PIWIL1
protein-codingpiwi like RNA-mediated gene silencing 1, the group of Piwi like RNA-mediated gene silencing family
Gene summary
This gene encodes a member of the PIWI subfamily of Argonaute proteins, evolutionarily conserved proteins containing both PAZ and Piwi motifs that play important roles in stem cell self-renewal, RNA silencing, and translational regulation in diverse organisms. The encoded protein may play a role as an intrinsic regulator of the self-renewal capacity of germline and hematopoietic stem cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.8 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 PIWIL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004764.5. 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 | 1 | 8 | 4 | 13 | ||
| missense | 86 | 3 | 89 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 87 | 11 | 4 | 103 |
Highest pathogenic variant AF is 0.00003107246
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004755.2 | 20 | MANE Select | |
| Ensembl | ENSP00000245255.3 | 20 | MANE Select | |
| RefSeq | NP_001177900.1 | 19 | Standard | |
| Ensembl | ENSP00000444353.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| piwil1 | Danio rerio | Structure: germ line cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- PIWI-interacting RNA (piRNA) biogenesis
- Gene Silencing by RNA
Biological Process
- regulation of translation
- multicellular organism development
- spermatogenesis
- spermatid development
- negative regulation of transposition
Molecular Function
- single-stranded RNA binding
- mRNA binding
- endoribonuclease activity
- protein binding
- protein kinase binding
Cellular Component
- nucleus
- cytoplasm
- chromatoid body
- P granule
- dense body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000245255
- Coding exons
- 20
- Length
- 34751
- Individuals with no LoFs
- 125684
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 64
- Defined
- 125748
- p
- 0.000255
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.90 | 310 | 491 | 0.631 | 0.0000273 | 5631 |
| Missense (PolyPhen) | 99 | 183.43 | 0.53972 | 2138 | ||
| Synonymous | -0.249 | 179 | 175 | 1.02 | 0.00000976 | 1631 |
| Loss of Function | 2.92 | 30 | 53.0 | 0.567 | 0.00000303 | 585 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00033 | 0.00033 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Endoribonuclease that plays a central role in postnatal germ cells 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 governs the methylation and subsequent repression of transposons. Directly binds methylated 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. Strongly prefers a uridine in the first position of their guide (g1U preference, also named 1U-bias). Not involved in the piRNA amplification loop, also named ping-pong amplification cycle. Acts as an endoribonuclease that cleaves transposon messenger RNAs. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Probable component of some RISC complex, which mediates RNA cleavage and translational silencing. Also plays a role in the formation of chromatoid bodies and is required for some miRNAs stability. Required to sequester RNF8 in the cytoplasm until late spermatogenesis; RNF8 being released upon ubiquitination and degradation of PIWIL1. {ECO:0000250|UniProtKB:Q9JMB7}.;
- Disease
- DISEASE: Note=Defects in PIWIL1 may be a cause of a disorder resulting in the absence of sperm (azoospermia) in the semen, leading to male infertility. Male sterility can be caused by defects in ubiquitination and degradation during late spermatogenesis. {ECO:0000269|PubMed:28552346}.;
Recessive Scores
- pRec
- 0.0992
Intolerance Scores
- LoFtool
- 0.822
- RVIS EVS
- -0.46
- RVIS percentile EVS
- 23.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.537
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |