TISIDB

Summary
Symbol	NSD1
Name	nuclear receptor binding SET domain protein 1
Aliases	ARA267; FLJ22263; KMT3B; STO; Sotos syndrome; SOTOS; SOTOS1; H3-K36-HMTase; H4-K20-HMTase; NR-binding SET do ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus. Chromosome
Domain	PF00855 PWWP domain PF00856 SET domain
Function	Histone methyltransferase. Preferentially methylates 'Lys-36' of histone H3 and 'Lys-20' of histone H4 (in vitro). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context.

> Gene Ontology [ TOP ]
Biological Process	GO:0000414 regulation of histone H3-K36 methylation GO:0006479 protein methylation GO:0008213 protein alkylation GO:0010452 histone H3-K36 methylation GO:0016570 histone modification GO:0016571 histone methylation GO:0018022 peptidyl-lysine methylation GO:0018105 peptidyl-serine phosphorylation GO:0018205 peptidyl-lysine modification GO:0018209 peptidyl-serine modification GO:0031056 regulation of histone modification GO:0031060 regulation of histone methylation GO:0032259 methylation GO:0033135 regulation of peptidyl-serine phosphorylation GO:0034770 histone H4-K20 methylation GO:0034968 histone lysine methylation GO:0043414 macromolecule methylation GO:0051098 regulation of binding GO:0051101 regulation of DNA binding GO:1902275 regulation of chromatin organization GO:1903025 regulation of RNA polymerase II regulatory region sequence-specific DNA binding GO:2000677 regulation of transcription regulatory region DNA binding
Molecular Function	GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding GO:0001046 core promoter sequence-specific DNA binding GO:0001047 core promoter binding GO:0003682 chromatin binding GO:0003714 transcription corepressor activity GO:0008134 transcription factor binding GO:0008168 methyltransferase activity GO:0008170 N-methyltransferase activity GO:0008276 protein methyltransferase activity GO:0008757 S-adenosylmethionine-dependent methyltransferase activity GO:0016278 lysine N-methyltransferase activity GO:0016279 protein-lysine N-methyltransferase activity GO:0016741 transferase activity, transferring one-carbon groups GO:0018024 histone-lysine N-methyltransferase activity GO:0030331 estrogen receptor binding GO:0035257 nuclear hormone receptor binding GO:0035258 steroid hormone receptor binding GO:0042054 histone methyltransferase activity GO:0042799 histone methyltransferase activity (H4-K20 specific) GO:0042974 retinoic acid receptor binding GO:0046965 retinoid X receptor binding GO:0046966 thyroid hormone receptor binding GO:0046975 histone methyltransferase activity (H3-K36 specific) GO:0050681 androgen receptor binding GO:0051427 hormone receptor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00310 Lysine degradation
Reactome	R-HSA-3247509: Chromatin modifying enzymes R-HSA-4839726: Chromatin organization R-HSA-3214841: PKMTs methylate histone lysines

Summary
Symbol	NSD1
Name	nuclear receptor binding SET domain protein 1
Aliases	ARA267; FLJ22263; KMT3B; STO; Sotos syndrome; SOTOS; SOTOS1; H3-K36-HMTase; H4-K20-HMTase; NR-binding SET do ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between NSD1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between NSD1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29213088	Head and neck squamous cell carcinoma; Squamous cell lung carcinoma; Sotos syndrome	Promote immunity (T cell function)	Further, the NSD1 subtype of HNSC displays an ‘immune cold’ phenotype characterized by low infiltration of tumor-associated leukocytes, particularly macrophages and CD8+ T cells, as well as low expression of genes encoding the immunotherapy target PD-1 immune checkpoint receptor and its ligands. Using an in vivo model, we demonstrate that NSD1 inactivation results in reduced T cell infiltration into the tumor microenvironment, implicating NSD1 as a tumor cell-intrinsic driver of an immune cold phenotype. Choufani et al. reported that germline NSD1 mutations are associated with widespread perturbation (primarily loss) of DNA methylation, i.e., methylation of cytosine to form 5-methylcytosine at CpG dinucleotides. NSD1 is not thought to methylate DNA; therefore H3K36me (or other histone marks) catalyzed by NSD1 apparently regulate DNA methylation. Inactivating mutations of NSD1 also deregulate DNA methylation in HNSC, as we and others have described a HNSC subtype characterized by widespread DNA hypomethylation, that is strongly enriched for NSD1 mutations. Inactivation mutation of NSD1 in head and neck squamous cell carcinoma shows low infiltration of macrophages and CD8+ cytotoxic T cell into tumor microenvironment in vivo, and low expression of PD-1 immune checkpoint receptor and ligand encoding genes. Thus, inactivation of NSD1 drives the immune cold phenotype, resistant to immunotherapy. Mutation of NSD1 also co-occur with worldwide hypomethylation of DNA in various cancers.
28067913	Head and Neck Squamous Cell Carcinoma	Promote immunity	The K36M substitution and NSD1 defects converge on altering methylation of histone H3 at K36 (H3K36), subsequently blocking cellular differentiation and promoting oncogenesis. Our data further indicate limited redundancy for NSD family members in HPV-negative HNSCCs and suggest a potential role for impaired H3K36 methylation in their development.

Summary
Symbol	NSD1
Name	nuclear receptor binding SET domain protein 1
Aliases	ARA267; FLJ22263; KMT3B; STO; Sotos syndrome; SOTOS; SOTOS1; H3-K36-HMTase; H4-K20-HMTase; NR-binding SET do ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of NSD1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	NSD1
Name	nuclear receptor binding SET domain protein 1
Aliases	ARA267; FLJ22263; KMT3B; STO; Sotos syndrome; SOTOS; SOTOS1; H3-K36-HMTase; H4-K20-HMTase; NR-binding SET do ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of NSD1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.025	0.901
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.087	0.944
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.023	0.981
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.173	0.568
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.078	0.977
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.295	0.934
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.247	0.533
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.277	0.877
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.235	0.905
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.286	0.812
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.736	0.666
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.083	0.0689

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of NSD1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	11.8	-11.8	0.488
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	4.1	3.3	0.61
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	5.1	2.3	0.647
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	6.2	16	0.53
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	50	14.3	35.7	0.491
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	8.3	-8.3	1

Summary
Symbol	NSD1
Name	nuclear receptor binding SET domain protein 1
Aliases	ARA267; FLJ22263; KMT3B; STO; Sotos syndrome; SOTOS; SOTOS1; H3-K36-HMTase; H4-K20-HMTase; NR-binding SET do ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NSD1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	NSD1
Name	nuclear receptor binding SET domain protein 1
Aliases	ARA267; FLJ22263; KMT3B; STO; Sotos syndrome; SOTOS; SOTOS1; H3-K36-HMTase; H4-K20-HMTase; NR-binding SET do ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NSD1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NSD1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NSD1
Name	nuclear receptor binding SET domain protein 1
Aliases	ARA267; FLJ22263; KMT3B; STO; Sotos syndrome; SOTOS; SOTOS1; H3-K36-HMTase; H4-K20-HMTase; NR-binding SET do ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NSD1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	NSD1
Name	nuclear receptor binding SET domain protein 1
Aliases	ARA267; FLJ22263; KMT3B; STO; Sotos syndrome; SOTOS; SOTOS1; H3-K36-HMTase; H4-K20-HMTase; NR-binding SET do ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NSD1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NSD1
Name	nuclear receptor binding SET domain protein 1
Aliases	ARA267; FLJ22263; KMT3B; STO; Sotos syndrome; SOTOS; SOTOS1; H3-K36-HMTase; H4-K20-HMTase; NR-binding SET do ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NSD1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NSD1
Name	nuclear receptor binding SET domain protein 1
Aliases	ARA267; FLJ22263; KMT3B; STO; Sotos syndrome; SOTOS; SOTOS1; H3-K36-HMTase; H4-K20-HMTase; NR-binding SET do ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NSD1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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