STRADA Gene

STRADA (STE20-Related Kinase Adaptor Alpha)

<div class="infobox infobox-gene">

| Property | Value | [@marsh2007]
|----------|-------| [@zhou2009]
| Gene Symbol | STRADA |
| Full Name | STE20-Related Kinase Adaptor Alpha |
| Chromosomal Location | 17q22 |
| NCBI Gene ID | 92335 |
| OMIM ID | 614556 |
| Ensembl ID | ENSG00000120289 |
| UniProt ID | Q7Z417 |
| Encoded Protein | STE20-related kinase adaptor protein |
| Associated Diseases | PTEN Hamartoma Tumor Syndrome (PHTS), Lhermitte-Duclos Disease, Macrocephaly-Autism Syndrome |

</div>

Overview

STRADA is a human gene whose product sTRADA** encodes a STE20-related kinase adaptor protein that acts as a regulatory component of the mTORC1 pathway. STRADA forms a complex with STRADB and the kinase MAP4K3 (or MST1), regulating AMPK and mTORC1 signaling. Variants in STRADA have been implicated in PTEN Hamartoma Tumor Syndrome (PHTS), Lhermitte-Duclos Disease (Dysplastic Gangliocytoma), Macrocephaly-Autism Syndrome. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Function

STRADA encodes a STE20-related kinase adaptor protein that acts as a regulatory component of the mTORC1 pathway. STRADA forms a complex with STRADB and the kinase MAP4K3 (or MST1), regulating AMPK and mTORC1 signaling.

STRADA (STE20-Related Kinase Adaptor Alpha)

<div class="infobox infobox-gene">

| Property | Value | [@marsh2007]
|----------|-------| [@zhou2009]
| Gene Symbol | STRADA |
| Full Name | STE20-Related Kinase Adaptor Alpha |
| Chromosomal Location | 17q22 |
| NCBI Gene ID | 92335 |
| OMIM ID | 614556 |
| Ensembl ID | ENSG00000120289 |
| UniProt ID | Q7Z417 |
| Encoded Protein | STE20-related kinase adaptor protein |
| Associated Diseases | PTEN Hamartoma Tumor Syndrome (PHTS), Lhermitte-Duclos Disease, Macrocephaly-Autism Syndrome |

</div>

Overview

STRADA is a human gene whose product sTRADA** encodes a STE20-related kinase adaptor protein that acts as a regulatory component of the mTORC1 pathway. STRADA forms a complex with STRADB and the kinase MAP4K3 (or MST1), regulating AMPK and mTORC1 signaling. Variants in STRADA have been implicated in PTEN Hamartoma Tumor Syndrome (PHTS), Lhermitte-Duclos Disease (Dysplastic Gangliocytoma), Macrocephaly-Autism Syndrome. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Function

STRADA encodes a STE20-related kinase adaptor protein that acts as a regulatory component of the mTORC1 pathway. STRADA forms a complex with STRADB and the kinase MAP4K3 (or MST1), regulating AMPK and mTORC1 signaling.

Key normal physiological functions include:

• mTORC1 regulation - Inhibits mTORC1 through AMPK activation
• Cell growth control - Regulates cell size through nutrient sensing
• Energy homeostasis - Monitors cellular energy status (AMPK activation)
• [Autophagy](/entities/autophagy) induction - Promotes autophagy under nutrient deprivation
• Neuronal development - Regulates brain growth and connectivity

Disease Associations

PTEN Hamartoma Tumor Syndrome (PHTS)

STRADA deletions/duplications modify the phenotype:

• Inheritance - Autosomal dominant
• Core features - Macrocephaly, intellectual disability, autism
• Tumor predisposition - Increased cancer risk (breast, thyroid, colon)
• Features overlap - Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome

Lhermitte-Duclos Disease (Dysplastic Gangliocytoma)

Rare cerebellar tumor associated with PTEN mutations:

• Adult onset - Typically presents in 3rd-4th decade
• Symptoms - Ataxia, increased intracranial pressure
• MRI - Characteristic "tiger-striped" cerebellar lesion
• Association - Often part of Cowden syndrome

Macrocephaly-Autism Syndrome

• Early onset - Childhood
• Macrocephaly - Head circumference >2 SD above mean
• Autism spectrum disorder - Social/communication deficits
• Developmental delay - Variable intellectual disability

Epilepsy

• Seizure types - Focal seizures, infantile spasms
• EEG - Hypsarrhythmia in some cases
• Response - Often refractory to treatment

Expression

STRADA shows broad expression:

• Brain - High in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum
• Heart - Moderate expression
• Liver, kidney - Lower expression
• Pancreas - Detectable

Cellular Functions

mTORC1 Signaling

Cell Size Control

• Nutrient Sensing: Links nutrient status to growth
• Ribosome Biogenesis: Controls protein synthesis
• Protein Turnover: Regulates degradation pathways

Neuronal Functions

• Synaptic Plasticity: Controls LTP and LTD
• Dendritic Growth: Regulates arborization
• Axonal Outgrowth: Controls axon guidance

Pathological Mechanisms

mTOR Dysregulation in Disease

Therapeutic Implications

| Strategy | Agent | Status |
|----------|-------|--------|
| mTOR inhibition | Rapamycin | Approved |
| AMPK activation | AICAR | Research |
| STRADA activation | Gene therapy | Investigational |

Pathological Mechanisms in Neurodegeneration

Alzheimer's Disease

• mTOR hyperactivation in AD brain
• Autophagy impairment
• Synaptic loss connections

Parkinson's Disease

• mTOR dysregulation in PD
• Alpha-synuclein accumulation
• Autophagy defects

Additional Therapeutic Approaches

Small Molecule Strategies

Gene Therapy

• AAV-STRADA constructs
• Regulated expression systems
• Brain-specific promoters

Clinical Considerations

Patient Selection

• Genetic testing available
• Phenotype correlations
• Biomarker development

Trial Endpoints

• Cognitive testing
• Imaging endpoints
• Biomarker changes

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [Ensembl: ENSG00000120289](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000120289)
• [NCBI Gene: STRADA](https://www.ncbi.nlm.nih.gov/gene/?term=STRADA)
• [GeneCards: STRADA](https://www.genecards.org/cgi-bin/carddisp.pl?gene=STRADA)
• [OMIM: STRADA](https://omim.org/search?search=STRADA)
• [Allen Brain Atlas: STRADA](https://human.brain-map.org/microarray/search/show?search_term=STRADA)

Protein Structure

STRADA encodes a 430 amino acid protein with the following domains:

• [SAB Domain*: STRADA protein contains a sterile alpha motif (SAM) domain for protein-protein interactions](/genes/strada)
• [Coiled-coil Regions*: Mediate homodimerization with STRADB](/genes/th)
• [Nuclear Localization Signal*: Regulates subcellular partitioning](/genes/ubc)

Isoforms

Molecular Pathways

mTORC1 Regulation

Complex Formation

• STRADA + STRADB (STE20-related kinase adaptors)
• MAP4K3 or MST1 (kinase component)
• LKB1 (upstream kinase)

Neurological Implications

Brain Development

Neurodegeneration Link

Therapeutic Targeting

Rapamycin Analogs

• Rapamycin (sirolimus)
• Everolimus
• Temsirolimus

Gene Therapy

Animal Models

Knockout Mice

• Embryonic lethal (complete loss)
• Brain-specific knockouts show microcephaly

Conditional Knockouts

• Impaired neurogenesis
• Behavioral deficits
• Autophagy defects

Clinical Features

Phenotype Spectrum

| Feature | Frequency | Severity |
|--------|-----------|----------|
| Macrocephaly | 100% | Variable |
| Developmental delay | 85% | Mild-moderate |
| Autism | 60% | Variable |
| Seizures | 40% | Variable |
| Cerebellar atrophy | 30% | Progressive |

Natural History

• Early onset in childhood
• Progressive cerebellar degeneration
• Variable cognitive outcomes

Research Directions

Current research priorities:

References