WWTR1
protein-codingWW domain containing transcription regulator 1
Gene summary
Enables transcription coactivator activity. Involved in several processes, including intracellular signal transduction; negative regulation of canonical Wnt signaling pathway; and positive regulation of cell differentiation. Located in cytosol and nuclear body. Is active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~219.5 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 WWTR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015472.6. 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 | 5 | 5 | ||||
| missense | 44 | 44 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 50 | 5 | 0 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056287.1 | 6 | MANE Select | |
| Ensembl | ENSP00000353847.3 | 6 | MANE Select | |
| RefSeq | NP_001161750.1 | 6 | Standard | |
| RefSeq | NP_001161752.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| wwtr1 | Danio rerio | Structure: compact layer of ventricle Quality: oblique orientation 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)
- Adipogenesis
- RUNX2 regulates osteoblast differentiation
- RUNX2 regulates bone development
Biological Process
- negative regulation of transcription by RNA polymerase II
- osteoblast differentiation
- tissue homeostasis
- negative regulation of protein phosphorylation
- heart process
Molecular Function
- transcription coactivator activity
- transcription corepressor activity
- protein binding
- protein homodimerization activity
Cellular Component
- nucleus
- nucleoplasm
- transcription factor complex
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000465804
- Coding exons
- 6
- Length
- 219480
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125745
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.12 | 180 | 227 | 0.792 | 0.0000115 | 2618 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
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}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.303
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |