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Fusion gene ID: 22608 |
FusionGeneSummary for MSH2_SPTLC1 |
 Fusion gene summary |
| Fusion gene information | Fusion gene name: MSH2_SPTLC1 | Fusion gene ID: 22608 | Hgene | Tgene | Gene symbol | MSH2 | SPTLC1 | Gene ID | 4436 | 10558 |
| Gene name | mutS homolog 2 | serine palmitoyltransferase long chain base subunit 1 | |
| Synonyms | COCA1|FCC1|HNPCC|HNPCC1|LCFS2 | HSAN1|HSN1|LBC1|LCB1|SPT1|SPTI | |
| Cytomap | 2p21-p16.3 | 9q22.31 | |
| Type of gene | protein-coding | protein-coding | |
| Description | DNA mismatch repair protein Msh2hMSH2mutS homolog 2, colon cancer, nonpolyposis type 1 | serine palmitoyltransferase 1LCB 1SPT 1long chain base biosynthesis protein 1serine C-palmitoyltransferaseserine-palmitoyl-CoA transferase 1 | |
| Modification date | 20180523 | 20180519 | |
| UniProtAcc | P43246 | O15269 | |
| Ensembl transtripts involved in fusion gene | ENST00000233146, ENST00000543555, ENST00000406134, ENST00000461394, | ENST00000262554, ENST00000482632, ENST00000337841, | |
| Fusion gene scores | * DoF score | 8 X 6 X 8=384 | 6 X 6 X 2=72 |
| # samples | 10 | 7 | |
| ** MAII score | log2(10/384*10)=-1.94110631094643 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(7/72*10)=-0.0406419844973459 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context | PubMed: MSH2 [Title/Abstract] AND SPTLC1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Functional or gene categories assigned by FusionGDB annotation | Tumor 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. DDR (DNA damage repair) gene involved fusion gene, retained protein feature but frameshift. | ||
| * 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 | MSH2 | GO:0006281 | DNA repair | 8942985 |
| Hgene | MSH2 | GO:0006298 | mismatch repair | 7923193|11555625 |
| Hgene | MSH2 | GO:0006301 | postreplication repair | 7923193 |
| Hgene | MSH2 | GO:0045910 | negative regulation of DNA recombination | 17715146 |
| Hgene | MSH2 | GO:0051096 | positive regulation of helicase activity | 17715146 |
| Tgene | SPTLC1 | GO:0030148 | sphingolipid biosynthetic process | 25332431 |
| Tgene | SPTLC1 | GO:0046513 | ceramide biosynthetic process | 25691431 |
| Tgene | SPTLC1 | GO:1904504 | positive regulation of lipophagy | 25332431 |
| 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 type | Source | Cancer type | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| TCGA | RV | UCS | TCGA-N8-A4PM-01A | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| * LD: Li Ding group's fusion gene list RV: Roel Verhaak group's fusion gene list ChiTaRs fusion database |
| 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. |
| ORF | Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| Frame-shift | ENST00000233146 | ENST00000262554 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| 5CDS-intron | ENST00000233146 | ENST00000482632 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| 5CDS-intron | ENST00000233146 | ENST00000337841 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| Frame-shift | ENST00000543555 | ENST00000262554 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| 5CDS-intron | ENST00000543555 | ENST00000482632 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| 5CDS-intron | ENST00000543555 | ENST00000337841 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| Frame-shift | ENST00000406134 | ENST00000262554 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| 5CDS-intron | ENST00000406134 | ENST00000482632 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| 5CDS-intron | ENST00000406134 | ENST00000337841 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| intron-3CDS | ENST00000461394 | ENST00000262554 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| intron-intron | ENST00000461394 | ENST00000482632 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
| intron-intron | ENST00000461394 | ENST00000337841 | MSH2 | chr2 | 47672796 | + | SPTLC1 | chr9 | 94800647 | - |
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FusionProtFeatures for MSH2_SPTLC1 |
| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| MSH2 | SPTLC1 |
