NLRP2
protein-codingNLR family pyrin domain containing 2, the group of NLR family|Pyrin domain containing
Gene summary
This gene is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family, and is predicted to contain an N-terminal pyrin effector domain (PYD), a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). Members of this gene family are thought to be important regulators of immune responses. This gene product interacts with components of the IkB kinase (IKK) complex, and can regulate both caspase-1 and NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity. The pyrin domain is necessary and sufficient for suppression of NF-kB activity. An allelic variant (rs147585490) has been found that is incapable of blocking the transcriptional activity of NF-kB. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]
- NALP2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~48.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0957230
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0957230
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Obstetric
Intervention: Obstetric
Rationale: Some individuals have been described as able to achieve successful pregnancies using IVF
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NLRP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017852.5. 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 | 7 | 59 | 5 | 71 | ||
| missense | 1 | 2 | 211 | 40 | 12 | 266 |
| nonsense | 2 | 1 | 8 | 11 | ||
| start loss | 0 | |||||
| frameshift | 1 | 13 | 14 | |||
| splice donor/acceptor (+/-2bp) | 1 | 8 | 9 | |||
| Total | 3 | 5 | 247 | 99 | 17 | 371 |
Highest pathogenic variant AF is 0.0005403938
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060322.1 | 12 | MANE Select | |
| Ensembl | ENSP00000409370.2 | 12 | MANE Select | |
| RefSeq | NP_001167552.1 | 12 | Standard | |
| RefSeq | NP_001167553.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nucleotide-binding Oligomerization Domain (NOD) pathway
Biological Process
- apoptotic process
- inflammatory response
- negative regulation of NF-kappaB transcription factor activity
- positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
- innate immune response
Molecular Function
- protein binding
- ATP binding
- Pyrin domain binding
Cellular Component
- nuclear chromosome, telomeric region
- cytoplasm
- Golgi apparatus
- cytosol
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000543010
- Coding exons
- 12
- Length
- 48013
- Individuals with no LoFs
- 125464
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 283
- Defined
- 125748
- p
- 0.00113
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -2.35 | 750 | 590 | 1.27 | 0.0000373 | 6952 |
| Missense (PolyPhen) | 183 | 161.88 | 1.1304 | 2158 | ||
| Synonymous | -4.82 | 360 | 261 | 1.38 | 0.0000188 | 2086 |
| Loss of Function | -1.13 | 53 | 44.8 | 1.18 | 0.00000264 | 505 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0015 | 0.0013 | notable |
| Latino/Admixed American | 0.00084 | 0.00084 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0.00065 | 0.00065 | rare |
| European (Non-Finnish) | 0.0013 | 0.0013 | notable |
| South Asian | 0.0018 | 0.0017 | notable |
| Other | 0.00098 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Suppresses TNF- and CD40-induced NFKB1 activity at the level of the IKK complex, by inhibiting NFKBIA degradation induced by TNF. When associated with PYCARD, activates CASP1, leading to the secretion of mature proinflammatory cytokine IL1B. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and CASP1 and whose function would be the activation of proinflammatory caspases. {ECO:0000269|PubMed:15456791}.;
Recessive Scores
- pRec
- 0.128
Intolerance Scores
- LoFtool
- 0.955
- RVIS EVS
- 1.2
- RVIS percentile EVS
- 92.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.827
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |