CARD8

caspase recruitment domain family member 8, the group of Caspase recruitment domain containing

Basic information

Region (hg38): 19:48180770-48255946

Links

ENSG00000105483 ∙ NCBI:22900 ∙ OMIM:609051 ∙ HGNC:17057 ∙ Uniprot:Q9Y2G2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• inflammatory bowel disease 30 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Inflammatory bowel disease 30	AD	Allergy/Immunology/Infectious; Gastrointestinal	The condition can involve sequelae of inflammatory bowel disease, and medical management (eg, with steroids, anti-IL1B monoclonal antibodies) have been described as beneficial	Allergy/Immunology/Infectious; Gastrointestinal	29408806

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CARD8 gene.

• not_provided (386 variants)
• not_specified (65 variants)
• CARD8-related_disorder (14 variants)
• Inflammatory_bowel_disease_30 (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CARD8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001184900.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	78	7	90
missense			211	10	6	227
nonsense			6			6
start loss			2			2
frameshift			18			18
splice donor/acceptor (+/-2bp)			6	1		7
Total	0	0	248	89	13

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CARD8	protein_coding	protein_coding	ENST00000391898	11	75177

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000177	0.969	125632	2	112	125746	0.000453

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.923	251	296	0.849	0.0000162	3520
Missense in Polyphen		84	96.456	0.87087		1225
Synonymous	0.178	112	114	0.979	0.00000617	1019
Loss of Function	2.01	13	23.5	0.552	0.00000109	287

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000620	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000653	0.000653
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000106	0.0000967
Middle Eastern	0.000653	0.000653
South Asian	0.00301	0.00288
Other	0.000168	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibits NF-kappa-B activation. May participate in a regulatory mechanism that coordinates cellular responses controlled by NF-kappa-B transcription factor. May be a component of the inflammasome, a protein complex which also includes PYCARD, NALP2 and CASP1 and whose function would be the activation of proinflammatory caspases.
• Pathway: NOD-like receptor signaling pathway - Homo sapiens (human);Nucleotide-binding Oligomerization Domain (NOD) pathway (Consensus)

Recessive Scores

• pRec: 0.0634

Intolerance Scores

• loftool: 0.983
• rvis_EVS: 1.18
• rvis_percentile_EVS: 92.79

Haploinsufficiency Scores

• pHI: 0.0674
• hipred: N
• hipred_score: 0.145
• ghis: 0.420

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.783

Gene Damage Prediction

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

Gene ontology

• Biological process: apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of tumor necrosis factor-mediated signaling pathway;negative regulation of lipopolysaccharide-mediated signaling pathway;negative regulation of NF-kappaB transcription factor activity;negative regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of interleukin-1 beta secretion;positive regulation of interleukin-1 beta secretion;inhibition of cysteine-type endopeptidase activity
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;protein-containing complex;inflammasome complex;NLRP3 inflammasome complex
• Molecular function: protein binding;cysteine-type endopeptidase activator activity involved in apoptotic process;NACHT domain binding;protein homodimerization activity;CARD domain binding