PIWIL4
protein-codingpiwi like RNA-mediated gene silencing 4, the group of Piwi like RNA-mediated gene silencing family
Gene summary
PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~77.6 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 PIWIL4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152431.3. 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 | 3 | 5 | 2 | 10 | ||
| missense | 100 | 11 | 2 | 113 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 104 | 16 | 4 | 124 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689644.2 | 20 | MANE Select | |
| Ensembl | ENSP00000299001.6 | 20 | MANE Select | |
| Ensembl | ENSP00000413838.2 | 13 | Standard | |
| Ensembl | ENSP00000439710.1 | 4 | Standard |
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
- negative regulation of transposition
- epithelial structure maintenance
Molecular Function
- endoribonuclease activity
- piRNA binding
Cellular Component
- nucleus
- cytoplasm
- P granule
- piP-body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000299001
- Coding exons
- 20
- Length
- 77582
- Individuals with no LoFs
- 125690
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 57
- Defined
- 125748
- p
- 0.000231
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.49 | 377 | 468 | 0.806 | 0.0000248 | 5578 |
| Missense (PolyPhen) | 79 | 109.26 | 0.72306 | 1269 | ||
| Synonymous | 1.14 | 151 | 170 | 0.889 | 0.00000911 | 1587 |
| Loss of Function | 3.79 | 18 | 45.6 | 0.395 | 0.00000217 | 562 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00086 | 0.00086 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00061 | 0.00056 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (By similarity). 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 (By similarity). 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 (By similarity). Associates with secondary piRNAs antisense and PIWIL2/MILI is required for such association (By similarity). The piRNA process acts upstream of known mediators of DNA methylation (By similarity). Does not show endonuclease activity (By similarity). Plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle, by acting as a 'slicer-incompetent' component that loads cleaved piRNAs from the 'slicer-competent' component PIWIL2 and target them on genomic transposon loci in the nucleus (By similarity). May be involved in the chromatin-modifying pathway by inducing 'Lys-9' methylation of histone H3 at some loci (PubMed:17544373). {ECO:0000250|UniProtKB:Q8CGT6, ECO:0000269|PubMed:17544373}.;
Recessive Scores
- pRec
- 0.0924
Intolerance Scores
- LoFtool
- 0.789
- RVIS EVS
- 1.27
- RVIS percentile EVS
- 93.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.771
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |