Browse CARD9

Summary
SymbolCARD9
Namecaspase recruitment domain family, member 9
Aliases CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location9q34
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
 
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
 
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
 
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
SymbolCARD9
Namecaspase recruitment domain family, member 9
Aliases CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location9q34
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
 
  Literatures describing the relation between CARD9 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28295265MelanomaPromote 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
SymbolCARD9
Namecaspase recruitment domain family, member 9
Aliases CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location9q34
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
  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
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCARD9
Namecaspase recruitment domain family, member 9
Aliases CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location9q34
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
 
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 Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.6280.0705
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.2630.11
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1680.808
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.2190.646
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.3080.865
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1040.963
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2720.52
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.6870.296
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2150.762
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.6180.0577
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 282.0490.0835
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.3270.0454
> Mutation difference between responders and non-responders
 
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 Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.305.30.507
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCARD9
Namecaspase recruitment domain family, member 9
Aliases CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location9q34
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
 
Summary
SymbolCARD9
Namecaspase recruitment domain family, member 9
Aliases CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location9q34
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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCARD9
Namecaspase recruitment domain family, member 9
Aliases CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location9q34
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
 
> Receptor
 
Summary
SymbolCARD9
Namecaspase recruitment domain family, member 9
Aliases CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CARD9 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCARD9
Namecaspase recruitment domain family, member 9
Aliases CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CARD9 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCARD9
Namecaspase recruitment domain family, member 9
Aliases CANDF2; hCARD9; Caspase recruitment domain-containing protein 9
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CARD9 collected from DrugBank database.
> Drugs from DrugBank database
 

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