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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:NPM1-ALK

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: NPM1-ALK
	FusionPDB ID: 59963
	FusionGDB2.0 ID: 59963
		Hgene	Tgene
	Gene symbol	NPM1	ALK
	Gene ID	4869	238
	Gene name	nucleophosmin 1	ALK receptor tyrosine kinase
	Synonyms	B23\|NPM	CD246\|NBLST3
	Cytomap	5q35.1	2p23.2-p23.1
	Type of gene	protein-coding	protein-coding
	Description	nucleophosminnucleolar protein NO38nucleophosmin (nucleolar phosphoprotein B23, numatrin)nucleophosmin/nucleoplasmin family, member 1testicular tissue protein Li 128	ALK tyrosine kinase receptorCD246 antigenanaplastic lymphoma receptor tyrosine kinasemutant anaplastic lymphoma kinase
	Modification date	20200329	20200329
	UniProtAcc	P06748	Q96BT7
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000296930, ENST00000351986, ENST00000393820, ENST00000517671,	ENST00000389048, ENST00000431873, ENST00000498037,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	21 X 25 X 6=3150	56 X 74 X 20=82880
	# samples	32	57
	** MAII score	log2(32/3150*10)=-3.29920801838728 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(57/82880*10)=-7.18391827352181 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: NPM1 [Title/Abstract] AND ALK [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	NPM1(170818803)-ALK(29446396), # samples:4
Anticipated loss of major functional domain due to fusion event.	NPM1-ALK 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. NPM1-ALK 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. NPM1-ALK 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. NPM1-ALK 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. NPM1-ALK seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. NPM1-ALK seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. NPM1-ALK seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF. NPM1-ALK seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. NPM1-ALK seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. NPM1-ALK seems lost the major protein functional domain in Tgene partner, which is a kinase 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	NPM1	GO:0006281	DNA repair	19188445
Hgene	NPM1	GO:0006334	nucleosome assembly	11602260
Hgene	NPM1	GO:0006913	nucleocytoplasmic transport	16041368
Hgene	NPM1	GO:0008104	protein localization	18420587
Hgene	NPM1	GO:0008284	positive regulation of cell proliferation	22528486
Hgene	NPM1	GO:0032071	regulation of endodeoxyribonuclease activity	19188445
Hgene	NPM1	GO:0034644	cellular response to UV	19160485
Hgene	NPM1	GO:0043066	negative regulation of apoptotic process	12882984
Hgene	NPM1	GO:0044387	negative regulation of protein kinase activity by regulation of protein phosphorylation	12882984
Hgene	NPM1	GO:0045727	positive regulation of translation	12882984
Hgene	NPM1	GO:0045893	positive regulation of transcription, DNA-templated	22528486
Hgene	NPM1	GO:0045944	positive regulation of transcription by RNA polymerase II	19160485
Hgene	NPM1	GO:0060699	regulation of endoribonuclease activity	19188445
Hgene	NPM1	GO:0060735	regulation of eIF2 alpha phosphorylation by dsRNA	12882984
Hgene	NPM1	GO:1902751	positive regulation of cell cycle G2/M phase transition	22528486
Tgene	ALK	GO:0016310	phosphorylation	9174053
Tgene	ALK	GO:0046777	protein autophosphorylation	9174053

Fusion gene breakpoints across NPM1 (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 ALK (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	anaplastic large cell lymphoma;Hodgkin disease;npn Hodgkin lymphoma	D45915	NPM1	chr5	170818803		ALK	chr2	29415642
ChimerKB3	.	.	NPM1	chr5	170818803	+	ALK	chr2	29415642	-
ChimerKB3	.	.	NPM1	chr5	170818803	+	ALK	chr2	29416090	-
ChimerKB3	.	.	NPM1	chr5	170818803	+	ALK	chr2	29432744	-
ChimerKB3	.	.	NPM1	chr5	170819820	+	ALK	chr2	29446394	-
ChimerKB4	.	.	NPM1	chr5	170818803	+	ALK	chr2	29416090	-
ChiTaRS5.0	N/A	D45915	NPM1	chr5	170818803	+	ALK	chr2	29446396	-
ChiTaRS5.0	N/A	DI348757	NPM1	chr5	170818803	+	ALK	chr2	29446396	-
ChiTaRS5.0	N/A	HW349670	NPM1	chr5	170818803	+	ALK	chr2	29446396	-
ChiTaRS5.0	N/A	S82740	NPM1	chr5	170819529	+	ALK	chr2	29447054	-
ChiTaRS5.0	N/A	U04946	NPM1	chr5	170818803	+	ALK	chr2	29446396	-

