PIWIL3
protein-codingpiwi like RNA-mediated gene silencing 3, the group of Piwi like RNA-mediated gene silencing family
Gene summary
This gene encodes a member of the PIWI subfamily of Argonaute family proteins. This subfamily of proteins contains a PAZ domain, found in proteins involved in RNA-mediated gene silencing, and a C-terminal Piwi domain. The encoded protein is thought to function in maintenance of germline cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~55.7 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 PIWIL3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001255975.1. 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 | 1 | 1 | 2 | |||
| missense | 133 | 12 | 3 | 148 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 134 | 12 | 4 | 150 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001242904.1 | 20 | MANE Select | |
| Ensembl | ENSP00000479524.2 | 20 | MANE Select | |
| RefSeq | NP_001008496.2 | 20 | Standard | |
| Ensembl | ENSP00000330031.5 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of translation
- multicellular organism development
- spermatogenesis
- cell differentiation
- gene silencing by RNA
Molecular Function
- RNA binding
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000332271
- Coding exons
- 20
- Length
- 55687
- Individuals with no LoFs
- 123424
- Homozygous LoFs
- 7
- Heterozygous LoFs
- 2317
- Defined
- 125748
- p
- 0.00928
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0134 | 499 | 498 | 1.00 | 0.0000276 | 5744 |
| Missense (PolyPhen) | 121 | 142.25 | 0.85059 | 1783 | ||
| Synonymous | 0.337 | 172 | 178 | 0.968 | 0.00000983 | 1667 |
| Loss of Function | 0.235 | 49 | 50.8 | 0.964 | 0.00000275 | 599 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.013 | 0.013 | notable |
| Latino/Admixed American | 0.012 | 0.012 | notable |
| Ashkenazi Jewish | 0.0025 | 0.0025 | notable |
| East Asian | 0.0077 | 0.0077 | notable |
| Finnish | 0.0021 | 0.0021 | notable |
| European (Non-Finnish) | 0.011 | 0.011 | notable |
| South Asian | 0.0070 | 0.0069 | notable |
| Other | 0.010 | 0.010 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (By similarity). {ECO:0000250|UniProtKB:Q9JMB7}.;
Recessive Scores
- pRec
- 0.0854
Intolerance Scores
- LoFtool
- 0.996
- RVIS EVS
- 2.43
- RVIS percentile EVS
- 98.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.757
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |