TISIDB

Summary
Symbol	KCND3
Name	potassium channel, voltage gated Shal related subfamily D, member 3
Aliases	Kv4.3; KSHIVB; SCA22; SCA19; spinocerebellar ataxia 22; spinocerebellar ataxia 19; potassium voltage-gated c ......
Chromosomal Location	1p13.2
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	Cell membrane Multi-pass membrane protein Cell membrane, sarcolemma Multi-pass membrane protein Cell projection, dendrite Note=Interaction with palmitoylated KCNIP2 and KCNIP3 enhances cell surface expression.
Domain	PF02214 BTB/POZ domain PF11879 Domain of unknown function (DUF3399) PF00520 Ion transport protein PF11601 Shal-type voltage-gated potassium channels
Function	Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.

> Gene Ontology [ TOP ]
Biological Process	GO:0003013 circulatory system process GO:0003015 heart process GO:0006813 potassium ion transport GO:0008015 blood circulation GO:0008016 regulation of heart contraction GO:0015672 monovalent inorganic cation transport GO:0034762 regulation of transmembrane transport GO:0034765 regulation of ion transmembrane transport GO:0035637 multicellular organismal signaling GO:0042391 regulation of membrane potential GO:0044057 regulation of system process GO:0051259 protein oligomerization GO:0051260 protein homooligomerization GO:0060047 heart contraction GO:0061337 cardiac conduction GO:0071435 potassium ion export GO:0071804 cellular potassium ion transport GO:0071805 potassium ion transmembrane transport GO:0086009 membrane repolarization GO:1903522 regulation of blood circulation
Molecular Function	GO:0005216 ion channel activity GO:0005244 voltage-gated ion channel activity GO:0005249 voltage-gated potassium channel activity GO:0005250 A-type (transient outward) potassium channel activity GO:0005261 cation channel activity GO:0005267 potassium channel activity GO:0015077 monovalent inorganic cation transmembrane transporter activity GO:0015079 potassium ion transmembrane transporter activity GO:0015267 channel activity GO:0015271 outward rectifier potassium channel activity GO:0022803 passive transmembrane transporter activity GO:0022832 voltage-gated channel activity GO:0022836 gated channel activity GO:0022838 substrate-specific channel activity GO:0022843 voltage-gated cation channel activity GO:0044325 ion channel binding GO:0046873 metal ion transmembrane transporter activity
Cellular Component	GO:0008076 voltage-gated potassium channel complex GO:0030425 dendrite GO:0034702 ion channel complex GO:0034703 cation channel complex GO:0034705 potassium channel complex GO:0042383 sarcolemma GO:1902495 transmembrane transporter complex GO:1990351 transporter complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-5576891: Cardiac conduction R-HSA-397014: Muscle contraction R-HSA-112316: Neuronal System R-HSA-5576894: Phase 1 - inactivation of fast Na+ channels R-HSA-1296071: Potassium Channels R-HSA-1296072: Voltage gated Potassium channels

Summary
Symbol	KCND3
Name	potassium channel, voltage gated Shal related subfamily D, member 3
Aliases	Kv4.3; KSHIVB; SCA22; SCA19; spinocerebellar ataxia 22; spinocerebellar ataxia 19; potassium voltage-gated c ......
Chromosomal Location	1p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KCND3 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	KCND3
Name	potassium channel, voltage gated Shal related subfamily D, member 3
Aliases	Kv4.3; KSHIVB; SCA22; SCA19; spinocerebellar ataxia 22; spinocerebellar ataxia 19; potassium voltage-gated c ......
Chromosomal Location	1p13.2
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 KCND3 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	KCND3
Name	potassium channel, voltage gated Shal related subfamily D, member 3
Aliases	Kv4.3; KSHIVB; SCA22; SCA19; spinocerebellar ataxia 22; spinocerebellar ataxia 19; potassium voltage-gated c ......
Chromosomal Location	1p13.2
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 KCND3 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	0.166	0.549
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.023	0.962
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.313	0.507
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.623	0.329
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.315	0.84
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.008	0.617
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.059	0.938
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.105	0.362
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-1.318	0.26
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.067	0.913
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	0.159	0.844
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-1.125	8.34e-07

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of KCND3 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	2.7	-2.7	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	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	19	11.8	7.2	0.672
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	23.1	18.2	4.9	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	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	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	7.9	3.7	4.2	0.636
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	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	KCND3
Name	potassium channel, voltage gated Shal related subfamily D, member 3
Aliases	Kv4.3; KSHIVB; SCA22; SCA19; spinocerebellar ataxia 22; spinocerebellar ataxia 19; potassium voltage-gated c ......
Chromosomal Location	1p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KCND3. 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	KCND3
Name	potassium channel, voltage gated Shal related subfamily D, member 3
Aliases	Kv4.3; KSHIVB; SCA22; SCA19; spinocerebellar ataxia 22; spinocerebellar ataxia 19; potassium voltage-gated c ......
Chromosomal Location	1p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KCND3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KCND3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KCND3
Name	potassium channel, voltage gated Shal related subfamily D, member 3
Aliases	Kv4.3; KSHIVB; SCA22; SCA19; spinocerebellar ataxia 22; spinocerebellar ataxia 19; potassium voltage-gated c ......
Chromosomal Location	1p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KCND3. 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	KCND3
Name	potassium channel, voltage gated Shal related subfamily D, member 3
Aliases	Kv4.3; KSHIVB; SCA22; SCA19; spinocerebellar ataxia 22; spinocerebellar ataxia 19; potassium voltage-gated c ......
Chromosomal Location	1p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KCND3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KCND3
Name	potassium channel, voltage gated Shal related subfamily D, member 3
Aliases	Kv4.3; KSHIVB; SCA22; SCA19; spinocerebellar ataxia 22; spinocerebellar ataxia 19; potassium voltage-gated c ......
Chromosomal Location	1p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KCND3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KCND3
Name	potassium channel, voltage gated Shal related subfamily D, member 3
Aliases	Kv4.3; KSHIVB; SCA22; SCA19; spinocerebellar ataxia 22; spinocerebellar ataxia 19; potassium voltage-gated c ......
Chromosomal Location	1p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KCND3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting KCND3.

ID	Name	Drug Type	Targets	#Targets
DB00280	Disopyramide	Small Molecule	CHRM1, CHRM2, CHRM3, KCND2, KCND3, KCNH2, ORM2, SCN5A	8
DB00321	Amitriptyline	Small Molecule	ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRB1, ADRB2, ADRB3, CHRM1, CHRM2, ......	35
DB00458	Imipramine	Small Molecule	ADRA1A, ADRA1B, ADRA1D, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, DRD1, D ......	25
DB06217	Vernakalant	Small Molecule	KCNA5, KCND3, KCNH2, SCN5A	4
DB06637	Dalfampridine	Small Molecule	KCNA1, KCNA10, KCNA2, KCNA3, KCNA4, KCNA5, KCNA6, KCNA7, KCNB1, KC ......	16
DB11633	Isavuconazole	Small Molecule	CACNA1C, KCNA5, KCND3, KCNH2, KCNJ11, KCNJ6, KCNJ9, KCNQ1, SCN5A	9

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