| Component of the post-replicative DNA mismatch repairsystem (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) whichbinds to DNA mismatches thereby initiating DNA repair. When bound,heterodimers bend the DNA helix and shields approximately 20 basepairs. MutS alpha recognizes single base mismatches anddinucleotide insertion-deletion loops (IDL) in the DNA. MutS betarecognizes larger insertion-deletion loops up to 13 nucleotideslong. After mismatch binding, MutS alpha or beta forms a ternarycomplex with the MutL alpha heterodimer, which is thought to beresponsible for directing the downstream MMR events, includingstrand discrimination, excision, and resynthesis. ATP binding andhydrolysis play a pivotal role in mismatch repair functions. TheATPase activity associated with MutS alpha regulates bindingsimilar to a molecular switch: mismatched DNA provokes ADP-->ATPexchange, resulting in a discernible conformational transitionthat converts MutS alpha into a sliding clamp capable ofhydrolysis-independent diffusion along the DNA backbone. Thistransition is crucial for mismatch repair. MutS alpha may alsoplay a role in DNA homologous recombination repair. In melanocytesmay modulate both UV-B-induced cell cycle regulation andapoptosis. {ECO:0000269|PubMed:10078208,ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730,ECO:0000269|PubMed:17611581, ECO:0000269|PubMed:21120944,ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679,ECO:0000269|PubMed:9822680}. | Serine palmitoyltransferase (SPT). The heterodimerformed with SPTLC2 or SPTLC3 constitutes the catalytic core. Thecomposition of the serine palmitoyltransferase (SPT) complexdetermines the substrate preference. The SPTLC1-SPTLC2-SPTSSAcomplex shows a strong preference for C16-CoA substrate, while theSPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA assubstrates, with a slight preference for C14-CoA. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoAsubstrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays anability to use a broader range of acyl-CoAs, without apparentpreference. {ECO:0000269|PubMed:19416851}. |
| 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, 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 . * 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. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| - In-frame and not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
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FusionGeneSequence for MSH2_SPTLC1 |
| 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 MSH2_SPTLC1 |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in . |
| Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160) |
| Hgene | Hgene's interactors | Tgene | Tgene's interactors |
| MSH2 | BRCA1, PTP4A3, BARD1, BLM, CHEK1, CHEK2, ATM, MLH1, MRE11A, NBN, RAD50, MSH6, RFC1, MSH3, ATR, MAX, MYC, ATRIP, PCNA, MSH2, EXO1, OTUB1, SLX4, PMS2, AIRE, PRKCZ, XPA, RPA4, MGMT, TP53, ESR1, ESR2, SNW1, CREBBP, FANCA, GRB7, RPP14, TK1, CDKN1A, SMN1, ANXA7, DTL, SMARCAD1, CDK9, NELFB, PMS1, RAD51, XRCC6, SIRT7, FANCD2, CDK2, HUS1, RAD1, RAD9A, MUTYH, SRSF5, SART1, SRSF11, SRSF7, IK, RBM25, SMARCA5, SRSF10, RPS24, TOP2B, SEPT9, RAD21, HNRNPD, SUPT16H, ERCC1, ERCC4, HDAC6, ATP6V1B2, CUL2, JUP, DPYSL3, XRCC5, NRD1, PDE3A, SEC23A, ST13, STAT3, SUPT5H, RPA3, RPA2, RPA1, POLK, REV1, CCDC8, SUMO2, SIRT6, ANXA6, DNAJC9, EIF3B, FEN1, AARS, CIAPIN1, DHX15, PFDN4, RECQL, RPLP0, RPS5, TRIP13, ZW10, NMD3, SNX27, TIPRL, TPP2, TPT1, NTRK1, CEP19, E2F3, CDC5L, RNF126, UBXN8, FAF2, USP10, ZNF746, CDC14B, RAF1, RPGRIP1L, BRIP1, TOP1, TOP2A, TOP3A, TRIM25, TES, MCM9, MCM8 | SPTLC1 | RGS20, C20orf24, MAGED1, ORMDL3, ATG4C, MYC, AUP1, ABCA1, CFTR, ADRB2, EGFR, FBXO6, JAK3, DYNLL1, MED12, NCSTN, TCEAL4, ARMC6, PTAR1, GTF2IRD1 |
| - Retained PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
| - Retained PPIs, but lost function due to frame-shift fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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RelatedDrugs for MSH2_SPTLC1 |
| Drugs targeting genes involved in this fusion gene. (DrugBank Version 5.1.0 2018-04-02) |
| Partner | Gene | UniProtAcc | DrugBank ID | Drug name | Drug activity | Drug type | Drug status |
| Tgene | SPTLC1 | O15269 | DB00114 | Pyridoxal Phosphate | Serine palmitoyltransferase 1 | small molecule | approved|investigational|nutraceutical |
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RelatedDiseases for MSH2_SPTLC1 |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
| Hgene | MSH2 | C2936783 | Colorectal cancer, hereditary nonpolyposis, type 1 | 48 | UNIPROT |
| Hgene | MSH2 | C0009405 | Hereditary Nonpolyposis Colorectal Neoplasms | 4 | CTD_human |
| Hgene | MSH2 | C0009404 | Colorectal Neoplasms | 1 | CTD_human |
| Hgene | MSH2 | C0919267 | ovarian neoplasm | 1 | CTD_human |
| Hgene | MSH2 | C2931459 | Lynch syndrome I (site-specific colonic cancer) | 1 | CTD_human |
| Tgene | SPTLC1 | C0020071 | Hereditary Sensory Autonomic Neuropathy, Type 1 | 4 | CTD_human;ORPHANET;UNIPROT |
Copyright 2018-Present -The University of Texas Health Science Center at Houston (UTHealth)
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