NLRP5
protein-codingNLR family pyrin domain containing 5, the group of Subcortical maternal complex|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). Expression of this gene is restricted to the oocyte. A mouse gene that encodes a maternal oocyte protein, similar to this encoded protein, is required for normal early embryogenesis. [provided by RefSeq, Jul 2008]
- NALP5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~62.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0007534
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0957231
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0957231
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Obstetric
Intervention: General
Rationale: Some individuals have been described as able to achieve successful pregnancies using IVF
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NLRP5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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 | 33 | 9 | 42 | |||
| missense | 106 | 35 | 4 | 145 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 2 | 1 | 107 | 68 | 13 | 191 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| Ensembl | ENSP00000375063.3 | 15 | MANE Select | |
| RefSeq | NP_001420634.1 | 14 | Standard | |
| Ensembl | ENSP00000471494.1 | 4 | Standard | |
| Ensembl | ENSP00000521055.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Preimplantation Embryo
Molecular Function
- ATP binding
Cellular Component
- nucleolus
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000390649
- Coding exons
- 15
- Length
- 62088
- Individuals with no LoFs
- 124515
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 164
- Defined
- 124679
- p
- 0.000658
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -2.21 | 863 | 698 | 1.24 | 0.0000419 | 7801 |
| Missense (PolyPhen) | 170 | 156.76 | 1.0845 | 2141 | ||
| Synonymous | -3.90 | 381 | 296 | 1.29 | 0.0000194 | 2395 |
| Loss of Function | 2.73 | 29 | 49.8 | 0.583 | 0.00000253 | 577 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00058 | 0.00058 | rare |
| Latino/Admixed American | 0.00044 | 0.00043 | rare |
| Ashkenazi Jewish | 0.0012 | 0.0012 | notable |
| East Asian | 0.00056 | 0.00056 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00077 | 0.00077 | rare |
| South Asian | 0.00075 | 0.00075 | rare |
| Other | 0.0012 | 0.0012 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: As a member of the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions. {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.504
- RVIS EVS
- 0.18
- RVIS percentile EVS
- 66.14
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.109
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |