UTHEALTH HOME ABOUT SBMI A-Z WEBMAIL INSIDE THE UNIVERSITY

Home

Download

Statistics

Examples

Help

Contact

level2

	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:CPS1-PLEKHM3

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: CPS1-PLEKHM3
	FusionPDB ID: 19095
	FusionGDB2.0 ID: 19095
		Hgene	Tgene
	Gene symbol	CPS1	PLEKHM3
	Gene ID	1589	389072
	Gene name	cytochrome P450 family 21 subfamily A member 2	pleckstrin homology domain containing M3
	Synonyms	CA21H\|CAH1\|CPS1\|CYP21\|CYP21B\|P450c21B	DAPR\|PLEKHM1L
	Cytomap	6p21.33	2q33.3
	Type of gene	protein-coding	protein-coding
	Description	steroid 21-hydroxylase21-OHasecytochrome P450 XXIcytochrome P450, family 21, subfamily A, polypeptide 2cytochrome P450, subfamily XXIA (steroid 21-hydroxylase, congenital adrenal hyperplasia), polypeptide 2cytochrome P450-C21Bsteroid 21 hydroxylase	pleckstrin homology domain-containing family M member 3PH domain-containing family M member 3differentiation associated protein
	Modification date	20200320	20200313
	UniProtAcc	P31327	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000233072, ENST00000430249, ENST00000451903, ENST00000497121,	ENST00000389247, ENST00000457206, ENST00000427836,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	10 X 11 X 4=440	7 X 4 X 5=140
	# samples	11	6
	** MAII score	log2(11/440*10)=-2 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(6/140*10)=-1.22239242133645 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: CPS1 [Title/Abstract] AND PLEKHM3 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	CPS1(211481265)-PLEKHM3(208693220), # samples:3
Anticipated loss of major functional domain due to fusion event.	CPS1-PLEKHM3 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. CPS1-PLEKHM3 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. CPS1-PLEKHM3 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. CPS1-PLEKHM3 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.

* 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	CPS1	GO:0006694	steroid biosynthetic process	25855791

Fusion gene breakpoints across CPS1 (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 PLEKHM3 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Top

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	SARC	TCGA-DX-A48K-01A	CPS1	chr2	211481265	+	PLEKHM3	chr2	208693220	-
ChimerDB4	SARC	TCGA-DX-AATS-01A	CPS1	chr2	211481265	-	PLEKHM3	chr2	208693220	-
ChimerDB4	SARC	TCGA-DX-AATS-01A	CPS1	chr2	211481265	+	PLEKHM3	chr2	208693220	-

Top

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)
ENST00000430249	CPS1	chr2	211481265	+	ENST00000427836	PLEKHM3	chr2	208693220	-	2954	2760	55	2937	960
ENST00000233072	CPS1	chr2	211481265	+	ENST00000427836	PLEKHM3	chr2	208693220	-	3077	2883	196	3060	954
ENST00000451903	CPS1	chr2	211481265	+	ENST00000427836	PLEKHM3	chr2	208693220	-	2026	1832	312	2009	565

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
ENST00000430249	ENST00000427836	CPS1	chr2	211481265	+	PLEKHM3	chr2	208693220	-	0.000956432	0.9990435
ENST00000233072	ENST00000427836	CPS1	chr2	211481265	+	PLEKHM3	chr2	208693220	-	0.000561446	0.9994386
ENST00000451903	ENST00000427836	CPS1	chr2	211481265	+	PLEKHM3	chr2	208693220	-	0.001724485	0.9982755

Top

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

>19095_19095_1_CPS1-PLEKHM3_CPS1_chr2_211481265_ENST00000233072_PLEKHM3_chr2_208693220_ENST00000427836_length(amino acids)=954AA_BP=895
MTRILTAFKVVRTLKTGFGFTNVTAHQKWKFSRPGIRLLSVKAQTAHIVLEDGTKMKGYSFGHPSSVAGEVVFNTGLGGYPEAITDPAYK
GQILTMANPIIGNGGAPDTTALDELGLSKYLESNGIKVSGLLVLDYSKDYNHWLATKSLGQWLQEEKVPAIYGVDTRMLTKIIRDKGTML
GKIEFEGQPVDFVDPNKQNLIAEVSTKDVKVYGKGNPTKVVAVDCGIKNNVIRLLVKRGAEVHLVPWNHDFTKMEYDGILIAGGPGNPAL
AEPLIQNVRKILESDRKEPLFGISTGNLITGLAAGAKTYKMSMANRGQNQPVLNITNKQAFITAQNHGYALDNTLPAGWKPLFVNVNDQT
NEGIMHESKPFFAVQFHPEVTPGPIDTEYLFDSFFSLIKKGKATTITSVLPKPALVASRVEVSKVLILGSGGLSIGQAGEFDYSGSQAVK
AMKEENVKTVLMNPNIASVQTNEVGLKQADTVYFLPITPQFVTEVIKAEQPDGLILGMGGQTALNCGVELFKRGVLKEYGVKVLGTSVES
IMATEDRQLFSDKLNEINEKIAPSFAVESIEDALKAADTIGYPVMIRSAYALGGLGSGICPNRETLMDLSTKAFAMTNQILVEKSVTGWK
EIEYEVVRDADDNCVTVCNMENVDAMGVHTGDSVVVAPAQTLSNAEFQMLRRTSINVVRHLGIVGECNIQFALHPTSMEYCIIEVNARLS
RSSALASKATGYPLAFIAAKIALGIPLPEIKNVVSGKTSACFEPSLDYMVTKIPRWDLDRFHGTSSRIGSSMKSVGEVMAIGRTFEESFQ
KALRMCHPSIEGFTPRLPMNKEWPSNLDLRKELSEPSSTRIYAIAKAIDDNMSLDEIEKLTYIDKWFLYKMRDILNMEKTLKGLNRCESC

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

>19095_19095_2_CPS1-PLEKHM3_CPS1_chr2_211481265_ENST00000430249_PLEKHM3_chr2_208693220_ENST00000427836_length(amino acids)=960AA_BP=901
MPQIIKMTRILTAFKVVRTLKTGFGFTNVTAHQKWKFSRPGIRLLSVKAQTAHIVLEDGTKMKGYSFGHPSSVAGEVVFNTGLGGYPEAI
TDPAYKGQILTMANPIIGNGGAPDTTALDELGLSKYLESNGIKVSGLLVLDYSKDYNHWLATKSLGQWLQEEKVPAIYGVDTRMLTKIIR
DKGTMLGKIEFEGQPVDFVDPNKQNLIAEVSTKDVKVYGKGNPTKVVAVDCGIKNNVIRLLVKRGAEVHLVPWNHDFTKMEYDGILIAGG
PGNPALAEPLIQNVRKILESDRKEPLFGISTGNLITGLAAGAKTYKMSMANRGQNQPVLNITNKQAFITAQNHGYALDNTLPAGWKPLFV
NVNDQTNEGIMHESKPFFAVQFHPEVTPGPIDTEYLFDSFFSLIKKGKATTITSVLPKPALVASRVEVSKVLILGSGGLSIGQAGEFDYS
GSQAVKAMKEENVKTVLMNPNIASVQTNEVGLKQADTVYFLPITPQFVTEVIKAEQPDGLILGMGGQTALNCGVELFKRGVLKEYGVKVL
GTSVESIMATEDRQLFSDKLNEINEKIAPSFAVESIEDALKAADTIGYPVMIRSAYALGGLGSGICPNRETLMDLSTKAFAMTNQILVEK
SVTGWKEIEYEVVRDADDNCVTVCNMENVDAMGVHTGDSVVVAPAQTLSNAEFQMLRRTSINVVRHLGIVGECNIQFALHPTSMEYCIIE
VNARLSRSSALASKATGYPLAFIAAKIALGIPLPEIKNVVSGKTSACFEPSLDYMVTKIPRWDLDRFHGTSSRIGSSMKSVGEVMAIGRT
FEESFQKALRMCHPSIEGFTPRLPMNKEWPSNLDLRKELSEPSSTRIYAIAKAIDDNMSLDEIEKLTYIDKWFLYKMRDILNMEKTLKGL

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

>19095_19095_3_CPS1-PLEKHM3_CPS1_chr2_211481265_ENST00000451903_PLEKHM3_chr2_208693220_ENST00000427836_length(amino acids)=565AA_BP=506
MFDSFFSLIKKGKATTITSVLPKPALVASRVEVSKVLILGSGGLSIGQAGEFDYSGSQAVKAMKEENVKTVLMNPNIASVQTNEVGLKQA
DTVYFLPITPQFVTEVIKAEQPDGLILGMGGQTALNCGVELFKRGVLKEYGVKVLGTSVESIMATEDRQLFSDKLNEINEKIAPSFAVES
IEDALKAADTIGYPVMIRSAYALGGLGSGICPNRETLMDLSTKAFAMTNQILVEKSVTGWKEIEYEVVRDADDNCVTVCNMENVDAMGVH
TGDSVVVAPAQTLSNAEFQMLRRTSINVVRHLGIVGECNIQFALHPTSMEYCIIEVNARLSRSSALASKATGYPLAFIAAKIALGIPLPE
IKNVVSGKTSACFEPSLDYMVTKIPRWDLDRFHGTSSRIGSSMKSVGEVMAIGRTFEESFQKALRMCHPSIEGFTPRLPMNKEWPSNLDL
RKELSEPSSTRIYAIAKAIDDNMSLDEIEKLTYIDKWFLYKMRDILNMEKTLKGLNRCESCGAVFHSECKEKSVPCPRCVRRELQKKQKS

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

Top

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/chr2:211481265/chr2:208693220)
- 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
CPS1 P31327	.
FUNCTION: Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.	FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

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

CPS1

chr2:211481265

chr2:208693220

ENST00000233072

219_404

895.6666666666666

1501.0

Domain

Note=Glutamine amidotransferase type-1

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000233072

551_743

895.6666666666666

1501.0

Domain

Note=ATP-grasp 1

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000430249

219_404

901.6666666666666

1507.0

Domain

Note=Glutamine amidotransferase type-1

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000430249

551_743

901.6666666666666

1507.0

Domain

Note=ATP-grasp 1

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000451903

219_404

444.6666666666667

1050.0

Domain

Note=Glutamine amidotransferase type-1

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000233072

39_218

895.6666666666666

1501.0

Region

Note=Anthranilate phosphoribosyltransferase homolog

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000430249

39_218

901.6666666666666

1507.0

Region

Note=Anthranilate phosphoribosyltransferase homolog

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000451903

39_218

444.6666666666667

1050.0

Region

Note=Anthranilate phosphoribosyltransferase homolog

Tgene

PLEKHM3

chr2:211481265

chr2:208693220

ENST00000389247

169_175

718.0

Compositional bias

Note=Poly-Gln

Tgene

PLEKHM3

chr2:211481265

chr2:208693220

ENST00000389247

211_308

718.0

Domain

PH 1

Tgene

PLEKHM3

chr2:211481265

chr2:208693220

ENST00000389247

361_456

718.0

Domain

PH 2

Tgene

PLEKHM3

chr2:211481265

chr2:208693220

ENST00000389247

669_722

718.0

Zinc finger

Note=Phorbol-ester/DAG-type

- 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

CPS1

chr2:211481265

chr2:208693220

ENST00000233072

1093_1284

895.6666666666666

1501.0

Domain

Note=ATP-grasp 2

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000233072

1355_1500

895.6666666666666

1501.0

Domain

MGS-like

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000430249

1093_1284

901.6666666666666

1507.0

Domain

Note=ATP-grasp 2

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000430249

1355_1500

901.6666666666666

1507.0

Domain

MGS-like

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000451903

1093_1284

444.6666666666667

1050.0

Domain

Note=ATP-grasp 2

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000451903

1355_1500

444.6666666666667

1050.0

Domain

MGS-like

Hgene

CPS1

chr2:211481265

chr2:208693220

ENST00000451903

551_743

444.6666666666667

1050.0

Domain

Note=ATP-grasp 1

Tgene

PLEKHM3

chr2:211481265

chr2:208693220

ENST00000427836

169_175

702.6666666666666

762.0

Compositional bias

Note=Poly-Gln

Tgene

PLEKHM3

chr2:211481265

chr2:208693220

ENST00000427836

211_308

702.6666666666666

762.0

Domain

PH 1

Tgene

PLEKHM3

chr2:211481265

chr2:208693220

ENST00000427836

361_456

702.6666666666666

762.0

Domain

PH 2

Tgene

PLEKHM3

chr2:211481265

chr2:208693220

ENST00000427836

669_722

702.6666666666666

762.0

Zinc finger

Note=Phorbol-ester/DAG-type

Top

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 >>>1762_CPS1_211481265_PLEKHM3_208693220_ranked_0.pdb	CPS1	211481265	211481265	ENST00000427836	PLEKHM3	chr2	208693220	-	MPQIIKMTRILTAFKVVRTLKTGFGFTNVTAHQKWKFSRPGIRLLSVKAQTAHIVLEDGTKMKGYSFGHPSSVAGEVVFNTGLGGYPEAI TDPAYKGQILTMANPIIGNGGAPDTTALDELGLSKYLESNGIKVSGLLVLDYSKDYNHWLATKSLGQWLQEEKVPAIYGVDTRMLTKIIR DKGTMLGKIEFEGQPVDFVDPNKQNLIAEVSTKDVKVYGKGNPTKVVAVDCGIKNNVIRLLVKRGAEVHLVPWNHDFTKMEYDGILIAGG PGNPALAEPLIQNVRKILESDRKEPLFGISTGNLITGLAAGAKTYKMSMANRGQNQPVLNITNKQAFITAQNHGYALDNTLPAGWKPLFV NVNDQTNEGIMHESKPFFAVQFHPEVTPGPIDTEYLFDSFFSLIKKGKATTITSVLPKPALVASRVEVSKVLILGSGGLSIGQAGEFDYS GSQAVKAMKEENVKTVLMNPNIASVQTNEVGLKQADTVYFLPITPQFVTEVIKAEQPDGLILGMGGQTALNCGVELFKRGVLKEYGVKVL GTSVESIMATEDRQLFSDKLNEINEKIAPSFAVESIEDALKAADTIGYPVMIRSAYALGGLGSGICPNRETLMDLSTKAFAMTNQILVEK SVTGWKEIEYEVVRDADDNCVTVCNMENVDAMGVHTGDSVVVAPAQTLSNAEFQMLRRTSINVVRHLGIVGECNIQFALHPTSMEYCIIE VNARLSRSSALASKATGYPLAFIAAKIALGIPLPEIKNVVSGKTSACFEPSLDYMVTKIPRWDLDRFHGTSSRIGSSMKSVGEVMAIGRT FEESFQKALRMCHPSIEGFTPRLPMNKEWPSNLDLRKELSEPSSTRIYAIAKAIDDNMSLDEIEKLTYIDKWFLYKMRDILNMEKTLKGL	960

Top

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.

CPS1_pLDDT.png

PLEKHM3_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.

Top

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

Top

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
CPS1
PLEKHM3

- 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

Top

Related Drugs to CPS1-PLEKHM3

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

Top

Related Diseases to CPS1-PLEKHM3

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