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
NSD1
LOCATION
5q35.2
LOCUSID
64324
ALIAS
ARA267,KMT3B,SOTOS,SOTOS1,STO
FUSION GENES
Show Gene Fusions

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

Article 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
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

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
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
379892942024Sotos syndrome with marked overgrowth in three Japanese patients with heterozygous likely pathogenic NSD1 variants: case reports with review of literature.0
380123902024H3K36 methyltransferase NSD1 protects against osteoarthritis through regulating chondrocyte differentiation and cartilage homeostasis.1
386849942024Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome.0
379892942024Sotos syndrome with marked overgrowth in three Japanese patients with heterozygous likely pathogenic NSD1 variants: case reports with review of literature.0
380123902024H3K36 methyltransferase NSD1 protects against osteoarthritis through regulating chondrocyte differentiation and cartilage homeostasis.1
386849942024Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome.0
362610882023Identification of alternative transcripts of NSD1 gene in Sotos Syndrome patients and healthy subjects.3
368332222023Molecular Analysis and Reclassification of NSD1 Gene Variants in a Cohort of Patients with Clinical Suspicion of Sotos Syndrome.3
371474242023NUP98::Nsd1 and FLT3-ITD collaborate to generate acute myeloid leukemia.0
373110542023Targeting KDM2A Enhances T-cell Infiltration in NSD1-Deficient Head and Neck Squamous Cell Carcinoma.1
362610882023Identification of alternative transcripts of NSD1 gene in Sotos Syndrome patients and healthy subjects.3
368332222023Molecular Analysis and Reclassification of NSD1 Gene Variants in a Cohort of Patients with Clinical Suspicion of Sotos Syndrome.3
371474242023NUP98::Nsd1 and FLT3-ITD collaborate to generate acute myeloid leukemia.0
373110542023Targeting KDM2A Enhances T-cell Infiltration in NSD1-Deficient Head and Neck Squamous Cell Carcinoma.1
350940882022NSD1 mutations deregulate transcription and DNA methylation of bivalent developmental genes in Sotos syndrome.7

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/nsd1-(nuclear-receptor-binding-su-(var)-enhancer-of-zeste-and-trithorax-domain-containing-protein-1