NSD3 (nuclear receptor binding SET domain protein 3)

Gene

• Entrez ID: 54904
• Gene name: Nuclear receptor binding SET domain protein 3
• Gene symbol: NSD3
• Synonyms (NCBI Gene): KMT3F, KMT3G, WHISTLE, WHSC1L1, pp14328
• Chromosome: 8
• Chromosome location: 8p11.23
• Summary: This gene is related to the Wolf-Hirschhorn syndrome candidate-1 gene and encodes a protein with PWWP (proline-tryptophan-tryptophan-proline) domains. This protein methylates histone H3 at lysine residues 4 and 27, which represses gene transcription. Two

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT651566	hsa-miR-4635	HITS-CLIP	23824327
MIRT651565	hsa-miR-526b-5p	HITS-CLIP	23824327
MIRT651564	hsa-miR-203a-3p	HITS-CLIP	23824327
MIRT651563	hsa-miR-7158-3p	HITS-CLIP	23824327
MIRT651562	hsa-miR-203b-3p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IBA
GO:0005515	Function	Protein binding	IPI	21516116, 21555454, 23455924, 25416956, 25640309, 29176719, 31527615, 32814053
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IC	16682010
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	IMP	21555454
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0006325	Process	Chromatin organization	IEA
GO:0006338	Process	Chromatin remodeling	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IBA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0008168	Function	Methyltransferase activity	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0032259	Process	Methylation	IEA
GO:0042054	Function	Histone methyltransferase activity	IEA
GO:0042800	Function	Histone H3K4 methyltransferase activity	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IMP	21555454
GO:0046872	Function	Metal ion binding	IEA
GO:0046975	Function	Histone H3K36 methyltransferase activity	IBA
GO:0046975	Function	Histone H3K36 methyltransferase activity	IEA
GO:0046975	Function	Histone H3K36 methyltransferase activity	IMP	21555454
GO:0046976	Function	Histone H3K27 methyltransferase activity	IEA
GO:0140537	Function	Transcription regulator activator activity	IMP	21555454
GO:0140938	Function	Histone H3 methyltransferase activity	TAS
GO:0140946	Function	Histone H3K4 dimethyltransferase activity	IDA	16682010
GO:0140946	Function	Histone H3K4 dimethyltransferase activity	IEA
GO:0140951	Function	Histone H3K27 trimethyltransferase activity	IDA	16682010
GO:0140952	Function	Histone H3K27 dimethyltransferase activity	IDA	16682010
GO:0140952	Function	Histone H3K27 dimethyltransferase activity	IEA

Other IDs

• MIM: 607083
• HGNC: 12767
• e!Ensembl: ENSG00000147548

Protein

• UniProt ID: Q9BZ95
• Protein name: Histone-lysine N-methyltransferase NSD3 (EC 2.1.1.370) (EC 2.1.1.371) (Nuclear SET domain-containing protein 3) (Protein whistle) (WHSC1-like 1 isoform 9 with methyltransferase activity to lysine) (Wolf-Hirschhorn syndrome candidate 1-like protein 1) (WHS
• Protein function: Histone methyltransferase. Preferentially dimethylates 'Lys-4' and 'Lys-27' of histone H3 forming H3K4me2 and H3K27me2. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for tran
• PDB: 2DAQ, 2NCZ, 2ND1, 4GND, 4GNE, 4GNF, 4GNG, 4RXJ, 5UPD, 6CEN, 6G24, 6G25, 6G27, 6G29, 6G2B, 6G2C, 6G2E, 6G2F, 6G2O, 6G3P, 6G3T, 7CRP, 7CRQ, 7CRR, 7JYN
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00855	PWWP	268 → 380	PWWP domain	Domain
  PF00855	PWWP	958 → 1049	PWWP domain	Domain
  PF17907	AWS	1104 → 1142	AWS domain	Domain
  PF00856	SET	1156 → 1262	SET domain	Family
  PF17982	C5HCH	1364 → 1413	NSD Cys-His rich domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in brain, heart and skeletal muscle. Expressed at lower level in liver and lung. {ECO:0000269|PubMed:11374904}.
• Sequence:

  MDFSFSFMQGIMGNTIQQPPQLIDSANIRQEDAFDNNSDIAEDGGQTPYEATLQQGFQYP
  ATTEDLPPLTNGYPSSISVYETQTKYQSYNQYPNGSANGFGAVRNFSPTDYYHSEIPNTR
  PHEILEKPSPPQPPPPPSVPQTVIPKKTGSPEIKLKITKTIQNGRELFESSLCGDLLNEV
  QASEHTKSKHESRKEKRKKSNKHDSSRSEERKSHKIPKLEPEEQNRPNERVDTVSEKPRE
  EPVLKEEAPVQPILSSVPTTEVSTGVKFQVGDLVWSKVGTYPWWPCMVSSDPQLEVHTKI
  NTRGAREYHVQFFSNQPERAWVHEKRVREYKGHKQYEELLAEATKQASNHSEKQKIRKPR
  PQRERAQWDIGIAHAEKALKMTREERIEQYTFIYIDKQPEEALSQAKKSVASKTEVKKTR
  RPRSVLNTQPEQTNAGEVASSLSSTEIRRHSQRRHTSAEEEEPPPVKIAWKTAAARKSLP
  ASITMHKGSLDLQKCNMSPVVKIEQVFALQNATGDGKFIDQFVYSTKGIGNKTEISVRGQ
  DRLIISTPNQRNEKPTQSVSSPEATSGSTGSVEKKQQRRSIRTRSESEKSTEVVPKKKIK
  KEQVETVPQATVKTGLQKGASEISDSCKPLKKRSRASTDVEMTSSAYRDTSDSDSRGLSD
  LQVGFGKQVDSPSATADADVSDVQSMDSSLSRRGTGMSKKDTVCQICESSGDSLIPCEGE
  CCKHFHLECLGLASLPDSKFICMECKTGQHPCFSCKVSGKDVKRCSVGACGKFYHEACVR
  KFPTAIFESKGFRCPQHCCSACSMEKDIHKASKGRMMRCLRCPVAYHSGDACIAAGSMLV
  SSYILICSNHSKRSSNSSAVNVGFCFVCARGLIVQDHSDPMFSSYAYKSHYLLNESNRAE
  LMKLPMIPSSSASKKKCEKGGRLLCCESCPASFHPECLSIEMPEGCWNCNDCKAGKKLHY
  KQIVWVKLGNYRWWPAEICNPRSVPLNIQGLKHDLGDFPVFFFGSHDYYWVHQGRVFPYV
  EGDKSFAEGQTSINKTFKKALEEAAKRFQELKAQRESKEALEIEKNSRKPPPYKHIKANK
  VIGKVQIQVADLSEIPRCNCKPADENPCGLESECLNRMLQYECHPQVCPAGDRCQNQCFT
  KRLYPDAEIIKTERRGWGLRTKRSIKKGEFVNEYVGELIDEEECRLRIKRAHENSVTNFY
  MLTVTKDRIIDAGPKGNYSRFMNHSCNPNCETQKWTVNGDVRVGLFALCDIPAGMELTFN
  YNLDCLGNGRTECHCGADNCSGFLGVRPKSACASTNEEKAKNAKLKQKRRKIKTEPKQMH
  EDYCFQCGDGGELVMCDKKDCPKAYHLLCLNLTQPPYGKWECPWHQCDECSSAAVSFCEF
  CPHSFCKDHEKGALVPSALEGRLCCSEHDPMAPVSPEYWSKIKCKWESQDHGEEVKE

• Sequence length: 1437

Pathways

KEGG:

Lysine degradation
Metabolic pathways

Reactome:

PKMTs methylate histone lysines

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NSD3-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nut midline carcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBSESSIVE-COMPULSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TOURETTE SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	24051013		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma of pancreas	Pancreatic adenocarcinoma	BEFREE	24051013		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	11374904, 20940404, 24051013, 27005559, 28484924		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	20940404, 27005559	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	20599755		★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	23011637		★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	23011637, 24051013, 31285596		★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	15983384	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	15983384, 21666749, 34358469	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	31190890		★☆☆☆☆ Found in Text Mining only
Head and Neck Carcinoma	Head And Neck Carcinoma	BEFREE	28102297		★☆☆☆☆ Found in Text Mining only
Head and Neck Neoplasms	Head and neck neoplasm	Pubtator	28102297	Associate	★☆☆☆☆ Found in Text Mining only
Hematologic Neoplasms	Hematologic Neoplasms	BEFREE	11986249		★☆☆☆☆ Found in Text Mining only
Invasive Ductal Breast Carcinoma	Invasive Duct and Lobular Carcinoma	BEFREE	28484924		★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	20599755, 26626481		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	11986249, 35303440	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	11986249, 17589499, 19380029, 26626481		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	BEFREE	24051013		★☆☆☆☆ Found in Text Mining only
Malignant Head and Neck Neoplasm	Head and neck cancer	BEFREE	28102297		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	11374904, 20940404, 24051013, 27005559, 28484924		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	23011637		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	17589499, 23011637, 24051013, 31285596		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	22421440, 23011637, 26411517, 30013365, 30320908, 31285596		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	24051013		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	BEFREE	17589499		★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	19380029		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	24051013, 26905262		★☆☆☆☆ Found in Text Mining only
Nephrosis	Nephrosis	BEFREE	28228401		★☆☆☆☆ Found in Text Mining only
Nephrotic Syndrome	Nephrotic Syndrome	BEFREE	28228401		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	15983384		★☆☆☆☆ Found in Text Mining only
NUT midline carcinoma	Carcinoma	BEFREE	24875858, 26490121		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteosarcoma	Osteosarcoma	BEFREE	28901481		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	28901481	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Ductal Adenocarcinoma	Pancreatic adenocarcinoma	BEFREE	15983384		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	37062069	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	30616239	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	29483656		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Small cell carcinoma of lung	Lung carcinoma	BEFREE	24051013		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	28102297	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of the head and neck	Carcinoma Of The Head And Neck	BEFREE	28102297		★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	34997561	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	30984543	Associate	★☆☆☆☆ Found in Text Mining only