ASpdb: an integrative knowledgebase of human protein isoforms from experimental and AI-predicted structures

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	Protein Summary
	AS Summary
	Protein Functional Features
	Gene Isoform Structures and Expression Levels
	Protein Structures
	pLDDT Score Distribution
	Ramachandran Plot of Protein Structures
	Potential Active Site Information
	Protein Structure and Feature Comparision
	Protein-Protein Interaction
	Related Drugs
	Related Diseases
	Clinically Important Variants

Protein:NSD2

Protein Summary

Gene summary

Gene name: NSD2
ASpdb.0 ID: 7468
	Gene
Gene symbol	NSD2
Gene ID	7468
Gene name	nuclear receptor binding SET domain protein 2
Synonyms	KMT3F\|KMT3G\|MMSET\|RAUST\|REIIBP\|TRX5\|WHS\|WHSC1
Cytomap	4p16.3
Type of gene	protein-coding
Description	histone-lysine N-methyltransferase NSD2IL5 promoter REII region-binding proteinWolf-Hirschhorn syndrome candidate 1multiple myeloma SET domain containing protein type IIInuclear SET domain-containing protein 2probable histone-lysine N-methyltransfera
Modification date	20240407
UniProtAcc	O96028

Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Gene	NSD2	GO:0005654	nucleoplasm	-

AS Summary

Information of the canonical protein with experimentally identified structure from PDB (2023).

UniProt Acc	File name	PDB ID	Method	Resolution	Chain	Start	End
O96028-1	O96028-1_5lsu_A.pdb	5LSU	X-ray	2.14	A	973	1203

ASpdb's canonical and alternatively spliced isoform information.

accession_id	gene_name	canonical_id	alternative_id	canonical_length	alternative_length	canonical_start	canonical_end	type	originalSEQ	variationSEQ	alternative_start	alternative_end
O96028	NSD2	O96028-1	O96028-2	1365	713	1	652	Deletion	none	none	0	0
O96028	NSD2	O96028-1	O96028-2	1365	713	653	712	Substitution	VSSKKSERGVTAKKEYVCQLCEKPGSLLLCEGPCCGAFHLACLGLSRRPEGRFTCSECAS	MAGSFCWRMLGLVSKVGNRARCFSSMAASEEELLDFSGSELQFNSCSLHLSLHPFFNFLL	1	60
O96028	NSD2	O96028-1	O96028-3	1365	647	628	647	Substitution	VSDSPGDEPSESPYESADET	LLWEPTPVKLDLNPAALYCT	628	647
O96028	NSD2	O96028-1	O96028-3	1365	647	648	1365	Deletion	none	none	647	647
O96028	NSD2	O96028-1	O96028-4	1365	584	1	781	Deletion	none	none	0	0
O96028	NSD2	O96028-1	O96028-5	1365	629	629	629	Substitution	S	K	629	629
O96028	NSD2	O96028-1	O96028-5	1365	629	630	1365	Deletion	none	none	629	629
O96028	NSD2	O96028-1	O96028-6	1365	484	472	484	Substitution	VAEHPDASGEEIE	STKLCFMLASFRI	472	484
O96028	NSD2	O96028-1	O96028-6	1365	484	485	1365	Deletion	none	none	484	484
O96028	NSD2	O96028-1	O96028-7	1365	273	255	273	Substitution	QKKSARQYHVQFFGDAPER	IFKSKKFEHLKTSQIVLKD	255	273
O96028	NSD2	O96028-1	O96028-7	1365	273	274	1365	Deletion	none	none	273	273

Multiple sequence alignment of our canonical and alternatively spliced NSD2

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of NSD2

UniProt-id	ENSG	ENST	ENSP
O96028-1	ENSG00000109685.19	ENST00000382891.9	ENSP00000372347.5
O96028-1	ENSG00000109685.19	ENST00000382892.6	ENSP00000372348.2
O96028-1	ENSG00000109685.19	ENST00000382895.7	ENSP00000372351.3
O96028-1	ENSG00000109685.19	ENST00000508803.6	ENSP00000423972.1
O96028-2	ENSG00000109685.19	ENST00000382888.3	ENSP00000372344.3
O96028-3	ENSG00000109685.19	ENST00000312087.10	ENSP00000308780.6
O96028-3	ENSG00000109685.19	ENST00000353275.9	ENSP00000329167.5
O96028-3	ENSG00000109685.19	ENST00000398261.6	ENSP00000381311.1
O96028-3	ENSG00000109685.19	ENST00000503128.5	ENSP00000425761.1
O96028-5	ENSG00000109685.19	ENST00000420906.6	ENSP00000399251.2
O96028-5	ENSG00000109685.19	ENST00000514045.5	ENSP00000421681.1
O96028-7	ENSG00000109685.19	ENST00000678714.1	ENSP00000504221.1

UniProt-id	NM ID	NP ID
O96028-1	NM_001042424.2	NP_001035889.1
O96028-1	NM_133330.2	NP_579877.1
O96028-1	NM_133331.2	NP_579878.1
O96028-1	NM_133335.3	NP_579890.1
O96028-1	XM_005248001.3	XP_005248058.1
O96028-3	NM_133334.2	NP_579889.1
O96028-3	XM_005248005.2	XP_005248062.1
O96028-4	XM_011513560.2	XP_011511862.1
O96028-5	NM_007331.1	NP_015627.1

Amino acid sequences of our canonical and alternatively spliced NSD2

accession_id	Protein sequence
O96028-1	MEFSIKQSPLSVQSVVKCIKMKQAPEILGSANGKTPSCEVNRECSVFLSKAQLSSSLQEGVMQKFNGHDALPFIPADKLKDLTSRVFNGE PGAHDAKLRFESQEMKGIGTPPNTTPIKNGSPEIKLKITKTYMNGKPLFESSICGDSAADVSQSEENGQKPENKARRNRKRSIKYDSLLE QGLVEAALVSKISSPSDKKIPAKKESCPNTGRDKDHLLKYNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKSARQYHVQFFGDA PERAWIFEKSLVAFEGEGQFEKLCQESAKQAPTKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMSVEERKAKFTFLYVGDQLHLNPQVA KEAGIAAESLGEMAESSGVSEEAAENPKSVREECIPMKRRRRAKLCSSAETLESHPDIGKSTPQKTAEADPRRGVGSPPGRKKTTVSMPR SRKGDAASQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKFALVAPVQAEEDSGNVNGKKRNHTKRIQDPTEDAE AEDTPRKRLRTDKHSLRKRDTITDKTARTSSYKAMEAASSLKSQAATKNLSDACKPLKKRNRASTAASSALGFSKSSSPSASLTENEVSD SPGDEPSESPYESADETQTEVSVSSKKSERGVTAKKEYVCQLCEKPGSLLLCEGPCCGAFHLACLGLSRRPEGRFTCSECASGIHSCFVC KESKTDVKRCVVTQCGKFYHEACVKKYPLTVFESRGFRCPLHSCVSCHASNPSNPRPSKGKMMRCVRCPVAYHSGDACLAAGCSVIASNS IICTAHFTARKGKRHHAHVNVSWCFVCSKGGSLLCCESCPAAFHPDCLNIEMPDGSWFCNDCRAGKKLHFQDIIWVKLGNYRWWPAEVCH PKNVPPNIQKMKHEIGEFPVFFFGSKDYYWTHQARVFPYMEGDRGSRYQGVRGIGRVFKNALQEAEARFREIKLQREARETQESERKPPP YKHIKVNKPYGKVQIYTADISEIPKCNCKPTDENPCGFDSECLNRMLMFECHPQVCPAGEFCQNQCFTKRQYPETKIIKTDGKGWGLVAK RDIRKGEFVNEYVGELIDEEECMARIKHAHENDITHFYMLTIDKDRIIDAGPKGNYSRFMNHSCQPNCETLKWTVNGDTRVGLFAVCDIP AGTELTFNYNLDCLGNEKTVCRCGASNCSGFLGDRPKTSTTLSSEEKGKKTKKKTRRRRAKGEGKRQSEDECFRCGDGGQLVLCDRKFCT KAYHLSCLGLGKRPFGKWECPWHHCDVCGKPSTSFCHLCPNSFCKEHQDGTAFSCTPDGRSYCCEHDLGAASVRSTKTEKPPPEPGKPKG
O96028-2	MAGSFCWRMLGLVSKVGNRARCFSSMAASEEELLDFSGSELQFNSCSLHLSLHPFFNFLLGIHSCFVCKESKTDVKRCVVTQCGKFYHEA CVKKYPLTVFESRGFRCPLHSCVSCHASNPSNPRPSKGKMMRCVRCPVAYHSGDACLAAGCSVIASNSIICTAHFTARKGKRHHAHVNVS WCFVCSKGGSLLCCESCPAAFHPDCLNIEMPDGSWFCNDCRAGKKLHFQDIIWVKLGNYRWWPAEVCHPKNVPPNIQKMKHEIGEFPVFF FGSKDYYWTHQARVFPYMEGDRGSRYQGVRGIGRVFKNALQEAEARFREIKLQREARETQESERKPPPYKHIKVNKPYGKVQIYTADISE IPKCNCKPTDENPCGFDSECLNRMLMFECHPQVCPAGEFCQNQCFTKRQYPETKIIKTDGKGWGLVAKRDIRKGEFVNEYVGELIDEEEC MARIKHAHENDITHFYMLTIDKDRIIDAGPKGNYSRFMNHSCQPNCETLKWTVNGDTRVGLFAVCDIPAGTELTFNYNLDCLGNEKTVCR CGASNCSGFLGDRPKTSTTLSSEEKGKKTKKKTRRRRAKGEGKRQSEDECFRCGDGGQLVLCDRKFCTKAYHLSCLGLGKRPFGKWECPW
O96028-3	MEFSIKQSPLSVQSVVKCIKMKQAPEILGSANGKTPSCEVNRECSVFLSKAQLSSSLQEGVMQKFNGHDALPFIPADKLKDLTSRVFNGE PGAHDAKLRFESQEMKGIGTPPNTTPIKNGSPEIKLKITKTYMNGKPLFESSICGDSAADVSQSEENGQKPENKARRNRKRSIKYDSLLE QGLVEAALVSKISSPSDKKIPAKKESCPNTGRDKDHLLKYNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKSARQYHVQFFGDA PERAWIFEKSLVAFEGEGQFEKLCQESAKQAPTKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMSVEERKAKFTFLYVGDQLHLNPQVA KEAGIAAESLGEMAESSGVSEEAAENPKSVREECIPMKRRRRAKLCSSAETLESHPDIGKSTPQKTAEADPRRGVGSPPGRKKTTVSMPR SRKGDAASQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKFALVAPVQAEEDSGNVNGKKRNHTKRIQDPTEDAE AEDTPRKRLRTDKHSLRKRDTITDKTARTSSYKAMEAASSLKSQAATKNLSDACKPLKKRNRASTAASSALGFSKSSSPSASLTENELLW
O96028-4	MMRCVRCPVAYHSGDACLAAGCSVIASNSIICTAHFTARKGKRHHAHVNVSWCFVCSKGGSLLCCESCPAAFHPDCLNIEMPDGSWFCND CRAGKKLHFQDIIWVKLGNYRWWPAEVCHPKNVPPNIQKMKHEIGEFPVFFFGSKDYYWTHQARVFPYMEGDRGSRYQGVRGIGRVFKNA LQEAEARFREIKLQREARETQESERKPPPYKHIKVNKPYGKVQIYTADISEIPKCNCKPTDENPCGFDSECLNRMLMFECHPQVCPAGEF CQNQCFTKRQYPETKIIKTDGKGWGLVAKRDIRKGEFVNEYVGELIDEEECMARIKHAHENDITHFYMLTIDKDRIIDAGPKGNYSRFMN HSCQPNCETLKWTVNGDTRVGLFAVCDIPAGTELTFNYNLDCLGNEKTVCRCGASNCSGFLGDRPKTSTTLSSEEKGKKTKKKTRRRRAK GEGKRQSEDECFRCGDGGQLVLCDRKFCTKAYHLSCLGLGKRPFGKWECPWHHCDVCGKPSTSFCHLCPNSFCKEHQDGTAFSCTPDGRS
O96028-5	MEFSIKQSPLSVQSVVKCIKMKQAPEILGSANGKTPSCEVNRECSVFLSKAQLSSSLQEGVMQKFNGHDALPFIPADKLKDLTSRVFNGE PGAHDAKLRFESQEMKGIGTPPNTTPIKNGSPEIKLKITKTYMNGKPLFESSICGDSAADVSQSEENGQKPENKARRNRKRSIKYDSLLE QGLVEAALVSKISSPSDKKIPAKKESCPNTGRDKDHLLKYNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKSARQYHVQFFGDA PERAWIFEKSLVAFEGEGQFEKLCQESAKQAPTKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMSVEERKAKFTFLYVGDQLHLNPQVA KEAGIAAESLGEMAESSGVSEEAAENPKSVREECIPMKRRRRAKLCSSAETLESHPDIGKSTPQKTAEADPRRGVGSPPGRKKTTVSMPR SRKGDAASQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKFALVAPVQAEEDSGNVNGKKRNHTKRIQDPTEDAE
O96028-6	MEFSIKQSPLSVQSVVKCIKMKQAPEILGSANGKTPSCEVNRECSVFLSKAQLSSSLQEGVMQKFNGHDALPFIPADKLKDLTSRVFNGE PGAHDAKLRFESQEMKGIGTPPNTTPIKNGSPEIKLKITKTYMNGKPLFESSICGDSAADVSQSEENGQKPENKARRNRKRSIKYDSLLE QGLVEAALVSKISSPSDKKIPAKKESCPNTGRDKDHLLKYNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKSARQYHVQFFGDA PERAWIFEKSLVAFEGEGQFEKLCQESAKQAPTKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMSVEERKAKFTFLYVGDQLHLNPQVA KEAGIAAESLGEMAESSGVSEEAAENPKSVREECIPMKRRRRAKLCSSAETLESHPDIGKSTPQKTAEADPRRGVGSPPGRKKTTVSMPR
O96028-7	MEFSIKQSPLSVQSVVKCIKMKQAPEILGSANGKTPSCEVNRECSVFLSKAQLSSSLQEGVMQKFNGHDALPFIPADKLKDLTSRVFNGE PGAHDAKLRFESQEMKGIGTPPNTTPIKNGSPEIKLKITKTYMNGKPLFESSICGDSAADVSQSEENGQKPENKARRNRKRSIKYDSLLE QGLVEAALVSKISSPSDKKIPAKKESCPNTGRDKDHLLKYNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGIFKSKKFEHLKTSQIV

Protein Functional Features

Main function of this protein. (from UniProt)

NSD2 (go to UniProt):O96028

Retention analysis result of 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.

Accession_id	Subsection	Start	End	Funcitonal feature	Splicing information
O96028	Domain	222	286	Note=PWWP 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00162	Type=Deletion;Start=1;End=652
O96028	Domain	222	286	Note=PWWP 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00162	Type=Deletion;Start=1;End=781
O96028	Domain	222	286	Note=PWWP 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00162	Type=Substitution;Start=255;End=273
O96028	Domain	222	286	Note=PWWP 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00162	Type=Deletion;Start=274;End=1365
O96028	Domain	880	942	Note=PWWP 2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00162	Type=Deletion;Start=648;End=1365
O96028	Domain	880	942	Note=PWWP 2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00162	Type=Deletion;Start=630;End=1365
O96028	Domain	880	942	Note=PWWP 2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00162	Type=Deletion;Start=485;End=1365
O96028	Domain	880	942	Note=PWWP 2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00162	Type=Deletion;Start=274;End=1365
O96028	Domain	1011	1061	Note=AWS;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00562	Type=Deletion;Start=648;End=1365
O96028	Domain	1011	1061	Note=AWS;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00562	Type=Deletion;Start=630;End=1365
O96028	Domain	1011	1061	Note=AWS;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00562	Type=Deletion;Start=485;End=1365
O96028	Domain	1011	1061	Note=AWS;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00562	Type=Deletion;Start=274;End=1365
O96028	Domain	1063	1180	Note=SET;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00190	Type=Deletion;Start=648;End=1365
O96028	Domain	1063	1180	Note=SET;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00190	Type=Deletion;Start=630;End=1365
O96028	Domain	1063	1180	Note=SET;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00190	Type=Deletion;Start=485;End=1365
O96028	Domain	1063	1180	Note=SET;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00190	Type=Deletion;Start=274;End=1365
O96028	Domain	1187	1203	Note=Post-SET;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00155	Type=Deletion;Start=648;End=1365
O96028	Domain	1187	1203	Note=Post-SET;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00155	Type=Deletion;Start=630;End=1365
O96028	Domain	1187	1203	Note=Post-SET;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00155	Type=Deletion;Start=485;End=1365
O96028	Domain	1187	1203	Note=Post-SET;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00155	Type=Deletion;Start=274;End=1365
O96028	DNA binding	453	521	Note=HMG box;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00267	Type=Deletion;Start=1;End=652
O96028	DNA binding	453	521	Note=HMG box;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00267	Type=Deletion;Start=1;End=781
O96028	DNA binding	453	521	Note=HMG box;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00267	Type=Substitution;Start=472;End=484
O96028	DNA binding	453	521	Note=HMG box;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00267	Type=Deletion;Start=485;End=1365
O96028	DNA binding	453	521	Note=HMG box;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00267	Type=Deletion;Start=274;End=1365
O96028	Zinc finger	667	713	Note=PHD-type 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Substitution;Start=653;End=712
O96028	Zinc finger	667	713	Note=PHD-type 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=648;End=1365
O96028	Zinc finger	667	713	Note=PHD-type 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=1;End=781
O96028	Zinc finger	667	713	Note=PHD-type 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=630;End=1365
O96028	Zinc finger	667	713	Note=PHD-type 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=485;End=1365
O96028	Zinc finger	667	713	Note=PHD-type 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=274;End=1365
O96028	Zinc finger	714	770	Note=PHD-type 2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=648;End=1365
O96028	Zinc finger	714	770	Note=PHD-type 2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=1;End=781
O96028	Zinc finger	714	770	Note=PHD-type 2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=630;End=1365
O96028	Zinc finger	714	770	Note=PHD-type 2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=485;End=1365
O96028	Zinc finger	714	770	Note=PHD-type 2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=274;End=1365
O96028	Zinc finger	831	875	Note=PHD-type 3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=648;End=1365
O96028	Zinc finger	831	875	Note=PHD-type 3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=630;End=1365
O96028	Zinc finger	831	875	Note=PHD-type 3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=485;End=1365
O96028	Zinc finger	831	875	Note=PHD-type 3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=274;End=1365
O96028	Zinc finger	1239	1286	Note=PHD-type 4%3B atypical;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=648;End=1365
O96028	Zinc finger	1239	1286	Note=PHD-type 4%3B atypical;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=630;End=1365
O96028	Zinc finger	1239	1286	Note=PHD-type 4%3B atypical;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=485;End=1365
O96028	Zinc finger	1239	1286	Note=PHD-type 4%3B atypical;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00146	Type=Deletion;Start=274;End=1365
O96028	Region	149	170	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=652
O96028	Region	149	170	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=781
O96028	Region	376	455	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=652
O96028	Region	376	455	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=781
O96028	Region	376	455	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=274;End=1365
O96028	Region	516	658	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=652
O96028	Region	516	658	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=653;End=712
O96028	Region	516	658	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=628;End=647
O96028	Region	516	658	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=648;End=1365
O96028	Region	516	658	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=781
O96028	Region	516	658	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=629;End=629
O96028	Region	516	658	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=630;End=1365
O96028	Region	516	658	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=485;End=1365
O96028	Region	516	658	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=274;End=1365
O96028	Region	1207	1232	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=648;End=1365
O96028	Region	1207	1232	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=630;End=1365
O96028	Region	1207	1232	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=485;End=1365
O96028	Region	1207	1232	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=274;End=1365
O96028	Region	1333	1365	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=648;End=1365
O96028	Region	1333	1365	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=630;End=1365
O96028	Region	1333	1365	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=485;End=1365
O96028	Region	1333	1365	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=274;End=1365
O96028	Compositional bias	385	408	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=652
O96028	Compositional bias	385	408	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=781
O96028	Compositional bias	385	408	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=274;End=1365
O96028	Compositional bias	519	566	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=652
O96028	Compositional bias	519	566	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=781
O96028	Compositional bias	519	566	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=485;End=1365
O96028	Compositional bias	519	566	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=274;End=1365
O96028	Compositional bias	567	590	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=652
O96028	Compositional bias	567	590	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=781
O96028	Compositional bias	567	590	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=485;End=1365
O96028	Compositional bias	567	590	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=274;End=1365
O96028	Compositional bias	602	630	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=652
O96028	Compositional bias	602	630	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=628;End=647
O96028	Compositional bias	602	630	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=781
O96028	Compositional bias	602	630	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=629;End=629
O96028	Compositional bias	602	630	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=630;End=1365
O96028	Compositional bias	602	630	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=485;End=1365
O96028	Compositional bias	602	630	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=274;End=1365
O96028	Compositional bias	642	658	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=652
O96028	Compositional bias	642	658	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=653;End=712
O96028	Compositional bias	642	658	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=628;End=647
O96028	Compositional bias	642	658	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=648;End=1365
O96028	Compositional bias	642	658	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=781
O96028	Compositional bias	642	658	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=630;End=1365
O96028	Compositional bias	642	658	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=485;End=1365
O96028	Compositional bias	642	658	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=274;End=1365

Gene Isoform Structures and Expression Levels for NSD2

Gene structures of our canonical and alternative spliced genes of NSD2
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Expression levels of gene isoforms across GTEx.

Expression levels of gene isoforms across TCGA.

Protein Structures

PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the 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.

3D view using mol* of O96028-1

3D view using mol* of O96028-2

3D view using mol* of O96028-3

3D view using mol* of O96028-4

3D view using mol* of O96028-5

3D view using mol* of O96028-6

3D view using mol* of O96028-7

pLDDT Score Distribution

pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

pLDDT distribution across the protein length of O96028-1

pLDDT distribution across the protein length of O96028-2

pLDDT distribution across the protein length of O96028-3

pLDDT distribution across the protein length of O96028-4

pLDDT distribution across the protein length of O96028-5

pLDDT distribution across the protein length of O96028-6

pLDDT distribution across the protein length of O96028-7

Ramachandran Plot of Protein Structures

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.

Ramachandran plot of O96028-1

Ramachandran plot of O96028-2

Ramachandran plot of O96028-3

Ramachandran plot of O96028-4

Ramachandran plot of O96028-5

Ramachandran plot of O96028-6

Potential Active Site Information

The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.

UniProt-id	Site score	Size	D score	Volume	Exposure	Enclosure	Contact	Phobic	Philic	Balance	Don/Acc	Residues
O96028-1	1.059	181	1.032	393.078	0.466	0.787	1.056	0.539	1.168	0.462	0.755	988,989,1072,1073,1074,1075,1092,1110,1113,1115,11 16,1117,1118,1119,1120,1138,1139,1140,1141,1142,11 77,1179,1183,1185,1186,1187,1188,1189,1190,1191,11 92,1193,1202
O96028-2	1.031	250	1.057	717.556	0.568	0.726	0.968	0.649	0.977	0.664	0.978	328,331,332,335,336,337,338,339,415,417,420,421,42 2,423,440,453,456,457,458,462,463,464,465,466,467, 468,477,479,480,486,487,488,489,490,525,527,531,53 3,534,535,536,537,538,539,540,541,550
O96028-3	1.002	183	1.042	536.452	0.638	0.661	0.833	0.453	0.902	0.502	1.077	20,21,22,23,24,26,229,230,231,232,233,234,235,261, 266,272,273,274,275,276,277,279,280,282,290,293,29 6,297,300,301,302,306,309,310,312,313,314,315,318
O96028-4	1.019	141	0.979	311.444	0.52	0.727	1.014	0.683	1.217	0.561	0.609	19,33,52,54,57,68,69,70,90,91,94,95,96,97,98,101,1 04,111,112,152,155,156,157,159,161,162,163,164,165 ,166,177
O96028-5	1.003	228	1.059	712.754	0.671	0.634	0.791	0.532	0.801	0.664	0.935	20,21,22,23,24,26,229,230,231,232,233,234,235,243, 251,261,263,266,272,273,274,275,276,277,279,280,28 2,290,291,293,294,296,297,300,301,302,306,309,310, 311,312,313,314,315,318,319,353
O96028-6	1.018	107	1.069	337.855	0.657	0.663	0.826	0.674	0.826	0.815	0.957	18,19,20,21,22,23,230,261,263,266,270,271,272,273, 274,275,276,321,347,349,352,353,354,355,357,360,36 5,367,368
O96028-7	1.007	117	1.031	430.808	0.64	0.698	0.88	0.336	1.006	0.334	1.076	41,42,43,44,45,46,219,220,226,227,228,229,230,231, 249,250,251,252,253,254,255,262,263,264,265,266,26 7,268,269

Protein Structure and Feature Comparision

Protein Structure Comparision Using Template Modeling Scores (TM-score).

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)

3D view using mol* of O96028-1_O96028-1_5lsu_A.pdb

Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of O96028-1_5lsu_A_O96028-2.pdb

3D view using mol* of O96028-1_5lsu_A_O96028-3.pdb

3D view using mol* of O96028-1_5lsu_A_O96028-4.pdb

3D view using mol* of O96028-1_5lsu_A_O96028-5.pdb

3D view using mol* of O96028-1_5lsu_A_O96028-6.pdb

3D view using mol* of O96028-1_5lsu_A_O96028-7.pdb

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of O96028-1_O96028-2.pdb

3D view using mol* of O96028-1_O96028-3.pdb

3D view using mol* of O96028-1_O96028-4.pdb

3D view using mol* of O96028-1_O96028-5.pdb

3D view using mol* of O96028-1_O96028-6.pdb

3D view using mol* of O96028-1_O96028-7.pdb

Protein Feature Comparison of the protein sequendary structures among the protiens.

./stats/secondary_structure/figure/O96028-1_vs_O96028-2.png

./stats/secondary_structure/figure/O96028-1_vs_O96028-3.png

./stats/secondary_structure/figure/O96028-1_vs_O96028-4.png

./stats/secondary_structure/figure/O96028-1_vs_O96028-5.png

./stats/secondary_structure/figure/O96028-1_vs_O96028-6.png

./stats/secondary_structure/figure/O96028-1_vs_O96028-7.png

Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.

./stats/relative_asa/O96028-1_vs_O96028-2.png

./stats/relative_asa/O96028-1_vs_O96028-3.png

./stats/relative_asa/O96028-1_vs_O96028-4.png

./stats/relative_asa/O96028-1_vs_O96028-5.png

./stats/relative_asa/O96028-1_vs_O96028-6.png

./stats/relative_asa/O96028-1_vs_O96028-7.png

Protein-Protein Interaction

Interactors from UniProt.

Accession_id

Subsection

Start

End

Funcitonal feature

Splicing information

Interactors from STRING.

Gene name

Interactors

Related Drugs to NSD2

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession

Gene name

DrugBank ID

Drug name

Drug group

Actions

Related Diseases to NSD2

Previous studies relating to the alternative splicing of NSD2 and disease information from the MeSH term (PubMed)

