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

    Gene ID: 64324, updated on 18-Nov-2024

    Summary

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    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

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    See NSD1 in Genome Data Viewer
    Location:
    5q35.3
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (177131798..177300213)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (177675008..177843448)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (176558799..176727214)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:176449401-176449938 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:176449939-176450475 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16670 Neighboring gene zinc finger protein 346 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:176488686-176489885 Neighboring gene FGFR4 5' regulatory region Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:176537235-176537734 Neighboring gene fibroblast growth factor receptor 4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23693 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:176558105-176558658 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancers GRCh37_chr5:176559765-176560316 and GRCh37_chr5:176560317-176560870 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:176560871-176561422 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:176561423-176561976 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16676 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:176692158-176693050 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:176693051-176693942 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:176696443-176697642 Neighboring gene ribosomal protein L21 pseudogene 60 Neighboring gene protein arginine methyltransferase 1 pseudogene 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:176722701-176723202 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:176723203-176723702 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:176727388-176727581 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:176728411-176729610 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16677 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:176730775-176731652 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23699 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23700 Neighboring gene PRELI domain containing 1 Neighboring gene RAB24, member RAS oncogene family Neighboring gene MAX dimerization protein 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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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    Related articles in PubMed

    1. Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Tatton-Brown K, et al. Am J Hum Genet, 2005 Aug. PMID 15942875, Free PMC Article
    2. Mutation analysis of the NSD1 gene in patients with autism spectrum disorders and macrocephaly. Buxbaum JD, et al. BMC Med Genet, 2007 Nov 14. PMID 18001468, Free PMC Article
    3. Disruption of NSD1 in Head and Neck Cancer Promotes Favorable Chemotherapeutic Responses Linked to Hypomethylation. Bui N, et al. Mol Cancer Ther, 2018 Jul. PMID 29636367, Free PMC Article
    4. Heterogeneity of NSD1 alterations in 116 patients with Sotos syndrome. Saugier-Veber P, et al. Hum Mutat, 2007 Nov. PMID 17565729
    5. Leukocyte cDNA analysis of NSD1 derived from confirmed Sotos syndrome patients. Duno M, et al. Ann Hum Genet, 2007 Nov. PMID 17561922

    See all (150) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Impact of NSD1 Alternative Transcripts in Actin Filament Formation and Cellular Division Pathways in Fibroblasts.
      Title: Impact of NSD1 Alternative Transcripts in Actin Filament Formation and Cellular Division Pathways in Fibroblasts.
    2. Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome.
      Title: Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome.
    3. 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.
    4. 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.
    5. 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.
    6. NUP98::Nsd1 and FLT3-ITD collaborate to generate acute myeloid leukemia.
      Title: NUP98::Nsd1 and FLT3-ITD collaborate to generate acute myeloid leukemia.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (92)

    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
    Genome-wide meta-analysis identifies new susceptibility loci for migraine.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    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
    located_in 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
    NP_001396230.1
    NP_001396231.1
    NP_001396232.1
    NP_001396233.1
    NP_001396234.1
    NP_001396235.1
    NP_001396236.1
    NP_001396237.1
    NP_001396238.1
    NP_071900.2
    NP_758859.2

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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

    1. NG_009821.1 RefSeqGene

      Range
      5001..172135
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_512

    mRNA and Protein(s)

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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

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

      Status: REVIEWED

      Source sequence(s)
      AC008570, AC027314, AC146507

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

      Status: REVIEWED

      Source sequence(s)
      AC008570, AC027314, AC146507

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

      Status: REVIEWED

      Source sequence(s)
      AC008570, AC027314, AC146507

    9. 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

    10. NM_001409309.1 → NP_001396238.1  histone-lysine N-methyltransferase, H3 lysine-36 specific isoform f

      Status: REVIEWED

      Source sequence(s)
      AC008570, AC027314, AC146507

    11. 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

    12. 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

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      177131798..177300213
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      177675008..177843448
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96L73.1 GenPept UniProtKB/Swiss-Prot:Q96L73

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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