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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:FBXO9-CD74

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: FBXO9-CD74
	FusionPDB ID: 29875
	FusionGDB2.0 ID: 29875
		Hgene	Tgene
	Gene symbol	FBXO9	CD74
	Gene ID	26268	972
	Gene name	F-box protein 9	CD74 molecule
	Synonyms	FBX9\|NY-REN-57\|VCIA1\|dJ341E18.2	DHLAG\|HLADG\|II\|Ia-GAMMA\|p33
	Cytomap	6p12.1	5q33.1
	Type of gene	protein-coding	protein-coding
	Description	F-box only protein 9F-box protein Fbx9cross-immune reaction antigen 1renal carcinoma antigen NY-REN-57	HLA class II histocompatibility antigen gamma chainCD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)CD74 molecule, major histocompatibility complex, class II invariant chainHLA-DR antigens-associated
	Modification date	20200313	20200313
	UniProtAcc	Q9UK97	P04233
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000244426, ENST00000323557, ENST00000370939, ENST00000461222,	ENST00000009530, ENST00000524315, ENST00000353334, ENST00000377795,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	6 X 7 X 3=126	31 X 31 X 11=10571
	# samples	7	39
	** MAII score	log2(7/126*10)=-0.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(39/10571*10)=-4.76049392566144 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: FBXO9 [Title/Abstract] AND CD74 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	FBXO9(52960462)-CD74(149782188), # samples:2
Anticipated loss of major functional domain due to fusion event.	FBXO9-CD74 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. FBXO9-CD74 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. FBXO9-CD74 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. FBXO9-CD74 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. FBXO9-CD74 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. FBXO9-CD74 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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)

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
Hgene	FBXO9	GO:0016567	protein ubiquitination	23263282
Hgene	FBXO9	GO:0031146	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	23263282
Tgene	CD74	GO:0001516	prostaglandin biosynthetic process	12782713
Tgene	CD74	GO:0001934	positive regulation of protein phosphorylation	24942581
Tgene	CD74	GO:0002792	negative regulation of peptide secretion	19849849
Tgene	CD74	GO:0033674	positive regulation of kinase activity	24942581
Tgene	CD74	GO:0043066	negative regulation of apoptotic process	12782713
Tgene	CD74	GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling	24942581
Tgene	CD74	GO:0043410	positive regulation of MAPK cascade	24942581
Tgene	CD74	GO:0043518	negative regulation of DNA damage response, signal transduction by p53 class mediator	17045821
Tgene	CD74	GO:0045657	positive regulation of monocyte differentiation	24942581
Tgene	CD74	GO:0045893	positive regulation of transcription, DNA-templated	24942581
Tgene	CD74	GO:0046598	positive regulation of viral entry into host cell	24942581
Tgene	CD74	GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation	17045821
Tgene	CD74	GO:0070374	positive regulation of ERK1 and ERK2 cascade	17045821\|24942581

Fusion gene breakpoints across FBXO9 (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 CD74 (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	LUAD	TCGA-64-1680-01A	FBXO9	chr6	52960462	+	CD74	chr5	149782188	-

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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)
ENST00000370939	FBXO9	chr6	52960462	+	ENST00000377795	CD74	chr5	149782188	-	2090	1413	292	1662	456
ENST00000323557	FBXO9	chr6	52960462	+	ENST00000377795	CD74	chr5	149782188	-	2213	1536	130	1785	551
ENST00000244426	FBXO9	chr6	52960462	+	ENST00000377795	CD74	chr5	149782188	-	2084	1407	172	1656	494

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
ENST00000370939	ENST00000377795	FBXO9	chr6	52960462	+	CD74	chr5	149782188	-	0.003023684	0.9969764
ENST00000323557	ENST00000377795	FBXO9	chr6	52960462	+	CD74	chr5	149782188	-	0.008427187	0.99157286
ENST00000244426	ENST00000377795	FBXO9	chr6	52960462	+	CD74	chr5	149782188	-	0.003610129	0.9963898

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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

>29875_29875_1_FBXO9-CD74_FBXO9_chr6_52960462_ENST00000244426_CD74_chr5_149782188_ENST00000377795_length(amino acids)=494AA_BP=412
MPDIIWVFPPQAEAEEDCHSDTVRADDDEENESPAETDLQAQLQMFRAQWMFELAPGVSSSNLENRPCRAARGSLQKTSADTKGKQEQAK
EEKARELFLKAVEEEQNGALYEAIKFYRRAMQLVPDIEFKITYTRSPDGDGVGNSYIEDNDDDSKMADLLSYFQQQLTFQESVLKLCQPE
LESSQIHISVLPMEVLMYIFRWVVSSDLDLRSLEQLSLVCRGFYICARDPEIWRLACLKVWGRSCIKLVPYTSWREMFLERPRVRFDGVY
ISKTTYIRQGEQSLDGFYRAWHQVEYYRYIRFFPDGHVMMLTTPEEPQSIVPRLRTRNTRTDAILLGHYRLSQDTDNQTKVFAVITKKKE
EKPLDYKYRYFRRVPVQEADQSFHVGLQLCSSGHQRFNKLIWIHHSCHITYKVTGTGGPVFWAGCDQAGSGPSPHVRAAEAVFNILPAPH

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

>29875_29875_2_FBXO9-CD74_FBXO9_chr6_52960462_ENST00000323557_CD74_chr5_149782188_ENST00000377795_length(amino acids)=551AA_BP=469
MPREDGCRTPGPQLLPLPGALLRPRTLLSSAAETGRSRHPDTQHPSSGGRCRGGTESPSSAAGRPASMAEAEEDCHSDTVRADDDEENES
PAETDLQAQLQMFRAQWMFELAPGVSSSNLENRPCRAARGSLQKTSADTKGKQEQAKEEKARELFLKAVEEEQNGALYEAIKFYRRAMQL
VPDIEFKITYTRSPDGDGVGNSYIEDNDDDSKMADLLSYFQQQLTFQESVLKLCQPELESSQIHISVLPMEVLMYIFRWVVSSDLDLRSL
EQLSLVCRGFYICARDPEIWRLACLKVWGRSCIKLVPYTSWREMFLERPRVRFDGVYISKTTYIRQGEQSLDGFYRAWHQVEYYRYIRFF
PDGHVMMLTTPEEPQSIVPRLRTRNTRTDAILLGHYRLSQDTDNQTKVFAVITKKKEEKPLDYKYRYFRRVPVQEADQSFHVGLQLCSSG
HQRFNKLIWIHHSCHITYKVTGTGGPVFWAGCDQAGSGPSPHVRAAEAVFNILPAPHSYSFLAPFSPQPLPHLPPCTSSHETLVPGSFVT

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

>29875_29875_3_FBXO9-CD74_FBXO9_chr6_52960462_ENST00000370939_CD74_chr5_149782188_ENST00000377795_length(amino acids)=456AA_BP=374
MQAQLQMFRAQWMFELAPGVSSSNLENRPCRAARGSLQKTSADTKGKQEQAKEEKARELFLKAVEEEQNGALYEAIKFYRRAMQLVPDIE
FKITYTRSPDGDGVGNSYIEDNDDDSKMADLLSYFQQQLTFQESVLKLCQPELESSQIHISVLPMEVLMYIFRWVVSSDLDLRSLEQLSL
VCRGFYICARDPEIWRLACLKVWGRSCIKLVPYTSWREMFLERPRVRFDGVYISKTTYIRQGEQSLDGFYRAWHQVEYYRYIRFFPDGHV
MMLTTPEEPQSIVPRLRTRNTRTDAILLGHYRLSQDTDNQTKVFAVITKKKEEKPLDYKYRYFRRVPVQEADQSFHVGLQLCSSGHQRFN
KLIWIHHSCHITYKVTGTGGPVFWAGCDQAGSGPSPHVRAAEAVFNILPAPHSYSFLAPFSPQPLPHLPPCTSSHETLVPGSFVTLGQDK

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

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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/chr6:52960462/chr5:149782188)
- 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
FBXO9 Q9UK97	CD74 P04233
FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of TTI1 and TELO2 in a CK2-dependent manner, thereby directly regulating mTOR signaling. SCF(FBXO9) recognizes and binds mTORC1-bound TTI1 and TELO2 when they are phosphorylated by CK2 following growth factor deprivation, leading to their degradation. In contrast, the SCF(FBXO9) does not mediate ubiquitination of TTI1 and TELO2 when they are part of the mTORC2 complex. As a consequence, mTORC1 is inactivated to restrain cell growth and protein translation, while mTORC2 is activated due to the relief of feedback inhibition by mTORC1. {ECO:0000269\|PubMed:23263282}.	FUNCTION: Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF.; FUNCTION: [Class-II-associated invariant chain peptide]: Binds to the peptide-binding site of MHC class II alpha/beta heterodimers forming an alpha-beta-CLIP complex, thereby preventing the loading of antigenic peptides to the MHC class II complex until its release by HLA-DM in the endosome. {ECO:0000269\|PubMed:1448172}.; FUNCTION: [Isoform p41]: Stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of antigen-presenting cells (APCs). Has antiviral activity by stymieing the endosomal entry of Ebola virus and coronaviruses, including SARS-CoV-2 (PubMed:32855215). Disrupts cathepsin-mediated Ebola virus glycoprotein processing, which prevents viral fusion and entry. This antiviral activity is specific to p41 isoform (PubMed:32855215). {ECO:0000250\|UniProtKB:P04441, ECO:0000269\|PubMed:32855215}.

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

FBXO9

chr6:52960462

chr5:149782188

ENST00000244426

185_236

411.6666666666667

448.0

Domain

F-box

Hgene

FBXO9

chr6:52960462

chr5:149782188

ENST00000323557

185_236

401.6666666666667

438.0

Domain

F-box

Hgene

FBXO9

chr6:52960462

chr5:149782188

ENST00000370939

185_236

367.6666666666667

404.0

Domain

F-box

Hgene

FBXO9

chr6:52960462

chr5:149782188

ENST00000244426

94_127

411.6666666666667

448.0

Repeat

Note=TPR

Hgene

FBXO9

chr6:52960462

chr5:149782188

ENST00000323557

94_127

401.6666666666667

438.0

Repeat

Note=TPR

Hgene

FBXO9

chr6:52960462

chr5:149782188

ENST00000370939

94_127

367.6666666666667

404.0

Repeat

Note=TPR

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000353334

210_271

208.33333333333334

233.0

Domain

Thyroglobulin type-1

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000377795

210_271

147.0

280.6666666666667

Domain

Thyroglobulin type-1

- 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

CD74

chr6:52960462

chr5:149782188

ENST00000009530

210_271

272.3333333333333

297.0

Domain

Thyroglobulin type-1

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000009530

1_46

272.3333333333333

297.0

Topological domain

Cytoplasmic

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000009530

73_296

272.3333333333333

297.0

Topological domain

Extracellular

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000353334

1_46

208.33333333333334

233.0

Topological domain

Cytoplasmic

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000353334

73_296

208.33333333333334

233.0

Topological domain

Extracellular

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000377795

1_46

147.0

280.6666666666667

Topological domain

Cytoplasmic

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000377795

73_296

147.0

280.6666666666667

Topological domain

Extracellular

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000009530

47_72

272.3333333333333

297.0

Transmembrane

Helical%3B Signal-anchor for type II membrane protein

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000353334

47_72

208.33333333333334

233.0

Transmembrane

Helical%3B Signal-anchor for type II membrane protein

Tgene

CD74

chr6:52960462

chr5:149782188

ENST00000377795

47_72

147.0

280.6666666666667

Transmembrane

Helical%3B Signal-anchor for type II membrane protein

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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

CD74

MIF, CD74, APP, HADHA, LAMTOR5, MAP3K1, TM4SF20, COPG1, COPG2, HLA-DPB1, HLA-DQA1, nef, CD44, AKAP8, ANKRD28, AP3D1, ARCN1, ASCC1, ASCC3, ASNS, CANX, CHAF1B, COPA, COPB1, COPB2, COPE, DDX60, DGKE, DNAJB11, DNAJB12, EIF1, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S3, EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L, EIF3M, EIF4A1, EIF4G1, EIF4G2, FKBP8, GANAB, GEMIN4, GRAMD1A, GTF2I, GTF3C1, HADHB, HMOX2, HUWE1, IPO13, IQGAP2, KPNB1, KRT1, LTN1, MAP1B, MTOR, NCAPD2, NCAPD3, NCAPH, OSBPL8, PCNA, PDAP1, PDCD4, PGRMC1, PGRMC2, PHB, POLR2E, POLR3A, POLR3B, PPP6R1, PPP6R3, PRRC2A, PRRC2B, PRRC2C, PSMC2, PSMD3, PSMD6, RCN1, RHOT2, RWDD1, SGPL1, SNRPE, SRP9, TBRG4, TJP2, TPP2, TUBA1A, TUBA1C, UBE3C, UBR4, UBR5, VDAC1, VWA8, YWHAB, YWHAE, YWHAQ, YWHAZ, IFITM3, FDFT1, POMGNT1, BET1, TMEM97, UPK2, TEX11, SERP1, SLC35B1, SEC22A, PLP1, TMEM254, C14orf1, TMEM243, TMEM60, FXYD6, CMTM7, CLDN19, LPAR3, CLEC7A, EDDM3B, C14orf180, PTCH1, TMEM120B, RTP2, PPAPDC1A, PGA4, SMIM1, CUL7, CCR1, ROPN1L, HLA-DRB3, HLA-DRB1, HLA-DRA,

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
FBXO9
CD74

- 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 FBXO9-CD74

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 FBXO9-CD74

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
Tgene	CD74	C0006142	Malignant neoplasm of breast	1	CTD_human
Tgene	CD74	C0007131	Non-Small Cell Lung Carcinoma	1	CTD_human
Tgene	CD74	C0023893	Liver Cirrhosis, Experimental	1	CTD_human
Tgene	CD74	C0162557	Liver Failure, Acute	1	CTD_human
Tgene	CD74	C0678222	Breast Carcinoma	1	CTD_human
Tgene	CD74	C1257931	Mammary Neoplasms, Human	1	CTD_human
Tgene	CD74	C1458155	Mammary Neoplasms	1	CTD_human
Tgene	CD74	C4704874	Mammary Carcinoma, Human	1	CTD_human