<div class="infobox infobox-gene">
<h3>WWTR1 (TAZ)</h3>
<table>
<tr><td><strong>Full Name</strong></td><td>WW Domain Containing Transcription Regulator 1</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>WWTR1 (TAZ)</td></tr> [@mao2021]
<tr><td><strong>Chromosomal Location</strong></td><td>3q25.1</td></tr> [@dupont2011]
<tr><td><strong>NCBI Gene ID</strong></td><td>[25937](https://www.ncbi.nlm.nih.gov/gene/25937)</td></tr> [@panciera2017]
<tr><td><strong>OMIM</strong></td><td>[607392](https://omim.org/entry/607392)</td></tr> [@rao2018]
<tr><td><strong>Ensembl</strong></td><td>[ENSG00000018408](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000018408)</td></tr> [@fan2022]
<tr><td><strong>UniProt (Protein)</strong></td><td>[Q9GZV5 (WW domain-containing transcription regulator 1)](https://www.uniprot.org/uniprot/Q9GZV5)</td></tr> [@zheng2019]
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis), Glioblastoma</td></tr>
</table>
</div>
<div class="infobox infobox-gene">
<h3>WWTR1 (TAZ)</h3>
<table>
<tr><td><strong>Full Name</strong></td><td>WW Domain Containing Transcription Regulator 1</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>WWTR1 (TAZ)</td></tr> [@mao2021]
<tr><td><strong>Chromosomal Location</strong></td><td>3q25.1</td></tr> [@dupont2011]
<tr><td><strong>NCBI Gene ID</strong></td><td>[25937](https://www.ncbi.nlm.nih.gov/gene/25937)</td></tr> [@panciera2017]
<tr><td><strong>OMIM</strong></td><td>[607392](https://omim.org/entry/607392)</td></tr> [@rao2018]
<tr><td><strong>Ensembl</strong></td><td>[ENSG00000018408](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000018408)</td></tr> [@fan2022]
<tr><td><strong>UniProt (Protein)</strong></td><td>[Q9GZV5 (WW domain-containing transcription regulator 1)](https://www.uniprot.org/uniprot/Q9GZV5)</td></tr> [@zheng2019]
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis), Glioblastoma</td></tr>
</table>
</div>
WWTR1 (WW Domain Containing Transcription Regulator 1), commonly known as TAZ (transcriptional co-activator with PDZ-binding motif), encodes a 400 amino acid transcriptional co-activator that functions as a central effector of the Hippo signaling pathway. TAZ is the paralog of [YAP1](/genes/yap1), and together they constitute the primary nuclear output of Hippo signaling. When the Hippo pathway is inactive (low [LATS1](/genes/lats1)/[LATS2](/genes/lats2) activity), TAZ accumulates in the nucleus, where it binds TEAD transcription factors and drives expression of genes controlling proliferation, survival, stemness, and mechanotransduction. In the nervous system, TAZ plays critical roles in astrocyte reactivity, neural stem cell maintenance, oligodendrocyte myelination, and neuronal survival, with its dysregulation increasingly linked to neurodegeneration and brain tumors.
Note: WWTR1/TAZ should not be confused with TAFAZZIN (also abbreviated TAZ), encoded by the TAFAZZIN gene on the X chromosome, which is involved in cardiolipin remodeling and Barth syndrome.
WWTR1 spans approximately 100 kb on chromosome 3q25.1 and contains 7 exons. The promoter is regulated by multiple transcription factors including [CREB](/genes/creb1), AP-1 ([FOS](/genes/fos)/[JUN](/genes/jun)), and TEADs themselves (creating a positive autoregulatory loop). Epigenetic regulation via [HDAC](/genes/hdac1)-mediated deacetylation and [DNA methylation](/entities/dna-methylation) modulates TAZ expression in a tissue-specific manner.
In the developing brain, TAZ is broadly expressed in neural progenitor cells, with high levels in the ventricular zone and subventricular zone. In the adult brain, TAZ expression is prominent in [astrocytes](/cell-types/astrocytes), [oligodendrocytes](/cell-types/oligodendrocytes), and [neural stem cells](/cell-types/neural-stem-cells) of the SVZ and SGZ, with lower but detectable levels in mature [neurons](/entities/neurons). The [Allen Brain Atlas](https://human.brain-map.org/) shows moderate expression across the [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and white matter tracts, with enrichment in glia-rich regions.
TAZ is a 400 amino acid protein containing a TEAD-binding domain (TBD) at the N-terminus, a single WW domain that recognizes PPxY motifs, a coiled-coil domain, a transcriptional activation domain (TAD), and a C-terminal PDZ-binding motif (absent in YAP). These structural features enable TAZ to integrate upstream Hippo signals with diverse transcriptional programs.
TAZ lacks intrinsic DNA-binding ability and functions exclusively as a transcriptional co-activator. Its primary transcription factor partners are the TEAD family (TEAD1-4), with additional interactions with:
TAZ activity is controlled by a phosphorylation-dependent cytoplasmic–nuclear shuttling mechanism:
TAZ is a critical mechanosensor that translates extracellular matrix (ECM) stiffness into transcriptional responses. On stiff substrates, cytoskeletal tension through actomyosin contractility (Rho–ROCK pathway) inhibits LATS1/2 and promotes TAZ nuclear entry. On soft substrates (mimicking the soft brain parenchyma), LATS1/2 are active and TAZ is excluded from the nucleus. This mechanosensing function is particularly relevant in the brain, where:
While TAZ and [YAP1](/genes/yap1) share ~50% sequence identity and are often functionally redundant, important differences exist:
TAZ plays distinctive roles in glial cell biology and neural development:
TAZ is dysregulated in [AD](/diseases/alzheimers-disease) in a cell-type-specific manner. In hippocampal neurons, [Aβ](/proteins/amyloid-beta)-induced oxidative stress activates the MST1–LATS1 cascade, leading to TAZ phosphorylation and degradation. Loss of nuclear TAZ deprives neurons of TEAD-dependent survival gene expression, contributing to [apoptosis](/entities/apoptosis). In reactive astrocytes surrounding amyloid plaques, however, TAZ is paradoxically upregulated — driven by ECM stiffening from plaque deposition and [TGF-β](/genes/tgfb1) signaling. Astrocytic nuclear TAZ drives the reactive astrogliosis program but may have both protective (scar formation, Aβ phagocytosis) and detrimental (chronic inflammation, synaptic stripping) consequences depending on disease stage.
[Tau](/genes/mapt) pathology further perturbs TAZ signaling: neurofibrillary tangles disrupt cytoskeletal tension and mechanotransduction, leading to aberrant TAZ activation in tangle-bearing neurons. TAZ overexpression in [tau](/proteins/tau)-expressing neuronal models modulates [GSK-3β](/genes/gsk3b) activity and paradoxically reduces tau phosphorylation at certain epitopes (AT8, PHF-1), suggesting a complex feedback relationship.
In [PD](/diseases/parkinsons-disease) models, [α-synuclein](/entities/snca) aggregation activates MST1, which phosphorylates LATS1/2 and leads to TAZ degradation in dopaminergic neurons. TAZ loss impairs mitochondrial quality control by reducing transcription of mitophagy regulators, exacerbating the [PINK1](/genes/pink1)/[Parkin](/genes/prkn) pathway deficiency characteristic of PD. Astrocytic TAZ is protective in PD: TAZ-positive reactive astrocytes in the substantia nigra upregulate [GDNF](/genes/gdnf) and [BDNF](/genes/bdnf), providing trophic support to surviving dopaminergic neurons. Conditional TAZ deletion in astrocytes worsens MPTP-induced dopaminergic neuron loss in mice.
TAZ expression is reduced in motor neurons of [ALS](/diseases/amyotrophic-lateral-sclerosis) patients and SOD1-G93A mice. Nuclear TAZ normally sustains expression of [TEAD4](/genes/tead4)-dependent genes involved in motor neuron identity and axonal maintenance. TAZ degradation via LATS1-dependent phosphorylation correlates with motor neuron degeneration. In ALS astrocytes, TAZ dynamics are altered: reactive astrocytes show increased nuclear TAZ, which drives the neuroinflammatory program including [C3](/genes/c3) complement upregulation — a hallmark of neurotoxic A1 astrocytes in ALS.
TAZ is frequently overexpressed or amplified in glioblastoma (GBM), particularly in the mesenchymal subtype. Nuclear TAZ–TEAD drives expression of mesenchymal transition genes, invasion-related genes ([MMP2](/genes/mmp2), MMP9), and stem cell maintenance factors ([CD44](/genes/cd44), [SOX2](/genes/sox2)). TAZ amplification at 3q25.1 is an independent poor prognostic factor in GBM. Conversely, LATS1/2-mediated TAZ inactivation suppresses GBM stem cell self-renewal, making the LATS1–TAZ axis a therapeutic target.
| Variant | Type | Association | Reference |
|---------|------|-------------|-----------|
| rs3811715 | Intronic | Nominal association with brain volume | [Genome-wide studies](https://www.ebi.ac.uk/gwas/) |
| 3q25.1 amplification | Copy number gain | GBM mesenchymal subtype, poor prognosis | [Bhat et al., 2011](https://doi.org/10.1016/j.ccr.2011.03.022) |
| c.475C>T (R159W) | Missense | Reduced TEAD binding, benign variant | [dbSNP](https://www.ncbi.nlm.nih.gov/snp/) |
| Promoter hypermethylation | Epigenetic | TAZ silencing in low-grade glioma | [Rao et al., 2018](https://doi.org/10.1038/s41388-018-0449-4) |
| Brain Region | Expression Level | Cell Types |
|---|---|---|
| Cerebral cortex (white matter) | High | Oligodendrocytes, astrocytes |
| Hippocampus | Moderate | Astrocytes, OPCs, low in neurons |
| Corpus callosum | High | Oligodendrocytes |
| SVZ/SGZ | Moderate-High | Neural stem cells |
| Spinal cord | Moderate | Astrocytes, oligodendrocytes |
| Substantia nigra | Low-Moderate | Astrocytes, dopaminergic neurons |
The following diagram shows the key molecular relationships involving WWTR1 (TAZ) — WW Domain Containing Transcription Regulator 1, Hippo Effector discovered through SciDEX knowledge graph analysis: