CARD18

protein-coding

caspase recruitment domain family member 18, the group of Caspase recruitment domain containing

Gene summary

Enables CARD domain binding activity and caspase binding activity. Involved in negative regulation of interleukin-1 beta production. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_021571.4

Inheritance

—

ClinVar variants

U:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.05

Max pathogenic AF

—

Genomic locus

chr11:105,137,714-105,531,697

External References & Databases

Ensembl (ENSG00000255501)

Transcript & Mutation Effects

hg38 • Region Span ~394.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CARD18 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021571.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			13 clinvar			13
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	14	0	0	14

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021571.4	RefSeq	NP_067546.1	2	MANE Select
ENST00000530950.2	Ensembl	ENSP00000436691.1	2	MANE Select
ENST00000526823.1	Ensembl	ENSP00000437035.1	1	Standard
ENST00000526823.2	Ensembl	ENSP00000437035.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NOD-like receptor signaling pathway - Homo sapiens (human)

Biological Process

proteolysis
inflammatory response
negative regulation of protein binding
regulation of apoptotic process
negative regulation of interleukin-1 beta secretion

Molecular Function

cysteine-type endopeptidase activity
cysteine-type endopeptidase inhibitor activity
protein binding
CARD domain binding
caspase binding

Cellular Component

protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000530950
Coding exons: 2
Length: 2006
Individuals with no LoFs: 124477
Homozygous LoFs: 4
Heterozygous LoFs: 125
Defined: 124606
p: 0.000518

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.522	57	46.9	1.21	0.00000224	593
Missense (PolyPhen)		17	13.021	1.3056		187
Synonymous	1.51	8	15.6	0.513	6.75e-7	163
Loss of Function	-0.0929	4	3.80	1.05	2.24e-7	50

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00019	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.0040	0.0039	notable
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits generation of IL-1-beta by interacting with caspase-1 and preventing its association with RIP2. Down-regulates the release of IL1B. {ECO:0000269|PubMed:11051551}.;

Intolerance Scores

LoFtool: 0.735
RVIS EVS: 0.17
RVIS percentile EVS: 65.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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