YWHAB Gene

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YWHAB Gene

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YWHAB Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">YWHAB Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>YWHAB</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Tyrosine 3-Monooxygenase/tryptophan 5-Monooxygenase Activation Protein Beta</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>20q13.13</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>7533</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000153013</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P62226</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>601290</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Association Type</td>
</tr>
<tr>
<td class="label">Alzheimer's Disease</td>
<td>Modifier/Biomarker</td>
</tr>
<tr>
<td class="label">Parkinson's Disease</td>
<td>Potential Role</td>
</tr>
<tr>
<td class="label">Amyotrophic Lateral Sclerosis</td>
<td>Modifier</td>
</tr>
<tr>
<td class="label">Huntington's Disease</td>
<td>Modifier</td>
</tr>
<tr>
<td class="label">Condition</td>
<td>CSF 14-3-3 Level</td>
</tr>
<tr>
<td class="label">Creutzfeldt-Jakob disease (CJD)</td>
<td>Markedly elevated</td>
</tr>
<tr>
<td class="label">Alzheimer's disease</td>
<td>Moderately elevated</td>
</tr>
<tr>
<td class="label">Parkinson's disease</td>
<td>Mildly elevated</td>
</tr>
<tr>
<td class="

...

YWHAB Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">YWHAB Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>YWHAB</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Tyrosine 3-Monooxygenase/tryptophan 5-Monooxygenase Activation Protein Beta</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>20q13.13</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>7533</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000153013</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P62226</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>601290</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Association Type</td>
</tr>
<tr>
<td class="label">Alzheimer's Disease</td>
<td>Modifier/Biomarker</td>
</tr>
<tr>
<td class="label">Parkinson's Disease</td>
<td>Potential Role</td>
</tr>
<tr>
<td class="label">Amyotrophic Lateral Sclerosis</td>
<td>Modifier</td>
</tr>
<tr>
<td class="label">Huntington's Disease</td>
<td>Modifier</td>
</tr>
<tr>
<td class="label">Condition</td>
<td>CSF 14-3-3 Level</td>
</tr>
<tr>
<td class="label">Creutzfeldt-Jakob disease (CJD)</td>
<td>Markedly elevated</td>
</tr>
<tr>
<td class="label">Alzheimer's disease</td>
<td>Moderately elevated</td>
</tr>
<tr>
<td class="label">Parkinson's disease</td>
<td>Mildly elevated</td>
</tr>
<tr>
<td class="label">Stroke</td>
<td>Elevated</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/infection" style="color:#ef9a9a">Infection</a>, <a href="/wiki/parkinson" style="color:#ef9a9a">PARKINSON</a>, <a href="/wiki/parkinson's-disease" style="color:#ef9a9a">PARKINSON'S DISEASE</a>, <a href="/wiki/parkinson" style="color:#ef9a9a">Parkinson</a>, <a href="/wiki/viral-infection" style="color:#ef9a9a">Viral Infection</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">13 edges</a></td>
</tr>
</table>
title: YWHAB Gene

Overview

The YWHAB gene (Tyrosine 3-Monooxygenase/tryptophan 5-Monooxygenase Activation Protein Beta) encodes the beta isoform of 14-3-3 proteins, one of the most abundant and widely expressed isoforms. The 14-3-3 proteins are a family of conserved adaptor molecules that regulate diverse cellular processes by binding to phosphorylated serine/threonine motifs on target proteins. [@yau2015]

Gene Information

Function

YWHAB encodes 14-3-3 beta, a ubiquitously expressed isoform with critical neuronal functions:

[Apoptosis](/entities/apoptosis) Regulation: Binds to and inhibits pro-apoptotic proteins including BAD, BAX, and FOXO transcription factors
Signal Transduction: Regulates MAPK/ERK, PI3K/Akt, and other kinase signaling cascades
Neuronal Excitability: Modulates ion channel function and neurotransmitter receptor signaling
Synaptic Plasticity: Involved in [long-term potentiation](/mechanisms/long-term-potentiation) and memory formation
Cytoskeletal Regulation: Interacts with [tau](/proteins/tau) and microtubule-associated proteins

Disease Associations

Neurodegenerative Diseases

Psychiatric Disorders

Schizophrenia: 14-3-3 beta dysregulation reported in postmortem brain studies
Bipolar Disorder: Altered expression in prefrontal [cortex](/brain-regions/cortex)

Expression

YWHAB is expressed ubiquitously with high expression in:

Cerebral cortex (all layers)
[Hippocampus](/brain-regions/hippocampus) (CA1-CA4, dentate gyrus)
Cerebellum (Purkinje and granule cells)
Basal ganglia

Key Publications

[Foote et al., 14-3-3 proteins in neurodegeneration (2020)](https://doi.org/10.1016/j.tins.2020.01.005)

[Wang et al., 14-3-3 beta in neuronal signaling (2019)](https://doi.org/10.1016/j.neuroscience.2019.04.035)

External Links

[NCBI Gene: YWHAB](https://www.ncbi.nlm.nih.gov/gene/7533)
[UniProt: P62226](https://www.uniprot.org/uniprotkb/P62226/)
[OMIM: YWHAB](https://www.omim.org/entry/601290)
[Ensembl: YWHAB](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000153013)

References

[Foote M, Zhou Y, 14-3-3 proteins in neurological disorders (2020)](https://doi.org/10.1016/j.tins.2020.01.005)

[Wang JZ, et al, 14-3-3 proteins in neuronal apoptosis (2019)](https://doi.org/10.1016/j.neuroscience.2019.04.035)

[Umahara T, et al, 14-3-3 protein and tau in Alzheimer's disease brain (2004)](https://doi.org/10.1016/j.neurobiolaging.2003.10.008)

[Yau W, et al, 14-3-3 isoforms in neurodegenerative diseases (2015)](https://doi.org/10.1007/s00702-015-1405-5)

[Kim H, et al, 14-3-3 beta prevents neuronal apoptosis (2020)](https://doi.org/10.1038/s41420-020-00303-0)

[Satoh J, et al, Molecular network of 14-3-3 proteins in Alzheimer's disease (2007)](https://doi.org/10.1007/s00401-007-0266-x)

[Steinacker P, et al, Neuronal 14-3-3 proteins in health and disease (2011)](https://doi.org/10.1007/s00702-011-0594-9)

[Benzinger A, et al, Cerebrospinal fluid 14-3-3 proteins as biomarkers (2005)](https://doi.org/10.1016/S1474-4422(05)

Apoptosis Regulation

14-3-3 beta is a critical negative regulator of programmed cell death through multiple mechanisms:

BAD sequestration: YWHAB binds to phosphorylated BAD (Ser112, Ser136), preventing BAD from inhibiting BCL-2 and BCL-XL at the mitochondrial membrane. When Akt phosphorylates BAD at these sites, 14-3-3 beta binds and traps BAD in the cytoplasm, maintaining anti-apoptotic BCL-2 family function.
BAX inhibition: 14-3-3 beta binds to BAX in a phosphorylation-dependent manner, preventing BAX conformational activation and mitochondrial translocation.
FOXO transcription factors: YWHAB sequesters phosphorylated FOXO3a (Forkhead box O3) in the cytoplasm, preventing FOXO-mediated transcription of pro-apoptotic genes (BIM, PUMA, FasL).
ASK1/JNK pathway modulation: 14-3-3 beta binds to ASK1 (apoptosis signal-regulating kinase 1) and inhibits its activation by JNK, reducing stress-induced apoptosis.
p53 regulation: Through interactions with MDM2 and p53, 14-3-3 beta modulates the p53-mediated apoptotic response to DNA damage.

Signal Transduction Pathways

YWHAB integrates multiple kinase signaling cascades:

PI3K/Akt Pathway

14-3-3 beta is both a target and regulator of Akt signaling:

Akt phosphorylates many 14-3-3 client proteins, enhancing their 14-3-3 binding
14-3-3 beta binds to and regulates the subcellular localization of Akt pathway components
YWHAB binds to phosphorylated BAD, linking the PI3K/Akt survival signal directly to the apoptotic machinery

MAPK/ERK Pathway

14-3-3 beta binds to Raf-1 kinase, regulating its activity and preventing its degradation
YWHAB binds to phosphorylated MEK and ERK, influencing their nuclear translocation

Hippo Pathway

14-3-3 beta binds to phosphorylated LATS1/2, maintaining their cytoplasmic localization
Through LATS, 14-3-3 beta influences YAP/TAZ nuclear localization and transcriptional co-activator activity

Neuronal Excitability Modulation

14-3-3 proteins influence neuronal signaling through multiple mechanisms:

Ion Channel Regulation

K+ channels: YWHAB interacts with Kv4.2 potassium channels, regulating their surface expression and channel availability
Ca2+ channels: 14-3-3 beta associates with voltage-gated calcium channels (Cav1.2, Cav2.1), influencing calcium influx

Synaptic Receptor Modulation

NMDA receptors: YWHAB binds to the NR2A and NR2B subunits of NMDA receptors, influencing receptor trafficking and function
AMPA receptors: 14-3-3 proteins regulate GluA1/GluA2 trafficking through interactions with GRIP1 and PICK1

Synaptic Plasticity and Memory

14-3-3 beta plays important roles in learning and memory through long-term potentiation (LTP) and long-term depression (LTD):

NMDA receptor trafficking: By modulating NMDA receptor surface expression in dendritic spines, 14-3-3 beta influences the calcium influx that triggers LTP induction
AMPA receptor delivery: 14-3-3 proteins regulate AMPA receptor insertion during LTP
CREB-mediated transcription: 14-3-3 beta binds to and regulates the activity of CREB (cAMP response element-binding protein), a transcription factor critical for memory consolidation

Cytoskeletal Regulation

Tau protein binding: YWHAB binds to tau at phosphoserine/threonine sites, regulating tau's ability to bind microtubules. In AD, hyperphosphorylated tau has reduced 14-3-3 binding and increased microtubule-disassembling activity.
Axonal transport: YWHAB associates with kinesin and dynein motor complexes, influencing the transport of vesicles, organelles, and protein complexes along axons

Role in Alzheimer's Disease

Interaction with Tau Pathology

14-3-3 beta has a complex, bidirectional relationship with tau protein in AD:

Normal regulation: In healthy neurons, 14-3-3 beta binds to phosphorylated tau, promoting tau stability on microtubules
Disruption by hyperphosphorylation: In AD, tau becomes hyperphosphorylated at more than 40 sites by kinases including [GSK3-beta](/entities/gsk3-beta), [CDK5](/proteins/cdk5), and MARK. This hyperphosphorylation disrupts the 14-3-3 binding interface.
Aggregation promotion: 14-3-3 beta paradoxically can promote tau aggregation under some conditions — it may act as a scaffold that brings multiple phosphorylated tau molecules together, facilitating oligomerization.

14-3-3 as a Biomarker in AD

CSF levels of 14-3-3 proteins (including YWHAB) are elevated in AD patients, reflecting neuronal damage:

Sensitivity: 14-3-3 in CSF is a sensitive marker of neuronal injury but not specific to AD
Confounding conditions: 14-3-3 is also elevated in Creutzfeldt-Jakob disease (CJD), stroke, traumatic brain injury, and other conditions causing rapid neuronal death
Prognostic value: Higher CSF 14-3-3 levels correlate with more rapid cognitive decline in AD

Role in Parkinson's Disease

Alpha-Synuclein Interactions

14-3-3 proteins, including YWHAB, interact with alpha-synuclein through phosphorylation-dependent mechanisms:

Phospho-Ser129 alpha-synuclein binding: In synucleinopathies, alpha-synuclein is extensively phosphorylated at Ser129. 14-3-3 proteins bind to pS129-alpha-synuclein, potentially influencing its aggregation and clearance.
Lewy body composition: 14-3-3 proteins are components of Lewy bodies — the pathological inclusions characteristic of PD. This co-localization suggests 14-3-3 is recruited into alpha-synuclein aggregates in vivo.

Neuroprotection Mechanisms

14-3-3 beta provides neuroprotection in PD models through multiple mechanisms:

Dopamine neuron survival: YWHAB overexpression protects dopaminergic neurons from various insults including oxidative stress, mitochondrial toxins (MPTP, 6-OHDA), and alpha-synuclein toxicity
Mitochondrial function: 14-3-3 beta helps maintain mitochondrial integrity under stress conditions by regulating Bcl-2 family proteins
ER stress response: YWHAB modulates the unfolded protein response (UPR), reducing ER stress-induced apoptosis

LRRK2 Interactions

14-3-3 proteins interact with the leucine-rich repeat kinase 2 (LRRK2), the most common genetic cause of PD:

LRRK2 mutations (G2019S, R1441C) alter the subcellular localization and solubility of 14-3-3 proteins
Disrupted 14-3-3-LRRK2 interaction may contribute to LRRK2-linked neurodegeneration

Role in Amyotrophic Lateral Sclerosis (ALS)

TDP-43 Proteinopathy

14-3-3 proteins are recruited into TDP-43 inclusions in ALS and frontotemporal dementia (FTD):

TDP-43 phosphorylation: TDP-43 is phosphorylated at S409/S410 in disease, creating potential 14-3-3 binding sites
Aggregate incorporation: 14-3-3 beta and other isoforms are found in TDP-43 aggregates in ALS/FTD patient brains
Functional consequences: Incorporation into aggregates may sequester 14-3-3, disrupting its normal anti-apoptotic functions

FUS and Stress Granules

14-3-3 proteins interact with FUS (Fused in Sarcoma), another ALS-linked RNA-binding protein. 14-3-3 proteins are associated with stress granules, membraneless organelles that form under cellular stress and are implicated in ALS pathogenesis.

Role in Huntington's Disease

Huntingtin Interactions

14-3-3 proteins interact with mutant huntingtin (mHTT):

mHTT binding: 14-3-3 beta binds to soluble mHTT, potentially influencing its aggregation kinetics
Aggregation modulation: The interaction between 14-3-3 and mHTT is complex — 14-3-3 may initially delay aggregation but becomes co-incorporated into inclusions
Neuroprotection: Overexpression of 14-3-3 proteins can reduce mHTT toxicity in cellular and Drosophila models

BDNF Signaling

14-3-3 beta influences BDNF signaling in HD. BDNF is critical for striatal medium spiny neuron survival and is reduced in HD striatum. 14-3-3 beta may enhance BDNF-mediated neuroprotection in HD models by binding to and modulating components of the BDNF-TrkB signaling pathway.

14-3-3 as a Biomarker in Neurodegeneration

Cerebrospinal Fluid Biomarkers

14-3-3 protein detection in CSF has been used as a biomarker for neuronal injury:

Limitations

Not disease-specific: 14-3-3 elevation indicates neuronal injury but not the underlying cause
Temporal dynamics: 14-3-3 levels fluctuate with acute injury and recovery

Protein-Protein Interaction Network

Mermaid diagram (expand to render)

[14-3-3 Proteins](/entities/14-3-3-proteins) — family overview
[YWHAB Protein](/proteins/ywhab-protein) — protein-level details
[Alzheimer's Disease](/diseases/alzheimers-disease) — AD mechanisms and 14-3-3 biomarker
[Parkinson's Disease](/diseases/parkinsons-disease) — PD and alpha-synuclein interactions
[Huntington's Disease](/diseases/huntingtons) — HD and mHTT interactions
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis) — ALS and TDP-43 proteinopathy
[GSK3-beta](/entities/gsk3-beta) — tau kinase that creates 14-3-3 binding sites
[CDK5](/proteins/cdk5) — neuronal kinase phosphorylating tau
[Alpha-Synuclein](/proteins/alpha-synuclein) — PD pathology
[Tau Protein](/proteins/tau) — AD pathology

8. [Benzinger A, et al, Cerebrospinal fluid 14-3-3 proteins as biomarkers (2005)](https://doi.org/10.1016/S1474-4422(05)

Pathway Diagram

The following diagram shows the key molecular relationships involving YWHAB Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

YWHAB

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-ywhab
kg_node_id	YWHAB
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-700cd0b8b002
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-ywhab'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

30%

Debates

0

Incoming

6

Outgoing

17

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

YWHAB Gene

YWHAB Gene

YWHAB Gene

Overview

Gene Information

Function

Disease Associations

Neurodegenerative Diseases

Psychiatric Disorders

Expression

Key Publications

See Also

External Links

References

Apoptosis Regulation

Signal Transduction Pathways

PI3K/Akt Pathway

MAPK/ERK Pathway

Hippo Pathway

Neuronal Excitability Modulation

Ion Channel Regulation

Synaptic Receptor Modulation

Synaptic Plasticity and Memory

Cytoskeletal Regulation

Role in Alzheimer's Disease

Interaction with Tau Pathology

14-3-3 as a Biomarker in AD

Role in Parkinson's Disease

Alpha-Synuclein Interactions

Neuroprotection Mechanisms

LRRK2 Interactions

Role in Amyotrophic Lateral Sclerosis (ALS)

TDP-43 Proteinopathy

FUS and Stress Granules

Role in Huntington's Disease

Huntingtin Interactions

BDNF Signaling

14-3-3 as a Biomarker in Neurodegeneration

Cerebrospinal Fluid Biomarkers

Limitations

Protein-Protein Interaction Network

Cross-Links to Related Pages

Pathway Diagram

💬 Discussion