TISIDB

Summary
Symbol	KCNMA1
Name	potassium channel, calcium activated large conductance subfamily M alpha, member 1
Aliases	KCa1.1; mSLO1; BK channel alpha subunit; maxiK channel; big potassium channel alpha subunit; SLO; potassium ......
Chromosomal Location	10q22
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
Domain	PF03493 Calcium-activated BK potassium channel alpha subunit PF00520 Ion transport protein
Function	Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).

> Gene Ontology [ TOP ]
Biological Process	GO:0001666 response to hypoxia GO:0003012 muscle system process GO:0003014 renal system process GO:0006813 potassium ion transport GO:0006875 cellular metal ion homeostasis GO:0006884 cell volume homeostasis GO:0006936 muscle contraction GO:0006939 smooth muscle contraction GO:0006970 response to osmotic stress GO:0007588 excretion GO:0008361 regulation of cell size GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0014832 urinary bladder smooth muscle contraction GO:0014848 urinary tract smooth muscle contraction GO:0015672 monovalent inorganic cation transport GO:0030004 cellular monovalent inorganic cation homeostasis GO:0030007 cellular potassium ion homeostasis GO:0032535 regulation of cellular component size GO:0034465 response to carbon monoxide GO:0034762 regulation of transmembrane transport GO:0034765 regulation of ion transmembrane transport GO:0036293 response to decreased oxygen levels GO:0042391 regulation of membrane potential GO:0045794 negative regulation of cell volume GO:0051592 response to calcium ion GO:0055067 monovalent inorganic cation homeostasis GO:0055075 potassium ion homeostasis GO:0060073 micturition GO:0060083 smooth muscle contraction involved in micturition GO:0070482 response to oxygen levels GO:0071804 cellular potassium ion transport GO:0071805 potassium ion transmembrane transport GO:0090066 regulation of anatomical structure size
Molecular Function	GO:0003779 actin binding GO:0005216 ion channel activity GO:0005227 calcium activated cation channel activity GO:0005244 voltage-gated ion channel activity GO:0005249 voltage-gated 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:0015269 calcium-activated 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:0022839 ion gated channel activity GO:0022843 voltage-gated cation channel activity GO:0046873 metal ion transmembrane transporter activity GO:0060072 large conductance calcium-activated potassium channel activity
Cellular Component	GO:0005901 caveola GO:0008076 voltage-gated potassium channel complex GO:0016324 apical plasma membrane GO:0034702 ion channel complex GO:0034703 cation channel complex GO:0034705 potassium channel complex GO:0044853 plasma membrane raft GO:0045121 membrane raft GO:0045177 apical part of cell GO:0098589 membrane region GO:0098857 membrane microdomain GO:1902495 transmembrane transporter complex GO:1990351 transporter complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04022 cGMP-PKG signaling pathway hsa04270 Vascular smooth muscle contraction hsa04911 Insulin secretion hsa04970 Salivary secretion hsa04972 Pancreatic secretion
Reactome	R-HSA-1296052: Ca2+ activated K+ channels R-HSA-109582: Hemostasis R-HSA-112316: Neuronal System R-HSA-392154: Nitric oxide stimulates guanylate cyclase R-HSA-418346: Platelet homeostasis R-HSA-1296071: Potassium Channels R-HSA-418457: cGMP effects

Summary
Symbol	KCNMA1
Name	potassium channel, calcium activated large conductance subfamily M alpha, member 1
Aliases	KCa1.1; mSLO1; BK channel alpha subunit; maxiK channel; big potassium channel alpha subunit; SLO; potassium ......
Chromosomal Location	10q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KCNMA1 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	KCNMA1
Name	potassium channel, calcium activated large conductance subfamily M alpha, member 1
Aliases	KCa1.1; mSLO1; BK channel alpha subunit; maxiK channel; big potassium channel alpha subunit; SLO; potassium ......
Chromosomal Location	10q22
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 KCNMA1 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	Second most enriched score: 0.88	Sensitive to T cell-mediated killing
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	KCNMA1
Name	potassium channel, calcium activated large conductance subfamily M alpha, member 1
Aliases	KCa1.1; mSLO1; BK channel alpha subunit; maxiK channel; big potassium channel alpha subunit; SLO; potassium ......
Chromosomal Location	10q22
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 KCNMA1 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	-1.239	0.00673
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.621	0.282
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.969	0.445
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.812	0.18
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.873	0.72
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.738	0.806
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.326	0.551
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.775	0.553
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.163	0.91
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.278	0.841
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	-0.223	0.914
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.267	0.176

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of KCNMA1 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	21.4	0	21.4	0.081
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	30	0	30	0.528
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	14.8	2.7	12.1	0.0439
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	14.8	3.4	11.4	0.0746
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	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	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	13.2	0	13.2	0.0705
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	18.8	0	18.8	0.228
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	KCNMA1
Name	potassium channel, calcium activated large conductance subfamily M alpha, member 1
Aliases	KCa1.1; mSLO1; BK channel alpha subunit; maxiK channel; big potassium channel alpha subunit; SLO; potassium ......
Chromosomal Location	10q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KCNMA1. 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	KCNMA1
Name	potassium channel, calcium activated large conductance subfamily M alpha, member 1
Aliases	KCa1.1; mSLO1; BK channel alpha subunit; maxiK channel; big potassium channel alpha subunit; SLO; potassium ......
Chromosomal Location	10q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KCNMA1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KCNMA1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KCNMA1
Name	potassium channel, calcium activated large conductance subfamily M alpha, member 1
Aliases	KCa1.1; mSLO1; BK channel alpha subunit; maxiK channel; big potassium channel alpha subunit; SLO; potassium ......
Chromosomal Location	10q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KCNMA1. 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	KCNMA1
Name	potassium channel, calcium activated large conductance subfamily M alpha, member 1
Aliases	KCa1.1; mSLO1; BK channel alpha subunit; maxiK channel; big potassium channel alpha subunit; SLO; potassium ......
Chromosomal Location	10q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KCNMA1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KCNMA1
Name	potassium channel, calcium activated large conductance subfamily M alpha, member 1
Aliases	KCa1.1; mSLO1; BK channel alpha subunit; maxiK channel; big potassium channel alpha subunit; SLO; potassium ......
Chromosomal Location	10q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KCNMA1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KCNMA1
Name	potassium channel, calcium activated large conductance subfamily M alpha, member 1
Aliases	KCa1.1; mSLO1; BK channel alpha subunit; maxiK channel; big potassium channel alpha subunit; SLO; potassium ......
Chromosomal Location	10q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KCNMA1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting KCNMA1.

ID	Name	Drug Type	Targets	#Targets
DB00356	Chlorzoxazone	Small Molecule	KCNMA1	1
DB00436	Bendroflumethiazide	Small Molecule	CA1, CA2, CA4, KCNMA1, SLC12A3	5
DB00721	Procaine	Small Molecule	CHRNA2, GRIN3A, HTR3A, KCNMA1, KCNMB1, KCNMB2, KCNMB3, KCNMB4, KCN ......	16
DB00774	Hydroflumethiazide	Small Molecule	ATP1A1, CA1, CA12, CA2, CA4, CA9, KCNMA1, SLC12A1	8
DB00999	Hydrochlorothiazide	Small Molecule	CA1, CA12, CA2, CA4, CA9, KCNMA1, SLC12A3	7
DB01003	Cromoglicic acid	Small Molecule	KCNMA1, S100P	2
DB01110	Miconazole	Small Molecule	KCNH2, KCNH6, KCNH7, KCNMA1, KCNMB1, KCNMB2, KCNMB3, KCNMB4, KCNN1 ......	15
DB01119	Diazoxide	Small Molecule	ATP1A1, CA1, CA2, KCNJ11, KCNMA1, SLC12A3	6
DB01159	Halothane	Small Molecule	ATP2C1, ATP5D, GABRA1, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GAB ......	33
DB04209	Dequalinium	Small Molecule	CNGA1, KCNMA1, XIAP	3
DB09089	Trimebutine	Small Molecule	CACNA1C, CACNA1D, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CAC ......	21

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