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
NSD2	9618163	WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma.	Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4 (4p16.3). The smallest region of overlap between WHS patients, the WHS critical region, has been confined to 165 kb, of which the complete sequence is known. We have identified and studied a 90 kb gene, designated as WHSC1 , mapping to the 165 kb WHS critical region. This 25 exon gene is expressed ubiquitously in early development and undergoes complex alternative splicing and differential polyadenylation. It encodes a 136 kDa protein containing four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain also found in the Drosophila dysmorphy gene ash -encoded protein, and a PHD-type zinc finger. It is expressed preferentially in rapidly growing embryonic tissues, in a pattern corresponding to affected organs in WHS patients. The nature of the protein motifs, the expression pattern and its mapping to the critical region led us to propose WHSC1 as a good candidate gene to be responsible for many of the phenotypic features of WHS. Finally, as a serendipitous finding, of the t(4;14) (p16.3;q32.3) translocations recently described in multiple myelomas, at least three breakpoints merge the IgH and WHSC1 genes, potentially causing fusion proteins replacing WHSC1 exons 1-4 by the IgH 5'-VDJ moiety.	D009101	Multiple Myeloma
NSD2	9618163	WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma.	Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4 (4p16.3). The smallest region of overlap between WHS patients, the WHS critical region, has been confined to 165 kb, of which the complete sequence is known. We have identified and studied a 90 kb gene, designated as WHSC1 , mapping to the 165 kb WHS critical region. This 25 exon gene is expressed ubiquitously in early development and undergoes complex alternative splicing and differential polyadenylation. It encodes a 136 kDa protein containing four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain also found in the Drosophila dysmorphy gene ash -encoded protein, and a PHD-type zinc finger. It is expressed preferentially in rapidly growing embryonic tissues, in a pattern corresponding to affected organs in WHS patients. The nature of the protein motifs, the expression pattern and its mapping to the critical region led us to propose WHSC1 as a good candidate gene to be responsible for many of the phenotypic features of WHS. Finally, as a serendipitous finding, of the t(4;14) (p16.3;q32.3) translocations recently described in multiple myelomas, at least three breakpoints merge the IgH and WHSC1 genes, potentially causing fusion proteins replacing WHSC1 exons 1-4 by the IgH 5'-VDJ moiety.	D013577	Syndrome
NSD2	9618163	WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma.	Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4 (4p16.3). The smallest region of overlap between WHS patients, the WHS critical region, has been confined to 165 kb, of which the complete sequence is known. We have identified and studied a 90 kb gene, designated as WHSC1 , mapping to the 165 kb WHS critical region. This 25 exon gene is expressed ubiquitously in early development and undergoes complex alternative splicing and differential polyadenylation. It encodes a 136 kDa protein containing four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain also found in the Drosophila dysmorphy gene ash -encoded protein, and a PHD-type zinc finger. It is expressed preferentially in rapidly growing embryonic tissues, in a pattern corresponding to affected organs in WHS patients. The nature of the protein motifs, the expression pattern and its mapping to the critical region led us to propose WHSC1 as a good candidate gene to be responsible for many of the phenotypic features of WHS. Finally, as a serendipitous finding, of the t(4;14) (p16.3;q32.3) translocations recently described in multiple myelomas, at least three breakpoints merge the IgH and WHSC1 genes, potentially causing fusion proteins replacing WHSC1 exons 1-4 by the IgH 5'-VDJ moiety.	D014178	Translocation, Genetic
NSD2	11337357	Translocation T(4;14)(p16.3;q32) is a recurrent genetic lesion in primary amyloidosis.	Primary amyloidosis is a fatal disorder characterized by low numbers of clonal plasma cells in the bone marrow and the systemic deposition of light chain fragments in the form of amyloid. The molecular pathobiology of amyloidosis is primarily unknown. Recently, a novel karyotypically undetectable t(4;14)(p16.3;q32) translocation has been identified in approximately 20% of multiple myeloma patients. The translocation leads to the apparent deregulation of two genes located on 4p16.3, the fibroblast growth-factor receptor 3 (FGFR3), and the putative transcription factor multiple myeloma SET domain (MMSET), and to the generation of IGH/MMSET hybrid transcripts. In this study, we investigated the presence of the t(4;14) translocation in 42 AL patients using a reverse transcriptase-polymerase chain reaction assay for the detection of IGH/MMSET transcripts. Chimeric transcripts were found in six patients (14%) and were consistent with a 4p16.3 breakpoint involving intron 3 and juxtaposing IGH regions to exon 4. In three of these cases, hybrid transcripts juxtaposing IGH regions to exon 5 were also observed and were probably the result of an alternative splicing skipping exon 4. Because all of the fusion transcripts (six of six) excluded exon 3, the first translated MMSET exon, only putative 5' truncated MMSET proteins could be generated. In conclusion, our results demonstrate that the t(4;14)(p16.3;q32) translocation is a recurrent genetic lesion in primary amyloidosis.	D000686	Amyloidosis
NSD2	11337357	Translocation T(4;14)(p16.3;q32) is a recurrent genetic lesion in primary amyloidosis.	Primary amyloidosis is a fatal disorder characterized by low numbers of clonal plasma cells in the bone marrow and the systemic deposition of light chain fragments in the form of amyloid. The molecular pathobiology of amyloidosis is primarily unknown. Recently, a novel karyotypically undetectable t(4;14)(p16.3;q32) translocation has been identified in approximately 20% of multiple myeloma patients. The translocation leads to the apparent deregulation of two genes located on 4p16.3, the fibroblast growth-factor receptor 3 (FGFR3), and the putative transcription factor multiple myeloma SET domain (MMSET), and to the generation of IGH/MMSET hybrid transcripts. In this study, we investigated the presence of the t(4;14) translocation in 42 AL patients using a reverse transcriptase-polymerase chain reaction assay for the detection of IGH/MMSET transcripts. Chimeric transcripts were found in six patients (14%) and were consistent with a 4p16.3 breakpoint involving intron 3 and juxtaposing IGH regions to exon 4. In three of these cases, hybrid transcripts juxtaposing IGH regions to exon 5 were also observed and were probably the result of an alternative splicing skipping exon 4. Because all of the fusion transcripts (six of six) excluded exon 3, the first translated MMSET exon, only putative 5' truncated MMSET proteins could be generated. In conclusion, our results demonstrate that the t(4;14)(p16.3;q32) translocation is a recurrent genetic lesion in primary amyloidosis.	D014178	Translocation, Genetic
NSD2	15677557	Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients.	Multiple myeloma (MM) is a B-lineage malignancy characterized by diverse genetic subtypes and clinical outcomes. The recurrent immunoglobulin heavy chain (IgH) switch translocation, t(4;14)(p16;q32), is associated with poor outcome, though the mechanism is unclear. Quantitative reverse-transcription-polymerase chain reaction (RT-PCR) for proposed target genes on a panel of myeloma cell lines and purified plasma cells showed that only transcripts originating from the WHSC1/MMSET/NSD2 gene are uniformly dysregulated in all t(4;14)POS patients. The different transcripts detected, multiple myeloma SET domain containing protein (MMSET I), MMSET II, Exon 4a/MMSET III, and response element II binding protein (RE-IIBP), are produced by alternative splicing and alternative transcription initiation events. Translation of the various transcripts, including those from major breakpoint region 4-2 (MB4-2) and MB4-3 breakpoint variants, was confirmed by transient transfection and immunoblotting. Green fluorescent protein (GFP)-tagged MMSET I and II, corresponding to proteins expressed in MB4-1 patients, localized to the nucleus but not nucleoli, whereas the MB4-2 and MB4-3 proteins concentrate in nucleoli. Cloning and localization of the Exon 4a/MMSET III splice variant, which contains the protein segment lost in the MB4-2 variant, identified a novel protein domain that prevents nucleolar localization. Kinetic studies using photobleaching suggest that the breakpoint variants are functionally distinct from wild-type proteins. In contrast, RE-IIBP is universally dysregulated and also potentially functional in all t(4;14)POS patients irrespective of fibroblast growth factor receptor 3 (FGFR3) expression or breakpoint type.	D009101	Multiple Myeloma
NSD2	15677557	Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients.	Multiple myeloma (MM) is a B-lineage malignancy characterized by diverse genetic subtypes and clinical outcomes. The recurrent immunoglobulin heavy chain (IgH) switch translocation, t(4;14)(p16;q32), is associated with poor outcome, though the mechanism is unclear. Quantitative reverse-transcription-polymerase chain reaction (RT-PCR) for proposed target genes on a panel of myeloma cell lines and purified plasma cells showed that only transcripts originating from the WHSC1/MMSET/NSD2 gene are uniformly dysregulated in all t(4;14)POS patients. The different transcripts detected, multiple myeloma SET domain containing protein (MMSET I), MMSET II, Exon 4a/MMSET III, and response element II binding protein (RE-IIBP), are produced by alternative splicing and alternative transcription initiation events. Translation of the various transcripts, including those from major breakpoint region 4-2 (MB4-2) and MB4-3 breakpoint variants, was confirmed by transient transfection and immunoblotting. Green fluorescent protein (GFP)-tagged MMSET I and II, corresponding to proteins expressed in MB4-1 patients, localized to the nucleus but not nucleoli, whereas the MB4-2 and MB4-3 proteins concentrate in nucleoli. Cloning and localization of the Exon 4a/MMSET III splice variant, which contains the protein segment lost in the MB4-2 variant, identified a novel protein domain that prevents nucleolar localization. Kinetic studies using photobleaching suggest that the breakpoint variants are functionally distinct from wild-type proteins. In contrast, RE-IIBP is universally dysregulated and also potentially functional in all t(4;14)POS patients irrespective of fibroblast growth factor receptor 3 (FGFR3) expression or breakpoint type.	D014178	Translocation, Genetic

Clinically important variants in NSD2

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance