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Fusion Protein:AHCYL1-DENND2D |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: AHCYL1-DENND2D | FusionPDB ID: 3049 | FusionGDB2.0 ID: 3049 | Hgene | Tgene | Gene symbol | AHCYL1 | DENND2D | Gene ID | 10768 | 79961 |
| Gene name | adenosylhomocysteinase like 1 | DENN domain containing 2D | |
| Synonyms | DCAL|IRBIT|PPP1R78|PRO0233|XPVKONA | - | |
| Cytomap | 1p13.3 | 1p13.3-p13.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | S-adenosylhomocysteine hydrolase-like protein 1DC-expressed AHCY-like moleculeIP(3)Rs binding protein released with IP(3)S-adenosyl homocysteine hydrolase homologS-adenosyl-L-homocysteine hydrolase 2adenosylhomocysteinase 2adoHcyase 2dendritic cell | DENN domain-containing protein 2DDENN/MADD domain containing 2DRP5-1180E21.2 | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | O43865 | Q9H6A0 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000475081, ENST00000369799, ENST00000359172, ENST00000393614, | ENST00000357640, ENST00000369752, ENST00000473682, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 12 X 9 X 4=432 | 3 X 3 X 2=18 |
| # samples | 14 | 3 | |
| ** MAII score | log2(14/432*10)=-1.6256044852185 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(3/18*10)=0.736965594166206 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: AHCYL1 [Title/Abstract] AND DENND2D [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | AHCYL1(110527794)-DENND2D(111737348), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | AHCYL1-DENND2D 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. AHCYL1-DENND2D 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. AHCYL1-DENND2D 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. AHCYL1-DENND2D 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 | AHCYL1 | GO:0006378 | mRNA polyadenylation | 19224921 |
| Hgene | AHCYL1 | GO:0031440 | regulation of mRNA 3'-end processing | 19224921 |
| Hgene | AHCYL1 | GO:0038166 | angiotensin-activated signaling pathway | 20584908 |
| Hgene | AHCYL1 | GO:0051592 | response to calcium ion | 18829453 |
| Fusion gene breakpoints across AHCYL1 (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 DENND2D (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 Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| 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. |
| Source | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | BRCA | TCGA-E9-A5FK-01A | AHCYL1 | chr1 | 110527794 | - | DENND2D | chr1 | 111737348 | - |
| ChimerDB4 | BRCA | TCGA-E9-A5FK-01A | AHCYL1 | chr1 | 110527794 | + | DENND2D | chr1 | 111737348 | - |
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Fusion ORF Analysis |
| 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) |
| ENST00000369799 | AHCYL1 | chr1 | 110527794 | + | ENST00000357640 | DENND2D | chr1 | 111737348 | - | 1689 | 487 | 40 | 1257 | 405 |
| ENST00000369799 | AHCYL1 | chr1 | 110527794 | + | ENST00000369752 | DENND2D | chr1 | 111737348 | - | 1689 | 487 | 40 | 1257 | 405 |
| 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 |
| ENST00000369799 | ENST00000357640 | AHCYL1 | chr1 | 110527794 | + | DENND2D | chr1 | 111737348 | - | 0.005534144 | 0.9944659 |
| ENST00000369799 | ENST00000369752 | AHCYL1 | chr1 | 110527794 | + | DENND2D | chr1 | 111737348 | - | 0.005534144 | 0.9944659 |
