CARD16
protein-codingcaspase recruitment domain family member 16, the group of Caspase recruitment domain containing
Gene summary
Enables several functions, including CARD domain binding activity; cysteine-type endopeptidase inhibitor activity; and enzyme binding activity. Involved in cellular response to lipopolysaccharide; negative regulation of interleukin-1 beta production; and regulation of signal transduction. Part of protease inhibitor complex. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~62.3 kbGenCC 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 CARD16 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_052889.4. 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 | 16 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 16 | 0 | 0 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_443121.1 | 3 | MANE Select | |
| Ensembl | ENSP00000509408.1 | 3 | MANE Select | |
| RefSeq | NP_001381509.1 | 2 | Standard | |
| Ensembl | ENSP00000510629.1 | 2 | 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
- negative regulation of tumor necrosis factor-mediated signaling pathway
- negative regulation of lipopolysaccharide-mediated signaling pathway
- negative regulation of protein binding
- positive regulation of I-kappaB kinase/NF-kappaB signaling
Molecular Function
- cysteine-type endopeptidase activity
- cysteine-type endopeptidase inhibitor activity
- protein binding
- kinase binding
- identical protein binding
Cellular Component
- protein-containing complex
- protease inhibitor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375706
- Coding exons
- 3
- Length
- 60106
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125731
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.471 | 115 | 102 | 1.13 | 0.00000528 | 1285 |
| Missense (PolyPhen) | 24 | 17.754 | 1.3518 | 258 | ||
| Synonymous | -1.50 | 50 | 38.2 | 1.31 | 0.00000201 | 367 |
| Loss of Function | 1.62 | 1 | 4.86 | 0.206 | 2.95e-7 | 54 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00074 | 0.00074 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Caspase inhibitor. Acts as a regulator of procaspase- 1/CASP1 activation implicated in the regulation of the proteolytic maturation of pro-interleukin-1 beta (IL1B) and its release during inflammation. Inhibits the release of IL1B in response to LPS in monocytes. Also induces NF-kappa-B activation during the pro- inflammatory cytokine response. Also able to inhibit CASP1- mediated neuronal cell death, TNF-alpha, hypoxia-, UV-, and staurosporine-mediated cell death but not ER stress-mediated cell death. Acts by preventing activation of caspases CASP1 and CASP4, possibly by preventing the interaction between CASP1 and RIPK2. {ECO:0000269|PubMed:11432859, ECO:0000269|PubMed:11536016, ECO:0000269|PubMed:16920334}.;
Intolerance Scores
- LoFtool
- 0.890
- RVIS EVS
- 0.19
- RVIS percentile EVS
- 67.03
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0302
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |