TISIDB

Summary
Symbol	CASK
Name	calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Aliases	LIN2; CAGH39; FGS4; TNRC8; trinucleotide repeat containing 8; CAMGUK; CMG; MICPCH; MRXSNA; calcium/calmoduli ......
Chromosomal Location	Xp11.4
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	Nucleus Cytoplasm Cell membrane Peripheral membrane protein
Domain	PF00625 Guanylate kinase PF02828 L27 domain PF00595 PDZ domain (Also known as DHR or GLGF) PF00069 Protein kinase domain PF07653 Variant SH3 domain
Function	Multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring and ion channel trafficking. Contributes to neural development and regulation of gene expression via interaction with the transcription factor TBR1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1.

> Gene Ontology [ TOP ]
Biological Process	GO:0001505 regulation of neurotransmitter levels GO:0001952 regulation of cell-matrix adhesion GO:0001953 negative regulation of cell-matrix adhesion GO:0006816 calcium ion transport GO:0006836 neurotransmitter transport GO:0007160 cell-matrix adhesion GO:0007162 negative regulation of cell adhesion GO:0007269 neurotransmitter secretion GO:0009116 nucleoside metabolic process GO:0009119 ribonucleoside metabolic process GO:0009123 nucleoside monophosphate metabolic process GO:0009126 purine nucleoside monophosphate metabolic process GO:0009132 nucleoside diphosphate metabolic process GO:0009135 purine nucleoside diphosphate metabolic process GO:0009150 purine ribonucleotide metabolic process GO:0009161 ribonucleoside monophosphate metabolic process GO:0009167 purine ribonucleoside monophosphate metabolic process GO:0009179 purine ribonucleoside diphosphate metabolic process GO:0009185 ribonucleoside diphosphate metabolic process GO:0010810 regulation of cell-substrate adhesion GO:0010812 negative regulation of cell-substrate adhesion GO:0010837 regulation of keratinocyte proliferation GO:0010839 negative regulation of keratinocyte proliferation GO:0010959 regulation of metal ion transport GO:0023061 signal release GO:0031589 cell-substrate adhesion GO:0032102 negative regulation of response to external stimulus GO:0042278 purine nucleoside metabolic process GO:0043270 positive regulation of ion transport GO:0043616 keratinocyte proliferation GO:0046037 GMP metabolic process GO:0046128 purine ribonucleoside metabolic process GO:0046710 GDP metabolic process GO:0050673 epithelial cell proliferation GO:0050678 regulation of epithelial cell proliferation GO:0050680 negative regulation of epithelial cell proliferation GO:0051924 regulation of calcium ion transport GO:0051928 positive regulation of calcium ion transport GO:0061041 regulation of wound healing GO:0061045 negative regulation of wound healing GO:0070509 calcium ion import GO:0070838 divalent metal ion transport GO:0072511 divalent inorganic cation transport GO:0090279 regulation of calcium ion import GO:0090280 positive regulation of calcium ion import GO:0090287 regulation of cellular response to growth factor stimulus GO:0090288 negative regulation of cellular response to growth factor stimulus GO:0099531 presynaptic process involved in chemical synaptic transmission GO:0099643 signal release from synapse GO:1901068 guanosine-containing compound metabolic process GO:1901657 glycosyl compound metabolic process GO:1903034 regulation of response to wounding GO:1903035 negative regulation of response to wounding
Molecular Function	GO:0004385 guanylate kinase activity GO:0004674 protein serine/threonine kinase activity GO:0005516 calmodulin binding GO:0016776 phosphotransferase activity, phosphate group as acceptor GO:0019201 nucleotide kinase activity GO:0019205 nucleobase-containing compound kinase activity GO:0042043 neurexin family protein binding
Cellular Component	GO:0005578 proteinaceous extracellular matrix GO:0005604 basement membrane GO:0005652 nuclear lamina GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0005929 cilium GO:0015629 actin cytoskeleton GO:0016323 basolateral plasma membrane GO:0016363 nuclear matrix GO:0030055 cell-substrate junction GO:0031253 cell projection membrane GO:0034399 nuclear periphery GO:0042734 presynaptic membrane GO:0044420 extracellular matrix component GO:0044441 ciliary part GO:0060170 ciliary membrane GO:0097060 synaptic membrane GO:0098793 presynapse

