| Property | Value |
|----------|-------|
| 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 |
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.
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 induction - Promotes autophagy under nutrient deprivation
- Neuronal development - Regulates brain growth and connectivity
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
Pathogenic mechanism: STRADA alterations affect mTORC1 dysregulation
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
- Early onset - Childhood
- Macrocephaly - Head circumference >2 SD above mean
- Autism spectrum disorder - Social/communication deficits
- Developmental delay - Variable intellectual disability
- Seizure types - Focal seizures, infantile spasms
- EEG - Hypsarrhythmia in some cases
- Response - Often refractory to treatment
STRADA shows broad expression:
- Brain - High in cortex, hippocampus, cerebellum
- Heart - Moderate expression
- Liver, kidney - Lower expression
- Pancreas - Detectable
Cellular localization: Cytoplasm, associated with membrane structures
STRADA is a critical regulator of mTORC1 through AMPK activation:
- Energy Sensing: Monitors cellular ATP/AMP ratios
- AMPK Phosphorylation: Activates AMPK via LKB1
- mTORC1 Inhibition: Blocks mTORC1 signaling
- Autophagy Induction: Promotes autophagosome formation
STRADA regulates cell size through:
- Nutrient Sensing: Links nutrient status to growth
- Ribosome Biogenesis: Controls protein synthesis
- Protein Turnover: Regulates degradation pathways
In neurons specifically:
- Synaptic Plasticity: Controls LTP and LTD
- Dendritic Growth: Regulates arborization
- Axonal Outgrowth: Controls axon guidance
Abnormal mTOR signaling contributes to:
- Rapidd Synaptic Dysfunction: Impaired plasticity
- Autophagy Block: Protein aggregate accumulation
- Neuronal Loss: Progressive degeneration
Targeting STRADA-mTOR pathway:
| Strategy |
Agent |
Status |
| mTOR inhibition |
Rapamycin |
Approved |
| AMPK activation |
AICAR |
Research |
| STRADA activation |
Gene therapy |
Investigational |
- mTOR hyperactivation in AD brain
- Autophagy impairment
- Synaptic loss connections
Developing STRADA-targeted therapies:
- AMPK Activators
- mTORC1 Inhibitors
- Autophagy Inducers
Viral vector delivery:
- AAV-STRADA constructs
- Regulated expression systems
- Brain-specific promoters
For STRADA-targeted therapies:
- Genetic testing available
- Phenotype correlations
- Biomarker development
Clinical trial measures:
- Cognitive testing
- Imaging endpoints
- Biomarker changes
STRADA encodes a 430 amino acid protein with the following domains:
Multiple isoforms generated through alternative splicing with tissue-specific expression.
STRADA is a critical regulator of mTORC1 signaling:
- AMPK Activation: STRADA promotes AMPK phosphorylation
- mTORC1 Inhibition: Activated AMPK inhibits mTORC1
- Nutrient Sensing: Links cellular energy status to growth
STRADA forms a heterotrimeric complex:
- STRADA + STRADB (STE20-related kinase adaptors)
- MAP4K3 or MST1 (kinase component)
- LKB1 (upstream kinase)
STRADA plays essential roles in brain development:
- Cortical Growth: Regulates neuronal proliferation
- Synaptogenesis: Controls synapse formation
- Myelination: Affects oligodendrocyte function
Emerging evidence connects STRADA to neurodegeneration:
- mTOR Dysregulation: Altered mTOR signaling in AD
- Autophagy Impairment: Defective autophagic clearance
- Protein Aggregation: Accumulation of toxic species
mTOR inhibitors being studied:
- Rapamycin (sirolimus)
- Everolimus
- Temsirolimus
| Agent |
Indication |
Status |
| Everolimus |
TSC, autism |
Clinical trials |
| Rapamycin |
Lhermitte-Duclos |
Case reports |
AAV-mediated STRADA delivery approaches.
STRADA-/- mice:
- Embryonic lethal (complete loss)
- Brain-specific knockouts show microcephaly
Brain-specific deletion models show:
- Impaired neurogenesis
- Behavioral deficits
- Autophagy defects
STRADA variants cause a spectrum of phenotypes:
| Feature |
Frequency |
Severity |
| Macrocephaly |
100% |
Variable |
| Developmental delay |
85% |
Mild-moderate |
| Autism |
60% |
Variable |
| Seizures |
40% |
Variable |
| Cerebellar atrophy |
30% |
Progressive |
- Early onset in childhood
- Progressive cerebellar degeneration
- Variable cognitive outcomes
Current research priorities:
- Understanding STRADA function in neurons
- Developing targeted therapeutics
- Biomarker development
- Gene replacement strategies