NLRP12
Basic information
Region (hg38): 19:53793740-53824403
Previous symbols: [ "NALP12" ]
Links
Phenotypes
GenCC
Source:
- familial cold autoinflammatory syndrome 2 (Moderate), mode of inheritance: AD
- familial cold autoinflammatory syndrome 2 (Strong), mode of inheritance: AD
- familial cold autoinflammatory syndrome 2 (Supportive), mode of inheritance: AD
- familial cold autoinflammatory syndrome 2 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Familial cold autoinflammatory syndrome 2 | AD | Allergy/Immunology/Infectious | Medical treatment (eg, with prednisone or colchicine) has been reported as effective in reducing fever | Allergy/Immunology/Infectious | 18230725; 22753383; 27314497; 27633793 |
ClinVar
This is a list of variants' phenotypes submitted to
- Familial cold autoinflammatory syndrome 2 (873 variants)
- not provided (161 variants)
- Autoinflammatory syndrome (137 variants)
- Inborn genetic diseases (46 variants)
- not specified (27 variants)
- Familial cold autoinflammatory syndrome (14 variants)
- NLRP12-related condition (11 variants)
- Multisystem inflammatory syndrome in children (2 variants)
- See cases (2 variants)
- Periodic fever syndrome (1 variants)
- NLRP12-associated autoinflammatory disease (1 variants)
- Childhood-onset schizophrenia (1 variants)
- FAMILIAL COLD AUTOINFLAMMATORY SYNDROME 2, SUSCEPTIBILITY TO (1 variants)
- NLRP12-related conditions (1 variants)
- Autoimmune interstitial lung disease-arthritis syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLRP12 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 | 13 | 176 | 12 | 201 | ||
missense | 477 | 20 | 505 | |||
nonsense | 21 | 26 | ||||
start loss | 1 | |||||
frameshift | 33 | 40 | ||||
inframe indel | 12 | 12 | ||||
splice donor/acceptor (+/-2bp) | 7 | |||||
splice region ? | 13 | 16 | 1 | 30 | ||
non coding ? | 10 | 38 | 48 | 96 | ||
Total | 4 | 9 | 572 | 236 | 67 |
Highest pathogenic variant AF is 0.00000658
Variants in NLRP12
This is a list of pathogenic ClinVar variants found in the NLRP12 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
19-53793759-T-G | Familial cold autoinflammatory syndrome 2 | Uncertain significance (Jan 13, 2018) | ||
19-53793783-C-A | Familial cold autoinflammatory syndrome | Benign (Jun 14, 2016) | ||
19-53793820-C-T | Familial cold autoinflammatory syndrome 2 | Benign (Jan 12, 2018) | ||
19-53793844-C-T | Familial cold autoinflammatory syndrome 2 | Benign (Jan 12, 2018) | ||
19-53793845-G-A | Familial cold autoinflammatory syndrome 2 | Benign (Jan 12, 2018) | ||
19-53793846-A-G | Familial cold autoinflammatory syndrome 2 | Benign (Jan 12, 2018) | ||
19-53793855-G-A | Familial cold autoinflammatory syndrome 2 | Benign (Jan 12, 2018) | ||
19-53793877-G-A | Familial cold autoinflammatory syndrome 2 | Benign (Jan 13, 2018) | ||
19-53793888-T-G | Familial cold autoinflammatory syndrome 2 | Uncertain significance (Jan 12, 2018) | ||
19-53793923-C-G | Familial cold autoinflammatory syndrome 2 | Uncertain significance (Jan 13, 2018) | ||
19-53793931-C-T | Familial cold autoinflammatory syndrome 2 | Benign (Jan 13, 2018) | ||
19-53793941-A-G | Familial cold autoinflammatory syndrome 2 | Uncertain significance (Jan 12, 2018) | ||
19-53793980-G-T | Familial cold autoinflammatory syndrome | Benign (May 14, 2021) | ||
19-53794050-C-T | Familial cold autoinflammatory syndrome 2 | Likely benign (Aug 17, 2023) | ||
19-53794054-A-C | Familial cold autoinflammatory syndrome 2 | Uncertain significance (Nov 25, 2019) | ||
19-53794055-G-A | Familial cold autoinflammatory syndrome 2 | Likely benign (Apr 20, 2023) | ||
19-53794055-G-C | Familial cold autoinflammatory syndrome 2 | Benign (May 24, 2023) | ||
19-53794059-A-G | NLRP12-related disorder | Uncertain significance (Jan 03, 2023) | ||
19-53794061-G-T | Familial cold autoinflammatory syndrome 2 | Uncertain significance (Jul 08, 2023) | ||
19-53794067-A-G | Familial cold autoinflammatory syndrome 2 | Likely benign (Mar 19, 2022) | ||
19-53794072-GTT-G | Uncertain significance (Oct 01, 2020) | |||
19-53794075-T-C | Familial cold autoinflammatory syndrome 2 | Uncertain significance (Mar 03, 2022) | ||
19-53794076-T-C | Autoinflammatory syndrome | Uncertain significance (Oct 01, 2018) | ||
19-53794083-C-G | Familial cold autoinflammatory syndrome 2 | Conflicting classifications of pathogenicity (Jul 13, 2020) | ||
19-53794083-C-T | Familial cold autoinflammatory syndrome 2 | Uncertain significance (Nov 28, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
NLRP12 | protein_coding | protein_coding | ENST00000324134 | 10 | 30792 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
3.65e-28 | 0.0000633 | 125009 | 3 | 736 | 125748 | 0.00294 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -1.71 | 729 | 610 | 1.20 | 0.0000402 | 6910 |
Missense in Polyphen | 250 | 202.5 | 1.2345 | 2518 | ||
Synonymous | -2.50 | 326 | 273 | 1.19 | 0.0000195 | 2164 |
Loss of Function | -0.258 | 41 | 39.3 | 1.04 | 0.00000201 | 461 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.0257 | 0.0257 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.00169 | 0.00169 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.00147 | 0.00142 |
Middle Eastern | 0.00169 | 0.00169 |
South Asian | 0.00291 | 0.00291 |
Other | 0.00245 | 0.00245 |
dbNSFP
Source:
- Function
- FUNCTION: May mediate activation of CASP1 via ASC and promote activation of NF-kappa-B via IKK.;
- Disease
- DISEASE: Familial cold autoinflammatory syndrome 2 (FCAS2) [MIM:611762]: A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. {ECO:0000269|PubMed:18230725}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- NOD-like receptor signaling pathway - Homo sapiens (human);Nucleotide-binding Oligomerization Domain (NOD) pathway
(Consensus)
Intolerance Scores
- loftool
- 0.275
- rvis_EVS
- -0.45
- rvis_percentile_EVS
- 24.22
Haploinsufficiency Scores
- pHI
- 0.126
- hipred
- N
- hipred_score
- 0.146
- ghis
- 0.495
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.230
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | High |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nlrp12
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; digestive/alimentary phenotype; immune system phenotype; neoplasm;
Gene ontology
- Biological process
- activation of cysteine-type endopeptidase activity involved in apoptotic process;signal transduction;negative regulation of signal transduction;negative regulation of protein autophosphorylation;negative regulation of NF-kappaB transcription factor activity;dendritic cell migration;regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of I-kappaB kinase/NF-kappaB signaling;regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of MHC class I biosynthetic process;regulation of interleukin-18 biosynthetic process;negative regulation of interleukin-6 biosynthetic process;negative regulation of Toll signaling pathway;negative regulation of cytokine secretion;negative regulation of interleukin-1 secretion;positive regulation of interleukin-1 beta secretion;negative regulation of inflammatory response;positive regulation of inflammatory response;negative regulation of ERK1 and ERK2 cascade;cellular response to cytokine stimulus;negative regulation of NIK/NF-kappaB signaling;positive regulation of NIK/NF-kappaB signaling
- Cellular component
- nucleus;cytoplasm
- Molecular function
- protein binding;ATP binding;cysteine-type endopeptidase activator activity involved in apoptotic process