TISIDB

Summary
Symbol	KDM5A
Name	lysine (K)-specific demethylase 5A
Aliases	RBBP2; JARID1A; retinoblastoma-binding protein 2; Jumonji, AT rich interactive domain 1A (RBBP2-like); jumon ......
Chromosomal Location	12p13.33
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, nucleolus Nucleus Note=Occupies promoters of genes involved in RNA metabolism and mitochondrial function.
Domain	PF01388 ARID/BRIGHT DNA binding domain PF02373 JmjC domain PF02375 jmjN domain PF00628 PHD-finger PF08429 PLU-1-like protein PF02928 C5HC2 zinc finger
Function	Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Regulates specific gene transcription through DNA-binding on 5'-CCGCCC-3' motif (PubMed:18270511). May stimulate transcription mediated by nuclear receptors. Involved in transcriptional regulation of Hox proteins during cell differentiation (PubMed:19430464). May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity). Seems to act as a transcriptional corepressor for some genes such as MT1F and to favor the proliferation of cancer cells (PubMed:27427228).

> Gene Ontology [ TOP ]
Biological Process	GO:0006476 protein deacetylation GO:0006482 protein demethylation GO:0007283 spermatogenesis GO:0007548 sex differentiation GO:0007623 circadian rhythm GO:0008214 protein dealkylation GO:0008406 gonad development GO:0008584 male gonad development GO:0016570 histone modification GO:0016575 histone deacetylation GO:0016577 histone demethylation GO:0031056 regulation of histone modification GO:0031057 negative regulation of histone modification GO:0031063 regulation of histone deacetylation GO:0031064 negative regulation of histone deacetylation GO:0032922 circadian regulation of gene expression GO:0034720 histone H3-K4 demethylation GO:0035601 protein deacylation GO:0045137 development of primary sexual characteristics GO:0046546 development of primary male sexual characteristics GO:0046661 male sex differentiation GO:0048232 male gamete generation GO:0048511 rhythmic process GO:0048608 reproductive structure development GO:0051346 negative regulation of hydrolase activity GO:0061458 reproductive system development GO:0070076 histone lysine demethylation GO:0070988 demethylation GO:0090311 regulation of protein deacetylation GO:0098732 macromolecule deacylation GO:1901725 regulation of histone deacetylase activity GO:1901726 negative regulation of histone deacetylase activity GO:1902275 regulation of chromatin organization GO:1905268 negative regulation of chromatin organization
Molecular Function	GO:0003682 chromatin binding GO:0003713 transcription coactivator activity GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016706 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors GO:0031490 chromatin DNA binding GO:0032451 demethylase activity GO:0032452 histone demethylase activity GO:0043566 structure-specific DNA binding GO:0051213 dioxygenase activity
Cellular Component	GO:0000307 cyclin-dependent protein kinase holoenzyme complex GO:0019907 cyclin-dependent protein kinase activating kinase holoenzyme complex GO:0019908 nuclear cyclin-dependent protein kinase holoenzyme complex GO:0032806 carboxy-terminal domain protein kinase complex GO:0032993 protein-DNA complex GO:0061695 transferase complex, transferring phosphorus-containing groups GO:1902554 serine/threonine protein kinase complex GO:1902911 protein kinase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-3247509: Chromatin modifying enzymes R-HSA-4839726: Chromatin organization R-HSA-3214842: HDMs demethylate histones

Summary
Symbol	KDM5A
Name	lysine (K)-specific demethylase 5A
Aliases	RBBP2; JARID1A; retinoblastoma-binding protein 2; Jumonji, AT rich interactive domain 1A (RBBP2-like); jumon ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KDM5A 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 [ TOP ]
There is no record.

Summary
Symbol	KDM5A
Name	lysine (K)-specific demethylase 5A
Aliases	RBBP2; JARID1A; retinoblastoma-binding protein 2; Jumonji, AT rich interactive domain 1A (RBBP2-like); jumon ......
Chromosomal Location	12p13.33
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

[ TOP ]

Statistical results of KDM5A 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	STARS Score: 3.94; FDR: 0.021	Resistant to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 4.62; FDR: 0.008	Resistant to T cell-mediated killing
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	KDM5A
Name	lysine (K)-specific demethylase 5A
Aliases	RBBP2; JARID1A; retinoblastoma-binding protein 2; Jumonji, AT rich interactive domain 1A (RBBP2-like); jumon ......
Chromosomal Location	12p13.33
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

[ TOP ]

Points in the above scatter plot represent the expression difference of KDM5A 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	-0.026	0.918
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.31	0.818
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.276	0.793
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.133	0.635
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.117	0.961
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.155	0.961
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.159	0.691
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.095	0.958
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.269	0.89
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.33	0.746
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	0.931	0.526
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.005	0.906

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of KDM5A 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	11.1	2.7	8.4	0.12
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	11.1	3.4	7.7	0.176
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	0	14.3	0.238
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	0	15.4	0.482
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
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	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
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	0	7.1	-7.1	0.467
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	KDM5A
Name	lysine (K)-specific demethylase 5A
Aliases	RBBP2; JARID1A; retinoblastoma-binding protein 2; Jumonji, AT rich interactive domain 1A (RBBP2-like); jumon ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KDM5A. 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	KDM5A
Name	lysine (K)-specific demethylase 5A
Aliases	RBBP2; JARID1A; retinoblastoma-binding protein 2; Jumonji, AT rich interactive domain 1A (RBBP2-like); jumon ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KDM5A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KDM5A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KDM5A
Name	lysine (K)-specific demethylase 5A
Aliases	RBBP2; JARID1A; retinoblastoma-binding protein 2; Jumonji, AT rich interactive domain 1A (RBBP2-like); jumon ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KDM5A. 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	KDM5A
Name	lysine (K)-specific demethylase 5A
Aliases	RBBP2; JARID1A; retinoblastoma-binding protein 2; Jumonji, AT rich interactive domain 1A (RBBP2-like); jumon ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KDM5A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KDM5A
Name	lysine (K)-specific demethylase 5A
Aliases	RBBP2; JARID1A; retinoblastoma-binding protein 2; Jumonji, AT rich interactive domain 1A (RBBP2-like); jumon ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KDM5A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KDM5A
Name	lysine (K)-specific demethylase 5A
Aliases	RBBP2; JARID1A; retinoblastoma-binding protein 2; Jumonji, AT rich interactive domain 1A (RBBP2-like); jumon ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KDM5A collected from DrugBank database.

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

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