PWP1
protein-codingPWP1 homolog, endonuclein, the group of WD repeat domain containing
Gene summary
The protein encoded by this gene contains several WD-40 repeats and is found mostly in the nucleus. The expression and localization of this protein are cell cycle dependent. Expression of this gene is upregulated in pancreatic adenocarcinoma. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~27.4 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 PWP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007062.3. 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 | 1 | 1 | ||||
| missense | 56 | 56 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 61 | 0 | 0 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008993.1 | 15 | MANE Select | |
| Ensembl | ENSP00000387365.3 | 15 | MANE Select | |
| RefSeq | NP_001304891.1 | 13 | Standard | |
| RefSeq | NP_001304892.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- miR-targeted genes in squamous cell - TarBase
Biological Process
- transcription, DNA-templated
- negative regulation of peptidyl-serine phosphorylation of STAT protein
- histone H4-K20 trimethylation
- ribosome biogenesis
- positive regulation of transcription of nucleolar large rRNA by RNA polymerase I
Molecular Function
- H4K20me3 modified histone binding
Cellular Component
- nucleus
- chromosome
- nucleolus
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000412830
- Coding exons
- 15
- Length
- 27436
- Individuals with no LoFs
- 125569
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 178
- Defined
- 125747
- p
- 0.000708
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.28 | 217 | 277 | 0.784 | 0.0000141 | 3311 |
| Missense (PolyPhen) | 49 | 70.546 | 0.69458 | 857 | ||
| Synonymous | -0.0916 | 98 | 96.9 | 1.01 | 0.00000504 | 912 |
| Loss of Function | 1.51 | 23 | 32.3 | 0.713 | 0.00000169 | 363 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0049 | 0.0048 | notable |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00071 | 0.00071 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00044 | 0.00044 | rare |
| South Asian | 0.00070 | 0.00069 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Chromatin-associated factor that regulates transcription (PubMed:29065309). Regulates Pol I-mediated rRNA biogenesis and, probably, Pol III-mediated transcription (PubMed:29065309). Regulates the epigenetic status of rDNA (PubMed:29065309). {ECO:0000269|PubMed:29065309}.;
Intolerance Scores
- LoFtool
- 0.923
- RVIS EVS
- -0.04
- RVIS percentile EVS
- 50.45
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.943
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |