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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:FNIP1-CYP3A4

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: FNIP1-CYP3A4
	FusionPDB ID: 30948
	FusionGDB2.0 ID: 30948
		Hgene	Tgene
	Gene symbol	FNIP1	CYP3A4
	Gene ID	96459	1576
	Gene name	folliculin interacting protein 1	cytochrome P450 family 3 subfamily A member 4
	Synonyms	-	CP33\|CP34\|CYP3A\|CYP3A3\|CYPIIIA3\|CYPIIIA4\|HLP\|NF-25\|P450C3\|P450PCN1
	Cytomap	5q31.1	7q22.1
	Type of gene	protein-coding	protein-coding
	Description	folliculin-interacting protein 1	cytochrome P450 3A41,4-cineole 2-exo-monooxygenase1,8-cineole 2-exo-monooxygenaseP450-III, steroid induciblealbendazole monooxygenasealbendazole monooxygenase (sulfoxide-forming)albendazole sulfoxidasecholesterol 25-hydroxylasecytochrome P450 3A3
	Modification date	20200327	20200327
	UniProtAcc	Q8TF40	Q9HB55
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000307954, ENST00000307968, ENST00000510461, ENST00000511848,	ENST00000354593, ENST00000336411,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	15 X 11 X 10=1650	4 X 4 X 3=48
	# samples	18	4
	** MAII score	log2(18/1650*10)=-3.1963972128035 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(4/48*10)=-0.263034405833794 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: FNIP1 [Title/Abstract] AND CYP3A4 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	FNIP1(131132523)-CYP3A4(99355851), # samples:1
Anticipated loss of major functional domain due to fusion event.	FNIP1-CYP3A4 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. FNIP1-CYP3A4 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. FNIP1-CYP3A4 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. FNIP1-CYP3A4 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	FNIP1	GO:0000122	negative regulation of transcription by RNA polymerase II	21209915
Hgene	FNIP1	GO:0001932	regulation of protein phosphorylation	18663353
Hgene	FNIP1	GO:0031334	positive regulation of protein complex assembly	25126726
Hgene	FNIP1	GO:0033138	positive regulation of peptidyl-serine phosphorylation	19914239
Tgene	CYP3A4	GO:0002933	lipid hydroxylation	14559847
Tgene	CYP3A4	GO:0008202	steroid metabolic process	14559847
Tgene	CYP3A4	GO:0008210	estrogen metabolic process	11555828\|12865317\|14559847
Tgene	CYP3A4	GO:0009822	alkaloid catabolic process	15039299
Tgene	CYP3A4	GO:0016098	monoterpenoid metabolic process	16401082
Tgene	CYP3A4	GO:0017144	drug metabolic process	15327587\|19219744
Tgene	CYP3A4	GO:0042572	retinol metabolic process	10681376
Tgene	CYP3A4	GO:0042573	retinoic acid metabolic process	11093772
Tgene	CYP3A4	GO:0042737	drug catabolic process	15039299
Tgene	CYP3A4	GO:0042738	exogenous drug catabolic process	18619574
Tgene	CYP3A4	GO:0046483	heterocycle metabolic process	15327587
Tgene	CYP3A4	GO:0055114	oxidation-reduction process	16401082\|19219744
Tgene	CYP3A4	GO:0070989	oxidative demethylation	15039299\|18619574

Fusion gene breakpoints across FNIP1 (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 CYP3A4 (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	LIHC	TCGA-DD-A73F-01A	FNIP1	chr5	131132523	-	CYP3A4	chr7	99355851	-

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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)
ENST00000307968	FNIP1	chr5	131132523	-	ENST00000336411	CYP3A4	chr7	99355851	-	645	92	161	0	54
ENST00000307954	FNIP1	chr5	131132523	-	ENST00000336411	CYP3A4	chr7	99355851	-	674	121	190	2	63
ENST00000510461	FNIP1	chr5	131132523	-	ENST00000336411	CYP3A4	chr7	99355851	-	741	188	257	51	68
ENST00000511848	FNIP1	chr5	131132523	-	ENST00000336411	CYP3A4	chr7	99355851	-	740	187	256	50	68

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
ENST00000307968	ENST00000336411	FNIP1	chr5	131132523	-	CYP3A4	chr7	99355851	-	0.9679813	0.032018688
ENST00000307954	ENST00000336411	FNIP1	chr5	131132523	-	CYP3A4	chr7	99355851	-	0.9764025	0.023597522
ENST00000510461	ENST00000336411	FNIP1	chr5	131132523	-	CYP3A4	chr7	99355851	-	0.9145837	0.085416354
ENST00000511848	ENST00000336411	FNIP1	chr5	131132523	-	CYP3A4	chr7	99355851	-	0.9312419	0.068758085

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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

>30948_30948_1_FNIP1-CYP3A4_FNIP1_chr5_131132523_ENST00000307954_CYP3A4_chr7_99355851_ENST00000336411_length(amino acids)=63AA_BP=1

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

>30948_30948_2_FNIP1-CYP3A4_FNIP1_chr5_131132523_ENST00000307968_CYP3A4_chr7_99355851_ENST00000336411_length(amino acids)=54AA_BP=1

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

>30948_30948_3_FNIP1-CYP3A4_FNIP1_chr5_131132523_ENST00000510461_CYP3A4_chr7_99355851_ENST00000336411_length(amino acids)=68AA_BP=1

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

>30948_30948_4_FNIP1-CYP3A4_FNIP1_chr5_131132523_ENST00000511848_CYP3A4_chr7_99355851_ENST00000336411_length(amino acids)=68AA_BP=1

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

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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/chr5:131132523/chr7:99355851)
- 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
FNIP1 Q8TF40	CYP3A4 Q9HB55
FUNCTION: Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:24081491). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (By similarity). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases (PubMed:24081491). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:27353360, PubMed:30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Required for B-cell development (By similarity). {ECO:0000250\|UniProtKB:Q68FD7, ECO:0000250\|UniProtKB:Q9P278, ECO:0000269\|PubMed:17028174, ECO:0000269\|PubMed:18663353, ECO:0000269\|PubMed:24081491, ECO:0000269\|PubMed:25126726, ECO:0000269\|PubMed:27353360, ECO:0000269\|PubMed:30699359}.	FUNCTION: Exhibits low testosterone 6-beta-hydroxylase activity.

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

- 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

FNIP1

chr5:131132523

chr7:99355851

ENST00000307968

96_99

30.666666666666668

1139.0

Compositional bias

Note=Poly-Ser

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000510461

96_99

30.666666666666668

1167.0

Compositional bias

Note=Poly-Ser

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000511848

96_99

30.666666666666668

509.0

Compositional bias

Note=Poly-Ser

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000307968

1102_1157

30.666666666666668

1139.0

Domain

dDENN FNIP1/2-type

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000307968

37_478

30.666666666666668

1139.0

Domain

uDENN FNIP1/2-type

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000307968

486_1092

30.666666666666668

1139.0

Domain

cDENN FNIP1/2-type

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000510461

1102_1157

30.666666666666668

1167.0

Domain

dDENN FNIP1/2-type

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000510461

37_478

30.666666666666668

1167.0

Domain

uDENN FNIP1/2-type

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000510461

486_1092

30.666666666666668

1167.0

Domain

cDENN FNIP1/2-type

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000511848

1102_1157

30.666666666666668

509.0

Domain

dDENN FNIP1/2-type

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000511848

37_478

30.666666666666668

509.0

Domain

uDENN FNIP1/2-type

Hgene

FNIP1

chr5:131132523

chr7:99355851

ENST00000511848

486_1092

30.666666666666668

509.0

Domain

cDENN FNIP1/2-type

Tgene

CYP3A4

chr5:131132523

chr7:99355851

ENST00000336411

2_22

472.0

504.0

Transmembrane

Helical

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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
FNIP1
CYP3A4

- 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
Hgene	FNIP1	chr5:131132523	chr7:99355851	ENST00000307968	-	1	17	929_1166	30.666666666666668	1139.0	HSP90AA1
Hgene	FNIP1	chr5:131132523	chr7:99355851	ENST00000510461	-	1	18	929_1166	30.666666666666668	1167.0	HSP90AA1
Hgene	FNIP1	chr5:131132523	chr7:99355851	ENST00000511848	-	1	13	929_1166	30.666666666666668	509.0	HSP90AA1

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Related Drugs to FNIP1-CYP3A4

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 FNIP1-CYP3A4

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