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Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >3049_3049_1_AHCYL1-DENND2D_AHCYL1_chr1_110527794_ENST00000369799_DENND2D_chr1_111737348_ENST00000357640_length(amino acids)=405AA_BP=149 MPVLDVASPPSTLALRACLRTAEVAARAGRSSELLFWFSCGRRRCPAALGCRTDKAWATAPQKPTQLDAGAGRRVGDRVSEGAARAGGRA PEGERGGGGGSAAGRAGRGMSMPDAMPLPGVGEELKQAKEIEDAEKYSFMATVTKAPKKFISLTRPLDSHLEHVDFSSLLHCLSFEQILQ IFASAVLERKIIFLAEGLSTLSQCIHAAAALLYPFSWAHTYIPVVPESLLATVCCPTPFMVGVQMRFQQEVMDSPMEEVLLVNLCEGTFL MSVGDEKDILPPKLQDDILDSLGQGINELKTAEQINEHVSGPFVQFFVKIVGHYASYIKREANGQGHFQERSFCKALTSKTNRRFVKKFV -------------------------------------------------------------- >3049_3049_2_AHCYL1-DENND2D_AHCYL1_chr1_110527794_ENST00000369799_DENND2D_chr1_111737348_ENST00000369752_length(amino acids)=405AA_BP=149 MPVLDVASPPSTLALRACLRTAEVAARAGRSSELLFWFSCGRRRCPAALGCRTDKAWATAPQKPTQLDAGAGRRVGDRVSEGAARAGGRA PEGERGGGGGSAAGRAGRGMSMPDAMPLPGVGEELKQAKEIEDAEKYSFMATVTKAPKKFISLTRPLDSHLEHVDFSSLLHCLSFEQILQ IFASAVLERKIIFLAEGLSTLSQCIHAAAALLYPFSWAHTYIPVVPESLLATVCCPTPFMVGVQMRFQQEVMDSPMEEVLLVNLCEGTFL MSVGDEKDILPPKLQDDILDSLGQGINELKTAEQINEHVSGPFVQFFVKIVGHYASYIKREANGQGHFQERSFCKALTSKTNRRFVKKFV -------------------------------------------------------------- |
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Fusion Protein Functional Features |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:110527794/chr1:111737348) - 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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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| AHCYL1 | DENND2D |
| FUNCTION: Multifaceted cellular regulator which coordinates several essential cellular functions including regulation of epithelial HCO3(-) and fluid secretion, mRNA processing and DNA replication. Regulates ITPR1 sensitivity to inositol 1,4,5-trisphosphate, competing for the common binding site and acting as endogenous 'pseudoligand' whose inhibitory activity can be modulated by its phosphorylation status. Promotes the formation of contact points between the endoplasmic reticulum (ER) and mitochondria, facilitating transfer of Ca(2+) from the ER to mitochondria (PubMed:27995898). Under normal cellular conditions, functions cooperatively with BCL2L10 to limit ITPR1-mediated Ca(2+) release but, under apoptotic stress conditions, dephosphorylated which promotes dissociation of both AHCYL1 and BCL2L10 from mitochondria-associated endoplasmic reticulum membranes, inhibits BCL2L10 interaction with ITPR1 and leads to increased Ca(2+) transfer to mitochondria which promotes apoptosis (PubMed:27995898). In the pancreatic and salivary ducts, at resting state, attenuates inositol 1,4,5-trisphosphate-induced calcium release by interacting with ITPR1 (PubMed:16793548). When extracellular stimuli induce ITPR1 phosphorylation or inositol 1,4,5-trisphosphate production, dissociates from ITPR1 to interact with CFTR and SLC26A6, mediating their synergistic activation by calcium and cAMP that stimulates the epithelial secretion of electrolytes and fluid (By similarity). Also activates basolateral SLC4A4 isoform 1 to coordinate fluid and HCO3(-) secretion (PubMed:16769890). Inhibits the effect of STK39 on SLC4A4 and CFTR by recruiting PP1 phosphatase which activates SLC4A4, SLC26A6 and CFTR through dephosphorylation (By similarity). Mediates the induction of SLC9A3 surface expression produced by Angiotensin-2 (PubMed:20584908). Depending on the cell type, activates SLC9A3 in response to calcium or reverses SLC9A3R2-dependent calcium inhibition (PubMed:18829453). May modulate the polyadenylation state of specific mRNAs, both by controlling the subcellular location of FIP1L1 and by inhibiting PAPOLA activity, in response to a stimulus that alters its phosphorylation state (PubMed:19224921). Acts as a (dATP)-dependent inhibitor of ribonucleotide reductase large subunit RRM1, controlling the endogenous dNTP pool and ensuring normal cell cycle progression (PubMed:25237103). In vitro does not exhibit any S-adenosyl-L-homocysteine hydrolase activity (By similarity). {ECO:0000250|UniProtKB:B5DFN2, ECO:0000250|UniProtKB:Q80SW1, ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:19224921, ECO:0000269|PubMed:20584908, ECO:0000269|PubMed:25237103, ECO:0000269|PubMed:27995898}. | FUNCTION: Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. {ECO:0000269|PubMed:20937701}. |
| 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. |
| - 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 |
| Tgene | DENND2D | chr1:110527794 | chr1:111737348 | ENST00000357640 | 5 | 12 | 226_359 | 215.0 | 472.0 | Domain | cDENN | |
| Tgene | DENND2D | chr1:110527794 | chr1:111737348 | ENST00000357640 | 5 | 12 | 361_445 | 215.0 | 472.0 | Domain | dDENN | |
| Tgene | DENND2D | chr1:110527794 | chr1:111737348 | ENST00000369752 | 5 | 12 | 226_359 | 212.0 | 469.0 | Domain | cDENN | |
| Tgene | DENND2D | chr1:110527794 | chr1:111737348 | ENST00000369752 | 5 | 12 | 361_445 | 212.0 | 469.0 | Domain | dDENN |
| - 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 |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000359172 | + | 1 | 17 | 318_322 | 0 | 484.0 | Nucleotide binding | NAD |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000359172 | + | 1 | 17 | 397_399 | 0 | 484.0 | Nucleotide binding | NAD |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000369799 | + | 1 | 17 | 318_322 | 40.0 | 531.0 | Nucleotide binding | NAD |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000369799 | + | 1 | 17 | 397_399 | 40.0 | 531.0 | Nucleotide binding | NAD |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000393614 | + | 1 | 17 | 318_322 | 0 | 484.0 | Nucleotide binding | NAD |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000393614 | + | 1 | 17 | 397_399 | 0 | 484.0 | Nucleotide binding | NAD |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000359172 | + | 1 | 17 | 281_448 | 0 | 484.0 | Region | NAD binding |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000359172 | + | 1 | 17 | 520_530 | 0 | 484.0 | Region | PDZ-binding |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000359172 | + | 1 | 17 | 65_92 | 0 | 484.0 | Region | PEST |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000369799 | + | 1 | 17 | 281_448 | 40.0 | 531.0 | Region | NAD binding |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000369799 | + | 1 | 17 | 520_530 | 40.0 | 531.0 | Region | PDZ-binding |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000369799 | + | 1 | 17 | 65_92 | 40.0 | 531.0 | Region | PEST |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000393614 | + | 1 | 17 | 281_448 | 0 | 484.0 | Region | NAD binding |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000393614 | + | 1 | 17 | 520_530 | 0 | 484.0 | Region | PDZ-binding |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000393614 | + | 1 | 17 | 65_92 | 0 | 484.0 | Region | PEST |
| Tgene | DENND2D | chr1:110527794 | chr1:111737348 | ENST00000357640 | 5 | 12 | 55_204 | 215.0 | 472.0 | Domain | uDENN | |
| Tgene | DENND2D | chr1:110527794 | chr1:111737348 | ENST00000369752 | 5 | 12 | 55_204 | 212.0 | 469.0 | Domain | uDENN |
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Fusion Protein-Protein Interaction |
| 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 from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| AHCYL1 | |
| DENND2D |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000359172 | + | 1 | 17 | 138_201 | 0 | 484.0 | BCL2L10 |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000369799 | + | 1 | 17 | 138_201 | 40.0 | 531.0 | BCL2L10 |
| Hgene | AHCYL1 | chr1:110527794 | chr1:111737348 | ENST00000393614 | + | 1 | 17 | 138_201 | 0 | 484.0 | BCL2L10 |
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Related Drugs to AHCYL1-DENND2D |
| 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 AHCYL1-DENND2D |
| 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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