TISIDB

Summary
Symbol	SLC12A2
Name	solute carrier family 12 (sodium/potassium/chloride transporter), member 2
Aliases	NKCC1; BSC; BSC2; PPP1R141; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; basolateral Na ......
Chromosomal Location	5q23.3
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	Membrane; Multi-pass membrane protein.
Domain	PF00324 Amino acid permease PF08403 Amino acid permease N-terminal PF03522 Solute carrier family 12
Function	Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.

> Gene Ontology [ TOP ]
Biological Process	GO:0006813 potassium ion transport GO:0006814 sodium ion transport GO:0006820 anion transport GO:0006821 chloride transport GO:0006884 cell volume homeostasis GO:0006970 response to osmotic stress GO:0006972 hyperosmotic response GO:0007214 gamma-aminobutyric acid signaling pathway GO:0007568 aging GO:0008361 regulation of cell size GO:0015672 monovalent inorganic cation transport GO:0015696 ammonium transport GO:0015698 inorganic anion transport GO:0030321 transepithelial chloride transport GO:0032535 regulation of cellular component size GO:0045795 positive regulation of cell volume GO:0070633 transepithelial transport GO:0070634 transepithelial ammonium transport GO:0072488 ammonium transmembrane transport GO:0090066 regulation of anatomical structure size GO:0098656 anion transmembrane transport GO:0098661 inorganic anion transmembrane transport GO:1902476 chloride transmembrane transport
Molecular Function	GO:0008509 anion transmembrane transporter activity GO:0008511 sodium:potassium:chloride symporter activity GO:0008519 ammonium transmembrane transporter activity GO:0015103 inorganic anion transmembrane transporter activity GO:0015108 chloride transmembrane transporter activity GO:0015291 secondary active transmembrane transporter activity GO:0015293 symporter activity GO:0015294 solute:cation symporter activity GO:0015296 anion:cation symporter activity GO:0015377 cation:chloride symporter activity GO:0022804 active transmembrane transporter activity GO:0022853 active ion transmembrane transporter activity
Cellular Component	GO:0016324 apical plasma membrane GO:0045177 apical part of cell

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04970 Salivary secretion hsa04972 Pancreatic secretion
Reactome	R-HSA-426117: Cation-coupled Chloride cotransporters R-HSA-425407: SLC-mediated transmembrane transport R-HSA-382551: Transmembrane transport of small molecules R-HSA-425393: Transport of inorganic cations/anions and amino acids/oligopeptides

Summary
Symbol	SLC12A2
Name	solute carrier family 12 (sodium/potassium/chloride transporter), member 2
Aliases	NKCC1; BSC; BSC2; PPP1R141; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; basolateral Na ......
Chromosomal Location	5q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SLC12A2 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	SLC12A2
Name	solute carrier family 12 (sodium/potassium/chloride transporter), member 2
Aliases	NKCC1; BSC; BSC2; PPP1R141; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; basolateral Na ......
Chromosomal Location	5q23.3
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 SLC12A2 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	logFC: -1.96; FDR: 0.04630	Resistant to T cell-mediated killing
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	SLC12A2
Name	solute carrier family 12 (sodium/potassium/chloride transporter), member 2
Aliases	NKCC1; BSC; BSC2; PPP1R141; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; basolateral Na ......
Chromosomal Location	5q23.3
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 SLC12A2 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	0.276	0.42
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.223	0.866
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.321	0.726
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.108	0.746
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.364	0.857
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.706	0.786
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.254	0.521
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.11	0.94
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.612	0.714
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.007	0.994
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	1.607	0.13
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.183	0.107

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SLC12A2 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	0	11.1	0.0181
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	0	11.1	0.0286
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	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
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	20	0	20	0.357
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	15.4	-15.4	0.482
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	16.7	-16.7	1

Summary
Symbol	SLC12A2
Name	solute carrier family 12 (sodium/potassium/chloride transporter), member 2
Aliases	NKCC1; BSC; BSC2; PPP1R141; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; basolateral Na ......
Chromosomal Location	5q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SLC12A2. 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	SLC12A2
Name	solute carrier family 12 (sodium/potassium/chloride transporter), member 2
Aliases	NKCC1; BSC; BSC2; PPP1R141; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; basolateral Na ......
Chromosomal Location	5q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SLC12A2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SLC12A2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SLC12A2
Name	solute carrier family 12 (sodium/potassium/chloride transporter), member 2
Aliases	NKCC1; BSC; BSC2; PPP1R141; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; basolateral Na ......
Chromosomal Location	5q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SLC12A2. 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	SLC12A2
Name	solute carrier family 12 (sodium/potassium/chloride transporter), member 2
Aliases	NKCC1; BSC; BSC2; PPP1R141; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; basolateral Na ......
Chromosomal Location	5q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SLC12A2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SLC12A2
Name	solute carrier family 12 (sodium/potassium/chloride transporter), member 2
Aliases	NKCC1; BSC; BSC2; PPP1R141; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; basolateral Na ......
Chromosomal Location	5q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SLC12A2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SLC12A2
Name	solute carrier family 12 (sodium/potassium/chloride transporter), member 2
Aliases	NKCC1; BSC; BSC2; PPP1R141; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; basolateral Na ......
Chromosomal Location	5q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SLC12A2 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting SLC12A2.

ID	Name	Drug Type	Targets	#Targets
DB00761	Potassium Chloride	Small Molecule	SLC12A1, SLC12A2, SLC12A4, SLC12A5, SLC12A6, SLC12A7	6
DB00887	Bumetanide	Small Molecule	CFTR, SLC12A1, SLC12A2, SLC12A4, SLC12A5	5
DB01325	Quinethazone	Small Molecule	CA1, CA2, SLC12A1, SLC12A2, SLC12A3	5

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