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Center for Computational Systems Medicine level1
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:ADCY3-HADHA

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADCY3-HADHA
FusionPDB ID: 2228
FusionGDB2.0 ID: 2228
HgeneTgene
Gene symbol

ADCY3

HADHA

Gene ID

114

3030

Gene nameadenylate cyclase 8hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha
SynonymsAC8|ADCY3|HBAC1ECHA|GBP|HADH|LCEH|LCHAD|MTPA|TP-ALPHA
Cytomap

8q24.22

2p23.3

Type of geneprotein-codingprotein-coding
Descriptionadenylate cyclase type 8ATP pyrophosphate-lyase 8HEL-S-172mPadenylate cyclase 8 (brain)adenylate cyclase type VIIIadenylyl cyclase 8adenylyl cyclase-8, brainca(2+)/calmodulin-activated adenylyl cyclaseepididymis secretory sperm binding protein Li trifunctional enzyme subunit alpha, mitochondrial3-ketoacyl-Coenzyme A (CoA) thiolase, alpha subunit3-oxoacyl-CoA thiolase78 kDa gastrin-binding proteingastrin-binding proteinhydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (
Modification date2020031320200313
UniProtAcc

O60266

P40939

Ensembl transtripts involved in fusion geneENST idsENST00000260600, ENST00000405392, 
ENST00000450524, 
ENST00000457468, 
ENST00000461025, ENST00000380649, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 5=2107 X 6 X 7=294
# samples 79
** MAII scorelog2(7/210*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/294*10)=-1.70781924850669
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: ADCY3 [Title/Abstract] AND HADHA [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADCY3(25141182)-HADHA(26417507), # samples:1
Anticipated loss of major functional domain due to fusion event.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
TgeneHADHA

GO:0035965

cardiolipin acyl-chain remodeling

23152787


check buttonFusion gene breakpoints across ADCY3 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across HADHA (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4LUSCTCGA-43-3394-01AADCY3chr2

25141182

-HADHAchr2

26417507

-


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Fusion ORF Analysis


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000260600ADCY3chr225141182-ENST00000380649HADHAchr226417507-281415278522198448

check buttonDeepORF 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.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000260600ENST00000380649ADCY3chr225141182-HADHAchr226417507-0.0021410160.99785894

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Fusion Amino Acid Sequences


check button 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

>2228_2228_1_ADCY3-HADHA_ADCY3_chr2_25141182_ENST00000260600_HADHA_chr2_26417507_ENST00000380649_length(amino acids)=448AA_BP=225
MPRNQGFSEPEYSAEYSAEYSVSLPSDPDRGVGRTHEISVRNSGSCLCLPRFMRLTFVPESLENLYQTYFKRQRHETLLVLVVFAALFDC
YVVVMCAVVFSSDKLASLAVAGIGLVLDIILFVLCKKGLLPDRVTRRVLPYVLWLLITAQIFSYLGLNFARAHAASDTVGWQVFFVFSFF
ITLPLSLSPIVIISVVSCVVHTLVLGVTVAQQQQEELKGMQLLREDGPGFYTTRCLAPMMSEVIRILQEGVDPKKLDSLTTSFGFPVGAA
TLVDEVGVDVAKHVAEDLGKVFGERFGGGNPELLTQMVSKGFLGRKSGKGFYIYQEGVKRKDLNSDMDSILASLKLPPKSEVSSDEDIQF

--------------------------------------------------------------

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Fusion Protein Functional Features


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr2:25141182/chr2:26417507)
- 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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
ADCY3

O60266

HADHA

P40939

FUNCTION: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis. Required for the perception of odorants. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet. {ECO:0000250|UniProtKB:Q8VHH7}.FUNCTION: Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:8135828, PubMed:1550553, 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 described here carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA thiolase activity (PubMed:8135828, PubMed:29915090, PubMed:30850536). Independently of the subunit beta, the trifunctional enzyme subunit alpha/HADHA also has a monolysocardiolipin acyltransferase activity (PubMed:23152787). It acylates monolysocardiolipin into cardiolipin, a major mitochondrial membrane phospholipid which plays a key role in apoptosis and supports mitochondrial respiratory chain complexes in the generation of ATP (PubMed:23152787). Allows the acylation of monolysocardiolipin with different acyl-CoA substrates including oleoyl-CoA for which it displays the highest activity (PubMed:23152787). {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:23152787, ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:8135828, ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536}.

check buttonRetention 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

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-1211_79225.01145.0Topological domainCytoplasmic
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121105_125225.01145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121139_159225.01145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121173_193225.01145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-12180_100225.01145.0TransmembraneHelical

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-1211062_1064225.01145.0Nucleotide bindingATP
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-1211069_1073225.01145.0Nucleotide bindingATP
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121324_329225.01145.0Nucleotide bindingATP
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121366_368225.01145.0Nucleotide bindingATP
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121402_632225.01145.0Topological domainCytoplasmic
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121854_1144225.01145.0Topological domainCytoplasmic
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121226_246225.01145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121381_401225.01145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121633_653225.01145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121664_684225.01145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121708_728225.01145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121754_774225.01145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121775_795225.01145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121833_853225.01145.0TransmembraneHelical


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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
ADCY3
HADHA


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to ADCY3-HADHA


check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to ADCY3-HADHA


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource