WWC1
protein-codingWW and C2 domain containing 1, the group of WWC family|Protein phosphatase 1 regulatory subunits|C2 and WW domain containing
Gene summary
The protein encoded by this gene is a cytoplasmic phosphoprotein that interacts with PRKC-zeta and dynein light chain-1. Alleles of this gene have been found that enhance memory in some individuals. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~180.7 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 WWC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015238.3. 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 | 4 | 4 | 8 | |||
| missense | 165 | 4 | 2 | 171 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 171 | 8 | 6 | 185 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056053.1 | 23 | MANE Select | |
| Ensembl | ENSP00000265293.4 | 23 | MANE Select | |
| RefSeq | NP_001155133.1 | 23 | Standard | |
| RefSeq | NP_001155134.1 | 23 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| wwc1 | Danio rerio | Structure: otolith Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Hippo signaling pathway - Homo sapiens (human)
- Hippo signaling pathway - multiple species - Homo sapiens (human)
- Signal Transduction
- NOTCH3 Intracellular Domain Regulates Transcription
- Signaling by NOTCH3
Biological Process
- negative regulation of transcription by RNA polymerase II
- positive regulation of transcription of Notch receptor target
- cell migration
- establishment of cell polarity
- regulation of intracellular transport
Molecular Function
- transcription coactivator activity
- protein binding
- kinase binding
- protein-containing complex scaffold activity
Cellular Component
- nucleus
- cytoplasm
- cytosol
- ruffle membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000521089
- Coding exons
- 23
- Length
- 180653
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125747
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.56 | 553 | 666 | 0.830 | 0.0000408 | 7222 |
| Missense (PolyPhen) | 192 | 263.11 | 0.72972 | 2892 | ||
| Synonymous | -0.125 | 271 | 268 | 1.01 | 0.0000160 | 2222 |
| Loss of Function | 5.24 | 19 | 64.4 | 0.295 | 0.00000355 | 693 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00041 | 0.00030 | rare |
| East Asian | 0.00022 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with NF2 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. Acts as a transcriptional coactivator of ESR1 which plays an essential role in DYNLL1-mediated ESR1 transactivation. Regulates collagen-stimulated activation of the ERK/MAPK cascade. Modulates directional migration of podocytes. Acts as a substrate for PRKCZ. Plays a role in cognition and memory performance. {ECO:0000269|PubMed:15081397, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:18596123, ECO:0000269|PubMed:18672031, ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:23778582}.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- LoFtool
- 0.682
- RVIS EVS
- -1.83
- RVIS percentile EVS
- 2.12
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.853
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |