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Fusion Protein:HADH-NCL |
Fusion Protein Summary |
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Fusion partner gene information | Fusion gene name: HADH-NCL | FusionPDB ID: 35586 | FusionGDB2.0 ID: 35586 | Hgene | Tgene | Gene symbol | HADH | NCL | Gene ID | 3033 | 80331 |
Gene name | hydroxyacyl-CoA dehydrogenase | DnaJ heat shock protein family (Hsp40) member C5 | |
Synonyms | HAD|HADH1|HADHSC|HCDH|HHF4|MSCHAD|SCHAD | CLN4|CLN4B|CSP|DNAJC5A|NCL|mir-941-2|mir-941-3|mir-941-4|mir-941-5 | |
Cytomap | 4q25 | 20q13.33 | |
Type of gene | protein-coding | protein-coding | |
Description | hydroxyacyl-coenzyme A dehydrogenase, mitochondrialL-3-hydroxyacyl-Coenzyme A dehydrogenase, short chainmedium and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenaseshort-chain 3-hydroxyacyl-CoA dehydrogenasetestis secretory sperm-binding protein Li | dnaJ homolog subfamily C member 5DnaJ (Hsp40) homolog, subfamily C, member 5ceroid-lipofuscinosis neuronal protein 4cysteine string protein alpha | |
Modification date | 20200320 | 20200328 | |
UniProtAcc | P55084 | Q969V3 | |
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000510728, ENST00000454409, ENST00000505878, ENST00000603302, ENST00000309522, ENST00000403312, | ENST00000322723, |
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 7 X 6 X 3=126 | 20 X 21 X 7=2940 |
# samples | 7 | 23 | |
** MAII score | log2(7/126*10)=-0.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(23/2940*10)=-3.67611038877935 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
Context (manual curation of fusion genes in FusionPDB) | PubMed: HADH [Title/Abstract] AND NCL [Title/Abstract] AND fusion [Title/Abstract] | ||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | HADH(108955491)-NCL(232322411), # samples:2 | ||
Anticipated loss of major functional domain due to fusion event. | HADH-NCL 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. HADH-NCL 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. HADH-NCL seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF. HADH-NCL seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF. HADH-NCL seems lost the major protein functional domain in Tgene partner, which is a essential gene 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) |
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Partner | Gene | GO ID | GO term | PubMed ID |
![]() * 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 Gene Sample Information |
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![]() * 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 |
ChiTaRS5.0 | N/A | BF348759 | HADH | chr4 | 108955491 | + | NCL | chr2 | 232322411 | - |
ChiTaRS5.0 | N/A | BQ314823 | HADH | chr4 | 108955491 | + | NCL | chr2 | 232322411 | - |
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Fusion ORF Analysis |
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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) |
ENST00000403312 | HADH | chr4 | 108955491 | + | ENST00000322723 | NCL | chr2 | 232322411 | - | 4340 | 1936 | 42 | 1139 | 365 |
ENST00000309522 | HADH | chr4 | 108955491 | + | ENST00000322723 | NCL | chr2 | 232322411 | - | 4219 | 1815 | 41 | 1018 | 325 |
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Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
ENST00000403312 | ENST00000322723 | HADH | chr4 | 108955491 | + | NCL | chr2 | 232322411 | - | 0.00091144 | 0.9990885 |
ENST00000309522 | ENST00000322723 | HADH | chr4 | 108955491 | + | NCL | chr2 | 232322411 | - | 0.00042435 | 0.9995757 |
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Fusion Amino Acid Sequences |
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>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >35586_35586_1_HADH-NCL_HADH_chr4_108955491_ENST00000309522_NCL_chr2_232322411_ENST00000322723_length(amino acids)=325AA_BP= MQGRVGPRPQSLAFRGCPPRASSLPGSPRCRRRCHTMAFVTRQFMRSVSSSSTASASAKKIIVKHVTVIGGGLMGAGIAQVAAATGHTVV LVDQTEDILAKSKKGIEESLRKVAKKKFAENLKAGDEFVEKTLSTIATSTDAASVVHSTDLVVEAIVENLKVKNELFKRLDKFAAEHTIF ASNTSSLQITSIANATTRQDRFAGLHFFNPVPVMKLVEVIKTPMTSQKTFESLVDFSKALGKHPVSCKDTPGFIVNRLLVPYLMEAIRLY -------------------------------------------------------------- >35586_35586_2_HADH-NCL_HADH_chr4_108955491_ENST00000403312_NCL_chr2_232322411_ENST00000322723_length(amino acids)=365AA_BP= MGRAGLEAPPPPCGVTGTPGARGLQGRVGPRPQSLAFRGCPPRASSLPGSPRCRRRCHTMAFVTRQFMRSVSSSSTASASAKKIIVKHVT VIGGGLMGAGIAQVAAATGHTVVLVDQTEDILAKSKKGIEESLRKVAKKKFAENLKAGDEFVEKTLSTIATSTDAASVVHSTDLVVEAIV ENLKVKNELFKRLDKFAAEHTIFASNTSSLQITSIANATTRQDRFAGLHFFNPVPVMKLVEVIKTPMTSQKTFESLVDFSKALGKHPVSC KDTPGFIVNRLLVPYLMEAIRLYERDFQTCGDSNSGLGFSLKGDASKEDIDTAMKLGAGYPMGPFELLDYVGLDTTKFIVDEDFTNTSDV -------------------------------------------------------------- |
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Fusion Protein Functional Features |
![]() Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr4:108955491/chr2:232322411) - 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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Hgene | Tgene |
HADH | NCL |
FUNCTION: Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:8135828, PubMed:29915090, PubMed:30850536). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA (PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids (PubMed:30850536). Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities, while the trifunctional enzyme subunit beta/HADHB described here bears the 3-ketoacyl-CoA thiolase activity (PubMed:8135828, PubMed:29915090, PubMed:30850536). {ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:8135828, ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536}. | FUNCTION: Component of a ribosome-associated translocon complex involved in multi-pass membrane protein transport into the endoplasmic reticulum (ER) membrane and biogenesis (PubMed:32820719). May antagonize Nodal signaling and subsequent organization of axial structures during mesodermal patterning, via its interaction with NOMO (By similarity). {ECO:0000250|UniProtKB:Q6NZ07, ECO:0000269|PubMed:32820719}. |
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- 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 | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 143_171 | 0 | 711.0 | Compositional bias | Note=Asp/Glu-rich (acidic) | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 185_209 | 0 | 711.0 | Compositional bias | Note=Asp/Glu-rich (acidic) | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 234_271 | 0 | 711.0 | Compositional bias | Note=Asp/Glu-rich (acidic) | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 649_698 | 0 | 711.0 | Compositional bias | Note=Arg/Gly/Phe-rich | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 307_383 | 0 | 711.0 | Domain | RRM 1 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 393_466 | 0 | 711.0 | Domain | RRM 2 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 486_560 | 0 | 711.0 | Domain | RRM 3 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 572_647 | 0 | 711.0 | Domain | RRM 4 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 58_135 | 0 | 711.0 | Region | Note=8 X 8 AA tandem repeats of X-T-P-X-K-K-X-X | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 105_112 | 0 | 711.0 | Repeat | Note=6 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 120_127 | 0 | 711.0 | Repeat | Note=7 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 128_135 | 0 | 711.0 | Repeat | Note=8 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 58_65 | 0 | 711.0 | Repeat | Note=1 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 75_82 | 0 | 711.0 | Repeat | Note=2 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 83_90 | 0 | 711.0 | Repeat | Note=3 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 91_98 | 0 | 711.0 | Repeat | Note=4 | |
Tgene | NCL | chr4:108955491 | chr2:232322411 | ENST00000322723 | 0 | 14 | 99_104 | 0 | 711.0 | Repeat | Note=5%3B truncated |
- 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 | HADH | chr4:108955491 | chr2:232322411 | ENST00000309522 | + | 1 | 8 | 34_39 | 0 | 315.0 | Nucleotide binding | NAD |
Hgene | HADH | chr4:108955491 | chr2:232322411 | ENST00000603302 | + | 1 | 9 | 34_39 | 0 | 332.0 | Nucleotide binding | NAD |
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Fusion Protein Structures |
![]() * Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
Fusion protein PDB link (fusion AA seq ID in FusionPDB) | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | AA seq | Len(AA seq) |
PDB file >>>719_HADH_108955491_NCL_232322411_ranked_0.pdb | HADH | 108955491 | 108955491 | ENST00000322723 | NCL | chr2 | 232322411 | - | MGRAGLEAPPPPCGVTGTPGARGLQGRVGPRPQSLAFRGCPPRASSLPGSPRCRRRCHTMAFVTRQFMRSVSSSSTASASAKKIIVKHVT VIGGGLMGAGIAQVAAATGHTVVLVDQTEDILAKSKKGIEESLRKVAKKKFAENLKAGDEFVEKTLSTIATSTDAASVVHSTDLVVEAIV ENLKVKNELFKRLDKFAAEHTIFASNTSSLQITSIANATTRQDRFAGLHFFNPVPVMKLVEVIKTPMTSQKTFESLVDFSKALGKHPVSC KDTPGFIVNRLLVPYLMEAIRLYERDFQTCGDSNSGLGFSLKGDASKEDIDTAMKLGAGYPMGPFELLDYVGLDTTKFIVDEDFTNTSDV | 365 |
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pLDDT score distribution |
![]() * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
HADH_pLDDT.png![]() |
NCL_pLDDT.png![]() |
![]() * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
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Ramachandran Plot of Fusion Protein Structure |
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Fusion AA seq ID in FusionPDB and their Ramachandran plots |
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Fusion Protein-Protein Interaction |
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Gene | PPI interactors |
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Gene | STRING network |
HADH | |
NCL |
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Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
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Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs to HADH-NCL |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to HADH-NCL |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Disease | Source | PMID |
![]() (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |