TISIDB

Summary
Symbol	NALCN
Name	sodium leak channel, non selective
Aliases	bA430M15.1; CanIon; VGCNL1; voltage gated channel like 1; sodium leak channel, non-selective; CLIFAHDD; IHPR ......
Chromosomal Location	13q32.3
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	PF00520 Ion transport protein
Function	Voltage-independent, cation-nonselective channel which is permeable to sodium, potassium and calcium ions. Regulates the resting membrane potential and controls neuronal excitability (PubMed:17448995). Neuropeptides such as neurotensin and substance P (SP) stimulate the firing of action potentials by activating NALCN through a SRC family kinases-dependent pathway. In addition to its baseline activity, NALCN activity is enhanced/modulated by several GPCRs. Required for normal respiratory rhythm and neonatal survival. Involved in systemic osmoregulation by controlling the serum sodium concentration. NALCN is partly responsible for the substance P-induced depolarization and regulation of the intestinal pace-making activity in the interstitial cells of Cajal. Plays a critical role in both maintenance of spontaneous firing of substantia nigra pars reticulata (SNr) neurons and physiological modulation of SNr neuron excitability (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001508 action potential GO:0006813 potassium ion transport GO:0006814 sodium ion transport GO:0006816 calcium ion transport GO:0015672 monovalent inorganic cation transport GO:0034762 regulation of transmembrane transport GO:0034765 regulation of ion transmembrane transport GO:0035725 sodium ion transmembrane transport GO:0042391 regulation of membrane potential GO:0051899 membrane depolarization GO:0060075 regulation of resting membrane potential GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0071804 cellular potassium ion transport GO:0071805 potassium ion transmembrane transport GO:0072511 divalent inorganic cation transport GO:0086010 membrane depolarization during action potential
Molecular Function	GO:0005216 ion channel activity GO:0005244 voltage-gated ion channel activity GO:0005261 cation channel activity GO:0005272 sodium channel activity GO:0015077 monovalent inorganic cation transmembrane transporter activity GO:0015081 sodium ion transmembrane transporter activity GO:0015267 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:0022840 leak channel activity GO:0022842 narrow pore channel activity GO:0046873 metal ion transmembrane transporter activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-983712: Ion channel transport R-HSA-2672351: Stimuli-sensing channels R-HSA-382551: Transmembrane transport of small molecules

Summary
Symbol	NALCN
Name	sodium leak channel, non selective
Aliases	bA430M15.1; CanIon; VGCNL1; voltage gated channel like 1; sodium leak channel, non-selective; CLIFAHDD; IHPR ......
Chromosomal Location	13q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between NALCN 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	NALCN
Name	sodium leak channel, non selective
Aliases	bA430M15.1; CanIon; VGCNL1; voltage gated channel like 1; sodium leak channel, non-selective; CLIFAHDD; IHPR ......
Chromosomal Location	13q32.3
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

[ TOP ]

Statistical results of NALCN 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	NALCN
Name	sodium leak channel, non selective
Aliases	bA430M15.1; CanIon; VGCNL1; voltage gated channel like 1; sodium leak channel, non-selective; CLIFAHDD; IHPR ......
Chromosomal Location	13q32.3
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 NALCN 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	-0.163	0.489
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.128	0.797
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.377	0.34
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.147	0.794
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.821	0.629
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.706	0.734
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.823	0.357
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.528	0.22
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.343	0.798
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.024	0.975
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	0.83	0.406
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.352	0.164

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of NALCN 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	28.6	0	28.6	0.0318
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	40	0	40	0.497
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	8.2	6.6	0.452
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	10.2	4.6	0.718
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	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	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	6.2	16	0.53
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	11.1	8.9	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	10.5	0	10.5	0.135
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	0	13.6	0.279
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	16.7	0	16.7	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	NALCN
Name	sodium leak channel, non selective
Aliases	bA430M15.1; CanIon; VGCNL1; voltage gated channel like 1; sodium leak channel, non-selective; CLIFAHDD; IHPR ......
Chromosomal Location	13q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NALCN. 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	NALCN
Name	sodium leak channel, non selective
Aliases	bA430M15.1; CanIon; VGCNL1; voltage gated channel like 1; sodium leak channel, non-selective; CLIFAHDD; IHPR ......
Chromosomal Location	13q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NALCN. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NALCN. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NALCN
Name	sodium leak channel, non selective
Aliases	bA430M15.1; CanIon; VGCNL1; voltage gated channel like 1; sodium leak channel, non-selective; CLIFAHDD; IHPR ......
Chromosomal Location	13q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NALCN. 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	NALCN
Name	sodium leak channel, non selective
Aliases	bA430M15.1; CanIon; VGCNL1; voltage gated channel like 1; sodium leak channel, non-selective; CLIFAHDD; IHPR ......
Chromosomal Location	13q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NALCN expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NALCN
Name	sodium leak channel, non selective
Aliases	bA430M15.1; CanIon; VGCNL1; voltage gated channel like 1; sodium leak channel, non-selective; CLIFAHDD; IHPR ......
Chromosomal Location	13q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NALCN and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NALCN
Name	sodium leak channel, non selective
Aliases	bA430M15.1; CanIon; VGCNL1; voltage gated channel like 1; sodium leak channel, non-selective; CLIFAHDD; IHPR ......
Chromosomal Location	13q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NALCN collected from DrugBank database.

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

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