |
Tgene | STK4 | GO:0018105 | peptidyl-serine phosphorylation | 16751106 |
Tgene | STK4 | GO:0032092 | positive regulation of protein binding | 22292086 |
Tgene | STK4 | GO:0033138 | positive regulation of peptidyl-serine phosphorylation | 19962960 |
Tgene | STK4 | GO:0035329 | hippo signaling | 20412773 |
Tgene | STK4 | GO:0035556 | intracellular signal transduction | 8566796 |
Tgene | STK4 | GO:0043065 | positive regulation of apoptotic process | 15109305 |
Tgene | STK4 | GO:0046777 | protein autophosphorylation | 11805089 |
Tgene | STK4 | GO:0050821 | protein stabilization | 19962960 |
![]() Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr7:22347958/chr20:43607084) - 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. |
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![]() * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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![]() * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Fusion Amino Acid Sequences |
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Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
ENST00000344041 | RAPGEF5 | chr7 | 22347958 | - | ENST00000372806 | STK4 | chr20 | 43607084 | + | 6665 | 534 | 1 | 1881 | 626 |
ENST00000344041 | RAPGEF5 | chr7 | 22347958 | - | ENST00000396731 | STK4 | chr20 | 43607084 | + | 1807 | 534 | 1 | 1806 | 602 |
ENST00000344041 | RAPGEF5 | chr7 | 22347958 | - | ENST00000372801 | STK4 | chr20 | 43607084 | + | 2409 | 534 | 1 | 1806 | 601 |
ENST00000344041 | RAPGEF5 | chr7 | 22347958 | - | ENST00000499879 | STK4 | chr20 | 43607084 | + | 5592 | 534 | 1 | 1716 | 571 |
ENST00000405243 | RAPGEF5 | chr7 | 22347958 | - | ENST00000372806 | STK4 | chr20 | 43607084 | + | 6895 | 764 | 9 | 2111 | 700 |
ENST00000405243 | RAPGEF5 | chr7 | 22347958 | - | ENST00000396731 | STK4 | chr20 | 43607084 | + | 2037 | 764 | 9 | 2036 | 675 |
ENST00000405243 | RAPGEF5 | chr7 | 22347958 | - | ENST00000372801 | STK4 | chr20 | 43607084 | + | 2639 | 764 | 9 | 2036 | 675 |
ENST00000405243 | RAPGEF5 | chr7 | 22347958 | - | ENST00000499879 | STK4 | chr20 | 43607084 | + | 5822 | 764 | 9 | 1946 | 645 |
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Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
ENST00000344041 | ENST00000372806 | RAPGEF5 | chr7 | 22347958 | - | STK4 | chr20 | 43607084 | + | 0.000714862 | 0.99928516 |
ENST00000344041 | ENST00000396731 | RAPGEF5 | chr7 | 22347958 | - | STK4 | chr20 | 43607084 | + | 0.002865872 | 0.9971341 |
ENST00000344041 | ENST00000372801 | RAPGEF5 | chr7 | 22347958 | - | STK4 | chr20 | 43607084 | + | 0.001626225 | 0.99837375 |
ENST00000344041 | ENST00000499879 | RAPGEF5 | chr7 | 22347958 | - | STK4 | chr20 | 43607084 | + | 0.001091768 | 0.9989083 |
ENST00000405243 | ENST00000372806 | RAPGEF5 | chr7 | 22347958 | - | STK4 | chr20 | 43607084 | + | 0.00139482 | 0.9986052 |
ENST00000405243 | ENST00000396731 | RAPGEF5 | chr7 | 22347958 | - | STK4 | chr20 | 43607084 | + | 0.00786677 | 0.9921332 |
ENST00000405243 | ENST00000372801 | RAPGEF5 | chr7 | 22347958 | - | STK4 | chr20 | 43607084 | + | 0.004996639 | 0.9950034 |
ENST00000405243 | ENST00000499879 | RAPGEF5 | chr7 | 22347958 | - | STK4 | chr20 | 43607084 | + | 0.00227656 | 0.9977234 |
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Get the fusion protein sequences from here. |
Fusion protein sequence information is available in the fasta format. >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP |
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Fusion Protein Breakpoint Sequences for RAPGEF5-STK4 |
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Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
RAPGEF5 | chr7 | 22347958 | STK4 | chr20 | 43607084 | 534 | 178 | VPLIPARGGICELSYGSVYKAIHKET |
RAPGEF5 | chr7 | 22347958 | STK4 | chr20 | 43607084 | 764 | 252 | VPLIPARGGICELSYGSVYKAIHKET |
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Potential FusionNeoAntigen Information of RAPGEF5-STK4 in HLA I |
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RAPGEF5-STK4_22347958_43607084.msa |
![]() * We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5) |
Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA I | FusionNeoAntigen peptide | Binding score | Immunogenic score | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B44:03 | CELSYGSVY | 0.9967 | 0.9075 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:01 | CELSYGSVY | 0.9957 | 0.933 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B15:03 | CELSYGSVY | 0.0516 | 0.5519 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B27:05 | ARGGICELSY | 0.9997 | 0.833 | 5 | 15 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B27:04 | ARGGICELSY | 0.9996 | 0.7519 | 5 | 15 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B27:02 | ARGGICELSY | 0.9996 | 0.5605 | 5 | 15 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:01 | ICELSYGSVY | 0.4715 | 0.7471 | 9 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B27:03 | ARGGICELSY | 0.997 | 0.846 | 5 | 15 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B44:26 | CELSYGSVY | 0.9967 | 0.9075 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B44:07 | CELSYGSVY | 0.9967 | 0.9075 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B44:13 | CELSYGSVY | 0.9967 | 0.9075 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:04 | CELSYGSVY | 0.9967 | 0.9375 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:07 | CELSYGSVY | 0.9962 | 0.9105 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:08 | CELSYGSVY | 0.9958 | 0.8534 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:05 | CELSYGSVY | 0.9957 | 0.933 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:06 | CELSYGSVY | 0.9938 | 0.9364 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:03 | CELSYGSVY | 0.9718 | 0.9293 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:11 | CELSYGSVY | 0.836 | 0.882 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B35:28 | CELSYGSVY | 0.6954 | 0.7624 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B35:20 | CELSYGSVY | 0.6433 | 0.7858 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B15:53 | CELSYGSVY | 0.3226 | 0.6679 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B48:02 | CELSYGSVY | 0.1429 | 0.7402 | 10 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B27:08 | ARGGICELSY | 0.9996 | 0.7308 | 5 | 15 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B27:10 | ARGGICELSY | 0.9996 | 0.8623 | 5 | 15 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B15:53 | ICELSYGSVY | 0.7771 | 0.6258 | 9 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:11 | ICELSYGSVY | 0.628 | 0.6346 | 9 | 19 |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 | HLA-B18:05 | ICELSYGSVY | 0.4715 | 0.7471 | 9 | 19 |
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Potential FusionNeoAntigen Information of RAPGEF5-STK4 in HLA II |
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![]() * We used NetMHCIIpan v4.1 (%rank<0.5). |
Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA II | FusionNeoAntigen peptide | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Fusion breakpoint peptide structures of RAPGEF5-STK4 |
![]() * The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA. |
File name | BPseq | Hgene | Tgene | Hchr | Hbp | Tchr | Tbp | AAlen |
7864 | RGGICELSYGSVYK | RAPGEF5 | STK4 | chr7 | 22347958 | chr20 | 43607084 | 534 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RAPGEF5-STK4 |
![]() * We used Glide to predict the interaction between HLAs and neoantigens. |
HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
HLA-B14:02 | 3BVN | 7864 | RGGICELSYGSVYK | -7.15543 | -7.26883 |
HLA-B14:02 | 3BVN | 7864 | RGGICELSYGSVYK | -4.77435 | -5.80965 |
HLA-B52:01 | 3W39 | 7864 | RGGICELSYGSVYK | -6.80875 | -6.92215 |
HLA-B52:01 | 3W39 | 7864 | RGGICELSYGSVYK | -4.20386 | -5.23916 |
HLA-A11:01 | 4UQ2 | 7864 | RGGICELSYGSVYK | -7.5194 | -8.5547 |
HLA-A11:01 | 4UQ2 | 7864 | RGGICELSYGSVYK | -6.9601 | -7.0735 |
HLA-A24:02 | 5HGA | 7864 | RGGICELSYGSVYK | -7.52403 | -7.63743 |
HLA-A24:02 | 5HGA | 7864 | RGGICELSYGSVYK | -5.82433 | -6.85963 |
HLA-B27:05 | 6PYJ | 7864 | RGGICELSYGSVYK | -3.28285 | -4.31815 |
HLA-B44:05 | 3DX8 | 7864 | RGGICELSYGSVYK | -5.91172 | -6.94702 |
HLA-B44:05 | 3DX8 | 7864 | RGGICELSYGSVYK | -4.24346 | -4.35686 |
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Vaccine Design for the FusionNeoAntigens of RAPGEF5-STK4 |
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Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 10 | 19 | CELSYGSVY | CTGTGAACTGTCCTATGGCAGCGTATA |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 5 | 15 | ARGGICELSY | TGCCAGAGGTGGCATCTGTGAACTGTCCTA |
RAPGEF5-STK4 | chr7 | 22347958 | chr20 | 43607084 | 9 | 19 | ICELSYGSVY | CATCTGTGAACTGTCCTATGGCAGCGTATA |
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Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide | FusionNEoAntigen RNA sequence |
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Information of the samples that have these potential fusion neoantigens of RAPGEF5-STK4 |
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Cancer type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
STAD | RAPGEF5-STK4 | chr7 | 22347958 | ENST00000344041 | chr20 | 43607084 | ENST00000372801 | TCGA-BR-8077-01A |
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Potential target of CAR-T therapy development for RAPGEF5-STK4 |
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![]() * Minus value of BPloci means that the break point is located before the CDS. |
- In-frame and retained 'Transmembrane'. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
![]() * We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image. |
Hgene | Hchr | Hbp | Henst | Tgene | Tchr | Tbp | Tenst | DeepLoc result |
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Related Drugs to RAPGEF5-STK4 |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to RAPGEF5-STK4 |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Disease | Source | PMID |
![]() (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |