TISIDB

Summary
Symbol	HDAC11
Name	histone deacetylase 11
Aliases	HD11
Chromosomal Location	3p25.1
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. Note=Predominantly nuclear.
Domain	PF00850 Histone deacetylase domain
Function	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes.

> Gene Ontology [ TOP ]
Biological Process	GO:0006476 protein deacetylation GO:0010001 glial cell differentiation GO:0014003 oligodendrocyte development GO:0016570 histone modification GO:0016575 histone deacetylation GO:0021782 glial cell development GO:0035601 protein deacylation GO:0042063 gliogenesis GO:0048709 oligodendrocyte differentiation GO:0070932 histone H3 deacetylation GO:0098732 macromolecule deacylation
Molecular Function	GO:0004407 histone deacetylase activity GO:0008134 transcription factor binding GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds GO:0016811 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides GO:0017136 NAD-dependent histone deacetylase activity GO:0019213 deacetylase activity GO:0031078 histone deacetylase activity (H3-K14 specific) GO:0032041 NAD-dependent histone deacetylase activity (H3-K14 specific) GO:0033558 protein deacetylase activity GO:0034979 NAD-dependent protein deacetylase activity
Cellular Component	GO:0000118 histone deacetylase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-2122947: NOTCH1 Intracellular Domain Regulates Transcription R-HSA-162582: Signal Transduction R-HSA-157118: Signaling by NOTCH R-HSA-1980143: Signaling by NOTCH1 R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2644603: Signaling by NOTCH1 in Cancer

> KEGG and Reactome Pathway

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KEGG

Reactome

R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-2122947: NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-162582: Signal Transduction
R-HSA-157118: Signaling by NOTCH
R-HSA-1980143: Signaling by NOTCH1
R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603: Signaling by NOTCH1 in Cancer

Summary
Symbol	HDAC11
Name	histone deacetylase 11
Aliases	HD11
Chromosomal Location	3p25.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HDAC11 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 HDAC11 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
21239696	Hodgkin Lymphoma	Inhibit immunity (T cell function)	The engagement of OX40L with the OX40 receptor is essential for the generation of antigen-specific memory T cells and for the induction of host antitumor immunity. Small interfering RNAs (siRNAs) that selectively inhibited HDAC11 expression, significantly up-regulated OX40L and induced apoptosis in HL cell lines, and silencing HDAC11 transcripts increased the production of tumor necrosis-α (TNF-α) and IL-17 in the supernatants of HL cells. Furthermore, HDACI-induced OX40L inhibited the generation of IL-10-producing type 1 T-reg cells. These results demonstrate for the first time that HDAC11 plays an essential role in regulating OX40L expression.

Summary
Symbol	HDAC11
Name	histone deacetylase 11
Aliases	HD11
Chromosomal Location	3p25.1
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 HDAC11 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	HDAC11
Name	histone deacetylase 11
Aliases	HD11
Chromosomal Location	3p25.1
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 HDAC11 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	0.335	0.365
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.131	0.923
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.481	0.654
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.178	0.772
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.344	0.801
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.84	0.622
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.06	0.863
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.244	0.823
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.196	0.877
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.197	0.871
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	0.076	0.965
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.17	0.113

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HDAC11 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	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	2.7	1	1
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	3.7	3.4	0.3	1
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	0	0	0	1
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	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	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	0	0	1

Summary
Symbol	HDAC11
Name	histone deacetylase 11
Aliases	HD11
Chromosomal Location	3p25.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HDAC11. 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	HDAC11
Name	histone deacetylase 11
Aliases	HD11
Chromosomal Location	3p25.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HDAC11. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HDAC11. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HDAC11
Name	histone deacetylase 11
Aliases	HD11
Chromosomal Location	3p25.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HDAC11. 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	HDAC11
Name	histone deacetylase 11
Aliases	HD11
Chromosomal Location	3p25.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HDAC11 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HDAC11
Name	histone deacetylase 11
Aliases	HD11
Chromosomal Location	3p25.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HDAC11 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HDAC11
Name	histone deacetylase 11
Aliases	HD11
Chromosomal Location	3p25.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HDAC11 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting HDAC11.

ID	Name	Drug Type	Targets	#Targets
DB05015	Belinostat	Small Molecule	HDAC1, HDAC10, HDAC11, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, H ......	11
DB06603	Panobinostat	Small Molecule	HDAC1, HDAC10, HDAC11, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, H ......	11

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