WWP1
protein-codingWW domain containing E3 ubiquitin protein ligase 1, the group of C2 and WW domain containing|HECT domain containing
Gene summary
WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 4 tandem WW domains and a HECT (homologous to the E6-associated protein carboxyl terminus) domain. The encoded protein belongs to a family of NEDD4-like proteins, which are E3 ubiquitin-ligase molecules and regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Alternative splicing of this gene generates at least 6 transcript variants; however, the full length nature of these transcripts has not been defined. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~135.9 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 WWP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007013.4. 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 | 1 | 2 | 3 | |||
| missense | 57 | 2 | 59 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 68 | 4 | 0 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008944.1 | 23 | MANE Select | |
| Ensembl | ENSP00000427793.1 | 23 | MANE Select | |
| Ensembl | ENSP00000265428.4 | 23 | Standard | |
| Ensembl | ENSP00000429076.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- TGF-Ncore
- TGF-beta Signaling Pathway
- Transcriptional regulation by RUNX2
Biological Process
- protein polyubiquitination
- ubiquitin-dependent protein catabolic process
- signal transduction
- central nervous system development
- protein ubiquitination
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- ubiquitin protein ligase activity
Cellular Component
- ubiquitin ligase complex
- nucleus
- cytoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000517970
- Coding exons
- 23
- Length
- 135683
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125748
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.81 | 315 | 490 | 0.643 | 0.0000256 | 6038 |
| Missense (PolyPhen) | 96 | 224.19 | 0.42821 | 2829 | ||
| Synonymous | 0.247 | 163 | 167 | 0.976 | 0.00000859 | 1679 |
| Loss of Function | 6.10 | 8 | 58.2 | 0.137 | 0.00000294 | 693 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000067 | 0.000054 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00015 | 0.00013 | rare |
| Other | 0.00019 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Ubiquitinates ERBB4 isoforms JM-A CYT-1 and JM-B CYT-1, KLF2, KLF5 and TP63 and promotes their proteasomal degradation. Ubiquitinates RNF11 without targeting it for degradation. Ubiquitinates and promotes degradation of TGFBR1; the ubiquitination is enhanced by SMAD7. Ubiquitinates SMAD6 and SMAD7. Ubiquitinates and promotes degradation of SMAD2 in response to TGF-beta signaling, which requires interaction with TGIF. {ECO:0000269|PubMed:12535537, ECO:0000269|PubMed:15221015, ECO:0000269|PubMed:15359284}.;
Recessive Scores
- pRec
- 0.142
Intolerance Scores
- LoFtool
- 0.389
- RVIS EVS
- -0.69
- RVIS percentile EVS
- 15.12
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |