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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein Structure
	pLDDT scores
	Ramachandran Plot of Fusion Protein Structure
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:HADH-HPGD

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: HADH-HPGD
	FusionPDB ID: 35582
	FusionGDB2.0 ID: 35582
		Hgene	Tgene
	Gene symbol	HADH	HPGD
	Gene ID	3033	3248
	Gene name	hydroxyacyl-CoA dehydrogenase	15-hydroxyprostaglandin dehydrogenase
	Synonyms	HAD\|HADH1\|HADHSC\|HCDH\|HHF4\|MSCHAD\|SCHAD	15-PGDH\|PGDH\|PGDH1\|PHOAR1\|SDR36C1
	Cytomap	4q25	4q34.1
	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	15-hydroxyprostaglandin dehydrogenase [NAD(+)]15-hydroxyprostaglandin dehydrogenase (NAD(+))NAD+-dependent 15-hydroxyprostaglandin dehydrogenasehydroxyprostaglandin dehydrogenase 15-(NAD)prostaglandin dehydrogenase 1short chain dehydrogenase/reductas
	Modification date	20200320	20200313
	UniProtAcc	P55084	O60760
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000309522, ENST00000403312, ENST00000603302, ENST00000505878, ENST00000454409, ENST00000510728,	ENST00000504433, ENST00000510901, ENST00000541923, ENST00000542498, ENST00000422112, ENST00000296521, ENST00000296522,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	7 X 6 X 3=126	2 X 2 X 2=8
	# samples	7	2
	** MAII score	log2(7/126*10)=-0.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(2/8*10)=1.32192809488736
Context (manual curation of fusion genes in FusionPDB)	PubMed: HADH [Title/Abstract] AND HPGD [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	HADH(108911220)-HPGD(175429943), # samples:4
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	HPGD	GO:0006693	prostaglandin metabolic process	16828555\|21072165
Tgene	HPGD	GO:0007179	transforming growth factor beta receptor signaling pathway	15574495
Tgene	HPGD	GO:0007565	female pregnancy	15531523
Tgene	HPGD	GO:0007567	parturition	15531523
Tgene	HPGD	GO:0045786	negative regulation of cell cycle	15574495

Fusion gene breakpoints across HADH (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 HPGD (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	UCEC	TCGA-AJ-A3NF-01A	HADH	chr4	108911220	-	HPGD	chr4	175429943	-
ChimerDB4	UCEC	TCGA-AJ-A3NF-01A	HADH	chr4	108911220	+	HPGD	chr4	175429943	-
ChimerDB4	UCEC	TCGA-AJ-A3NF	HADH	chr4	108911220	+	HPGD	chr4	175429943	-

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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)
ENST00000603302	HADH	chr4	108911220	+	ENST00000296522	HPGD	chr4	175429943	-	2607	351	42	827	261
ENST00000603302	HADH	chr4	108911220	+	ENST00000296521	HPGD	chr4	175429943	-	1162	351	42	563	173
ENST00000403312	HADH	chr4	108911220	+	ENST00000296522	HPGD	chr4	175429943	-	2607	351	42	827	261
ENST00000403312	HADH	chr4	108911220	+	ENST00000296521	HPGD	chr4	175429943	-	1162	351	42	563	173
ENST00000309522	HADH	chr4	108911220	+	ENST00000296522	HPGD	chr4	175429943	-	2537	281	41	757	238
ENST00000309522	HADH	chr4	108911220	+	ENST00000296521	HPGD	chr4	175429943	-	1092	281	41	493	150

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
ENST00000603302	ENST00000296522	HADH	chr4	108911220	+	HPGD	chr4	175429943	-	0.000706739	0.9992932
ENST00000603302	ENST00000296521	HADH	chr4	108911220	+	HPGD	chr4	175429943	-	0.040315192	0.95968485
ENST00000403312	ENST00000296522	HADH	chr4	108911220	+	HPGD	chr4	175429943	-	0.000706739	0.9992932
ENST00000403312	ENST00000296521	HADH	chr4	108911220	+	HPGD	chr4	175429943	-	0.040315192	0.95968485
ENST00000309522	ENST00000296522	HADH	chr4	108911220	+	HPGD	chr4	175429943	-	0.000345029	0.999655
ENST00000309522	ENST00000296521	HADH	chr4	108911220	+	HPGD	chr4	175429943	-	0.006506751	0.99349326

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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

>35582_35582_1_HADH-HPGD_HADH_chr4_108911220_ENST00000309522_HPGD_chr4_175429943_ENST00000296521_length(amino acids)=150AA_BP=80
MQGRVGPRPQSLAFRGCPPRASSLPGSPRCRRRCHTMAFVTRQFMRSVSSSSTASASAKKIIVKHVTVIGGGLMGAGIAQVSVISGTYLG

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

>35582_35582_2_HADH-HPGD_HADH_chr4_108911220_ENST00000309522_HPGD_chr4_175429943_ENST00000296522_length(amino acids)=238AA_BP=80
MQGRVGPRPQSLAFRGCPPRASSLPGSPRCRRRCHTMAFVTRQFMRSVSSSSTASASAKKIIVKHVTVIGGGLMGAGIAQVSVISGTYLG
LDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAANLMNSGVRLNAICPGFVNTAILESIEKEENMGQYIEYKD

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

>35582_35582_3_HADH-HPGD_HADH_chr4_108911220_ENST00000403312_HPGD_chr4_175429943_ENST00000296521_length(amino acids)=173AA_BP=103
MGRAGLEAPPPPCGVTGTPGARGLQGRVGPRPQSLAFRGCPPRASSLPGSPRCRRRCHTMAFVTRQFMRSVSSSSTASASAKKIIVKHVT

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

>35582_35582_4_HADH-HPGD_HADH_chr4_108911220_ENST00000403312_HPGD_chr4_175429943_ENST00000296522_length(amino acids)=261AA_BP=103
MGRAGLEAPPPPCGVTGTPGARGLQGRVGPRPQSLAFRGCPPRASSLPGSPRCRRRCHTMAFVTRQFMRSVSSSSTASASAKKIIVKHVT
VIGGGLMGAGIAQVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAANLMNSGVRLNAICPGF

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

>35582_35582_5_HADH-HPGD_HADH_chr4_108911220_ENST00000603302_HPGD_chr4_175429943_ENST00000296521_length(amino acids)=173AA_BP=103
MGRAGLEAPPPPCGVTGTPGARGLQGRVGPRPQSLAFRGCPPRASSLPGSPRCRRRCHTMAFVTRQFMRSVSSSSTASASAKKIIVKHVT

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

>35582_35582_6_HADH-HPGD_HADH_chr4_108911220_ENST00000603302_HPGD_chr4_175429943_ENST00000296522_length(amino acids)=261AA_BP=103
MGRAGLEAPPPPCGVTGTPGARGLQGRVGPRPQSLAFRGCPPRASSLPGSPRCRRRCHTMAFVTRQFMRSVSSSSTASASAKKIIVKHVT
VIGGGLMGAGIAQVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAANLMNSGVRLNAICPGF

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

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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/chr4:108911220/chr4:175429943)
- 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
HADH P55084	HPGD O60760
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: Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide. {ECO:0000269\|PubMed:10824118, ECO:0000269\|PubMed:11672424, ECO:0000269\|PubMed:12244105, ECO:0000269\|PubMed:12627223, ECO:0000269\|PubMed:15113825, ECO:0000269\|PubMed:16547010, ECO:0000269\|PubMed:19939518, ECO:0000269\|PubMed:9353279, ECO:0000269\|PubMed:9425264}.

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.

- 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

chr4:108911220

chr4:175429943

ENST00000309522

34_39

44.0

315.0

Nucleotide binding

NAD

Hgene

HADH

chr4:108911220

chr4:175429943

ENST00000603302

34_39

44.0

332.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000296521

151_155

108.0

179.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000296522

151_155

108.0

267.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000422112

12_20

199.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000422112

151_155

199.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000422112

36_37

199.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000422112

63_65

199.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000510901

12_20

146.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000510901

151_155

146.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000510901

36_37

146.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000510901

63_65

146.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000541923

12_20

146.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000541923

151_155

146.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000541923

36_37

146.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000541923

63_65

146.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000542498

151_155

108.0

144.0

Nucleotide binding

NAD

- 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

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000296521

12_20

108.0

179.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000296521

36_37

108.0

179.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000296521

63_65

108.0

179.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000296522

12_20

108.0

267.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000296522

36_37

108.0

267.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000296522

63_65

108.0

267.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000542498

12_20

108.0

144.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000542498

36_37

108.0

144.0

Nucleotide binding

NAD

Tgene

HPGD

chr4:108911220

chr4:175429943

ENST00000542498

63_65

108.0

144.0

Nucleotide binding

NAD

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Fusion Protein Structures

PDB and CIF files of the predicted fusion proteins
* 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 >>>443_HADH_108911220_HPGD_175429943_ranked_0.pdb	HADH	108911220	108911220	ENST00000296521	HPGD	chr4	175429943	-	MGRAGLEAPPPPCGVTGTPGARGLQGRVGPRPQSLAFRGCPPRASSLPGSPRCRRRCHTMAFVTRQFMRSVSSSSTASASAKKIIVKHVT VIGGGLMGAGIAQVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAANLMNSGVRLNAICPGF	261

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pLDDT score distribution

pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

HADH_pLDDT.png

HPGD_pLDDT.png

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

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Ramachandran Plot of Fusion Protein Structure

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

Fusion AA seq ID in FusionPDB and their Ramachandran plots

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Fusion Protein-Protein Interaction

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 from validated records (BIOGRID-3.4.160)

Gene

PPI interactors

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
HADH
HPGD

- 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

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Related Drugs to HADH-HPGD

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 HADH-HPGD

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