NSD1 Gene

HGNC Family	Chromatin-modifying enzymes, Zinc fingers
Name	nuclear receptor binding SET domain protein 1
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNSD1 is a critical epigenetic regulator whose dosage is central to normal human development. Numerous studies have demonstrated that haploinsufficiency of NSD1—through point mutations, frameshifts, and chromosomal microdeletions—underlies Sotos syndrome, an overgrowth disorder characterized by distinctive facial features, macrocephaly, learning disabilities, and variable additional clinical features. In these patients, genotype–phenotype correlations suggest that while intragenic mutations are more common in non‐deletion cases, microdeletions (often of paternal origin) are associated with less-prominent overgrowth but more severe intellectual disability. In addition, a subset of patients with clinically overlapping phenotypes (including Weaver syndrome and even Silver–Russell syndrome features) have been found to harbor NSD1 alterations, thereby highlighting the essential role of NSD1 dosage in regulating growth and neurodevelopment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, NSD1 functions as a nuclear receptor–binding SET domain histone methyltransferase that primarily dimethylates histone H3 on lysine 36 (H3K36me2), a modification typically associated with active transcription. Structural and biochemical analyses have revealed that NSD1 contains an autoregulatory post-SET loop that modulates substrate access to its catalytic site, while its conserved domains—such as the PHD fingers and PWWP motifs—mediate selective interactions with modified histones and nuclear receptor partners. Such interactions are crucial for orchestrating transcriptional networks during development, as NSD1 binding upstream of key genes (e.g., BMP4) influences RNA polymerase II recruitment and transcriptional initiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its developmental roles, NSD1 has emerged as an important player in oncogenesis. Recurrent rearrangements—such as the NUP98–NSD1 fusion—drive leukemogenesis in acute myeloid leukemia by sustaining aberrant expression of HOX gene clusters and interfering with differentiation, and NSD1 also modulates key signaling pathways such as NF-κB via methylation of its p65 subunit. In a variety of solid tumors—including head and neck squamous cell carcinoma, clear cell renal cell carcinoma, and pancreatic adenocarcinoma—loss or dysregulation of NSD1 is linked to widespread alterations in DNA methylation, impaired histone modification patterns, and differential responses to chemotherapeutics. Moreover, experimental studies in murine models underscore that cooperation between NSD1 alterations and other oncogenic events (such as FLT3 internal tandem duplications) exacerbates leukemic transformation, while CRISPR-based ablation of NSD1 can influence sensitivity to targeted treatments (for example, altering EZH2 inhibitor efficacy). These collective findings position NSD1 as a pivotal epigenetic regulator whose disruption contributes to tumor diversity, prognosis, and potential therapeutic vulnerabilities."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Naohiro Kurotaki, Kiyoshi Imaizumi, Naoki Harada, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/345647"}], "href": "https://doi.org/10.1086/345647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12464997"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12464997"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "M Rio, L Clech, J Amiel, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Familial Sotos syndrome caused by a novel missense mutation, C2175S, in NSD1 and associated with normal intelligence, insulin dependent diabetes, bronchial asthma, and lipedema."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2009.06.001"}], "href": "https://doi.org/10.1016/j.ejmg.2009.06.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19545651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19545651"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Claudia Fagali, Fernando Kok, Pablo Nicola, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MLPA analysis in 30 Sotos syndrome patients revealed one total NSD1 deletion and two partial deletions not previously reported."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2009.07.001"}], "href": "https://doi.org/10.1016/j.ejmg.2009.07.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19596467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19596467"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "J Sachwitz, R Meyer, G Fekete, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Role for the nuclear receptor-binding SET domain protein 1 (NSD1) methyltransferase in coordinating lysine 36 methylation at histone 3 with RNA polymerase II function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1002653107"}], "href": "https://doi.org/10.1073/pnas.1002653107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20837538"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20837538"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Sarah E Graham, Sara E Tweedy, Heather A Carlson "}, {"type": "b", "children": [{"type": "t", "text": "Dynamic behavior of the post-SET loop region of NSD1: Implications for histone binding and drug development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pro.2912"}], "href": "https://doi.org/10.1002/pro.2912"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26940890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26940890"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "N Kurotaki, N Harada, K Yoshiura, et al. 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Synonyms	ARA267, KMT3B, STO, SOTOS1, SOTOS
Proteins	NSD1_HUMAN
NCBI Gene ID	64324
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NSD1 has 8,688 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 131 datasets.

Click the + buttons to view associations for NSD1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NSD1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NSD1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of NSD1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of NSD1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NSD1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of NSD1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NSD1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of NSD1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NSD1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NSD1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NSD1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of NSD1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with NSD1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NSD1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NSD1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NSD1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NSD1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of NSD1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with NSD1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with NSD1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing NSD1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of NSD1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NSD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NSD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NSD1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with NSD1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of NSD1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NSD1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NSD1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NSD1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with NSD1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NSD1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by NSD1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving NSD1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving NSD1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NSD1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NSD1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with NSD1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with NSD1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NSD1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NSD1 gene from the ENCODE Histone Modification Site Profiles dataset.