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1500931: Cell-Cell communication R-HSA-212676: Dopamine Neurotransmitter Release Cycle R-HSA-1474244: Extracellular matrix organization R-HSA-6794361: Interactions of neurexins and neuroligins at synapses R-HSA-373753: Nephrin interactions R-HSA-112316: Neuronal System R-HSA-112310: Neurotransmitter Release Cycle R-HSA-3000171: Non-integrin membrane-ECM interactions R-HSA-6794362: Protein-protein interactions at synapses R-HSA-3000170: Syndecan interactions R-HSA-112315: Transmission across Chemical Synapses

> KEGG and Reactome Pathway

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KEGG

Reactome

R-HSA-1500931: Cell-Cell communication
R-HSA-212676: Dopamine Neurotransmitter Release Cycle
R-HSA-1474244: Extracellular matrix organization
R-HSA-6794361: Interactions of neurexins and neuroligins at synapses
R-HSA-373753: Nephrin interactions
R-HSA-112316: Neuronal System
R-HSA-112310: Neurotransmitter Release Cycle
R-HSA-3000171: Non-integrin membrane-ECM interactions
R-HSA-6794362: Protein-protein interactions at synapses
R-HSA-3000170: Syndecan interactions
R-HSA-112315: Transmission across Chemical Synapses

Summary
Symbol	CASK
Name	calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Aliases	LIN2; CAGH39; FGS4; TNRC8; trinucleotide repeat containing 8; CAMGUK; CMG; MICPCH; MRXSNA; calcium/calmoduli ......
Chromosomal Location	Xp11.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CASK 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	CASK
Name	calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Aliases	LIN2; CAGH39; FGS4; TNRC8; trinucleotide repeat containing 8; CAMGUK; CMG; MICPCH; MRXSNA; calcium/calmoduli ......
Chromosomal Location	Xp11.4
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 CASK 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	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CASK
Name	calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Aliases	LIN2; CAGH39; FGS4; TNRC8; trinucleotide repeat containing 8; CAMGUK; CMG; MICPCH; MRXSNA; calcium/calmoduli ......
Chromosomal Location	Xp11.4
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 CASK 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	-0.194	0.473
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.04	0.973
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.302	0.711
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.202	0.556
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.175	0.931
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.232	0.932
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.055	0.875
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.153	0.926
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.352	0.771
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	1.228	0.459
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.13	0.0814

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CASK 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	5.9	-5.9	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	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
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	3.7	1.7	2	0.532
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	12.5	-1.4	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	14.3	10.7	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	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	CASK
Name	calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Aliases	LIN2; CAGH39; FGS4; TNRC8; trinucleotide repeat containing 8; CAMGUK; CMG; MICPCH; MRXSNA; calcium/calmoduli ......
Chromosomal Location	Xp11.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CASK. 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	CASK
Name	calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Aliases	LIN2; CAGH39; FGS4; TNRC8; trinucleotide repeat containing 8; CAMGUK; CMG; MICPCH; MRXSNA; calcium/calmoduli ......
Chromosomal Location	Xp11.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CASK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CASK. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CASK
Name	calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Aliases	LIN2; CAGH39; FGS4; TNRC8; trinucleotide repeat containing 8; CAMGUK; CMG; MICPCH; MRXSNA; calcium/calmoduli ......
Chromosomal Location	Xp11.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CASK. 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	CASK
Name	calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Aliases	LIN2; CAGH39; FGS4; TNRC8; trinucleotide repeat containing 8; CAMGUK; CMG; MICPCH; MRXSNA; calcium/calmoduli ......
Chromosomal Location	Xp11.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CASK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CASK
Name	calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Aliases	LIN2; CAGH39; FGS4; TNRC8; trinucleotide repeat containing 8; CAMGUK; CMG; MICPCH; MRXSNA; calcium/calmoduli ......
Chromosomal Location	Xp11.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CASK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CASK
Name	calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Aliases	LIN2; CAGH39; FGS4; TNRC8; trinucleotide repeat containing 8; CAMGUK; CMG; MICPCH; MRXSNA; calcium/calmoduli ......
Chromosomal Location	Xp11.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CASK collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CASK.

ID	Name	Drug Type	Targets	#Targets
DB01942	Formic Acid	Small Molecule	ACYP2, CA2, CASK, CTBP1, CYTH2, FGF1, GGACT, GPHN, HMOX1, NOS1, PV ......	12

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