CARD9
Caspase recruitment domain-containing protein 9
Also known as: CARD9_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9H257
- Gene
- CARD9
- Ensembl
- ENSG00000187796
- Chromosome
- 9
- Canonical length
- 536 aa
- Protein class
- Disease related genes, Human disease related genes, Predicted intracellular proteins
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene is a member of the CARD protein family, which is defined by the presence of a characteristic caspase-associated recruitment domain (CARD). CARD is a protein interaction domain known to participate in activation or suppression of CARD containing members of the caspase family, and thus plays an important regulatory role in cell apoptosis. This protein was identified by its selective association with the CARD domain of BCL10, a postive regulator of apoptosis and NF-kappaB activation, and is thought to function as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-kappaB. Several alternatively spliced transcript variants have been observed, but their full-length nature is not clearly defined. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
536 residues, UniProt reviewed canonical sequence.
>Q9H257|CARD9
1 MSDYENDDEC WSVLEGFRVT LTSVIDPSRI TPYLRQCKVL NPDDEEQVLS DPNLVIRKRK
61 VGVLLDILQR TGHKGYVAFL ESLELYYPQL YKKVTGKEPA RVFSMIIDAS GESGLTQLLM
121 TEVMKLQKKV QDLTALLSSK DDFIKELRVK DSLLRKHQER VQRLKEECEA GSRELKRCKE
181 ENYDLAMRLA HQSEEKGAAL MRNRDLQLEI DQLKHSLMKA EDDCKVERKH TLKLRHAMEQ
241 RPSQELLWEL QQEKALLQAR VQELEASVQE GKLDRSSPYI QVLEEDWRQA LRDHQEQANT
301 IFSLRKDLRQ GEARRLRCME EKEMFELQCL ALRKDSKMYK DRIEAILLQM EEVAIERDQA
361 IATREELHAQ HARGLQEKDA LRKQVRELGE KADELQLQVF QCEAQLLAVE GRLRRQQLET
421 LVLSSDLEDG SPRRSQELSL PQDLEDTQLS DKGCLAGGGS PKQPFAALHQ EQVLRNPHDA
481 GLSSGEPPEK ERRRLKESFE NYRRKRALRK MQKGWRQGEE DRENTTGSDN TDTEGSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CARD9 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.46
- Highest tissue expression
- 8.1 nTPM
Expression across tissuesHPA
Tissue
- spleen: 8.1 nTPM
- bone marrow: 6.8 nTPM
- appendix: 2.8 nTPM
- lung: 2.5 nTPM
- spinal cord: 1.9 nTPM
- cervix: 1.5 nTPM
Single-cell type
- microglia: 23 nCPM
- renal collecting duct principal cells: 4.8 nCPM
- oocytes: 4.6 nCPM
- astrocytes: 2.1 nCPM
- podocytes: 2.1 nCPM
- brain inhibitory neurons: 1.7 nCPM
Immune cell
- intermediate monocyte: 56 nTPM
- non-classical monocyte: 49 nTPM
- classical monocyte: 33 nTPM
- myeloid DC: 25 nTPM
- total PBMC: 14 nTPM
- eosinophil: 10 nTPM
Brain region
- cerebellum: 5.5 nTPM
- medulla oblongata: 3.7 nTPM
- white matter: 3.4 nTPM
- spinal cord: 2.6 nTPM
- thalamus: 2.6 nTPM
- pons: 2.4 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CARD9.
Disease | AllUniProt
Conditions CARD9 is implicated in, by any mechanism.
- Immunodeficiency 103, susceptibility to fungal infections (IMD103) MIM:212050
Disease | GeneticClinVar
24 pathogenic / likely-pathogenic of 627 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Predisposition to invasive fungal disease due to CARD9 deficiency
- Inherited Immunodeficiency Diseases
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.13
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.1
- DepMap mean gene effect
- -0.06
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antifungal innate immune response
- apoptotic signaling pathway
- defense response to Gram-positive bacterium
- defense response to virus
- host-mediated modulation of intestinal microbiota composition
- immunoglobulin mediated immune response
- JNK cascade
- neutrophil mediated immunity
- positive regulation of canonical NF-kappaB signal transduction
- positive regulation of chemokine production
- positive regulation of cytokine production
- positive regulation of cytokine production involved in inflammatory response
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of granulocyte macrophage colony-stimulating factor production
- positive regulation of innate immune response
- positive regulation of interleukin-17 production
- positive regulation of interleukin-6 production
- positive regulation of JNK cascade
- positive regulation of macrophage cytokine production
- positive regulation of NF-kappaB transcription factor activity
- positive regulation of stress-activated MAPK cascade
- positive regulation of T-helper 17 type immune response
- positive regulation of tumor necrosis factor production
- protein homooligomerization
- regulation of apoptotic process
- regulation of immune response
- regulation of interleukin-2 production
- response to aldosterone
- response to exogenous dsRNA
- response to muramyl dipeptide
- response to peptidoglycan
- response to xenobiotic stimulus
- stress-activated MAPK cascade
Molecular functions
- CARD domain binding
- identical protein binding
- metal ion binding
- protein homodimerization activity
- signaling adaptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- CARD domain
- Death-like domain superfamily
- Caspase recruitment domain
- CARD9, CARD domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CARD9 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CARD9 as an antibody target. Whether an autoantibody or antibody against CARD9 could matter depends on whether native CARD9 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CARD9 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label CARD9 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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