NSD1 nuclear receptor binding SET domain protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NSD1provided by HGNC
Official Full Name: nuclear receptor binding SET domain protein 1provided by HGNC
Primary source: HGNC:HGNC:14234
See related: Ensembl:ENSG00000165671 MIM:606681; AllianceGenome:HGNC:14234
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: STO; KMT3B; SOTOS; ARA267; SOTOS1
Summary: This gene encodes a protein containing a SET domain, 2 LXXLL motifs, 3 nuclear translocation signals (NLSs), 4 plant homeodomain (PHD) finger regions, and a proline-rich region. The encoded protein enhances androgen receptor (AR) transactivation, and this enhancement can be increased further in the presence of other androgen receptor associated coregulators. This protein may act as a nucleus-localized, basic transcriptional factor and also as a bifunctional transcriptional regulator. Mutations of this gene have been associated with Sotos syndrome and Weaver syndrome. One version of childhood acute myeloid leukemia is the result of a cryptic translocation with the breakpoints occurring within nuclear receptor-binding Su-var, enhancer of zeste, and trithorax domain protein 1 on chromosome 5 and nucleoporin, 98-kd on chromosome 11. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Sep 2018]
Expression: Ubiquitous expression in testis (RPKM 4.4), thyroid (RPKM 4.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q35.3

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (177131798..177300213)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (177675008..177843448)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (176560016..176727214)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sotos syndrome with marked overgrowth in three Japanese patients with heterozygous likely pathogenic NSD1 variants: case reports with review of literature.
Title: Sotos syndrome with marked overgrowth in three Japanese patients with heterozygous likely pathogenic NSD1 variants: case reports with review of literature.
H3K36 methyltransferase NSD1 protects against osteoarthritis through regulating chondrocyte differentiation and cartilage homeostasis.
Title: H3K36 methyltransferase NSD1 protects against osteoarthritis through regulating chondrocyte differentiation and cartilage homeostasis.
Targeting KDM2A Enhances T-cell Infiltration in NSD1-Deficient Head and Neck Squamous Cell Carcinoma.
Title: Targeting KDM2A Enhances T-cell Infiltration in NSD1-Deficient Head and Neck Squamous Cell Carcinoma.
NUP98::Nsd1 and FLT3-ITD collaborate to generate acute myeloid leukemia.
Title: NUP98::Nsd1 and FLT3-ITD collaborate to generate acute myeloid leukemia.
Molecular Analysis and Reclassification of NSD1 Gene Variants in a Cohort of Patients with Clinical Suspicion of Sotos Syndrome.
Title: Molecular Analysis and Reclassification of NSD1 Gene Variants in a Cohort of Patients with Clinical Suspicion of Sotos Syndrome.
NSD1 gene evolves under episodic selection within primates and mutations of specific exons in humans cause Sotos syndrome.
Title: NSD1 gene evolves under episodic selection within primates and mutations of specific exons in humans cause Sotos syndrome.
Identification of alternative transcripts of NSD1 gene in Sotos Syndrome patients and healthy subjects.
Title: Identification of alternative transcripts of NSD1 gene in Sotos Syndrome patients and healthy subjects.
Reversal of Clinical Phenotype of Sotos Syndrome Due to Microduplication of NSD1 Gene.
Title: Reversal of Clinical Phenotype of Sotos Syndrome Due to Microduplication of NSD1 Gene.
NSD1 mediates antagonism between SWI/SNF and polycomb complexes and is required for transcriptional activation upon EZH2 inhibition.
Title: NSD1 mediates antagonism between SWI/SNF and polycomb complexes and is required for transcriptional activation upon EZH2 inhibition.
NSD1 mutations deregulate transcription and DNA methylation of bivalent developmental genes in Sotos syndrome.
Title: NSD1 mutations deregulate transcription and DNA methylation of bivalent developmental genes in Sotos syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (90)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Sotos syndrome MedGen: C0175695 OMIM: 117550 GeneReviews: Sotos Syndrome	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-07-27) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-07-27) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies new susceptibility loci for migraine. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_13653-13654:1002893061:1 (e-PCR)
- UniSTS:267524

WI-14959 (e-PCR)
- UniSTS:32007

RH92299 (e-PCR)
- UniSTS:91406

bac51977T (e-PCR)
- UniSTS:181534

RH68619 (e-PCR)
- UniSTS:59179

D5S2221E (e-PCR)
- UniSTS:154427

D5S2260E (e-PCR)
- UniSTS:154466

RH80203 (e-PCR)
- UniSTS:84323

RH18384 (e-PCR)
- UniSTS:38502

G35510 (e-PCR)
- UniSTS:44150

Hrmt1l2 (e-PCR), detects polymorphism
- UniSTS:275867

WI-11713 (e-PCR)
- UniSTS:5321

SGC34971 (e-PCR)
- UniSTS:75001

WI-21083 (e-PCR)
- UniSTS:77305

SHGC-24370 (e-PCR)
- UniSTS:77306

Clone Names

FLJ10684, FLJ22263, FLJ44628, DKFZp666C163

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	ISS Inferred from Sequence or Structural Similarity more info
enables histone H3 methyltransferase activity	TAS Traceable Author Statement more info
enables histone H3K36 dimethyltransferase activity	IEA Inferred from Electronic Annotation more info
enables histone H3K36 methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables histone H3K36 methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables histone H3K36 methyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone H3K36 methyltransferase activity	ISS Inferred from Sequence or Structural Similarity more info
enables histone H4K20 methyltransferase activity	ISS Inferred from Sequence or Structural Similarity more info
enables nuclear androgen receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables nuclear estrogen receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables nuclear retinoic acid receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables nuclear retinoid X receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables nuclear thyroid hormone receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription coregulator activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription corepressor activity	ISS Inferred from Sequence or Structural Similarity more info
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in methylation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of RNA polymerase II regulatory region sequence-specific DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of peptidyl-serine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of chromatin	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: histone-lysine N-methyltransferase, H3 lysine-36 specific

Names: H3-K36-HMTase; H4-K20-HMTase; NR-binding SET domain-containing protein; androgen receptor coactivator 267 kDa protein; androgen receptor-associated coregulator 267; androgen receptor-associated protein of 267 kDa; histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific; lysine N-methyltransferase 3B; nuclear receptor SET domain-containing protein 1; nuclear receptor-binding SET domain-containing protein 1

NP_001352613.2

EC 2.1.1.357

NP_001396230.1

EC 2.1.1.357

NP_001396231.1

EC 2.1.1.357

NP_001396232.1

EC 2.1.1.357

NP_001396233.1

EC 2.1.1.357

NP_001396234.1

EC 2.1.1.357

NP_001396235.1

EC 2.1.1.357

NP_001396236.1

EC 2.1.1.357

NP_001396237.1

EC 2.1.1.357

NP_001396238.1

EC 2.1.1.357

NP_071900.2

EC 2.1.1.357

NP_758859.2

EC 2.1.1.357

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009821.1 RefSeqGene

Range

5001..172135

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_512

mRNA and Protein(s)

NM_001365684.2 → NP_001352613.2 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform a

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507

Consensus CDS

CCDS4413.1

UniProtKB/TrEMBL

A0A8I5QJP2, D6RA58

Related

ENSP00000343209.5, ENST00000347982.9
NM_001409301.1 → NP_001396230.1 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform b

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507

UniProtKB/Swiss-Prot

Q96L73, Q96PD8, Q96RN7
NM_001409302.1 → NP_001396231.1 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform b

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507

UniProtKB/Swiss-Prot

Q96L73, Q96PD8, Q96RN7
NM_001409303.1 → NP_001396232.1 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform b

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507

UniProtKB/Swiss-Prot

Q96L73, Q96PD8, Q96RN7

Related

ENSP00000508426.1, ENST00000687453.1
NM_001409304.1 → NP_001396233.1 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform c

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507

Related

ENST00000688613.1
NM_001409305.1 → NP_001396234.1 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform d

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507
NM_001409306.1 → NP_001396235.1 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform e

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507
NM_001409307.1 → NP_001396236.1 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform e

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507
NM_001409308.1 → NP_001396237.1 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform a

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507

UniProtKB/TrEMBL

A0A8I5QJP2, D6RA58

Related

ENSP00000423372.3, ENST00000508896.7
NM_001409309.1 → NP_001396238.1 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform f

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507
NM_022455.5 → NP_071900.2 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform b

See identical proteins and their annotated locations for NP_071900.2

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507

Consensus CDS

CCDS4412.1

UniProtKB/Swiss-Prot

Q96L73, Q96PD8, Q96RN7

UniProtKB/TrEMBL

B2RWP5

Related

ENSP00000395929.2, ENST00000439151.7

Conserved Domains (12) summary

cd05837
Location:319 → 429

MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...

cd05838
Location:1754 → 1848

WHSC1_related; The PWWP domain was first identified in the WHSC1 (Wolf-Hirschhorn syndrome candidate 1) protein, a protein implicated in Wolf-Hirschhorn syndrome (WHS). When translocated, WHSC1 plays a role in lymphoid multiple myeloma (MM) disease, also known as ...

smart00570
Location:1891 → 1941

AWS; associated with SET domains

smart00317
Location:1942 → 2065

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

cd15648
Location:1545 → 1587

PHD1_NSD1_2; PHD finger 1 found in nuclear receptor-binding SET domain-containing protein NSD1 and NSD2

cd15650
Location:1592 → 1638

PHD2_NSD1; PHD finger 2 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1)

cd15653
Location:1639 → 1692

PHD3_NSD1; PHD finger 3 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1)

cd15656
Location:1709 → 1748

PHD4_NSD1; PHD finger 4 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1)

cd15659
Location:2120 → 2162

PHD5_NSD1; PHD finger 5 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1)

cl26267
Location:1431 → 1587

ING; Inhibitor of growth proteins N-terminal histone-binding

cl26386
Location:2438 → 2663

DNA_pol3_gamma3; DNA polymerase III subunits gamma and tau domain III

cl26464
Location:2208 → 2574

Atrophin-1; Atrophin-1 family
NM_172349.5 → NP_758859.2 histone-lysine N-methyltransferase, H3 lysine-36 specific isoform a

Status: REVIEWED

Source sequence(s)

AC008570, AC027314, AC146507

Consensus CDS

CCDS4413.1

UniProtKB/TrEMBL

A0A8I5QJP2, D6RA58

Related

ENSP00000346111.5, ENST00000354179.9