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Fusion Protein:HNRNPA2B1-CALM1 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: HNRNPA2B1-CALM1 | FusionPDB ID: 37063 | FusionGDB2.0 ID: 37063 | Hgene | Tgene | Gene symbol | HNRNPA2B1 | CALM1 | Gene ID | 3181 | 801 |
| Gene name | heterogeneous nuclear ribonucleoprotein A2/B1 | calmodulin 1 | |
| Synonyms | HNRNPA2|HNRNPB1|HNRPA2|HNRPA2B1|HNRPB1|IBMPFD2|RNPA2|SNRPB1 | CALML2|CAM2|CAM3|CAMB|CAMC|CAMI|CAMIII|CPVT4|DD132|LQT14|PHKD|caM | |
| Cytomap | 7p15.2 | 14q32.11 | |
| Type of gene | protein-coding | protein-coding | |
| Description | heterogeneous nuclear ribonucleoproteins A2/B1HNRNPA2B1/MYC fusionepididymis secretory sperm binding proteinhnRNP A2 / hnRNP B1nuclear ribonucleoprotein particle A2 protein | calmodulin-1Calmodulin-2Calmodulin-3calmodulin 1 (phosphorylase kinase, delta)phosphorylase kinase subunit deltaphosphorylase kinase, delta subunitprepro-calmodulin 1 | |
| Modification date | 20200314 | 20200329 | |
| UniProtAcc | P22626 Main function of 5'-partner protein: FUNCTION: Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-dependent and serves to condense and stabilize the transcripts and minimize tangling and knotting. Packaging plays a role in various processes such as transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs (PubMed:19099192). Forms hnRNP particles with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. Involved in transport of specific mRNAs to the cytoplasm in oligodendrocytes and neurons: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) or the A2RE11 (derivative 11 nucleotide oligonucleotide) sequence motifs present on some mRNAs, and promotes their transport to the cytoplasm (PubMed:10567417). Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion (By similarity). Also binds other RNA molecules, such as primary miRNA (pri-miRNAs): acts as a nuclear 'reader' of the N6-methyladenosine (m6A) mark by specifically recognizing and binding a subset of nuclear m6A-containing pri-miRNAs. Binding to m6A-containing pri-miRNAs promotes pri-miRNA processing by enhancing binding of DGCR8 to pri-miRNA transcripts (PubMed:26321680). Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs (PubMed:24356509). Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A-containing pre-mRNAs (PubMed:26321680). Plays also a role in the activation of the innate immune response (PubMed:31320558). Mechanistically, senses the presence of viral DNA in the nucleus, homodimerizes and is demethylated by JMJD6 (PubMed:31320558). In turn, translocates to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to interferon alpha/beta production (PubMed:31320558). {ECO:0000250|UniProtKB:A7VJC2, ECO:0000269|PubMed:10567417, ECO:0000269|PubMed:24356509, ECO:0000269|PubMed:26321680, ECO:0000303|PubMed:19099192}.; FUNCTION: (Microbial infection) Involved in the transport of HIV-1 genomic RNA out of the nucleus, to the microtubule organizing center (MTOC), and then from the MTOC to the cytoplasm: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) sequence motifs present on HIV-1 genomic RNA, and promotes its transport. {ECO:0000269|PubMed:15294897, ECO:0000269|PubMed:17004321}. | P0DP23 Main function of 5'-partner protein: FUNCTION: Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endomplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335). {ECO:0000269|PubMed:16760425, ECO:0000269|PubMed:23893133, ECO:0000269|PubMed:26969752, ECO:0000269|PubMed:27165696, ECO:0000269|PubMed:28890335, ECO:0000269|PubMed:31454269}.; FUNCTION: (Microbial infection) Required for Legionella pneumophila SidJ glutamylase activity. {ECO:0000269|PubMed:31330532}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000354667, ENST00000356674, ENST00000476233, | ENST00000544280, ENST00000553542, ENST00000555132, ENST00000356978, ENST00000447653, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 43 X 37 X 14=22274 | 13 X 14 X 3=546 |
| # samples | 50 | 15 | |
| ** MAII score | log2(50/22274*10)=-5.47728875772656 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(15/546*10)=-1.86393845042397 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: HNRNPA2B1 [Title/Abstract] AND CALM1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: HNRNPA2B1 [Title/Abstract] AND CALM1 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | HNRNPA2B1(26240192)-CALM1(90866409), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | HNRNPA2B1-CALM1 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. HNRNPA2B1-CALM1 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) |
| Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Hgene | HNRNPA2B1 | GO:0006397 | mRNA processing | 2557628 |
| Hgene | HNRNPA2B1 | GO:0006406 | mRNA export from nucleus | 10567417 |
| Hgene | HNRNPA2B1 | GO:0031053 | primary miRNA processing | 26321680 |
| Hgene | HNRNPA2B1 | GO:0050658 | RNA transport | 17004321 |
| Hgene | HNRNPA2B1 | GO:1990428 | miRNA transport | 24356509 |
| Tgene | CALM1 | GO:0010880 | regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum | 20226167 |
| Tgene | CALM1 | GO:0032516 | positive regulation of phosphoprotein phosphatase activity | 8631777 |
| Tgene | CALM1 | GO:0035307 | positive regulation of protein dephosphorylation | 8631777 |
| Tgene | CALM1 | GO:0051343 | positive regulation of cyclic-nucleotide phosphodiesterase activity | 8631777 |
| Tgene | CALM1 | GO:0051592 | response to calcium ion | 7607248 |
| Tgene | CALM1 | GO:0060314 | regulation of ryanodine-sensitive calcium-release channel activity | 22067155 |
| Tgene | CALM1 | GO:0060315 | negative regulation of ryanodine-sensitive calcium-release channel activity | 26164367 |
| Tgene | CALM1 | GO:0060316 | positive regulation of ryanodine-sensitive calcium-release channel activity | 20226167 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr7:26240192/chr14:90866409) - 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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| Retention analysis results 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, are available here. |
| Fusion gene breakpoints across HNRNPA2B1 (5'-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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| Fusion gene breakpoints across CALM1 (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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Fusion Amino Acid Sequences |
| Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
| 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) |
| ENST00000354667 | HNRNPA2B1 | chr7 | 26240192 | - | ENST00000356978 | CALM1 | chr14 | 90866409 | + | 4166 | 175 | 169 | 621 | 150 |
| ENST00000354667 | HNRNPA2B1 | chr7 | 26240192 | - | ENST00000447653 | CALM1 | chr14 | 90866409 | + | 977 | 175 | 169 | 621 | 150 |
| ENST00000356674 | HNRNPA2B1 | chr7 | 26240192 | - | ENST00000356978 | CALM1 | chr14 | 90866409 | + | 4166 | 175 | 169 | 621 | 150 |
| ENST00000356674 | HNRNPA2B1 | chr7 | 26240192 | - | ENST00000447653 | CALM1 | chr14 | 90866409 | + | 977 | 175 | 169 | 621 | 150 |
| DeepORF 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. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
| ENST00000354667 | ENST00000356978 | HNRNPA2B1 | chr7 | 26240192 | - | CALM1 | chr14 | 90866409 | + | 0.000774509 | 0.9992255 |
| ENST00000354667 | ENST00000447653 | HNRNPA2B1 | chr7 | 26240192 | - | CALM1 | chr14 | 90866409 | + | 0.001439246 | 0.9985607 |
| ENST00000356674 | ENST00000356978 | HNRNPA2B1 | chr7 | 26240192 | - | CALM1 | chr14 | 90866409 | + | 0.000774509 | 0.9992255 |
| ENST00000356674 | ENST00000447653 | HNRNPA2B1 | chr7 | 26240192 | - | CALM1 | chr14 | 90866409 | + | 0.001439246 | 0.9985607 |
| Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones. |
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 HNRNPA2B1-CALM1 |
| +/-13 AA sequence from the breakpoints of the fusion protein sequences. |
| Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
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Potential FusionNeoAntigen Information of HNRNPA2B1-CALM1 in HLA I |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * 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) |
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Potential FusionNeoAntigen Information of HNRNPA2B1-CALM1 in HLA II |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * 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 HNRNPA2B1-CALM1 |
| 3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens * 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. |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HNRNPA2B1-CALM1 |
| Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens * We used Glide to predict the interaction between HLAs and neoantigens. |
| HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
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Vaccine Design for the FusionNeoAntigens of HNRNPA2B1-CALM1 |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs. |
| 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 HNRNPA2B1-CALM1 |
| These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens. |
| Cancer type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
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Potential target of CAR-T therapy development for HNRNPA2B1-CALM1 |
| Predicted 3D structure. We used RoseTTAFold. |
| Retention 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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features * 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 |
| Subcellular localization prediction of the transmembrane domain retained fusion proteins * 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 HNRNPA2B1-CALM1 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to HNRNPA2B1-CALM1 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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