NLRP7
protein-codingNLR family pyrin domain containing 7, the group of Pyrin domain containing|NLR family
Gene summary
This gene encodes a member of the NACHT, leucine rich repeat, and PYD containing (NLRP) protein family. It has an N-terminal pyrin domain, followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region. NLRP proteins are implicated in the activation of proinflammatory caspases through multiprotein complexes called inflammasomes. This gene may act as a feedback regulator of caspase-1-dependent interleukin 1-beta secretion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
- NALP7
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~42.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0016785
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009273
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009273
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Obstetric; Oncologic
Intervention: Obstetric; Oncologic
Rationale: Women are likely to have pregnancies with hydatidiform moles, with a high risk of persistent trophoblastic disease, including requiring chemotherapeutic treatment, and awareness may allow reproductive planning and/or surveillance measures, which may allow early detection and treatment
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NLRP7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001127255.2. 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 | 31 | 21 | 52 | |||
| missense | 7 | 7 | 185 | 30 | 1 | 230 |
| nonsense | 3 | 6 | 9 | |||
| start loss | 0 | |||||
| frameshift | 4 | 7 | 5 | 16 | ||
| splice donor/acceptor (+/-2bp) | 1 | 4 | 3 | 8 | ||
| Total | 15 | 18 | 230 | 51 | 1 | 315 |
Highest pathogenic variant AF is 0.0002013723
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001120727.1 | 10 | MANE Select | |
| Ensembl | ENSP00000468706.1 | 10 | MANE Select | |
| RefSeq | NP_001392460.1 | 10 | Standard | |
| RefSeq | NP_631915.2 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- NOD-like receptor signaling pathway - Homo sapiens (human)
- Nucleotide-binding Oligomerization Domain (NOD) pathway
Biological Process
- negative regulation of endopeptidase activity
- negative regulation of protein processing
- negative regulation of interleukin-1 beta secretion
- positive regulation of interleukin-1 beta secretion
- cellular response to lipopolysaccharide
Molecular Function
- ATP binding
- aspartic-type endopeptidase inhibitor activity
- interleukin-1 binding
- caspase binding
Cellular Component
- cellular_component
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000588756
- Coding exons
- 10
- Length
- 42804
- Individuals with no LoFs
- 125618
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 130
- Defined
- 125748
- p
- 0.000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.510 | 613 | 579 | 1.06 | 0.0000365 | 6811 |
| Missense (PolyPhen) | 138 | 134.81 | 1.0237 | 1813 | ||
| Synonymous | -2.81 | 310 | 253 | 1.22 | 0.0000180 | 2018 |
| Loss of Function | 1.47 | 30 | 40.0 | 0.750 | 0.00000194 | 482 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00098 | 0.00062 | rare |
| Latino/Admixed American | 0.00055 | 0.00055 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.0013 | 0.0013 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00044 | 0.00044 | rare |
| South Asian | 0.00062 | 0.00062 | rare |
| Other | 0.00098 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibits CASP1/caspase-1-dependent IL1B secretion. {ECO:0000269|PubMed:15817483}.;
- Disease
- DISEASE: Hydatidiform mole, recurrent, 1 (HYDM1) [MIM:231090]: A disorder characterized by excessive trophoblast development that produces a growing mass of tissue inside the uterus at the beginning of a pregnancy. It leads to abnormal pregnancies with no embryo, and cystic degeneration of the chorionic villi. {ECO:0000269|PubMed:16462743, ECO:0000269|PubMed:19246479}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.121
Intolerance Scores
- LoFtool
- 0.900
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.12
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.108
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |