PAWR
protein-codingpro-apoptotic WT1 regulator
Gene summary
This gene encodes a tumor suppressor protein that selectively induces apoptosis in cancer cells through intracellular and extracellular mechanisms. The intracellular mechanism involves the inhibition of pro-survival pathways and the activation of Fas-mediated apoptosis, while the extracellular mechanism involves the binding of a secreted form of this protein to glucose regulated protein 78 (GRP78) on the cell surface, which leads to activation of the extrinsic apoptotic pathway. This gene is located on the unstable human chromosomal 12q21 region and is often deleted or mutated different tumors. The encoded protein also plays an important role in the progression of age-related diseases. [provided by RefSeq, Aug 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~116.0 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 PAWR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002583.4. 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 | 2 | 1 | 3 | |||
| missense | 40 | 40 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 43 | 0 | 1 | 44 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002574.2 | 6 | MANE Select | |
| Ensembl | ENSP00000328088.4 | 6 | MANE Select | |
| RefSeq | NP_001341661.1 | 6 | Standard | |
| RefSeq | NP_001341662.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Coregulation of Androgen receptor activity
- Ceramide signaling pathway
Biological Process
- negative regulation of transcription by RNA polymerase II
- apoptotic process
- positive regulation of gene expression
- negative regulation of B cell proliferation
- interleukin-2 biosynthetic process
Molecular Function
- transcription corepressor activity
- actin binding
- protein binding
- enzyme binding
- leucine zipper domain binding
Cellular Component
- nuclear chromatin
- nucleus
- cytoplasm
- actin filament
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000328827
- Coding exons
- 6
- Length
- 116119
- Individuals with no LoFs
- 125662
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125666
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.495 | 117 | 133 | 0.879 | 0.00000623 | 2138 |
| Missense (PolyPhen) | 45 | 60.504 | 0.74375 | 908 | ||
| Synonymous | -0.666 | 59 | 52.8 | 1.12 | 0.00000250 | 693 |
| Loss of Function | 2.31 | 4 | 13.0 | 0.307 | 7.13e-7 | 175 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000019 | 0.000018 | rare |
| South Asian | 0.000082 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Pro-apoptopic protein capable of selectively inducing apoptosis in cancer cells, sensitizing the cells to diverse apoptotic stimuli and causing regression of tumors in animal models. Induces apoptosis in certain cancer cells by activation of the Fas prodeath pathway and coparallel inhibition of NF-kappa-B transcriptional activity. Inhibits the transcriptional activation and augments the transcriptional repression mediated by WT1. Down- regulates the anti-apoptotic protein BCL2 via its interaction with WT1. Seems also to be a transcriptional repressor by itself. May be directly involved in regulating the amyloid precursor protein (APP) cleavage activity of BACE1. {ECO:0000269|PubMed:11585763}.;
Recessive Scores
- pRec
- 0.291
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.894
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |