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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
	Related Drugs
	Related Diseases

Fusion gene:ADCY3-HADHA (FusionGDB2 ID:2228)

Fusion Gene Summary for ADCY3-HADHA

Fusion gene summary

Fusion gene information	Fusion gene name: ADCY3-HADHA
	Fusion gene ID: 2228
		Hgene	Tgene
	Gene symbol	ADCY3	HADHA
	Gene ID	114	3030
	Gene name	adenylate cyclase 8	hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha
	Synonyms	AC8\|ADCY3\|HBAC1	ECHA\|GBP\|HADH\|LCEH\|LCHAD\|MTPA\|TP-ALPHA
	Cytomap	8q24.22	2p23.3
	Type of gene	protein-coding	protein-coding
	Description	adenylate 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 date	20200313	20200313
	UniProtAcc	O60266	P40939
	Ensembl transtripts involved in fusion gene	ENST00000260600, ENST00000405392, ENST00000450524,	ENST00000457468, ENST00000461025, ENST00000380649,
Fusion gene scores	* DoF score	7 X 6 X 5=210	7 X 6 X 7=294
	# samples	7	9
	** MAII score	log2(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	PubMed: ADCY3 [Title/Abstract] AND HADHA [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	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)

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
Tgene	HADHA	GO:0035965	cardiolipin acyl-chain remodeling	23152787

Fusion 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.

Fusion 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.

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	LUSC	TCGA-43-3394-01A	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-

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Fusion Gene ORF analysis for ADCY3-HADHA

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
5CDS-intron	ENST00000260600	ENST00000457468	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-
5CDS-intron	ENST00000260600	ENST00000461025	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-
In-frame	ENST00000260600	ENST00000380649	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-
intron-3CDS	ENST00000405392	ENST00000380649	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-
intron-3CDS	ENST00000450524	ENST00000380649	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-
intron-intron	ENST00000405392	ENST00000457468	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-
intron-intron	ENST00000405392	ENST00000461025	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-
intron-intron	ENST00000450524	ENST00000457468	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-
intron-intron	ENST00000450524	ENST00000461025	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-

ORFfinder result based on the fusion transcript sequence of in-frame fusion genes.

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)

ENST00000260600

ADCY3

chr2

25141182

ENST00000380649

HADHA

chr2

26417507

2814

1527

852

2198

448

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
ENST00000260600	ENST00000380649	ADCY3	chr2	25141182	-	HADHA	chr2	26417507	-	0.002141016	0.99785894

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Fusion Genomic Features for ADCY3-HADHA

FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

1-p

p (fusion gene breakpoint)

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for ADCY3-HADHA

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.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
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}.

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
download page

* 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

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

1_79

225

1145.0

Topological domain

Cytoplasmic

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

105_125

225

1145.0

Transmembrane

Helical

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

139_159

225

1145.0

Transmembrane

Helical

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

173_193

225

1145.0

Transmembrane

Helical

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

80_100

225

1145.0

Transmembrane

Helical

- 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

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

1062_1064

225

1145.0

Nucleotide binding

ATP

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

1069_1073

225

1145.0

Nucleotide binding

ATP

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

324_329

225

1145.0

Nucleotide binding

ATP

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

366_368

225

1145.0

Nucleotide binding

ATP

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

402_632

225

1145.0

Topological domain

Cytoplasmic

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

854_1144

225

1145.0

Topological domain

Cytoplasmic

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

226_246

225

1145.0

Transmembrane

Helical

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

381_401

225

1145.0

Transmembrane

Helical

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

633_653

225

1145.0

Transmembrane

Helical

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

664_684

225

1145.0

Transmembrane

Helical

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

708_728

225

1145.0

Transmembrane

Helical

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

754_774

225

1145.0

Transmembrane

Helical

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

775_795

225

1145.0

Transmembrane

Helical

Hgene

ADCY3

chr2:25141182

chr2:26417507

ENST00000260600

833_853

225

1145.0

Transmembrane

Helical

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Fusion Gene Sequence for ADCY3-HADHA

For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>2228_2228_1_ADCY3-HADHA_ADCY3_chr2_25141182_ENST00000260600_HADHA_chr2_26417507_ENST00000380649_length(transcript)=2814nt_BP=1527nt
CGGGCCTGACGGCGGGAGATCGCGCTCCGGCCGGGCCCCGAGGCGCTGCCGGGGCGGCGCGGCTCTGCGGGGAGCAGCCCTCGGGCGCGC
CGAGCTCTCCCGCCCCAGCCCGCGCGGGGACCGTCCCGGAGCACGCGGTGGCCGAGTTCCCGCACAGGTAAACGCAGGGGCAGGGCCAGG
CTTCCGGGGGGGAAGACAGCGCCCCGAGCGTGGGAAGGGGGCCGGATCGGAGCCCGAGCCTCCAAGGGTTTGGTGGAAAAAGGAAGTAAA
CAGAAGGAAGGCTCAGGAATCCCCCACGATGGTCCTGATTTCTTTCCGGCACATTTTATTTACAGCTTCTAAGGACTGGGCCTGGAGGGA
ATTTAGGTGAGGAAGTCGGGGACTGAGAAAGAAGAGATGACAGAGAGAAACCGGTTACCAGGGATGGAAAGGCGGCTAGGCCCTTCCACA
AGCCAGGGACAGGAAATTGAGTGTCTGGCGTGGACAGGACTAAGTGTGCCTGCGGTGGGCGGTGGTGTGAGCCGGGGGTGGCAGGGAAGG
CCCTGGGTTGGGAGGCTCTTGCAGCAGAGATCCTTTTATGAGGGTTAGGGCGGGTCATGGGGAAACCGCAAGGTAGGAGGGAAGAGGTGC
TTCTACTCAGCAATGCCCTTTTCAGTTCTAGCTGATCAGTGCTACCTGTGCTCTGGAAACCCGCTCTGCGTTCCTGCTGGAGGTGGCCTC
CCCTCCGCCCCAGACAAGAAGAGGCCCTCAGCCCTCCCCCGGTCTCAGAGAGCCCTGAGAGGAGGCCCAGTCCAGAGCTCTTCCTCCGTT
CCCAGTCCACTTCTCTAGGGCCAGTAGCAGACACCAGCCAGTATGCCGAGGAACCAGGGCTTCTCCGAGCCCGAATACTCGGCCGAGTAC
TCAGCCGAGTACTCCGTCAGCCTGCCCTCCGACCCTGACCGCGGGGTGGGCCGGACCCATGAAATCTCGGTCCGGAACTCGGGCTCCTGC
CTGTGCCTGCCTCGCTTCATGCGGCTGACTTTCGTGCCGGAGTCCTTGGAGAACCTCTACCAGACCTACTTCAAAAGGCAGCGCCACGAG
ACCCTGCTGGTGCTGGTGGTCTTTGCAGCCCTCTTTGACTGCTACGTGGTGGTCATGTGTGCTGTGGTCTTCTCCAGCGACAAGCTGGCT
TCCCTCGCCGTGGCTGGAATTGGACTGGTGTTGGACATCATCCTCTTCGTGCTCTGCAAAAAGGGGCTGCTCCCGGACCGGGTCACCCGC
AGAGTGCTGCCCTACGTGCTGTGGCTGCTCATAACCGCCCAGATCTTCTCCTACCTGGGCCTGAACTTCGCGCGTGCCCACGCGGCTAGT
GACACGGTGGGCTGGCAGGTCTTCTTTGTCTTCTCCTTCTTCATCACGCTGCCCCTCAGCCTCAGCCCCATCGTGATCATCTCCGTGGTC
TCCTGTGTGGTGCACACGTTGGTCCTGGGGGTCACCGTGGCCCAGCAGCAGCAGGAGGAGCTCAAGGGGATGCAGCTGCTGCGGGAGGAT
GGACCTGGCTTCTATACTACCAGGTGTCTTGCGCCCATGATGTCTGAAGTCATCCGAATCCTCCAGGAAGGAGTTGACCCGAAGAAGCTG
GATTCCCTGACCACAAGCTTTGGCTTTCCTGTGGGTGCCGCCACACTGGTGGATGAAGTTGGTGTGGATGTAGCGAAACATGTGGCGGAA
GATCTGGGCAAAGTCTTTGGGGAGCGGTTTGGAGGTGGAAACCCAGAACTGCTGACACAGATGGTGTCCAAGGGCTTCCTAGGTCGTAAA
TCTGGGAAGGGCTTTTACATCTATCAGGAGGGTGTGAAGAGGAAGGATTTGAATTCTGACATGGATAGTATTTTAGCGAGTCTGAAGCTG
CCTCCTAAGTCTGAAGTCTCATCAGACGAAGACATCCAGTTCCGCCTGGTGACAAGATTTGTGAATGAGGCAGTCATGTGCCTGCAAGAG
GGGATCTTGGCCACACCTGCAGAGGGAGACATCGGAGCCGTCTTTGGGCTTGGCTTCCCGCCTTGTCTGGGAGGGCCTTTCCGCTTTGTG
GATCTGTATGGCGCCCAGAAGATAGTGGACCGGCTCAAGAAATATGAAGCTGCCTATGGAAAACAGTTCACCCCATGCCAGCTGCTAGCT
GACCATGCTAACAGCCCTAACAAGAAGTTCTACCAGTGAGCAGGCCTCATGCCTCGCTCAGTCAGTGCACTAACCCCAGCTGCCGGCAGT
GCTGGTTCTCCAACAGAGTGGTGTCTAGATTTATCAGAGTAACGAGAAGACAAACTCCGGCACTGGGTTTGCTCCCTGATTAAAGTGCCT
TCAGCCAAGACCATCTCTCCCTCCTGGTGAAGTGTGACTTCGAATTAGTTTGCACTTCCTGTTGGAAGGTAGAGCCCACTGCTCATTGTA
TAAGCCCCGAGGCCTAGAGTGGCAGCCAAGAGCCATCTGAAGCCACCTCTCTGCCTGTTCCTCCCAAGAGGCCAGGGTGGCCAGGGGTGG
TGAGGGCAGTTCTGCACCCAGCCAAACACATAACAATAAAAACCAAACTCTGTGTCAGCATCTTTGCCCTTCTGGTTTAAACGCCTCCTT
CAAAAAGCAATCTGGAAGAAAGCCCTGTGCTTTGGGGGAGTAAGAATGTGTGTGCAGAATTCTAGGCAGCACCTTAGGGAGGGACTGGGA
TGAGAGAAAGTGGGACCTGGTGGGCTCAACCACACACACCTGTCTGTGCAGATGCTTTGCCCAGGCTTCTCACCACGGTGTACCGGGATA

>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 Gene PPI Analysis for ADCY3-HADHA

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)

Hgene

Hgene's interactors

Tgene

Tgene's interactors

- 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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Related Drugs for ADCY3-HADHA

Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)

Partner

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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Related Diseases for ADCY3-HADHA

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source