TISIDB

Summary
Symbol	SCN8A
Name	sodium channel, voltage gated, type VIII alpha subunit
Aliases	Nav1.6; NaCh6; PN4; CerIII; sodium channel, voltage gated, type VIII, alpha polypeptide; sodium channel, vol ......
Chromosomal Location	12q13.1
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 ; SUBCELLULAR LOCATION: Isoform 5: Cytoplasmic vesicle. Note=Some vesicles are localized adjacent to melanoma invadopodia and macrophage podosomes. Does not localize to the plasma membrane.
Domain	PF00520 Ion transport protein PF00612 IQ calmodulin-binding motif PF06512 Sodium ion transport-associated PF11933 Cytoplasmic domain of voltage-gated Na+ ion channel
Function	Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation.

> Gene Ontology [ TOP ]
Biological Process	GO:0001508 action potential GO:0006814 sodium ion transport GO:0007272 ensheathment of neurons GO:0007422 peripheral nervous system development GO:0008366 axon ensheathment GO:0015672 monovalent inorganic cation transport GO:0019226 transmission of nerve impulse GO:0019228 neuronal action potential GO:0034762 regulation of transmembrane transport GO:0034765 regulation of ion transmembrane transport GO:0035637 multicellular organismal signaling GO:0035725 sodium ion transmembrane transport GO:0042391 regulation of membrane potential GO:0042552 myelination GO:0051899 membrane depolarization GO:0060078 regulation of postsynaptic membrane potential GO:0086010 membrane depolarization during action potential
Molecular Function	GO:0005216 ion channel activity GO:0005244 voltage-gated ion channel activity GO:0005248 voltage-gated sodium 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:0046873 metal ion transmembrane transporter activity GO:1905030 voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential
Cellular Component	GO:0001518 voltage-gated sodium channel complex GO:0030016 myofibril GO:0030017 sarcomere GO:0030018 Z disc GO:0030424 axon GO:0031674 I band GO:0033267 axon part GO:0033268 node of Ranvier GO:0034702 ion channel complex GO:0034703 cation channel complex GO:0034706 sodium channel complex GO:0043194 axon initial segment GO:0043292 contractile fiber GO:0044304 main axon GO:0044449 contractile fiber part GO:1902495 transmembrane transporter complex GO:1990351 transporter complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-422475: Axon guidance R-HSA-5576891: Cardiac conduction R-HSA-1266738: Developmental Biology R-HSA-445095: Interaction between L1 and Ankyrins R-HSA-373760: L1CAM interactions R-HSA-397014: Muscle contraction R-HSA-5576892: Phase 0 - rapid depolarisation

Summary
Symbol	SCN8A
Name	sodium channel, voltage gated, type VIII alpha subunit
Aliases	Nav1.6; NaCh6; PN4; CerIII; sodium channel, voltage gated, type VIII, alpha polypeptide; sodium channel, vol ......
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SCN8A 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	SCN8A
Name	sodium channel, voltage gated, type VIII alpha subunit
Aliases	Nav1.6; NaCh6; PN4; CerIII; sodium channel, voltage gated, type VIII, alpha polypeptide; sodium channel, vol ......
Chromosomal Location	12q13.1
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 SCN8A 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	SCN8A
Name	sodium channel, voltage gated, type VIII alpha subunit
Aliases	Nav1.6; NaCh6; PN4; CerIII; sodium channel, voltage gated, type VIII, alpha polypeptide; sodium channel, vol ......
Chromosomal Location	12q13.1
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 SCN8A 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	-0.017	0.943
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.496	0.284
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.394	0.302
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.581	0.171
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.459	0.767
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.74	0.722
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.345	0.565
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.947	0.34
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.24	0.814
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.533	0.3
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	0.62	0.362
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.479	0.0305

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SCN8A 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	7.4	0	7.4	0.0709
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	7.4	0	7.4	0.096
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	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	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	5.3	0	5.3	0.507
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	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	SCN8A
Name	sodium channel, voltage gated, type VIII alpha subunit
Aliases	Nav1.6; NaCh6; PN4; CerIII; sodium channel, voltage gated, type VIII, alpha polypeptide; sodium channel, vol ......
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SCN8A. 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	SCN8A
Name	sodium channel, voltage gated, type VIII alpha subunit
Aliases	Nav1.6; NaCh6; PN4; CerIII; sodium channel, voltage gated, type VIII, alpha polypeptide; sodium channel, vol ......
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SCN8A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SCN8A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SCN8A
Name	sodium channel, voltage gated, type VIII alpha subunit
Aliases	Nav1.6; NaCh6; PN4; CerIII; sodium channel, voltage gated, type VIII, alpha polypeptide; sodium channel, vol ......
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SCN8A. 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	SCN8A
Name	sodium channel, voltage gated, type VIII alpha subunit
Aliases	Nav1.6; NaCh6; PN4; CerIII; sodium channel, voltage gated, type VIII, alpha polypeptide; sodium channel, vol ......
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SCN8A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SCN8A
Name	sodium channel, voltage gated, type VIII alpha subunit
Aliases	Nav1.6; NaCh6; PN4; CerIII; sodium channel, voltage gated, type VIII, alpha polypeptide; sodium channel, vol ......
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SCN8A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SCN8A
Name	sodium channel, voltage gated, type VIII alpha subunit
Aliases	Nav1.6; NaCh6; PN4; CerIII; sodium channel, voltage gated, type VIII, alpha polypeptide; sodium channel, vol ......
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SCN8A collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting SCN8A.

ID	Name	Drug Type	Targets	#Targets
DB00313	Valproic Acid	Small Molecule	ABAT, ACADSB, ALDH5A1, HDAC2, HDAC9, OGDH, PPARA, PPARD, PPARG, SC ......	23
DB05232	Tetrodotoxin	Small Molecule	SCN1A, SCN2A, SCN3A, SCN8A	4
DB05541	Brivaracetam	Small Molecule	SCN10A, SCN11A, SCN1A, SCN1B, SCN2A, SCN2B, SCN3A, SCN3B, SCN4A, S ......	15

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