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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:TMEM135-CLMP

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: TMEM135-CLMP
	FusionPDB ID: 91673
	FusionGDB2.0 ID: 91673
		Hgene	Tgene
	Gene symbol	TMEM135	CLMP
	Gene ID	65084	79827
	Gene name	transmembrane protein 135	CXADR like membrane protein
	Synonyms	PMP52	ACAM\|ASAM\|CSBM\|CSBS
	Cytomap	11q14.2	11q24.1
	Type of gene	protein-coding	protein-coding
	Description	transmembrane protein 135peroxisomal membrane protein 52	CXADR-like membrane proteinCAR-like membrane proteinadipocyte-specific adhesion moleculecoxsackie- and adenovirus receptor-like membrane protein
	Modification date	20200313	20200313
	UniProtAcc	.	Q9H6B4
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000305494, ENST00000340353, ENST00000355734, ENST00000532959, ENST00000535167,	ENST00000530371, ENST00000448775,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	17 X 12 X 8=1632	2 X 2 X 2=8
	# samples	20	2
	** MAII score	log2(20/1632*10)=-3.02856915219677 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: TMEM135 [Title/Abstract] AND CLMP [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	TMEM135(86802437)-CLMP(122955421), # samples:4
Anticipated loss of major functional domain due to fusion event.	TMEM135-CLMP 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. TMEM135-CLMP 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. TMEM135-CLMP 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. TMEM135-CLMP 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

Fusion gene breakpoints across TMEM135 (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 CLMP (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	BRCA	TCGA-A8-A06Z-01A	TMEM135	chr11	86802437	-	CLMP	chr11	122955421	-
ChimerDB4	BRCA	TCGA-A8-A06Z-01A	TMEM135	chr11	86802437	+	CLMP	chr11	122955421	-
ChimerDB4	BRCA	TCGA-A8-A06Z	TMEM135	chr11	86802437	+	CLMP	chr11	122955421	-

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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)
ENST00000340353	TMEM135	chr11	86802437	+	ENST00000448775	CLMP	chr11	122955421	-	2681	598	124	1533	469
ENST00000305494	TMEM135	chr11	86802437	+	ENST00000448775	CLMP	chr11	122955421	-	2518	435	27	1370	447
ENST00000355734	TMEM135	chr11	86802437	+	ENST00000448775	CLMP	chr11	122955421	-	2540	457	10	1392	460

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
ENST00000340353	ENST00000448775	TMEM135	chr11	86802437	+	CLMP	chr11	122955421	-	0.007763933	0.9922361
ENST00000305494	ENST00000448775	TMEM135	chr11	86802437	+	CLMP	chr11	122955421	-	0.005592036	0.994408
ENST00000355734	ENST00000448775	TMEM135	chr11	86802437	+	CLMP	chr11	122955421	-	0.006342004	0.993658

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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

>91673_91673_1_TMEM135-CLMP_TMEM135_chr11_86802437_ENST00000305494_CLMP_chr11_122955421_ENST00000448775_length(amino acids)=447AA_BP=136
MFLVMAALSKSIPHNCYEIGHTWHPSCRVSFLQITGGALEESLKIYAPLYLIAAILRKRKLDYYLHKLLPEILQSASFLTANGALYMAFF
CILRKILGKFYSWTPGFGAALPASYVAILIERKSRRGLLTIYMANLVITYSSRHVYNNLTEEQKGRVAFASNFLAGDASLQIEPLKPSDE
GRYTCKVKNSGRYVWSHVILKVLVRPSKPKCELEGELTEGSDLTLQCESSSGTEPIVYYWQRIREKEGEDERLPPKSRIDYNHPGRVLLQ
NLTMSYSGLYQCTAGNEAGKESCVVRVTVQYVQSIGMVAGAVTGIVAGALLIFLLVWLLIRRKDKERYEEEERPNEIREDAEAPKARLVK

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

>91673_91673_2_TMEM135-CLMP_TMEM135_chr11_86802437_ENST00000340353_CLMP_chr11_122955421_ENST00000448775_length(amino acids)=469AA_BP=158
MAAGLSRPSLQGSGSPPPVFSALFLVMAALSKSIPHNCYEIGHTWHPSCRVSFLQITGGALEESLKIYAPLYLIAAILRKRKLDYYLHKL
LPEILQSASFLTANGALYMAFFCILRKILGKFYSWTPGFGAALPASYVAILIERKSRRGLLTIYMANLVITYSSRHVYNNLTEEQKGRVA
FASNFLAGDASLQIEPLKPSDEGRYTCKVKNSGRYVWSHVILKVLVRPSKPKCELEGELTEGSDLTLQCESSSGTEPIVYYWQRIREKEG
EDERLPPKSRIDYNHPGRVLLQNLTMSYSGLYQCTAGNEAGKESCVVRVTVQYVQSIGMVAGAVTGIVAGALLIFLLVWLLIRRKDKERY
EEEERPNEIREDAEAPKARLVKPSSSSSGSRSSRSGSSSTRSTANSASRSQRTLSTDAAPQPGLATQAYSLVGPEVRGSEPKKVHHANLT

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

>91673_91673_3_TMEM135-CLMP_TMEM135_chr11_86802437_ENST00000355734_CLMP_chr11_122955421_ENST00000448775_length(amino acids)=460AA_BP=149
MQGSGSPPPVFSALFLVMAALSKSIPHNCYEIGHTWHPSCRVSFLQITGGALEESLKIYAPLYLIAAILRKRKLDYYLHKLLPEILQSAS
FLTANGALYMAFFCILRKILGKFYSWTPGFGAALPASYVAILIERKSRRGLLTIYMANLVITYSSRHVYNNLTEEQKGRVAFASNFLAGD
ASLQIEPLKPSDEGRYTCKVKNSGRYVWSHVILKVLVRPSKPKCELEGELTEGSDLTLQCESSSGTEPIVYYWQRIREKEGEDERLPPKS
RIDYNHPGRVLLQNLTMSYSGLYQCTAGNEAGKESCVVRVTVQYVQSIGMVAGAVTGIVAGALLIFLLVWLLIRRKDKERYEEEERPNEI
REDAEAPKARLVKPSSSSSGSRSSRSGSSSTRSTANSASRSQRTLSTDAAPQPGLATQAYSLVGPEVRGSEPKKVHHANLTKAETTPSMI

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

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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/chr11:86802437/chr11:122955421)
- 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
.	CLMP Q9H6B4
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.	FUNCTION: May be involved in the cell-cell adhesion. May play a role in adipocyte differentiation and development of obesity. Is required for normal small intestine development. {ECO:0000269\|PubMed:14573622, ECO:0000269\|PubMed:15563274, ECO:0000269\|PubMed:22155368}.

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

TMEM135

chr11:86802437

chr11:122955421

ENST00000305494

68_88

132.0

459.0

Transmembrane

Helical

Hgene

TMEM135

chr11:86802437

chr11:122955421

ENST00000305494

96_116

132.0

459.0

Transmembrane

Helical

Hgene

TMEM135

chr11:86802437

chr11:122955421

ENST00000340353

68_88

132.0

437.0

Transmembrane

Helical

Hgene

TMEM135

chr11:86802437

chr11:122955421

ENST00000340353

96_116

132.0

437.0

Transmembrane

Helical

Tgene

CLMP

chr11:86802437

chr11:122955421

ENST00000448775

265_268

62.0

374.0

Compositional bias

Note=Poly-Glu

Tgene

CLMP

chr11:86802437

chr11:122955421

ENST00000448775

288_314

62.0

374.0

Compositional bias

Note=Ser-rich

Tgene

CLMP

chr11:86802437

chr11:122955421

ENST00000448775

135_224

62.0

374.0

Domain

Note=Ig-like C2-type 2

Tgene

CLMP

chr11:86802437

chr11:122955421

ENST00000448775

257_373

62.0

374.0

Topological domain

Cytoplasmic

Tgene

CLMP

chr11:86802437

chr11:122955421

ENST00000448775

236_256

62.0

374.0

Transmembrane

Helical

- 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

TMEM135

chr11:86802437

chr11:122955421

ENST00000305494

149_169

132.0

459.0

Transmembrane

Helical

Hgene

TMEM135

chr11:86802437

chr11:122955421

ENST00000305494

298_318

132.0

459.0

Transmembrane

Helical

Hgene

TMEM135

chr11:86802437

chr11:122955421

ENST00000305494

331_351

132.0

459.0

Transmembrane

Helical

Hgene

TMEM135

chr11:86802437

chr11:122955421

ENST00000305494

380_400

132.0

459.0

Transmembrane

Helical

Hgene

TMEM135

chr11:86802437

chr11:122955421

ENST00000340353

149_169

132.0

437.0

Transmembrane

Helical

Hgene

TMEM135

chr11:86802437

chr11:122955421

ENST00000340353

298_318

132.0

437.0

Transmembrane

Helical

Hgene

TMEM135

chr11:86802437

chr11:122955421

ENST00000340353

331_351

132.0

437.0

Transmembrane

Helical

Hgene

TMEM135

chr11:86802437

chr11:122955421

ENST00000340353

380_400

132.0

437.0

Transmembrane

Helical

Tgene

CLMP

chr11:86802437

chr11:122955421

ENST00000448775

19_127

62.0

374.0

Domain

Note=Ig-like C2-type 1

Tgene

CLMP

chr11:86802437

chr11:122955421

ENST00000448775

19_235

62.0

374.0

Topological domain

Extracellular

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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 >>>986_TMEM135_86802437_CLMP_122955421_986_TMEM135_86802437_CLMP_122955421_ranked_0.pdb	TMEM135	86802437	86802437	ENST00000448775	CLMP	chr11	122955421	-	MAAGLSRPSLQGSGSPPPVFSALFLVMAALSKSIPHNCYEIGHTWHPSCRVSFLQITGGALEESLKIYAPLYLIAAILRKRKLDYYLHKL LPEILQSASFLTANGALYMAFFCILRKILGKFYSWTPGFGAALPASYVAILIERKSRRGLLTIYMANLVITYSSRHVYNNLTEEQKGRVA FASNFLAGDASLQIEPLKPSDEGRYTCKVKNSGRYVWSHVILKVLVRPSKPKCELEGELTEGSDLTLQCESSSGTEPIVYYWQRIREKEG EDERLPPKSRIDYNHPGRVLLQNLTMSYSGLYQCTAGNEAGKESCVVRVTVQYVQSIGMVAGAVTGIVAGALLIFLLVWLLIRRKDKERY EEEERPNEIREDAEAPKARLVKPSSSSSGSRSSRSGSSSTRSTANSASRSQRTLSTDAAPQPGLATQAYSLVGPEVRGSEPKKVHHANLT	469

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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.

TMEM135_pLDDT.png

CLMP_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
TMEM135
CLMP

- 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 TMEM135-CLMP

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 TMEM135-CLMP

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