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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)
ENST00000517671	NPM1	chr5	170818803	+	ENST00000389048	ALK	chr2	29446396	-	2628	487	42	2177	711
ENST00000296930	NPM1	chr5	170818803	+	ENST00000389048	ALK	chr2	29446396	-	2794	653	70	2343	757
ENST00000351986	NPM1	chr5	170818803	+	ENST00000389048	ALK	chr2	29446396	-	2613	472	42	2162	706
ENST00000393820	NPM1	chr5	170818803	+	ENST00000389048	ALK	chr2	29446396	-	2591	450	20	2140	706

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
ENST00000517671	ENST00000389048	NPM1	chr5	170818803	+	ALK	chr2	29446396	-	0.002362132	0.99763787
ENST00000296930	ENST00000389048	NPM1	chr5	170818803	+	ALK	chr2	29446396	-	0.001957753	0.9980422
ENST00000351986	ENST00000389048	NPM1	chr5	170818803	+	ALK	chr2	29446396	-	0.002376777	0.99762326
ENST00000393820	ENST00000389048	NPM1	chr5	170818803	+	ALK	chr2	29446396	-	0.002370775	0.9976292

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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

>59963_59963_1_NPM1-ALK_NPM1_chr5_170818803_ENST00000296930_ALK_chr2_29446396_ENST00000389048_length(amino acids)=757AA_BP=194
MKSACAGRLRYGGGRASEHARGGGTWEALARSSGSIYKRGEPASFPWCDSVLRGCSLEQRSFISVRLLSYLSACRHPMEDSMDMDMSPLR
PQNYLFGCELKADKDYHFKVDNDENEHQLSLRTVSLGAGAKDELHIVEAEAMNYEGSPIKVTLATLKMSVQPTVSLGGFEITPPVVLRLK
CGSGPVHISGQHLVVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEG
QVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAM
LDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTW
SFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGP
LVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSSGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVH
GSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEPSSLTANMKEVPLFRLRHFPCGNVN

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

>59963_59963_2_NPM1-ALK_NPM1_chr5_170818803_ENST00000351986_ALK_chr2_29446396_ENST00000389048_length(amino acids)=706AA_BP=143
MRGCSLEQRSFISVRLLSYLSACRHPMEDSMDMDMSPLRPQNYLFGCELKADKDYHFKVDNDENEHQLSLRTVSLGAGAKDELHIVEAEA
MNYEGSPIKVTLATLKMSVQPTVSLGGFEITPPVVLRLKCGSGPVHISGQHLVVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNP
NYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIG
VSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMA
RDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQ
CWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSSGKAAK
KPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPN

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

>59963_59963_3_NPM1-ALK_NPM1_chr5_170818803_ENST00000393820_ALK_chr2_29446396_ENST00000389048_length(amino acids)=706AA_BP=143
MRGCSLEQRSFISVRLLSYLSACRHPMEDSMDMDMSPLRPQNYLFGCELKADKDYHFKVDNDENEHQLSLRTVSLGAGAKDELHIVEAEA
MNYEGSPIKVTLATLKMSVQPTVSLGGFEITPPVVLRLKCGSGPVHISGQHLVVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNP
NYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIG
VSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMA
RDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQ
CWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSSGKAAK
KPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPN

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

>59963_59963_4_NPM1-ALK_NPM1_chr5_170818803_ENST00000517671_ALK_chr2_29446396_ENST00000389048_length(amino acids)=711AA_BP=148
MAPKLRKDKDFGDVFSGRTELKNKVPACRHPMEDSMDMDMSPLRPQNYLFGCELKADKDYHFKVDNDENEHQLSLRTVSLGAGAKDELHI
VEAEAMNYEGSPIKVTLATLKMSVQPTVSLGGFEITPPVVLRLKCGSGPVHISGQHLVVYRRKHQELQAMQMELQSPEYKLSKLRTSTIM
TDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNI
VRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIG
DFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVY
RIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSS
GKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSC

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

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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/chr5:170818803/chr2:29446396)
- 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
NPM1 P06748	ALK Q96BT7
FUNCTION: Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). {ECO:0000269\|PubMed:12882984, ECO:0000269\|PubMed:16107701, ECO:0000269\|PubMed:17015463, ECO:0000269\|PubMed:18809582, ECO:0000269\|PubMed:19188445, ECO:0000269\|PubMed:20352051, ECO:0000269\|PubMed:21084279, ECO:0000269\|PubMed:22002061, ECO:0000269\|PubMed:22528486, ECO:0000269\|PubMed:25956029}.	FUNCTION: Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain (PubMed:20123966, PubMed:20308323, PubMed:31079898). Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys)(PubMed:20308323). Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly) (PubMed:21285950). Required for normal survival after DNA damage (PubMed:20308323). May inhibit apoptosis and promote cell survival and angiogenesis (PubMed:19293182). {ECO:0000269\|PubMed:19293182, ECO:0000269\|PubMed:20123966, ECO:0000269\|PubMed:20308323, ECO:0000269\|PubMed:21285950, ECO:0000269\|PubMed:31079898}.

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

NPM1

chr5:170818803

chr2:29446396

ENST00000296930

1_9

117.33333333333333

295.0

Compositional bias

Note=Met-rich

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000351986

1_9

117.33333333333333

266.0

Compositional bias

Note=Met-rich

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000393820

1_9

117.33333333333333

260.0

Compositional bias

Note=Met-rich

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000517671

1_9

117.33333333333333

295.0

Compositional bias

Note=Met-rich

Tgene

ALK

chr5:170818803

chr2:29446396

ENST00000389048

1116_1392

1057.3333333333333

1621.0

Domain

Protein kinase

Tgene

ALK

chr5:170818803

chr2:29446396

ENST00000389048

1197_1199

1057.3333333333333

1621.0

Region

Note=Inhibitor binding

Tgene

ALK

chr5:170818803

chr2:29446396

ENST00000389048

1060_1620

1057.3333333333333

1621.0

Topological domain

Cytoplasmic

- 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

NPM1

chr5:170818803

chr2:29446396

ENST00000296930

120_132

117.33333333333333

295.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000296930

161_188

117.33333333333333

295.0

Compositional bias

Note=Asp/Glu-rich (highly acidic)

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000351986

120_132

117.33333333333333

266.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000351986

161_188

117.33333333333333

266.0

Compositional bias

Note=Asp/Glu-rich (highly acidic)

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000393820

120_132

117.33333333333333

260.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000393820

161_188

117.33333333333333

260.0

Compositional bias

Note=Asp/Glu-rich (highly acidic)

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000517671

120_132

117.33333333333333

295.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000517671

161_188

117.33333333333333

295.0

Compositional bias

Note=Asp/Glu-rich (highly acidic)

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000296930

152_157

117.33333333333333

295.0

Motif

Nuclear localization signal

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000296930

191_197

117.33333333333333

295.0

Motif

Nuclear localization signal

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000351986

152_157

117.33333333333333

266.0

Motif

Nuclear localization signal

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000351986

191_197

117.33333333333333

266.0

Motif

Nuclear localization signal

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000393820

152_157

117.33333333333333

260.0

Motif

Nuclear localization signal

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000393820

191_197

117.33333333333333

260.0

Motif

Nuclear localization signal

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000517671

152_157

117.33333333333333

295.0

Motif

Nuclear localization signal

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000517671

191_197

117.33333333333333

295.0

Motif

Nuclear localization signal

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000296930

243_294

117.33333333333333

295.0

Region

Note=Required for nucleolar localization

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000351986

243_294

117.33333333333333

266.0

Region

Note=Required for nucleolar localization

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000393820

243_294

117.33333333333333

260.0

Region

Note=Required for nucleolar localization

Hgene

NPM1

chr5:170818803

chr2:29446396

ENST00000517671

243_294

117.33333333333333

295.0

Region

Note=Required for nucleolar localization

Tgene

ALK

chr5:170818803

chr2:29446396

ENST00000389048

816_940

1057.3333333333333

1621.0

Compositional bias

Note=Gly-rich

Tgene

ALK

chr5:170818803

chr2:29446396

ENST00000389048

264_427

1057.3333333333333

1621.0

Domain

MAM 1

Tgene

ALK

chr5:170818803

chr2:29446396

ENST00000389048

437_473

1057.3333333333333

1621.0

Domain

Note=LDL-receptor class A

Tgene

ALK

chr5:170818803

chr2:29446396

ENST00000389048

478_636

1057.3333333333333

1621.0

Domain

MAM 2

Tgene

ALK

chr5:170818803

chr2:29446396

ENST00000389048

19_1038

1057.3333333333333

1621.0

Topological domain

Extracellular

Tgene

ALK

chr5:170818803

chr2:29446396

ENST00000389048

1039_1059

1057.3333333333333

1621.0

Transmembrane

Helical

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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 >>>1525_NPM1_170818803_ALK_29446396_ranked_0.pdb	NPM1	170818803	170818803	ENST00000389048	ALK	chr2	29446396	-	MKSACAGRLRYGGGRASEHARGGGTWEALARSSGSIYKRGEPASFPWCDSVLRGCSLEQRSFISVRLLSYLSACRHPMEDSMDMDMSPLR PQNYLFGCELKADKDYHFKVDNDENEHQLSLRTVSLGAGAKDELHIVEAEAMNYEGSPIKVTLATLKMSVQPTVSLGGFEITPPVVLRLK CGSGPVHISGQHLVVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEG QVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAM LDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTW SFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGP LVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSSGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVH GSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEPSSLTANMKEVPLFRLRHFPCGNVN	757

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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.

NPM1_pLDDT.png

ALK_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

NPM1

TCERG1, LYAR, USF2, HIST3H3, SWAP70, HAND2, NCL, OTUB1, AKT1, CDT1, RRP1B, Rrp1b, GRB2, CENPF, CASKIN1, CDC14A, PIK3R1, NUP98, PPID, GRB7, NCAPG, NUMA1, NSUN2, PADI4, TP53, BARD1, BRCA1, H2AFX, CDKN2A, HMGA2, HMGA1, HCVgp1, YY1, HIST1H3A, HIST2H2AC, HIST2H2BE, HIST1H4A, EP300, tat, PML, RARA, CTNNBL1, FANCA, FANCC, TFAP2A, HDAC1, HDAC2, SMARCA4, DOT1L, ACACA, HNRNPM, HNRNPU, DDX21, HIST1H1C, SIRT1, YBX1, PC, YBX3, H1FX, HIST1H1A, ESR1, Trp53, Cdkn2a, CDK5RAP3, ZNF668, UBC, RYK, SMN1, CD4, YWHAQ, USP36, CTCF, HDAC5, CDKN1A, NOP56, CENPA, AFF1, DYRK2, TOP1, CDK2, SREK1, SENP3, RB1, PARP1, HJURP, ARRB1, ARRB2, SIRT7, NPM3, NPM1, FBXO25, IRF1, CUL3, CUL4A, CUL5, CUL2, CUL1, COPS5, COPS6, DCUN1D1, CAND1, MDM2, PA2G4, PPP2R1A, MID1, GZF1, APEX1, COPS2, PLCG1, FBXO6, GAPDH, SIAH1, PTBP1, SRSF1, APP, RPL14, RPS6, RPL24, RPL6, NAP1L1, HNRNPR, RPS4X, PRPF6, LAMP2, SURF4, RPL10L, NAP1L4, ZYX, NUP62, NUP50, RPL5, YWHAE, FMNL1, CPSF6, HNRNPH1, PAPOLG, JUNB, MC4R, HIVEP2, CPSF1, CPSF2, CPSF4, CPSF3, FN1, VCAM1, CSNK2A1, NOS2, UBL4A, ITGA4, CBX2, CBX4, CBX8, PHB, EIF2AK2, XPO1, GZMM, PAN2, CD81, IGSF8, ICAM1, PRKCZ, KIF11, SQSTM1, FLNA, LLGL1, HSP90AA1, TRIM21, TUBA1C, HSP90AB1, PARD6B, CDC37, TUBB3, MRPL46, KCTD2, CLTC, MRPL50, VCP, KCTD5, MRPL12, HSPA5, PTRF, MRPL52, EEF1A1, KCTD17, TAB1, BAG2, ANXA2, EIF5A, PPIL4, MRPL38, STK38, FLNB, LGALS1, C1QBP, COPB1, MRPL37, MRPL49, KEAP1, PRDX4, WDR26, PSMC4, SDPR, SLC25A3, RPS12, EEF1B2, NIPSNAP1, EEF1G, MRPL39, DDX3X, RNH1, OSBPL1A, EIF3H, MRPL54, ENO1, MYCBP, MRPL18, MAP1B, PSMD1, EEF1D, DNAJC13, HSPB1, CFL1, FLNC, PPP1CC, RPLP1, CEP152, SNRPD1, ATP5A1, ARHGAP5, PRKAR1A, MRPL53, GID8, YWHAZ, CCT2, EIF3E, LAMB2, DICER1, CHCHD4, MRPL19, SNRPD2, GRWD1, TPR, PSMD4, PSMC5, PPP2CA, UNC5C, SLC25A5, PTPN14, RPS5, TTC27, BOLA2, EIF4A1, TUFM, S100A10, IMPG1, NUDT21, UTRN, MRPL44, EIF3M, MRPL43, PKM, IMPDH2, TRRAP, CHCHD6, RANBP6, EIF3I, TAB2, MRPL24, DZIP1, IPO5, AGR2, MRPS30, ICT1, PRDX6, TCP1, RCOR1, GRN, TXN, RPLP0, PCBP1, MRPL28, MRPL10, TAF3, EPAS1, CHCHD3, TXNDC12, ELMO2, SRRT, MRPL11, EIF2S1, SNRPF, KTN1, FGD6, UQCRH, RBBP4, DNAJA1, CTTN, USP15, NUDCD1, RPS28, JAK1, PROS1, PYGB, KDR, EEF2, FASN, AKAP11, CSNK2B, DNAJA2, EIF3G, DHX15, MRPS26, HNRNPA0, DOCK4, PRKCI, VASP, COPE, SAMM50, TEX15, PSME3, PPM1G, COPG1, CALU, S100A11, HSPA4, PSMD12, POLR2E, TRIM28, SLAIN2, RPL10, GOLGA2, GOLGA3, PRKCA, IPO9, PARK7, SPIN1, PPA1, BANP, DSTN, GNAI2, HOXA7, ABCC1, RELA, ACY1, TARDBP, PARK2, KPNA1, ARMCX3, LIMCH1, OSBP, TRMT61A, rev, RPA1, RPA2, RPA3, ERG, LGR4, STAU1, ELF4, AURKA, HUWE1, FUS, COX8A, NPM2, MOV10, NXF1, PHF6, CUL7, OBSL1, CCDC8, SIRT6, EBNA1BP2, NOL12, RPL10A, POP4, ZNF22, NSA2, TAF1D, NIFK, RPL26L1, NIP7, RPL4, RPF1, CCDC137, KNOP1, RBM28, RPL7A, POP1, DDX24, FTSJ3, RRS1, RPL3, ZFP62, ZNF512, DDX56, DDX27, GLYR1, MAK16, CEBPZ, RSL1D1, HP1BP3, REXO4, DDX31, MYBBP1A, NOP16, C3orf17, RRP8, GNL2, PAPD5, RSL24D1, SURF6, GTPBP4, KIAA0020, NOP2, NVL, GLTSCR2, URB1, RPL23A, GPATCH4, TEX10, RPS8, NOC3L, BRIX1, DDX54, PWP1, RBM34, NMNAT1, CENPC, SENP5, RPL36AL, PAK1IP1, ZNF800, RPL7L1, RPL37A, RPF2, PELP1, NOC2L, RPP40, RBMX2, CENPV, PPAN-P2RY11, SDAD1, RPP38, RPP25, SPTY2D1, RPP25L, POP7, RPS6KB2, UTP15, NTRK1, EWSR1, CLK1, HIST1H3E, BYSL, CHD1, DDX1, DECR1, EIF1AX, EIF4G2, FBL, FAU, HIST1H1D, HIST1H1B, RPSA, MKI67, MPG, EXOSC10, RPL7, RPL8, RPL9, RPL11, RPL13, RPL15, RPL17, RPL18, RPL18A, RPL19, RPL21, RPL22, RPL27, RPL27A, RPL29, RPL32, RPL37, RPL38, RPS2, RPS3, RPS3A, RPS9, RPS10, RPS11, RPS13, RPS14, RPS15, RPS16, RPS17, RPS18, RPS19, RPS20, RPS21, RPS23, RPS24, RPS25, RPS27, RPS29, SKIV2L, SRP72, XPC, IFRD2, HIST1H2BC, SMARCA5, CGGBP1, EIF3A, EIF3C, PABPC4, USP10, TTC37, JADE3, ABCF2, G3BP1, GNB2L1, EMG1, IGF2BP3, PSIP1, SUPT16H, RPL35, PDCD11, LARP4B, RRP12, LARP1, RPL13A, RPL36, MTHFD1L, AHCTF1, FAM98A, SERBP1, GNL3, SND1, NOB1, RPS27L, DDX47, EIF3L, RTCB, TRMT112, DHX29, MTPAP, NAT10, TSR1, NKRF, MEPCE, BCCIP, PNO1, MRPS22, WDR18, SCAF1, NOL6, DDX50, CCDC86, MUS81, ZNF622, DHX57, H2AFV, LARP4, WBSCR22, Eif3a, Eif3e, Ktn1, Rpl35, Srp72, Rrbp1, GAN, HEMGN, TMUB1, CRY1, DNAJB4, MCM2, GLI1, Mdm2, SP1, U2AF2, RC3H1, EIF2S2, EGFR, WWP2, CD24, ZNF746, DDX51, MAGED2, HNRNPA2B1, HNRNPD, HNRNPA1, RPL23, RPS7, HIST1H2BB, HIST1H2AA, CBX3, CYLD, INO80B, LMNA, YAP1, MTF1, BRD1, HDAC6, FBXW7, CENPW, API5, CTNNB1, MAP2K3, BMP4, CCNT1, DIMT1, MATN2, TRIP4, CUL4B, UBE2M, PRPF8, EFTUD2, AAR2, PIH1D1, CHD3, RNF4, CHD4, LARP7, RNF31, TNF, FAM188B, SPDL1, HEXIM1, SNAI1, RECQL4, GPC1, REST, ZFP36L2, MYC, CDK9, Prkab1, NEK2, METTL3, METTL14, KIAA1429, RC3H2, PSMA3, ACTC1, ESR2, FAF1, RBX1, BRCA2, DISC1, NR2C2, UBQLN2, MTDH, GADD45A, AGRN, ATXN3, VRK1, VRK3, DYRK1A, SNRNP70, ITFG1, GHET1, ARAF, HMGB1, BIRC3, NFX1, BRD7, N, SOX2, PPIA, CACYBP, RNR1, CMTR1, ARIH2, PLEKHA4, RAD18, PINK1, WHSC1, FANCD2, SAMD12, LINC01554, ZC3H18, CAMK2A, FYN, PTPN12, RPS6KA3, STX7, IL7R, GPC3, RP1, KMT2A, SUZ12, BSX, LEMD1, ZCCHC7, SYNE2, ZBTB9, R3HDM4, ZNF496, PIKFYVE, COL8A1, PMS2, TRDN, PLCZ1, ASPM, TTN, SETD2, BDP1, C4orf47, CFAP54, HIST2H2BC, AIM2, SYT7, LTN1, EPRS, FST, LMOD1, MCAM, RPL34, MYT1, DYNC1I2, KIF22, ZNF181, ATAT1, TRMT10B, RBM44, ANKS3, FILIP1, FAM9A, SUPT20H, THOC2, CENPI, BICD1, CCL13, JPH2, NDST4, SARDH, SLC27A6, LECT2, HMGN4, OPA1, ITGB1, HIVEP1, PNRC1, PDE4DIP, CAPRIN2, C1orf110, MICAL1, STAB2, CEP63, NGRN, CAMSAP3, ARHGEF9, SNIP1, ORF14, ILF3, LRRC31, DUX4, CIT, ANLN, AURKB, CHMP4B, CHMP4C, ECT2, KIF14, KIF20A, KIF23, PRC1, BRD3, SP110, TRIM24, ZMYND8, LRRC59, NMRAL1, SUMO2, Rnf183, BRD4, NUPR1, RBM45, CIC, Apc2, RBM39, FBP1, ASXL1, vpr, RIN3, DNAJC19, DNAJC25, DNAJC2, OGT, DDRGK1, UFL1, CD3EAP, DDX23, HIST1H2BG, ACTG1, ALKBH4, DNAJC10, GLUD2, HIST1H2AE, HIST1H3F, HIST1H4J, HLCS, HSPA1B, MALT1, PEG10, PLD3, UBB, AIP, BCORL1, BID, CSK, LCK, PSMG1, RAB21, RBM11, VDAC1, RPL31, ZNF330, TRIM37, FZR1, WDR5, PAGE4, NUDCD2, NAA40, BGLT3, CCDC140, RPL23AP32, MTG2, NGDN, UTP18, PRPF4B, WDR74, WDR36, DKC1, DDX52, EPB41L5, ZBTB11, H2AFY, CIRH1A, SRSF5, DUSP11, DDX10, TSPYL1, IMP3, RBM19, NOM1, ZC3HAV1, RPP14, UTP14A, WDR12, DNTTIP2, MPHOSPH10, RRP1, WDR3, BUD13, RPLP2, C14orf169, ZNF771, AATF, C1orf35, OASL, NLE1, BMS1, BOP1, STAU2, TAF1C, WDR55, ZNF638, RFC1, FYTTD1, WDR43, C7orf50, SRPK2, LUC7L, FAM111A, PBRM1, NOL10, TAF1A, TBL3, ZNF770, BAZ1B, ESF1, TTF1, LAS1L, RPP30, ZNF16, RRP15, ABT1, SPRTN, ULK1, TRAF6, BTF3, SLFN11, NLRP7, RCHY1, DIDO1, CCNF, FAM129A, ATR, ATM, PSMD9, ZEB1,

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
NPM1
ALK

- 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 NPM1-ALK

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 NPM1-ALK

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
Hgene	NPM1	C0026998	Acute Myeloid Leukemia, M1	6	CTD_human;ORPHANET
Hgene	NPM1	C1879321	Acute Myeloid Leukemia (AML-M2)	6	CTD_human;ORPHANET
Hgene	NPM1	C0023467	Leukemia, Myelocytic, Acute	5	CGI;CTD_human
Hgene	NPM1	C0023487	Acute Promyelocytic Leukemia	2	CGI;CTD_human;ORPHANET
Hgene	NPM1	C0024623	Malignant neoplasm of stomach	1	CTD_human
Hgene	NPM1	C0038356	Stomach Neoplasms	1	CTD_human
Hgene	NPM1	C0152013	Adenocarcinoma of lung (disorder)	1	CTD_human
Hgene	NPM1	C0206182	Lymphomatoid Papulosis	1	ORPHANET
Hgene	NPM1	C0265965	Dyskeratosis Congenita	1	CTD_human;GENOMICS_ENGLAND
Hgene	NPM1	C1148551	X-Linked Dyskeratosis Congenita	1	CTD_human
Hgene	NPM1	C1301362	Primary Cutaneous Anaplastic Large Cell Lymphoma	1	ORPHANET
Hgene	NPM1	C1708349	Hereditary Diffuse Gastric Cancer	1	CTD_human
Hgene	NPM1	C2930974	Acute erythroleukemia	1	CTD_human
Hgene	NPM1	C2930975	Acute erythroleukemia - M6a subtype	1	CTD_human
Hgene	NPM1	C2930976	Acute myeloid leukemia FAB-M6	1	CTD_human
Hgene	NPM1	C2930977	Acute erythroleukemia - M6b subtype	1	CTD_human
Tgene	ALK	C0007131	Non-Small Cell Lung Carcinoma	28	CGI;CTD_human
Tgene	ALK	C0027819	Neuroblastoma	13	CGI;CTD_human;ORPHANET
Tgene	ALK	C0152013	Adenocarcinoma of lung (disorder)	8	CGI;CTD_human
Tgene	ALK	C2751681	NEUROBLASTOMA, SUSCEPTIBILITY TO, 3	8	CLINGEN;UNIPROT
Tgene	ALK	C0206180	Ki-1+ Anaplastic Large Cell Lymphoma	6	CGI;CTD_human
Tgene	ALK	C0334121	Inflammatory Myofibroblastic Tumor	4	CGI;CTD_human;ORPHANET
Tgene	ALK	C0018199	Granuloma, Plasma Cell	3	CTD_human
Tgene	ALK	C0007621	Neoplastic Cell Transformation	2	CTD_human
Tgene	ALK	C0027627	Neoplasm Metastasis	2	CTD_human
Tgene	ALK	C0238463	Papillary thyroid carcinoma	2	ORPHANET
Tgene	ALK	C0001973	Alcoholic Intoxication, Chronic	1	PSYGENET
Tgene	ALK	C0006118	Brain Neoplasms	1	CGI;CTD_human
Tgene	ALK	C0006142	Malignant neoplasm of breast	1	CTD_human
Tgene	ALK	C0007134	Renal Cell Carcinoma	1	CTD_human
Tgene	ALK	C0011570	Mental Depression	1	PSYGENET
Tgene	ALK	C0011581	Depressive disorder	1	PSYGENET
Tgene	ALK	C0027643	Neoplasm Recurrence, Local	1	CTD_human
Tgene	ALK	C0036341	Schizophrenia	1	PSYGENET
Tgene	ALK	C0079744	Diffuse Large B-Cell Lymphoma	1	CTD_human
Tgene	ALK	C0085269	Plasma Cell Granuloma, Pulmonary	1	CTD_human
Tgene	ALK	C0153633	Malignant neoplasm of brain	1	CGI;CTD_human
Tgene	ALK	C0278601	Inflammatory Breast Carcinoma	1	CTD_human
Tgene	ALK	C0279702	Conventional (Clear Cell) Renal Cell Carcinoma	1	CTD_human
Tgene	ALK	C0496899	Benign neoplasm of brain, unspecified	1	CTD_human
Tgene	ALK	C0678222	Breast Carcinoma	1	CTD_human
Tgene	ALK	C0750974	Brain Tumor, Primary	1	CTD_human
Tgene	ALK	C0750977	Recurrent Brain Neoplasm	1	CTD_human
Tgene	ALK	C0750979	Primary malignant neoplasm of brain	1	CTD_human
Tgene	ALK	C1257931	Mammary Neoplasms, Human	1	CTD_human
Tgene	ALK	C1266042	Chromophobe Renal Cell Carcinoma	1	CTD_human
Tgene	ALK	C1266043	Sarcomatoid Renal Cell Carcinoma	1	CTD_human
Tgene	ALK	C1266044	Collecting Duct Carcinoma of the Kidney	1	CTD_human
Tgene	ALK	C1306837	Papillary Renal Cell Carcinoma	1	CTD_human
Tgene	ALK	C1332079	Anaplastic Large Cell Lymphoma, ALK-Positive	1	ORPHANET
Tgene	ALK	C1458155	Mammary Neoplasms	1	CTD_human
Tgene	ALK	C1527390	Neoplasms, Intracranial	1	CTD_human
Tgene	ALK	C2931189	Neural crest tumor	1	ORPHANET
Tgene	ALK	C3899155	hereditary neuroblastoma	1	GENOMICS_ENGLAND
Tgene	ALK	C4704874	Mammary Carcinoma, Human	1	CTD_human