TISIDB

Summary
Symbol	CARD9
Name	caspase recruitment domain family, member 9
Aliases	CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location	9q34
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	Cytoplasm
Domain	PF00619 Caspase recruitment domain
Function	Adapter protein that plays a key role in innate immune response to a number of intracellular pathogens, such as C.albicans and L.monocytogenes. Is at the crossroads of ITAM-tyrosine kinase and the Toll-like receptors (TLR) and NOD2 signaling pathways. Probably controls various innate immune response pathways depending on the intracellular pathogen. In response to L.monocytogenes infection, acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B. Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (By similarity). Controls CLEC7A (dectin-1)-mediated myeloid cell activation induced by the yeast cell wall component zymosan, leading to cytokine production and innate anti-fungal immunity: acts by regulating BCL10-MALT1-mediated NF-kappa-B activation pathway. Activates NF-kappa-B via BCL10. In response to the hyphal form of C.albicans, mediates CLEC6A (dectin-2)-induced I-kappa-B kinase ubiquitination, leading to NF-kappa-B activation via interaction with BCL10. In response to fungal infection, may be required for the development and subsequent differentiation of interleukin 17-producing T helper (TH-17) cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0002218 activation of innate immune response GO:0002220 innate immune response activating cell surface receptor signaling pathway GO:0002223 stimulatory C-type lectin receptor signaling pathway GO:0002237 response to molecule of bacterial origin GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0007254 JNK cascade GO:0009615 response to virus GO:0009620 response to fungus GO:0031098 stress-activated protein kinase signaling cascade GO:0031349 positive regulation of defense response GO:0032494 response to peptidoglycan GO:0032495 response to muramyl dipeptide GO:0032623 interleukin-2 production GO:0032635 interleukin-6 production GO:0032640 tumor necrosis factor production GO:0032663 regulation of interleukin-2 production GO:0032675 regulation of interleukin-6 production GO:0032680 regulation of tumor necrosis factor production GO:0032755 positive regulation of interleukin-6 production GO:0032760 positive regulation of tumor necrosis factor production GO:0032872 regulation of stress-activated MAPK cascade GO:0032874 positive regulation of stress-activated MAPK cascade GO:0042035 regulation of cytokine biosynthetic process GO:0042089 cytokine biosynthetic process GO:0042094 interleukin-2 biosynthetic process GO:0042107 cytokine metabolic process GO:0042226 interleukin-6 biosynthetic process GO:0042493 response to drug GO:0042533 tumor necrosis factor biosynthetic process GO:0042534 regulation of tumor necrosis factor biosynthetic process GO:0042742 defense response to bacterium GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043330 response to exogenous dsRNA GO:0043331 response to dsRNA GO:0043410 positive regulation of MAPK cascade GO:0045076 regulation of interleukin-2 biosynthetic process GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045408 regulation of interleukin-6 biosynthetic process GO:0046328 regulation of JNK cascade GO:0046330 positive regulation of JNK cascade GO:0050830 defense response to Gram-positive bacterium GO:0051403 stress-activated MAPK cascade GO:0051607 defense response to virus GO:0070302 regulation of stress-activated protein kinase signaling cascade GO:0070304 positive regulation of stress-activated protein kinase signaling cascade GO:0071706 tumor necrosis factor superfamily cytokine production GO:0098542 defense response to other organism GO:1901652 response to peptide GO:1903555 regulation of tumor necrosis factor superfamily cytokine production GO:1903557 positive regulation of tumor necrosis factor superfamily cytokine production
Molecular Function	GO:0050700 CARD domain binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04621 NOD-like receptor signaling pathway
Reactome	R-HSA-5621481: C-type lectin receptors (CLRs) R-HSA-5607764: CLEC7A (Dectin-1) signaling R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-168638: NOD1/2 Signaling Pathway R-HSA-168643: Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways

Summary
Symbol	CARD9
Name	caspase recruitment domain family, member 9
Aliases	CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CARD9 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

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Literatures describing the relation between CARD9 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28295265	Melanoma	Promote immunity (T cell function)	In vivo, Dectin-1-mediated Card9 activation after vaccination drives both expansion and activation of Ag-specific CTLs, resulting in long-lasting CTL responses that are sufficient to protect mice from tumor challenge. This Dectin-1-induced antitumor immune response was independent of NK cell function and completely abrogated in Card9-deficient mice.

Summary
Symbol	CARD9
Name	caspase recruitment domain family, member 9
Aliases	CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location	9q34
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 CARD9 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	CARD9
Name	caspase recruitment domain family, member 9
Aliases	CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location	9q34
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 CARD9 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	-0.628	0.0705
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.263	0.11
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.168	0.808
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.219	0.646
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.308	0.865
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.104	0.963
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.272	0.52
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.687	0.296
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.215	0.762
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.618	0.0577
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	2.049	0.0835
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.327	0.0454

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of CARD9 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	0	1.4	-1.4	1
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	0	1.7	-1.7	1
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	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
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	4.5	0	4.5	1
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	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	CARD9
Name	caspase recruitment domain family, member 9
Aliases	CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CARD9. 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	CARD9
Name	caspase recruitment domain family, member 9
Aliases	CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CARD9. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CARD9. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CARD9
Name	caspase recruitment domain family, member 9
Aliases	CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CARD9. 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	CARD9
Name	caspase recruitment domain family, member 9
Aliases	CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CARD9 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CARD9
Name	caspase recruitment domain family, member 9
Aliases	CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CARD9 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CARD9
Name	caspase recruitment domain family, member 9
Aliases	CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CARD9 collected from DrugBank database.

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

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