TISIDB

Summary
Symbol	KDM5D
Name	lysine (K)-specific demethylase 5D
Aliases	KIAA0234; HYA; HY; SMCY; JARID1D; Jumonji, AT rich interactive domain 1D (RBP2-like); Smcy homolog, Y-linked ......
Chromosomal Location	Yq11
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
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'. May play a role in spermatogenesis. Involved in transcriptional repression of diverse metastasis-associated genes; in this function seems to cooperate with ZMYND8. Suppresses prostate cancer cell invasion. Regulates androgen receptor (AR) transcriptional activity by demethylating H3K4me3 active transcription marks.

> Gene Ontology [ TOP ]
Biological Process	GO:0002250 adaptive immune response GO:0002443 leukocyte mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002456 T cell mediated immunity GO:0002457 T cell antigen processing and presentation GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0006482 protein demethylation GO:0008214 protein dealkylation GO:0016570 histone modification GO:0016577 histone demethylation GO:0019882 antigen processing and presentation GO:0034720 histone H3-K4 demethylation GO:0070076 histone lysine demethylation GO:0070988 demethylation
Molecular Function	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:0032451 demethylase activity GO:0032452 histone demethylase activity GO:0032453 histone demethylase activity (H3-K4 specific) GO:0051213 dioxygenase activity
Cellular Component	-

> 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	KDM5D
Name	lysine (K)-specific demethylase 5D
Aliases	KIAA0234; HYA; HY; SMCY; JARID1D; Jumonji, AT rich interactive domain 1D (RBP2-like); Smcy homolog, Y-linked ......
Chromosomal Location	Yq11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KDM5D 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 KDM5D and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19251937	Urothelial carcinoma	Promote immunity	Animals treated with subtotal RF ablation showed significant increases in tumor-specific class I and II responses to HY antigens and tumor regression.
24141010	B Acute Lymphoblastic Leukemia	Promote immunity	In contrast, restriction of HY expression to hematopoietic tissues restored MB49 responses but resulted in a loss of antileukemia responses.

Summary
Symbol	KDM5D
Name	lysine (K)-specific demethylase 5D
Aliases	KIAA0234; HYA; HY; SMCY; JARID1D; Jumonji, AT rich interactive domain 1D (RBP2-like); Smcy homolog, Y-linked ......
Chromosomal Location	Yq11
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 KDM5D 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	KDM5D
Name	lysine (K)-specific demethylase 5D
Aliases	KIAA0234; HYA; HY; SMCY; JARID1D; Jumonji, AT rich interactive domain 1D (RBP2-like); Smcy homolog, Y-linked ......
Chromosomal Location	Yq11
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 KDM5D 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	0.534	0.393
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.015	0.361
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.676	0.0468
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	1.428	0.141
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.113	0.96
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	3.108	0.34
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.452	0.764
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-2.475	0.234
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.411	0.521
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.583	0.582
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	-0.052	0.969
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.496	0.445

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of KDM5D 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	7.1	0	7.1	0.452
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	25	0	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	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	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
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	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	2.6	0	2.6	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	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	KDM5D
Name	lysine (K)-specific demethylase 5D
Aliases	KIAA0234; HYA; HY; SMCY; JARID1D; Jumonji, AT rich interactive domain 1D (RBP2-like); Smcy homolog, Y-linked ......
Chromosomal Location	Yq11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KDM5D. 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	KDM5D
Name	lysine (K)-specific demethylase 5D
Aliases	KIAA0234; HYA; HY; SMCY; JARID1D; Jumonji, AT rich interactive domain 1D (RBP2-like); Smcy homolog, Y-linked ......
Chromosomal Location	Yq11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KDM5D. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KDM5D. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KDM5D
Name	lysine (K)-specific demethylase 5D
Aliases	KIAA0234; HYA; HY; SMCY; JARID1D; Jumonji, AT rich interactive domain 1D (RBP2-like); Smcy homolog, Y-linked ......
Chromosomal Location	Yq11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KDM5D. 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	KDM5D
Name	lysine (K)-specific demethylase 5D
Aliases	KIAA0234; HYA; HY; SMCY; JARID1D; Jumonji, AT rich interactive domain 1D (RBP2-like); Smcy homolog, Y-linked ......
Chromosomal Location	Yq11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KDM5D expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KDM5D
Name	lysine (K)-specific demethylase 5D
Aliases	KIAA0234; HYA; HY; SMCY; JARID1D; Jumonji, AT rich interactive domain 1D (RBP2-like); Smcy homolog, Y-linked ......
Chromosomal Location	Yq11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KDM5D and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KDM5D
Name	lysine (K)-specific demethylase 5D
Aliases	KIAA0234; HYA; HY; SMCY; JARID1D; Jumonji, AT rich interactive domain 1D (RBP2-like); Smcy homolog, Y-linked ......
Chromosomal Location	Yq11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KDM5D collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting KDM5D.

ID	Name	Drug Type	Targets	#Targets
DB00126	Vitamin C	Small Molecule	ALKBH2, ALKBH3, BBOX1, DBH, EGLN1, EGLN2, EGLN3, KDM5D, LCT, OGFOD ......	23

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