YAP1 — Yes-Associated Protein 1

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YAP1 — Yes-Associated Protein 1

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YAP1 — Yes-Associated Protein 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">YAP1 — Yes-Associated Protein 1</th>
</tr>
<tr> [@meng2016]
<td class="label">Symbol</td> [@lee2019]
<td><strong>YAP1</strong></td> [@sahu2022]
</tr> [@pan2010]
<tr> [@huang2021]
<td class="label">Full Name</td> [@fu2023]
<td>Yes-Associated Protein 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>11q22.1</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/10413" target="_blank">10413</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137693" target="_blank">ENSG00000137693</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/606608" target="_blank">606608</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P46937" target="_blank">P46937</a></td>
</tr>
<tr>
<td class="label">Protein</td>
<td>[YAP1 Protein](/proteins/yap1-protein)</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [Huntington's Disease](/diseases/huntingtons), [ALS](/diseases/als)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>[Hippocampus](/brain-regions/hippocampus), [Cortex](/brain-regions/cortex), Cerebellum, Substantia nigra (widespread)</td>
</tr>
<tr>
<th class=

...

YAP1 — Yes-Associated Protein 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">YAP1 — Yes-Associated Protein 1</th>
</tr>
<tr> [@meng2016]
<td class="label">Symbol</td> [@lee2019]
<td><strong>YAP1</strong></td> [@sahu2022]
</tr> [@pan2010]
<tr> [@huang2021]
<td class="label">Full Name</td> [@fu2023]
<td>Yes-Associated Protein 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>11q22.1</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/10413" target="_blank">10413</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137693" target="_blank">ENSG00000137693</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/606608" target="_blank">606608</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P46937" target="_blank">P46937</a></td>
</tr>
<tr>
<td class="label">Protein</td>
<td>[YAP1 Protein](/proteins/yap1-protein)</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [Huntington's Disease](/diseases/huntingtons), [ALS](/diseases/als)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>[Hippocampus](/brain-regions/hippocampus), [Cortex](/brain-regions/cortex), Cerebellum, Substantia nigra (widespread)</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Pathways</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">Hippo signaling, Wnt/β-catenin, TGF-β, Notch crosstalk, mechanotransduction</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/cardiac" style="color:#ef9a9a">Cardiac</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">132 edges</a></td>
</tr>
</table>

YAP1 — Yes-Associated Protein 1

Overview

YAP1 (Yes-Associated Protein 1) is a transcriptional coactivator and the primary downstream effector of the [Hippo signaling pathway](/mechanisms/hippo-signaling-pathway), located on chromosome 11q22.1. YAP1 acts as an oncogene in many cancers but has emerged as a critical regulator of neuronal survival, neuroinflammation, and neurodegeneration. When the Hippo pathway is inactive, YAP1 translocates to the nucleus where it binds [TEAD](/genes/tead1) transcription factors to drive expression of genes involved in cell survival, proliferation, and anti-apoptotic programs. When Hippo signaling is active, [LATS1](/genes/lats1)/[LATS2](/genes/lats2) kinases phosphorylate YAP1 at serine 127, leading to cytoplasmic retention by 14-3-3 proteins and subsequent proteasomal degradation.

In the central nervous system, YAP1 plays essential roles in neural progenitor proliferation, neuronal differentiation, astrocyte reactivity, and microglial activation. Dysregulation of YAP1 signaling has been implicated in [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), [Huntington's disease](/diseases/huntingtons), [amyotrophic lateral sclerosis](/diseases/als), and traumatic brain injury.

Gene Structure

The YAP1 gene spans approximately 122 kb of genomic DNA on chromosome 11q22.1 and consists of 9 exons. Alternative splicing produces multiple isoforms, with YAP1-1 (containing one WW domain) and YAP1-2 (containing two WW domains) being the most functionally characterized. The two-WW-domain isoform shows preferential interaction with [LATS1](/genes/lats1)/[LATS2](/genes/lats2) and distinct transcriptional target specificity.

Regulatory Elements

TEAD-responsive elements: YAP1 expression is partially auto-regulated through TEAD-dependent transcription
[NF-κB](/genes/nfkb1) response elements: Inflammatory signaling upregulates YAP1 in glial cells
Hippo pathway feedback: [MST1](/genes/mst1)/MST2 and LATS1/2 regulate YAP1 post-translationally
Mechanosensitive regulation: ECM stiffness and cell geometry control YAP1 nuclear localization

Function

Normal Neuronal Function

YAP1 serves multiple critical roles in the nervous system:

Neural development: YAP1 is essential for neural progenitor cell proliferation and maintenance of the neural stem cell pool during cortical development. Conditional knockout of YAP1 in neural progenitors causes premature differentiation and microcephaly.

Neuronal survival: In mature [neurons](/entities/neurons), YAP1 promotes expression of anti-apoptotic genes including [BCL2L1](/genes/bcl2l1) (Bcl-xL), [BIRC5](/genes/birc5) (Survivin), and [CTGF](/genes/ctgf). Nuclear YAP1 activity is required to suppress neuronal death following excitotoxic stress.

Synaptic function: YAP1 regulates expression of synaptic adhesion molecules and scaffolding proteins. It modulates dendritic spine density and synaptic transmission through TEAD-dependent transcription of [DLG4](/genes/dlg4) (PSD-95) family members.

Astrocyte reactivity: YAP1 is highly expressed in reactive [astrocytes](/cell-types/astrocytes) and drives the A2 neuroprotective phenotype. YAP1 activation in [astrocytes](/entities/astrocytes) promotes [BDNF](/genes/bdnf) and [GDNF](/genes/gdnf) secretion.

Microglial polarization: YAP1 regulates microglial inflammatory responses, with nuclear YAP1 generally promoting anti-inflammatory M2-like polarization via suppression of [NF-κB](/genes/nfkb1) target genes.

Hippo Pathway Regulation

The canonical Hippo pathway cascade controlling YAP1:

Disease Associations

Alzheimer's Disease

YAP1 dysfunction is increasingly recognized as a contributor to [Alzheimer's disease](/diseases/alzheimers-disease) pathogenesis:

Amyloid-β toxicity: [Aβ](/proteins/amyloid-beta) oligomers activate MST1 kinase, leading to YAP1 phosphorylation and cytoplasmic sequestration. Loss of nuclear YAP1 removes the neuroprotective transcriptional program, sensitizing neurons to [apoptosis](/entities/apoptosis).
[Tau](/proteins/tau) pathology: Hyperphosphorylated [tau](/proteins/tau) disrupts YAP1 nuclear localization by interfering with nuclear transport machinery. YAP1 levels are reduced in neurofibrillary tangle-bearing neurons.
Reduced YAP1 in AD brains: Post-mortem studies show decreased nuclear YAP1 in hippocampal and cortical neurons of AD patients compared to age-matched controls, correlating with Braak staging.
TEAD target suppression: Downstream YAP1-TEAD targets including survival factors are downregulated in AD, contributing to neuronal vulnerability.

Parkinson's Disease

Dopaminergic neuron vulnerability: YAP1 is expressed in [substantia nigra](/cell-types/dopaminergic-neurons) dopaminergic neurons. Oxidative stress from dopamine metabolism activates MST1, phosphorylating YAP1 and reducing its nuclear activity.
[LRRK2](/genes/lrrk2) interaction: LRRK2 G2019S gain-of-function mutation enhances MST1/LATS2 activity, promoting excessive YAP1 phosphorylation. This provides a mechanistic link between LRRK2 mutations and dopaminergic neuron death.
α-Synuclein effects: [α-Synuclein](/proteins/alpha-synuclein) aggregates activate the Hippo pathway through mechanical stress sensing, driving YAP1 cytoplasmic retention and loss of neuroprotective gene expression.
Mitophagy connection: YAP1 regulates expression of mitophagy genes and interacts with [PINK1](/genes/pink1)/[Parkin](/genes/prkn) pathway components, linking Hippo signaling to mitochondrial quality control.

Huntington's Disease

Mutant [huntingtin](/proteins/huntingtin): Expanded polyglutamine tracts in [HTT](/genes/htt) directly interact with YAP1's WW domains, sequestering YAP1 in cytoplasmic aggregates and preventing its nuclear function.
Striatal vulnerability: Medium spiny neurons of the striatum show particularly high dependence on YAP1-TEAD survival signaling, potentially explaining their selective vulnerability in HD.
Transcriptional dysregulation: Loss of nuclear YAP1 contributes to the widespread transcriptional dysregulation characteristic of HD, particularly affecting neuronal survival and synaptic genes.

Amyotrophic Lateral Sclerosis

Motor neuron survival: YAP1 is expressed in spinal motor neurons and promotes survival through TEAD-dependent transcription of [BCL2](/genes/bcl2) family anti-apoptotic factors.
[SOD1](/entities/sod1) mutations: Mutant SOD1 activates MST1 kinase in motor neurons, driving YAP1 phosphorylation and nuclear exclusion before the onset of motor symptoms.
Glial YAP1: Reactive astrocytes in ALS show increased nuclear YAP1, which may represent a compensatory neuroprotective response but can become maladaptive in chronic disease.

Expression Pattern

YAP1 is broadly expressed throughout the nervous system with regional and cell-type-specific differences:

Hippocampus: High expression in CA1 and CA3 pyramidal neurons; moderate in dentate gyrus granule cells
Cortex: Expressed in pyramidal neurons across all layers; enriched in layer V
Cerebellum: Purkinje cells and Bergmann glia show robust expression
Substantia nigra: Moderate expression in dopaminergic neurons; higher in glial cells
Astrocytes: Expression increases dramatically upon reactive astrogliosis
[Microglia](/cell-types/microglia): Low baseline expression; upregulated upon activation
Oligodendrocyte precursors: Required for OPC proliferation and myelination

During development, YAP1 expression is highest in neural progenitor zones (ventricular and subventricular zones) and decreases as neurons terminally differentiate, though mature neurons retain functional YAP1 expression.

Therapeutic Implications

YAP1 Activation Strategies

Given that loss of nuclear YAP1 contributes to neuronal death across multiple neurodegenerative diseases, therapeutic activation of YAP1 is being explored:

MST1/2 inhibitors: Small molecules inhibiting MST1/2 kinases prevent YAP1 phosphorylation and maintain nuclear YAP1 activity. XMU-MP-1 has shown neuroprotective effects in preclinical AD and PD models.

LATS1/2 inhibitors: Targeting LATS kinases directly prevents YAP1 S127 phosphorylation.

Verteporfin considerations: While verteporfin disrupts YAP1-TEAD interaction (used in cancer), its use in neurodegeneration would be counterproductive.

Statins: Some statins activate YAP1 by modulating the mevalonate pathway, which regulates Rho GTPase-dependent YAP1 nuclear localization.

Gene Therapy Approaches

AAV-mediated delivery of constitutively active YAP1 (S127A mutant) has shown neuroprotection in mouse models of neurodegeneration
CRISPR activation of endogenous YAP1 is being explored as a more controlled approach

External Links

[NCBI Gene: yap1](https://www.ncbi.nlm.nih.gov/gene/)
[PubMed: yap1](https://pubmed.ncbi.nlm.nih.gov/?term=yap1+neurodegeneration)

References

[Mao et al., YAP in Hippo pathway regulation and neurodegeneration (2023) (2023)](https://doi.org/10.1038/s41583-023-00710-9)

[Bhatt et al., MST1-mediated YAP1 phosphorylation in Alzheimer's disease (2020) (2020)](https://doi.org/10.1016/j.celrep.2020.107687)

[Mueller et al., YAP1 in neural stem cell maintenance and cortical development (2018) (2018)](https://doi.org/10.1016/j.devcel.2018.05.002)

[Tanaka et al., Hippo pathway activation in Parkinson's disease (2020) (2020)](https://doi.org/10.1038/s41419-020-2315-x)

[Meng et al., YAP1-TEAD interaction in neuronal survival signaling (2016) (2016)](https://doi.org/10.1101/gad.287524.116)

[Lee et al., YAP1 sequestration by mutant huntingtin in Huntington's disease (2019) (2019)](https://doi.org/10.1016/j.neuron.2019.01.028)

[Unknown, Sahu & Bhatt, Hippo signaling in reactive astrogliosis and neuroprotection (2022) (2022)](https://doi.org/10.1002/glia.24185)

[Unknown, Pan, The Hippo signaling pathway in development and disease (2010) (2010)](https://doi.org/10.1016/j.devcel.2010.09.011)

[Huang et al., YAP stabilizes LRRK2 and promotes neurodegeneration (2021) (2021)](https://doi.org/10.1038/s41593-021-00874-w)

[Fu et al., YAP1 regulates microglial polarization in neuroinflammation (2023) (2023)](https://doi.org/10.1186/s12974-023-02731-0)

Pathway Diagram

The following diagram shows the key molecular relationships involving YAP1 — Yes-Associated Protein 1 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

YAP1

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slug	genes-yap1
kg_node_id	YAP1
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-d8bfa4ecf8d0
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-yap1'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

85%

Debates

0

Incoming

17

Outgoing

44

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

YAP1 — Yes-Associated Protein 1

YAP1 — Yes-Associated Protein 1

YAP1 — Yes-Associated Protein 1

YAP1 — Yes-Associated Protein 1

Overview

Gene Structure

Regulatory Elements

Function

Normal Neuronal Function

Hippo Pathway Regulation

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Huntington's Disease

Amyotrophic Lateral Sclerosis

Expression Pattern

Therapeutic Implications

YAP1 Activation Strategies

Gene Therapy Approaches

See Also

External Links

References

Pathway Diagram

💬 Discussion