FusionGDB Logo

Home

Download

Statistics

Examples

Help

Contact
Center for Computational Systems Medicine
leaf

Fusion Gene Summary

leaf

Fusion Gene ORF analysis

leaf

Fusion Genomic Features

leaf

Fusion Protein Features

leaf

Fusion Gene Sequence

leaf

Fusion Gene PPI analysis

leaf

Related Drugs

leaf

Related Diseases

Fusion gene:HTRA2-APP (FusionGDB2 ID:37913)

Fusion Gene Summary for HTRA2-APP

check button Fusion gene summary
Fusion gene informationFusion gene name: HTRA2-APP
Fusion gene ID: 37913
HgeneTgene
Gene symbol

HTRA2

APP

Gene ID

27429

351

Gene nameHtrA serine peptidase 2amyloid beta precursor protein
SynonymsMGCA8|OMI|PARK13|PRSS25AAA|ABETA|ABPP|AD1|APPI|CTFgamma|CVAP|PN-II|PN2|preA4
Cytomap

2p13.1

21q21.3

Type of geneprotein-codingprotein-coding
Descriptionserine protease HTRA2, mitochondrialHtrA-like serine proteaseOmi stress-regulated endoproteaseepididymis secretory sperm binding proteinhigh temperature requirement protein A2protease, serine, 25serine protease 25serine proteinase OMIamyloid-beta precursor proteinalzheimer disease amyloid proteinamyloid beta (A4) precursor proteinamyloid beta A4 proteinamyloid precursor proteinbeta-amyloid peptidebeta-amyloid peptide(1-40)beta-amyloid peptide(1-42)beta-amyloid precursor protei
Modification date2020031320200329
UniProtAcc

O43464

Q8NEU8

Ensembl transtripts involved in fusion geneENST00000258080, ENST00000467961, 
ENST00000352222, 		ENST00000346798, 
ENST00000354192, ENST00000348990, 
ENST00000357903, ENST00000358918, 
ENST00000359726, ENST00000448388, 
ENST00000440126, ENST00000439274, 
ENST00000474136, 
Fusion gene scores* DoF score1 X 1 X 1=125 X 18 X 10=4500
# samples 127
** MAII scorelog2(1/1*10)=3.32192809488736log2(27/4500*10)=-4.05889368905357
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: HTRA2 [Title/Abstract] AND APP [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointHTRA2(74756786)-APP(27347440), # 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
HgeneHTRA2

GO:0006508

proteolysis

25118933

HgeneHTRA2

GO:0010942

positive regulation of cell death

11583623

HgeneHTRA2

GO:0034605

cellular response to heat

10971580

HgeneHTRA2

GO:0035458

cellular response to interferon-beta

17297443

HgeneHTRA2

GO:0043280

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

11583623|11604410|17297443

HgeneHTRA2

GO:0044257

cellular protein catabolic process

17297443

HgeneHTRA2

GO:0071300

cellular response to retinoic acid

17297443

TgeneAPP

GO:0001934

positive regulation of protein phosphorylation

11404397

TgeneAPP

GO:0008285

negative regulation of cell proliferation

22944668

TgeneAPP

GO:1905606

regulation of presynapse assembly

19726636


check buttonFusion gene breakpoints across HTRA2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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

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
ChimerDB4STADTCGA-D7-8570-01AHTRA2chr2

74756786

+APPchr21

27347440

-


Top

Fusion Gene ORF analysis for HTRA2-APP

check button 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.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5UTR-3CDSENST00000258080ENST00000346798HTRA2chr2

74756786

+APPchr21

27347440

-
5UTR-3CDSENST00000258080ENST00000354192HTRA2chr2

74756786

+APPchr21

27347440

-
5UTR-3CDSENST00000258080ENST00000348990HTRA2chr2

74756786

+APPchr21

27347440

-
5UTR-3CDSENST00000258080ENST00000357903HTRA2chr2

74756786

+APPchr21

27347440

-
5UTR-3CDSENST00000258080ENST00000358918HTRA2chr2

74756786

+APPchr21

27347440

-
5UTR-3CDSENST00000258080ENST00000359726HTRA2chr2

74756786

+APPchr21

27347440

-
5UTR-3CDSENST00000258080ENST00000448388HTRA2chr2

74756786

+APPchr21

27347440

-
5UTR-3CDSENST00000258080ENST00000440126HTRA2chr2

74756786

+APPchr21

27347440

-
5UTR-3CDSENST00000258080ENST00000439274HTRA2chr2

74756786

+APPchr21

27347440

-
5UTR-intronENST00000258080ENST00000474136HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000467961ENST00000346798HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000467961ENST00000354192HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000467961ENST00000348990HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000467961ENST00000357903HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000467961ENST00000358918HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000467961ENST00000359726HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000467961ENST00000448388HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000467961ENST00000440126HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000467961ENST00000439274HTRA2chr2

74756786

+APPchr21

27347440

-
intron-intronENST00000467961ENST00000474136HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000352222ENST00000346798HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000352222ENST00000354192HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000352222ENST00000348990HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000352222ENST00000357903HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000352222ENST00000358918HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000352222ENST00000359726HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000352222ENST00000448388HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000352222ENST00000440126HTRA2chr2

74756786

+APPchr21

27347440

-
intron-3CDSENST00000352222ENST00000439274HTRA2chr2

74756786

+APPchr21

27347440

-
intron-intronENST00000352222ENST00000474136HTRA2chr2

74756786

+APPchr21

27347440

-

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

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

Top

Fusion Genomic Features for HTRA2-APP


check buttonFusionAI 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.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonDistribution 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.

check buttonDistribution 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.

Top

Fusion Protein Features for HTRA2-APP


check button Go to

FGviewer for the breakpoints of :-:

.
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
HTRA2

O43464

APP

Q8NEU8

FUNCTION: Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive. {ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:19502560}.FUNCTION: Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:26583432, PubMed:15016378, PubMed:24879834). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Plays a role in immune response by modulating phagocytosis, inflammatory and innate immune responses. In macrophages, enhances Fc-gamma receptor-mediated phagocytosis through interaction with RAB31 leading to activation of PI3K/Akt signaling. In response to LPS, modulates inflammatory responses by playing a key role on the regulation of TLR4 signaling and in the nuclear translocation of RELA/NF-kappa-B p65 and the secretion of pro- and anti-inflammatory cytokines. Also functions as a negative regulator of innate immune response via inhibition of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Plays a role in endosomal trafficking of TGFBR1 from the endosomes to the nucleus (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting ans insulin signaling pathways and adaptative thermogenesis (PubMed:24879834) (By similarity). In muscle, negatively regulates adiponectin-simulated glucose uptake and fatty acid oxidation by inhibiting adiponectin signaling pathway through APPL1 sequestration thereby antagonizing APPL1 action (By similarity). In muscles, negativeliy regulates insulin-induced plasma membrane recruitment of GLUT4 and glucose uptake through interaction with TBC1D1 (PubMed:24879834). Plays a role in cold and diet-induced adaptive thermogenesis by activating ventromedial hypothalamus (VMH) neurons throught AMPK inhibition which enhances sympathetic outflow to subcutaneous white adipose tissue (sWAT), sWAT beiging and cold tolerance (By similarity). Also plays a role in other signaling pathways namely Wnt/beta-catenin, HGF and glucocorticoid receptor signaling (PubMed:19433865) (By similarity). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865). May affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor. Required for fibroblast migration through HGF cell signaling (By similarity). {ECO:0000250|UniProtKB:Q8K3G9, ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:19433865, ECO:0000269|PubMed:24879834, ECO:0000269|PubMed:26583432}.

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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


Top

Fusion Gene Sequence for HTRA2-APP


check button 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.

Top

Fusion Gene PPI Analysis for HTRA2-APP


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 (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


Top

Related Drugs for HTRA2-APP


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

Top

Related Diseases for HTRA2-APP


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneHTRA2C43106503-METHYLGLUTACONIC ACIDURIA, TYPE VIII4CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneHTRA2C1853202PARKINSON DISEASE 13, AUTOSOMAL DOMINANT, SUSCEPTIBILITY TO3CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneHTRA2C0007787Transient Ischemic Attack1CTD_human
HgeneHTRA2C0027947Neutropenia1GENOMICS_ENGLAND
HgeneHTRA2C0242422Parkinsonian Disorders1CTD_human
HgeneHTRA2C0242423Ramsay Hunt Paralysis Syndrome1CTD_human
HgeneHTRA2C0472381Posterior Circulation Transient Ischemic Attack1CTD_human
HgeneHTRA2C0751019Carotid Circulation Transient Ischemic Attack1CTD_human
HgeneHTRA2C0751020Transient Ischemic Attack, Vertebrobasilar Circulation1CTD_human
HgeneHTRA2C0751021Crescendo Transient Ischemic Attacks1CTD_human
HgeneHTRA2C0751022Brain Stem Ischemia, Transient1CTD_human
HgeneHTRA2C0752097Autosomal Dominant Juvenile Parkinson Disease1CTD_human
HgeneHTRA2C0752098Autosomal Dominant Parkinsonism1CTD_human
HgeneHTRA2C0752100Autosomal Recessive Parkinsonism1CTD_human
HgeneHTRA2C0752101Parkinsonism, Experimental1CTD_human
HgeneHTRA2C0752104Familial Juvenile Parkinsonism1CTD_human
HgeneHTRA2C0752105Parkinsonism, Juvenile1CTD_human
HgeneHTRA2C0917805Transient Cerebral Ischemia1CTD_human
HgeneHTRA2C1527335Transient Ischemic Attack, Anterior Circulation1CTD_human
HgeneHTRA2C1868675PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE1CTD_human
TgeneAPPC0002395Alzheimer's Disease63CTD_human;UNIPROT
TgeneAPPC0011265Presenile dementia35CTD_human
TgeneAPPC0276496Familial Alzheimer Disease (FAD)35CTD_human
TgeneAPPC0494463Alzheimer Disease, Late Onset35CTD_human
TgeneAPPC0546126Acute Confusional Senile Dementia35CTD_human
TgeneAPPC0750900Alzheimer's Disease, Focal Onset35CTD_human
TgeneAPPC0750901Alzheimer Disease, Early Onset35CTD_human
TgeneAPPC0025261Memory Disorders16CTD_human
TgeneAPPC0233794Memory impairment16CTD_human
TgeneAPPC0751292Age-Related Memory Disorders16CTD_human
TgeneAPPC0751293Memory Disorder, Semantic16CTD_human
TgeneAPPC0751294Memory Disorder, Spatial16CTD_human
TgeneAPPC0751295Memory Loss16CTD_human
TgeneAPPC0027746Nerve Degeneration11CTD_human
TgeneAPPC0023186Learning Disorders8CTD_human
TgeneAPPC0751262Adult Learning Disorders8CTD_human
TgeneAPPC0751263Learning Disturbance8CTD_human
TgeneAPPC0751265Learning Disabilities8CTD_human
TgeneAPPC1330966Developmental Academic Disorder8CTD_human
TgeneAPPC2751536CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED7CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneAPPC0009241Cognition Disorders5CTD_human
TgeneAPPC0011570Mental Depression5PSYGENET
TgeneAPPC0011581Depressive disorder5PSYGENET
TgeneAPPC0234544Todd Paralysis5CTD_human
TgeneAPPC0522224Paralysed5CTD_human
TgeneAPPC0497327Dementia3CTD_human;GENOMICS_ENGLAND
TgeneAPPC2931672Cerebral hemorrhage with amyloidosis, hereditary, Dutch type3CTD_human;ORPHANET
TgeneAPPC0270715Degenerative Diseases, Central Nervous System2CTD_human
TgeneAPPC0333463Senile Plaques2CTD_human
TgeneAPPC0524851Neurodegenerative Disorders2CTD_human
TgeneAPPC0600467Neurogenic Inflammation2CTD_human
TgeneAPPC0751733Degenerative Diseases, Spinal Cord2CTD_human
TgeneAPPC2751494CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED, ARCTIC VARIANT2CTD_human
TgeneAPPC2936349Plaque, Amyloid2CTD_human
TgeneAPPC3888307CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED, FLEMISH VARIANT2CTD_human
TgeneAPPC3888308CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED, ITALIAN VARIANT2CTD_human
TgeneAPPC3888309CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED, IOWA VARIANT2CTD_human
TgeneAPPC0002622Amnesia1CTD_human
TgeneAPPC0002726Amyloidosis1CTD_human
TgeneAPPC0003469Anxiety Disorders1CTD_human
TgeneAPPC0005586Bipolar Disorder1PSYGENET
TgeneAPPC0006111Brain Diseases1CTD_human
TgeneAPPC0011573Endogenous depression1PSYGENET
TgeneAPPC0016667Fragile X Syndrome1CTD_human
TgeneAPPC0023893Liver Cirrhosis, Experimental1CTD_human
TgeneAPPC0027540Necrosis1CTD_human
TgeneAPPC0033141Cardiomyopathies, Primary1CTD_human
TgeneAPPC0036529Myocardial Diseases, Secondary1CTD_human
TgeneAPPC0036572Seizures1GENOMICS_ENGLAND
TgeneAPPC0037928Spinal Cord Diseases1CTD_human
TgeneAPPC0038002Splenomegaly1CTD_human
TgeneAPPC0038454Cerebrovascular accident1GENOMICS_ENGLAND
TgeneAPPC0043094Weight Gain1CTD_human
TgeneAPPC0085220Cerebral Amyloid Angiopathy1CTD_human
TgeneAPPC0085584Encephalopathies1CTD_human
TgeneAPPC0231341Premature aging syndrome1CTD_human
TgeneAPPC0233750Hysterical amnesia1CTD_human
TgeneAPPC0233796Temporary Amnesia1CTD_human
TgeneAPPC0234985Mental deterioration1CTD_human
TgeneAPPC0236795Dissociative Amnesia1CTD_human
TgeneAPPC0262497Global Amnesia1CTD_human
TgeneAPPC0270612Leukoencephalopathy1GENOMICS_ENGLAND
TgeneAPPC0338582Sporadic Cerebral Amyloid Angiopathy1CTD_human
TgeneAPPC0338630Senile Paranoid Dementia1CTD_human
TgeneAPPC0338656Impaired cognition1CTD_human
TgeneAPPC0376280Anxiety States, Neurotic1CTD_human
TgeneAPPC0553692Brain hemorrhage1GENOMICS_ENGLAND
TgeneAPPC0750906Tactile Amnesia1CTD_human
TgeneAPPC0750907Amnestic State1CTD_human
TgeneAPPC0751071Familial Dementia1CTD_human
TgeneAPPC0751156FRAXA Syndrome1CTD_human
TgeneAPPC0751157FRAXE Syndrome1CTD_human
TgeneAPPC0878544Cardiomyopathies1CTD_human
TgeneAPPC0948008Ischemic stroke1GENOMICS_ENGLAND
TgeneAPPC1270972Mild cognitive disorder1CTD_human
TgeneAPPC1279420Anxiety neurosis (finding)1CTD_human