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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:ALCAM-PARN

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: ALCAM-PARN
	FusionPDB ID: 3818
	FusionGDB2.0 ID: 3818
		Hgene	Tgene
	Gene symbol	ALCAM	PARN
	Gene ID	214	5073
	Gene name	activated leukocyte cell adhesion molecule	poly(A)-specific ribonuclease
	Synonyms	CD166\|MEMD	DAN\|DKCB6\|PFBMFT4
	Cytomap	3q13.11	16p13.12
	Type of gene	protein-coding	protein-coding
	Description	CD166 antigen	poly(A)-specific ribonuclease PARNdeadenylating nucleasedeadenylation nucleasepolyadenylate-specific ribonuclease
	Modification date	20200320	20200313
	UniProtAcc	Q13740	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000306107, ENST00000472644, ENST00000389927, ENST00000481337, ENST00000486979,	ENST00000566021, ENST00000341484, ENST00000420015, ENST00000437198, ENST00000539279,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	15 X 13 X 6=1170	9 X 8 X 4=288
	# samples	17	9
	** MAII score	log2(17/1170*10)=-2.78290187833307 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(9/288*10)=-1.67807190511264 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: ALCAM [Title/Abstract] AND PARN [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	ALCAM(105086325)-PARN(14576684), # samples:2
Anticipated loss of major functional domain due to fusion event.	ALCAM-PARN 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. ALCAM-PARN 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
Tgene	PARN	GO:0000495	box H/ACA snoRNA 3'-end processing	22442037
Tgene	PARN	GO:0010587	miRNA catabolic process	25049417
Tgene	PARN	GO:0071051	polyadenylation-dependent snoRNA 3'-end processing	22442037

Fusion gene breakpoints across ALCAM (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 PARN (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	STAD	TCGA-CD-A4MI	ALCAM	chr3	105086325	+	PARN	chr16	14576684	-
ChimerDB4	UCEC	TCGA-B5-A11N	ALCAM	chr3	105086325	+	PARN	chr16	14576684	-

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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)
ENST00000306107	ALCAM	chr3	105086325	+	ENST00000437198	PARN	chr16	14576684	-	2029	573	392	1012	206
ENST00000306107	ALCAM	chr3	105086325	+	ENST00000420015	PARN	chr16	14576684	-	1457	573	392	1012	206
ENST00000306107	ALCAM	chr3	105086325	+	ENST00000341484	PARN	chr16	14576684	-	1125	573	392	1012	206
ENST00000306107	ALCAM	chr3	105086325	+	ENST00000539279	PARN	chr16	14576684	-	1062	573	392	1012	206
ENST00000472644	ALCAM	chr3	105086325	+	ENST00000437198	PARN	chr16	14576684	-	1595	139	66	578	170
ENST00000472644	ALCAM	chr3	105086325	+	ENST00000420015	PARN	chr16	14576684	-	1023	139	66	578	170
ENST00000472644	ALCAM	chr3	105086325	+	ENST00000341484	PARN	chr16	14576684	-	691	139	66	578	170
ENST00000472644	ALCAM	chr3	105086325	+	ENST00000539279	PARN	chr16	14576684	-	628	139	66	578	170

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
ENST00000306107	ENST00000437198	ALCAM	chr3	105086325	+	PARN	chr16	14576684	-	0.007057557	0.99294245
ENST00000306107	ENST00000420015	ALCAM	chr3	105086325	+	PARN	chr16	14576684	-	0.009631019	0.990369
ENST00000306107	ENST00000341484	ALCAM	chr3	105086325	+	PARN	chr16	14576684	-	0.014333971	0.985666
ENST00000306107	ENST00000539279	ALCAM	chr3	105086325	+	PARN	chr16	14576684	-	0.015223854	0.98477614
ENST00000472644	ENST00000437198	ALCAM	chr3	105086325	+	PARN	chr16	14576684	-	0.004212467	0.99578756
ENST00000472644	ENST00000420015	ALCAM	chr3	105086325	+	PARN	chr16	14576684	-	0.008627999	0.991372
ENST00000472644	ENST00000341484	ALCAM	chr3	105086325	+	PARN	chr16	14576684	-	0.011654555	0.9883455
ENST00000472644	ENST00000539279	ALCAM	chr3	105086325	+	PARN	chr16	14576684	-	0.012841049	0.9871589

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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

>3818_3818_1_ALCAM-PARN_ALCAM_chr3_105086325_ENST00000306107_PARN_chr16_14576684_ENST00000341484_length(amino acids)=206AA_BP=60
MPLRRDPPARGHRGARDDAPSCGVDSVSGPPRRRRNMESKGASSCRLLFCLLISATVFRPAVNTSKYAESYRIQTYAEYMGRKQEEKQIK
RKWTEDSWKEADSKRLNPQCIPYTLQNHYYRNNSFTAPSTVGKRNLSPSQEEAGLEDGVSGEISDTELEQTDSCAEPLSEGRKKAKKLKR

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

>3818_3818_2_ALCAM-PARN_ALCAM_chr3_105086325_ENST00000306107_PARN_chr16_14576684_ENST00000420015_length(amino acids)=206AA_BP=60
MPLRRDPPARGHRGARDDAPSCGVDSVSGPPRRRRNMESKGASSCRLLFCLLISATVFRPAVNTSKYAESYRIQTYAEYMGRKQEEKQIK
RKWTEDSWKEADSKRLNPQCIPYTLQNHYYRNNSFTAPSTVGKRNLSPSQEEAGLEDGVSGEISDTELEQTDSCAEPLSEGRKKAKKLKR

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

>3818_3818_3_ALCAM-PARN_ALCAM_chr3_105086325_ENST00000306107_PARN_chr16_14576684_ENST00000437198_length(amino acids)=206AA_BP=60
MPLRRDPPARGHRGARDDAPSCGVDSVSGPPRRRRNMESKGASSCRLLFCLLISATVFRPAVNTSKYAESYRIQTYAEYMGRKQEEKQIK
RKWTEDSWKEADSKRLNPQCIPYTLQNHYYRNNSFTAPSTVGKRNLSPSQEEAGLEDGVSGEISDTELEQTDSCAEPLSEGRKKAKKLKR

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

>3818_3818_4_ALCAM-PARN_ALCAM_chr3_105086325_ENST00000306107_PARN_chr16_14576684_ENST00000539279_length(amino acids)=206AA_BP=60
MPLRRDPPARGHRGARDDAPSCGVDSVSGPPRRRRNMESKGASSCRLLFCLLISATVFRPAVNTSKYAESYRIQTYAEYMGRKQEEKQIK
RKWTEDSWKEADSKRLNPQCIPYTLQNHYYRNNSFTAPSTVGKRNLSPSQEEAGLEDGVSGEISDTELEQTDSCAEPLSEGRKKAKKLKR

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

>3818_3818_5_ALCAM-PARN_ALCAM_chr3_105086325_ENST00000472644_PARN_chr16_14576684_ENST00000341484_length(amino acids)=170AA_BP=24
MESKGASSCRLLFCLLISATVFRPAVNTSKYAESYRIQTYAEYMGRKQEEKQIKRKWTEDSWKEADSKRLNPQCIPYTLQNHYYRNNSFT

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

>3818_3818_6_ALCAM-PARN_ALCAM_chr3_105086325_ENST00000472644_PARN_chr16_14576684_ENST00000420015_length(amino acids)=170AA_BP=24
MESKGASSCRLLFCLLISATVFRPAVNTSKYAESYRIQTYAEYMGRKQEEKQIKRKWTEDSWKEADSKRLNPQCIPYTLQNHYYRNNSFT

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

>3818_3818_7_ALCAM-PARN_ALCAM_chr3_105086325_ENST00000472644_PARN_chr16_14576684_ENST00000437198_length(amino acids)=170AA_BP=24
MESKGASSCRLLFCLLISATVFRPAVNTSKYAESYRIQTYAEYMGRKQEEKQIKRKWTEDSWKEADSKRLNPQCIPYTLQNHYYRNNSFT

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

>3818_3818_8_ALCAM-PARN_ALCAM_chr3_105086325_ENST00000472644_PARN_chr16_14576684_ENST00000539279_length(amino acids)=170AA_BP=24
MESKGASSCRLLFCLLISATVFRPAVNTSKYAESYRIQTYAEYMGRKQEEKQIKRKWTEDSWKEADSKRLNPQCIPYTLQNHYYRNNSFT

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

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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/chr3:105086325/chr16:14576684)
- 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
ALCAM Q13740	.
FUNCTION: Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts (PubMed:7760007, PubMed:15496415, PubMed:15048703, PubMed:16352806, PubMed:23169771, PubMed:24945728). Promotes T-cell activation and proliferation via its interactions with CD6 (PubMed:15048703, PubMed:16352806, PubMed:24945728). Contributes to the formation and maturation of the immunological synapse via its interactions with CD6 (PubMed:15294938, PubMed:16352806). Mediates homotypic interactions with cells that express ALCAM (PubMed:15496415, PubMed:16352806). Required for normal hematopoietic stem cell engraftment in the bone marrow (PubMed:24740813). Mediates attachment of dendritic cells onto endothelial cells via homotypic interaction (PubMed:23169771). Inhibits endothelial cell migration and promotes endothelial tube formation via homotypic interactions (PubMed:15496415, PubMed:23169771). Required for normal organization of the lymph vessel network. Required for normal hematopoietic stem cell engraftment in the bone marrow. Plays a role in hematopoiesis; required for normal numbers of hematopoietic stem cells in bone marrow. Promotes in vitro osteoblast proliferation and differentiation (By similarity). Promotes neurite extension, axon growth and axon guidance; axons grow preferentially on surfaces that contain ALCAM. Mediates outgrowth and pathfinding for retinal ganglion cell axons (By similarity). {ECO:0000250\|UniProtKB:P42292, ECO:0000269\|PubMed:15048703, ECO:0000269\|PubMed:15294938, ECO:0000269\|PubMed:15496415, ECO:0000269\|PubMed:16352806, ECO:0000269\|PubMed:24945728, ECO:0000269\|PubMed:7760007}.; FUNCTION: [Isoform 3]: Inhibits activities of membrane-bound isoforms by competing for the same interaction partners. Inhibits cell attachment via homotypic interactions. Promotes endothelial cell migration. Inhibits endothelial cell tube formation. {ECO:0000269\|PubMed:15496415}.	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

- 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

ALCAM

chr3:105086325

chr16:14576684

ENST00000306107

125_234

24.333333333333332

1201.0

Domain

Note=Ig-like V-type 2

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000306107

245_328

24.333333333333332

1201.0

Domain

Note=Ig-like C2-type 1

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000306107

28_120

24.333333333333332

1201.0

Domain

Note=Ig-like V-type 1

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000306107

333_409

24.333333333333332

1201.0

Domain

Note=Ig-like C2-type 2

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000306107

416_501

24.333333333333332

1201.0

Domain

Note=Ig-like C2-type 3

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000472644

125_234

24.333333333333332

1319.6666666666667

Domain

Note=Ig-like V-type 2

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000472644

245_328

24.333333333333332

1319.6666666666667

Domain

Note=Ig-like C2-type 1

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000472644

28_120

24.333333333333332

1319.6666666666667

Domain

Note=Ig-like V-type 1

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000472644

333_409

24.333333333333332

1319.6666666666667

Domain

Note=Ig-like C2-type 2

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000472644

416_501

24.333333333333332

1319.6666666666667

Domain

Note=Ig-like C2-type 3

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000306107

28_527

24.333333333333332

1201.0

Topological domain

Extracellular

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000306107

550_583

24.333333333333332

1201.0

Topological domain

Cytoplasmic

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000472644

28_527

24.333333333333332

1319.6666666666667

Topological domain

Extracellular

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000472644

550_583

24.333333333333332

1319.6666666666667

Topological domain

Cytoplasmic

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000306107

528_549

24.333333333333332

1201.0

Transmembrane

Helical

Hgene

ALCAM

chr3:105086325

chr16:14576684

ENST00000472644

528_549

24.333333333333332

1319.6666666666667

Transmembrane

Helical

Tgene

PARN

chr3:105086325

chr16:14576684

ENST00000341484

178_245

432.3333333333333

579.0

Domain

R3H

Tgene

PARN

chr3:105086325

chr16:14576684

ENST00000420015

178_245

447.3333333333333

594.0

Domain

R3H

Tgene

PARN

chr3:105086325

chr16:14576684

ENST00000437198

178_245

493.3333333333333

640.0

Domain

R3H

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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 >>>289_ALCAM_105086325_PARN_14576684_ranked_0.pdb	ALCAM	105086325	105086325	ENST00000539279	PARN	chr16	14576684	-	MPLRRDPPARGHRGARDDAPSCGVDSVSGPPRRRRNMESKGASSCRLLFCLLISATVFRPAVNTSKYAESYRIQTYAEYMGRKQEEKQIK RKWTEDSWKEADSKRLNPQCIPYTLQNHYYRNNSFTAPSTVGKRNLSPSQEEAGLEDGVSGEISDTELEQTDSCAEPLSEGRKKAKKLKR	206

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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.

ALCAM_pLDDT.png

PARN_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
ALCAM
PARN

- 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 ALCAM-PARN

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 ALCAM-PARN

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