NSD1 (Nuclear receptor-binding, su (var), enhancer-of-zeste and trithorax domain-containing protein 1

2002-03-01   Lyndal Kearney 

Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK

Identity

HGNC
LOCATION
5q35.2
LOCUSID
ALIAS
ARA267,KMT3B,SOTOS,SOTOS1,STO
FUSION GENES

DNA/RNA

Description

At least 23 exons. cDNA is 8552 bp, 8088 bp open reading frame

Transcription

Two transcripts: 9.0 and 10 kb

Proteins

Atlas Image

Description

2696 amino acids. Murine Nsd1 is a nuclear protein containing SET, proline-tryptophan-tryptophan-proline (PWWP) and plant homedomain protein (PHD) finger domains. The protein has two distinct nuclear receptor (NR)-interaction domains (NID-L, NID+L). Human NSD1 shows 86% identity to the murine Nsd1 at the nucleotide level and 83% at the amino acid level, retaining the nuclear interaction domains (NID) as well as the SET/SAC and PHD finger domains.

Expression

Widely expressed

Function

Features of a basic transcription factor, also of a bifunctional transcriptional regulator, (similar to murine Nsd1)

Homology

NSD2: (Wolf-Hirschhorn syndrome critical region on 4p); NSD3: expressed in tumour cell lines

Implicated in

Entity name
t(5;11)(q35;p15.5)/ acute non lymphoblastic leukemia (AML)
Disease
De novo childhood AML
Prognosis
Only 5 cases reported. All had poor response to treatment/short survival
Cytogenetics
Cryptic: associated with del(5q) (sole cytogenetic abnormality) or a normal karyotype
Hybrid gene
5 NUP98- 3 NSD1 ; NSD1-NUP98 also present in all cases tested
Fusion protein
NH2 NUP98- COOH NSD1: Fuses the FXFG portion of NUP98 to the SET, SAC and PHD finger domains of NSD1. NSD1-NUP98: Fuses the RNA-binding domain of NSD1 to the NID domain NUP98

Bibliography

Pubmed IDLast YearTitleAuthors
113749042001NSD3, a new SET domain-containing gene, maps to 8p12 and is amplified in human breast cancer cell lines.Angrand PO et al
118957892002A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid leukemia with apparently normal karyotypes, identified by a multiplex fluorescence in situ hybridization telomere assay.Brown J et al
96288761998Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators.Huang N et al
114934822001A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia.Jaju RJ et al
103977451999A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer Cytogenetics Group (UKCCG)Jaju RJ et al
117331442001Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene.Kurotaki N et al
116814082001NUP98 gene fusions in hematologic malignancies.Lam DH et al
96181631998WHSC1, 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.Stec I et al

Other Information

Locus ID:

NCBI: 64324
MIM: 606681
HGNC: 14234
Ensembl: ENSG00000165671

Variants:

dbSNP: 64324
ClinVar: 64324
TCGA: ENSG00000165671
COSMIC: NSD1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000165671ENST00000347982Q96L73
ENSG00000165671ENST00000354179Q96L73
ENSG00000165671ENST00000375350H7BYB0
ENSG00000165671ENST00000439151Q96L73
ENSG00000165671ENST00000503056D6RBP3
ENSG00000165671ENST00000504457A0A1D5RMR9
ENSG00000165671ENST00000508029D6RE14
ENSG00000165671ENST00000508896D6RA58
ENSG00000165671ENST00000510954D6RBV9
ENSG00000165671ENST00000511258D6RG26
ENSG00000165671ENST00000515735D6RA90
ENSG00000165671ENST00000638627A0A1W2PS55
ENSG00000165671ENST00000644863A0A1W2PS55

Expression (GTEx)

0
5
10
15
20
25
30

Pathways

PathwaySourceExternal ID
Lysine degradationKEGGko00310
Lysine degradationKEGGhsa00310
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
PKMTs methylate histone lysinesREACTOMER-HSA-3214841

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
175894992007NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis.136
118963892002Haploinsufficiency of NSD1 causes Sotos syndrome.124
200807982010Regulation of NF-kappaB by NSD1/FBXL11-dependent reversible lysine methylation of p65.101
218134472011NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern.65
159428752005Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.58
211964962011The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation.57
124649972003NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.45
266906732015NSD1 mutations generate a genome-wide DNA methylation signature.42
208375382010Role for the nuclear receptor-binding SET domain protein 1 (NSD1) methyltransferase in coordinating lysine 36 methylation at histone 3 with RNA polymerase II function.38
259424512015The NSD family of protein methyltransferases in human cancer.28

Citation

Lyndal Kearney

NSD1 (Nuclear receptor-binding, su (var), enhancer-of-zeste and trithorax domain-containing protein 1

Atlas Genet Cytogenet Oncol Haematol. 2002-03-01

Online version: http://atlasgeneticsoncology.org/gene/356/nsd1id356