CARD9

caspase recruitment domain family member 9, the group of Caspase recruitment domain containing

Basic information

Region (hg38): 9:136363956-136373681

Links

ENSG00000187796

∙ NCBI:64170 ∙ OMIM:607212 ∙ HGNC:16391 ∙ Uniprot:Q9H257 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

predisposition to invasive fungal disease due to CARD9 deficiency (Supportive), mode of inheritance: AR
predisposition to invasive fungal disease due to CARD9 deficiency (Strong), mode of inheritance: AR
deep dermatophytosis (Strong), mode of inheritance: AR
predisposition to invasive fungal disease due to CARD9 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 103, susceptibility to fungal infections	AR	Allergy/Immunology/Infectious	Individuals can have recurrent (and lethal) fungal infections, and surveillance, prophylaxis, and early treatment may be beneficial	Allergy/Immunology/Infectious	19864672; 22703878; 23335372; 24131138

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CARD9 gene.

Predisposition_to_invasive_fungal_disease_due_to_CARD9_deficiency (518 variants)
Inborn_genetic_diseases (87 variants)
not_provided (26 variants)
CARD9-related_disorder (13 variants)
Inherited_Immunodeficiency_Diseases (1 variants)
not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CARD9 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000052813.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	151 clinvar	5 clinvar	159
missense		1 clinvar	243 clinvar	13 clinvar		257
nonsense	8 clinvar		3 clinvar			11
start loss						0
frameshift	7 clinvar	2 clinvar	1 clinvar			10
splice donor/acceptor (+/-2bp)		4 clinvar		1 clinvar		5
Total	15	7	250	165	5

Highest pathogenic variant AF is 0.00002311948

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CARD9	protein_coding	protein_coding	ENST00000371732	12	11779

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.15e-13	0.244	124676	2	856	125534	0.00342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0997	355	360	0.985	0.0000263	3444
Missense in Polyphen		79	108.54	0.72786		975
Synonymous	-1.56	184	159	1.16	0.0000113	1023
Loss of Function	1.04	22	27.9	0.788	0.00000128	312

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00215	0.00214
Ashkenazi Jewish	0.00722	0.00719
East Asian	0.000439	0.000435
Finnish	0.000926	0.000878
European (Non-Finnish)	0.00554	0.00547
Middle Eastern	0.000439	0.000435
South Asian	0.00210	0.00209
Other	0.00247	0.00245

dbNSFP

Source: dbNSFP

Function: 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. {ECO:0000250, ECO:0000269|PubMed:11053425}.;
Disease: DISEASE: Candidiasis, familial, 2 (CANDF2) [MIM:212050]: A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans. {ECO:0000269|PubMed:19864672, ECO:0000269|PubMed:23335372, ECO:0000269|PubMed:24131138}. Note=The disease is caused by mutations affecting the gene represented in this entry. Defects induce reduced numbers of CD4(+) Th17 lymphocytes as well as a lack of monocyte-derived cytokines in response to Candida strains. Neutrophils show a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae (PubMed:23335372). {ECO:0000269|PubMed:23335372}.;
Pathway: NOD-like receptor signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Nucleotide-binding Oligomerization Domain (NOD) pathway;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Innate Immune System;Immune System (Consensus)

Recessive Scores

pRec: 0.139

Intolerance Scores

loftool: 0.827
rvis_EVS: -0.59
rvis_percentile_EVS: 18.23

Haploinsufficiency Scores

pHI: 0.0928
hipred: Y
hipred_score: 0.533
ghis: 0.537

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.814

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Card9
Phenotype: hematopoietic system phenotype; homeostasis/metabolism phenotype; immune system phenotype;

Gene ontology

Biological process: stimulatory C-type lectin receptor signaling pathway;I-kappaB kinase/NF-kappaB signaling;response to fungus;response to peptidoglycan;response to muramyl dipeptide;positive regulation of interleukin-6 production;positive regulation of tumor necrosis factor production;positive regulation of stress-activated MAPK cascade;regulation of tumor necrosis factor biosynthetic process;regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;response to exogenous dsRNA;regulation of interleukin-2 biosynthetic process;innate immune response;regulation of interleukin-6 biosynthetic process;positive regulation of JNK cascade;defense response to Gram-positive bacterium;defense response to virus
Cellular component: cytoplasm;cytosol;plasma membrane
Molecular function: protein binding;protein homodimerization activity;CARD domain binding