NLRP9
protein-codingNLR family pyrin domain containing 9, the group of NLR family|Pyrin domain containing
Gene summary
The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). This protein may play a regulatory role in the innate immune system as similar family members belong to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5. [provided by RefSeq, Jul 2008]
- NALP9
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.0 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 NLRP9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_176820.4. 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 | 2 | 4 | 5 | 11 | ||
| missense | 144 | 15 | 3 | 162 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 146 | 20 | 8 | 174 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_789790.2 | 9 | MANE Select | |
| Ensembl | ENSP00000331857.2 | 9 | MANE Select | |
| Ensembl | ENSP00000465253.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- inflammatory response
- positive regulation of interleukin-18 production
- innate immune response
- defense response to virus
- pyroptosis
Molecular Function
- protein binding
- ATP binding
Cellular Component
- inflammasome complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000332836
- Coding exons
- 9
- Length
- 29971
- Individuals with no LoFs
- 125314
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 432
- Defined
- 125748
- p
- 0.00173
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.643 | 564 | 523 | 1.08 | 0.0000269 | 6555 |
| Missense (PolyPhen) | 114 | 120.71 | 0.94437 | 1771 | ||
| Synonymous | -1.66 | 244 | 213 | 1.14 | 0.0000125 | 1845 |
| Loss of Function | 0.0291 | 37 | 37.2 | 0.995 | 0.00000191 | 492 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0023 | 0.0022 | notable |
| Latino/Admixed American | 0.0016 | 0.0016 | notable |
| Ashkenazi Jewish | 0.0023 | 0.0023 | notable |
| East Asian | 0.0044 | 0.0043 | notable |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.0012 | 0.0012 | notable |
| South Asian | 0.0032 | 0.0030 | notable |
| Other | 0.0012 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: As the sensor component of the NLRP9 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens, including rotavirus, initiates the formation of the inflammasome polymeric complex, made of NLRP9, PYCARD and CASP1. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and release in the extracellular milieu. The active cytokines stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. NLRP9 inflammasome activation may be initiated by DHX9 interaction with viral double-stranded RNA (dsRNA), preferentially to short dsRNA segments. {ECO:0000269|PubMed:28636595}.;
Recessive Scores
- pRec
- 0.0823
Intolerance Scores
- LoFtool
- 0.693
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 45.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0987
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |