WWTR1
WW domain containing transcription regulator 1
Basic information
Region (hg38): 3:149517235-149736714
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (38 variants)
- not_provided (9 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the WWTR1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015472.6. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | |||||
| missense | 41 | 41 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 41 | 5 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| WWTR1 | protein_coding | protein_coding | ENST00000465804 | 6 | 219480 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.939 | 0.0609 | 125742 | 0 | 3 | 125745 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.12 | 180 | 227 | 0.792 | 0.0000115 | 2618 |
| Missense in Polyphen | 42 | 74.206 | 0.56599 | 862 | ||
| Synonymous | -0.00992 | 94 | 93.9 | 1.00 | 0.00000499 | 787 |
| Loss of Function | 3.46 | 2 | 17.7 | 0.113 | 8.75e-7 | 170 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation. Regulates the nuclear accumulation of SMADS and has a key role in coupling them to the transcriptional machinery such as the mediator complex. Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition. {ECO:0000269|PubMed:11118213, ECO:0000269|PubMed:18227151, ECO:0000269|PubMed:18568018, ECO:0000269|PubMed:19010321}.;
- Pathway
- Hippo signaling pathway - Homo sapiens (human);Hippo signaling pathway - multiple species - Homo sapiens (human);Adipogenesis;RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;YAP1- and WWTR1 (TAZ)-stimulated gene expression;SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription;TGF_beta_Receptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;Signaling by Hippo;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members
(Consensus)
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- loftool
- 0.303
- rvis_EVS
- 0.13
- rvis_percentile_EVS
- 63
Haploinsufficiency Scores
- pHI
- 0.644
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.513
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Wwtr1
- Phenotype
- liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype;
Zebrafish Information Network
- Gene name
- wwtr1
- Affected structure
- compact layer of ventricle
- Phenotype tag
- abnormal
- Phenotype quality
- oblique orientation
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;osteoblast differentiation;tissue homeostasis;negative regulation of protein phosphorylation;heart process;regulation of transcription, DNA-templated;transcription initiation from RNA polymerase II promoter;negative regulation of protein kinase activity;positive regulation of cell population proliferation;positive regulation of epithelial to mesenchymal transition;protein ubiquitination;stem cell division;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;glomerulus development;multicellular organism growth;hippo signaling;negative regulation of fat cell differentiation;positive regulation of transcription by RNA polymerase II;mesenchymal cell differentiation;cilium assembly;regulation of SMAD protein signal transduction;kidney morphogenesis;regulation of metanephric nephron tubule epithelial cell differentiation;negative regulation of canonical Wnt signaling pathway
- Cellular component
- nucleus;nucleoplasm;transcription factor complex;cytoplasm;cytosol;nuclear body
- Molecular function
- transcription coactivator activity;transcription corepressor activity;protein binding;protein homodimerization activity