PYCARD
PYD and CARD domain containing, the group of Pyrin domain containing|Caspase recruitment domain containing
Basic information
Region (hg38): 16:31201486-31203450
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PYCARD gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 6 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 6 | 1 | 1 |
Variants in PYCARD
This is a list of pathogenic ClinVar variants found in the PYCARD region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 16-31201703-C-T | not specified | Uncertain significance (Mar 20, 2023) | ||
| 16-31201765-C-T | Likely benign (Jun 26, 2018) | |||
| 16-31201803-C-G | not specified | Uncertain significance (Jan 26, 2022) | ||
| 16-31201831-A-G | Benign (Dec 13, 2017) | |||
| 16-31202471-G-A | not specified | Uncertain significance (Oct 03, 2024) | ||
| 16-31202507-C-T | not specified | Uncertain significance (Nov 24, 2024) | ||
| 16-31202518-C-T | not specified | Uncertain significance (Jul 14, 2024) | ||
| 16-31202663-C-T | not specified | Uncertain significance (Nov 07, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PYCARD | protein_coding | protein_coding | ENST00000247470 | 3 | 1966 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000198 | 0.297 | 125141 | 0 | 3 | 125144 | 0.0000120 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.405 | 103 | 115 | 0.894 | 0.00000596 | 1227 |
| Missense in Polyphen | 24 | 39.095 | 0.61388 | 438 | ||
| Synonymous | -0.740 | 62 | 55.0 | 1.13 | 0.00000284 | 418 |
| Loss of Function | -0.445 | 5 | 4.04 | 1.24 | 1.72e-7 | 48 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000271 | 0.0000265 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3. Involved in macrophage pyroptosis, a caspase-1-dependent inflammatory form of cell death and is the major constituent of the ASC pyroptosome which forms upon potassium depletion and rapidly recruits and activates caspase-1. In innate immune response believed to act as an integral adapter in the assembly of the inflammasome which activates caspase-1 leading to processing and secretion of proinflammatory cytokines. The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions. Required for recruitment of caspase-1 to inflammasomes containing certain pattern recognition receptors, such as NLRP2, NLRP3, AIM2 and probably IFI16. In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1. In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation. May be involved in DDX58-triggered proinflammatory responses and inflammasome activation. Isoform 2 may have a regulating effect on the function as inflammasome adapter. Isoform 3 seems to inhibit inflammasome- mediated maturation of interleukin-1 beta. In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8. In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form. Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways. For regulation of NF-kappa-B activating and inhibiting functions have been reported. Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK. Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing. Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA (PubMed:28314590). {ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:12486103, ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:14499617, ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:16585594, ECO:0000269|PubMed:16964285, ECO:0000269|PubMed:16982856, ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:17599095, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19234215, ECO:0000269|PubMed:19494289, ECO:0000269|PubMed:21487011, ECO:0000269|PubMed:22732093, ECO:0000269|PubMed:28314590}.;
- Pathway
- Pertussis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Legionellosis - Homo sapiens (human);Influenza A - Homo sapiens (human);Cytosolic DNA-sensing pathway - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Nucleotide-binding Oligomerization Domain (NOD) pathway;TYROBP Causal Network;Neutrophil degranulation;The NLRP3 inflammasome;Inflammasomes;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;CLEC7A/inflammasome pathway;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Innate Immune System;Immune System;Direct p53 effectors;The AIM2 inflammasome
(Consensus)
Recessive Scores
- pRec
- 0.173
Intolerance Scores
- loftool
- 0.693
- rvis_EVS
- 0.13
- rvis_percentile_EVS
- 62.74
Haploinsufficiency Scores
- pHI
- 0.441
- hipred
- N
- hipred_score
- 0.285
- ghis
- 0.582
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.891
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pycard
- Phenotype
- homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; immune system phenotype; digestive/alimentary phenotype; neoplasm; normal phenotype; hematopoietic system phenotype;
Gene ontology
- Biological process
- myeloid dendritic cell activation;activation of innate immune response;positive regulation of defense response to virus by host;myeloid dendritic cell activation involved in immune response;positive regulation of antigen processing and presentation of peptide antigen via MHC class II;positive regulation of adaptive immune response;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;inflammatory response;signal transduction;intrinsic apoptotic signaling pathway in response to DNA damage;regulation of autophagy;regulation of tumor necrosis factor-mediated signaling pathway;positive regulation of actin filament polymerization;regulation of protein stability;negative regulation of NF-kappaB transcription factor activity;interleukin-1 beta production;negative regulation of interferon-beta production;positive regulation of interferon-gamma production;positive regulation of interleukin-6 production;positive regulation of tumor necrosis factor production;tumor necrosis factor-mediated signaling pathway;positive regulation of activated T cell proliferation;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;positive regulation of apoptotic process;regulation of GTPase activity;negative regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;neutrophil degranulation;macropinocytosis;innate immune response;positive regulation of JNK cascade;positive regulation of interleukin-1 beta secretion;positive regulation of phagocytosis;defense response to Gram-negative bacterium;positive regulation of T cell activation;positive regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;protein homooligomerization;defense response to virus;positive regulation of ERK1 and ERK2 cascade;cellular response to lipopolysaccharide;cellular response to interleukin-1;cellular response to tumor necrosis factor;negative regulation of protein serine/threonine kinase activity;intrinsic apoptotic signaling pathway by p53 class mediator;positive regulation of chemokine secretion;positive regulation of release of cytochrome c from mitochondria;activation of cysteine-type endopeptidase activity;negative regulation of cytokine production involved in inflammatory response;positive regulation of T cell migration;positive regulation of interleukin-8 secretion;positive regulation of interleukin-6 secretion;positive regulation of cysteine-type endopeptidase activity;positive regulation of interleukin-10 secretion;positive regulation of extrinsic apoptotic signaling pathway;regulation of intrinsic apoptotic signaling pathway
- Cellular component
- extracellular region;nucleus;nucleolus;cytoplasm;mitochondrion;endoplasmic reticulum;cytosol;IkappaB kinase complex;secretory granule lumen;azurophil granule lumen;neuronal cell body;NLRP1 inflammasome complex;NLRP3 inflammasome complex;AIM2 inflammasome complex
- Molecular function
- protease binding;interleukin-6 receptor binding;protein binding;tropomyosin binding;cysteine-type endopeptidase activator activity involved in apoptotic process;myosin I binding;enzyme binding;Pyrin domain binding;identical protein binding;protein homodimerization activity;ion channel binding;protein dimerization activity;BMP receptor binding;cysteine-type endopeptidase activity involved in apoptotic process