Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

NSD1

contributors: mct - updated : 28-06-2018

HGNC name	nuclear receptor binding SET domain protein 1
HGNC id	14234

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	STO Sotos syndrome
Location	5q35.2      Physical location : 176.560.079 - 176.727.213
Synonym name	androgen receptor-associated coregulator 267
	H4-K20-HMTase
	lysine N-methyltransferase 3B
	NR-binding SET domain-containing protein
	H3-K36-HMTase
	histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific
Synonym symbol(s)	ARA267, FLJ22263, FLJ44628, KMT3B, DKFZp666C163, FLJ10684
EC.number	2.1.1.43

DNA

TYPE	functioning gene
STRUCTURE	166.38 kb     23 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_172349 24 - 12213 NP_758859 - 2427 - 2007 17565729 short isoform NM_022455 23 - 12998 NP_071900 - 2696 - 2007 17565729 long isoform

EXPRESSION

Type

widely

constitutive of

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen       highly Cardiovascular heart       highly Endocrine pancreas       moderately Lymphoid/Immune thymus         Nervous brain       moderately   spinal cord       highly Reproductive male system prostate     moderately Respiratory lung       moderately Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Lymphoid         Muscular striatum skeletal     Nervous central

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text

brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three C5HCH and four plant homeodomains (PHDs), which are implicated in chromatin regulation and are zinc finger like motifs characterized by cysteine and histidine residues
	two PWWP (proline-2 tryptophan-proline)domains (one in N-terminus)
	two nuclear receptor-interaction domains (NID)
	ten putative nuclear localization signals
	a single FSXXLXXL motif facilitates its interactions with the NR2E/F subfamily
	several motifs, lysine methyltransferase SET domain and four zinc-binding PHD fingers, in the C-terminal half that are undoubtedly critical for its proposed functions in signaling and chromatin regulation

HOMOLOGY

interspecies

homolog to murine Nsd1

Homologene

FAMILY	histone-lysine methyltransferase family
	nuclear receptor binding SET domain (NSD) protein family

CATEGORY

regulatory , receptor nuclear

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	SET-domain histone lysine methyltransferase, maybe acting as a nucleus-localized, basic transcriptional factor and also as a bifunctional transcriptional regulator
	may be involved in imprinting of the chromosome 11p15 region
	may be functioning as a bifunctional transcriptional regulator activating or repressing transcription in response to ligand binding
	acting as a histone methyltransferase
	involved in the regulation of gene expression through stimulating the transition of RNA polymerase II from an initiation to fully elongation-competent state
	SET-domain histone methyltransferase that primarily di-methylates nucleosomal histone H3 lysine 36 (H3K36), through an autoregulatory mechanism
	autoregulatory mechanism of NSD1, providing insight into the molecular mechanism of the nucleosomal substrate selectivity of this disease-related H3K36 methyltransferase
	critical in maintaining the chromatin integrity
	NSD1, NSD2 and NSD3, have crucial roles in chromatin regulation and are implicated in oncogenesis

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with ZNF496
	CFDP1, Sec23 homolog A (SEC23A), and nuclear receptor binding SET domain protein 1 (NSD1), contain consensus GTF2I binding sites in their proximal promoters
	binds near various promoter elements and regulates multiple genes that appear to have a concerted role in various processes, such as cell growth/cancer, keratin biology, and bone morphogenesis
	regulates RNA polymerase II recruitment to BMP4, and failure to do so leads to reduced gene expression and abrogated levels of H3K36Me and C-terminal domain phosphorylation
	NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

STO , WVSS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       fused with NUP98 in t(5;11)(q35;p15.5) in acute myeloid leukemia constitutional germinal mutation       in Beckwith-Wiedemann syndrome tumoral     --low   by hypermethylation was a common event in neuroblastomas and gliomas (NSD1 hypermethylation was a predictor of poor outcome in high-risk neuroblastoma constitutional     --over   activates NF-kappaB and reverses the inhibitory effect of KDM2A, whereas reduced expression of NSD1 decreases NF-kappaB activation tumoral   amplification     in multiple myeloma, lung cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer brain   therapeutic implications because NSD1 DNA methylation-associated silencing is associated with poor outcome and there are now clinically approved DNA demethylating agents that may be able to restore NSD1 functionality with potential tumor growth inhibitory

ANIMAL & CELL MODELS