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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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STRADA
STE20 related adaptor alpha
Chromosome 17 Β· 17q23.3
NCBI Gene: 92335Ensembl: ENSG00000266173.7HGNC: HGNC:30172UniProt: A0A1W2PPG2
52PubMed Papers
20Diseases
0Drugs
24Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein kinase activityprotein phosphorylationG1 to G0 transitionprotein bindingpolyhydramnios, megalencephaly, and symptomatic epilepsyRolandic epilepsyself-limited epilepsy with centrotemporal spikesneurodegenerative disease
✦AI Summary

STRADA (STE20-related adaptor alpha) is a pseudokinase that functions as a critical regulator of the mechanistic target of rapamycin (mTOR) pathway. STRADA operates as a catalytically inactive protein that forms a complex with CAB39/MO25 to bind and activate the tumor suppressor LKB1, promoting its conformational change to an active state 1. This LKB1-STRADA interaction enables LKB1 to phosphorylate and activate downstream AMP-activated protein kinase family members, which regulate cellular energy sensing and proliferation 1. Biallelic pathogenic STRADA mutations cause Pretzel Syndrome (PMSE), an autosomal recessive mTORopathy characterized by polyhydramnios, megalencephaly, drug-resistant epilepsy, and severe developmental delay 23. Loss of STRADA function results in mTOR pathway hyperactivation during cortical development, leading to delayed neurogenesis, excessive neural stem cell and outer radial glia expansion, and abnormal primary cilia architecture 24. In ventral forebrain development, STRADA deficiency causes delayed interneuron differentiation with altered cell fate specification 4. Clinically, mTOR pathway inhibitors like sirolimus and rapamycin show therapeutic potential in STRADA deficiency, offering promise for ameliorating seizures and neurodevelopmental abnormalities 34. Additionally, STRADA expression is downregulated during sevoflurane postconditioning-mediated cardioprotection against hypoxia-reoxygenation injury 5.

Sources cited
1
STRADA is a catalytically inactive pseudokinase that forms a complex with MO25 to activate LKB1, which phosphorylates AMPK family kinases
PMID: 16756488
2
STRADA mutations cause Pretzel Syndrome with mTOR pathway hyperactivation leading to megalencephaly, delayed neurogenesis, and abnormal cortical development
PMID: 33619909
3
STRADA mutations are associated with polyhydramnios, megalencephaly, epilepsy, and developmental delay; sirolimus (mTOR inhibitor) improves seizure control
PMID: 30311510
4
STRADA deficiency causes delayed forebrain neurogenesis with increased progenitor proliferation and altered interneuron specification; rapamycin rescues phenotypes
PMID: 40462897
5
STRADA expression is downregulated during sevoflurane postconditioning-mediated cardioprotection via miR-107 upregulation
PMID: 32332694
Disease Associationsβ“˜20
polyhydramnios, megalencephaly, and symptomatic epilepsyOpen Targets
0.76Strong
Rolandic epilepsyOpen Targets
0.45Moderate
self-limited epilepsy with centrotemporal spikesOpen Targets
0.45Moderate
neurodegenerative diseaseOpen Targets
0.41Moderate
Severe global developmental delayOpen Targets
0.37Weak
Alzheimer diseaseOpen Targets
0.28Weak
lysosomal storage diseaseOpen Targets
0.27Weak
multiple sclerosisOpen Targets
0.27Weak
Parkinson diseaseOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
epilepsyOpen Targets
0.11Weak
PolyhydramniosOpen Targets
0.11Weak
Intellectual disabilityOpen Targets
0.11Weak
Female infertility due to fertilization defectOpen Targets
0.07Suggestive
atrial fibrillationOpen Targets
0.06Suggestive
response to statinOpen Targets
0.06Suggestive
oocyte maturation defect 14Open Targets
0.06Suggestive
oocyte maturation defect 5Open Targets
0.06Suggestive
female infertility due to oocyte meiotic arrestOpen Targets
0.06Suggestive
cleft palate-lateral synechia syndromeOpen Targets
0.06Suggestive
Pathogenic Variants24
NM_001003787.4(STRADA):c.36+1G>ALikely pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy|not provided
β˜…β˜…β˜†β˜†2025
NM_001003787.4(STRADA):c.682C>T (p.Arg228Ter)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 228
NM_001003787.4(STRADA):c.37-1G>CLikely pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy|not provided
β˜…β˜…β˜†β˜†2023
NM_001003787.4(STRADA):c.28C>T (p.Arg10Ter)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2025β†’ Residue 10
NM_001003787.4(STRADA):c.95-2A>CLikely pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2025
NM_001003787.4(STRADA):c.891dup (p.Cys298fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 298
NM_001003787.4(STRADA):c.254_255del (p.Val85fs)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2024β†’ Residue 85
NM_001003787.4(STRADA):c.526del (p.Leu176fs)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2024β†’ Residue 176
NM_001003787.4(STRADA):c.457+1G>TLikely pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2024
NM_001003787.4(STRADA):c.54del (p.Lys18fs)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2024β†’ Residue 18
NM_001003787.4(STRADA):c.828_853del (p.Val277fs)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2024β†’ Residue 277
NM_001003787.4(STRADA):c.101del (p.Pro34fs)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2024β†’ Residue 34
NM_001003787.4(STRADA):c.156del (p.Phe53fs)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2023β†’ Residue 53
NM_001003787.4(STRADA):c.630C>G (p.Tyr210Ter)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2023β†’ Residue 210
NM_001003787.4(STRADA):c.751C>T (p.Gln251Ter)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2023β†’ Residue 251
NM_001003787.4(STRADA):c.207C>G (p.Tyr69Ter)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2022β†’ Residue 69
NM_001003787.4(STRADA):c.491del (p.Met164fs)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2022β†’ Residue 164
NM_001003787.4(STRADA):c.458-1G>ALikely pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2022
NM_001003787.4(STRADA):c.1036C>T (p.Arg346Ter)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜…β˜†β˜†β˜†2022β†’ Residue 346
NM_001003787.4(STRADA):c.842dup (p.Asp281fs)Pathogenic
Polyhydramnios, megalencephaly, and symptomatic epilepsy
β˜†β˜†β˜†β˜†2021β†’ Residue 281
View on ClinVar β†—
Related Genes
STK25Protein interaction100%STK11IPProtein interaction91%PRKAA1Protein interaction91%PRKAA2Protein interaction91%PRKAB1Protein interaction91%PRKAB2Protein interaction91%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
67%
Brain
58%
Lung
57%
Liver
47%
Heart
24%
Gene Interaction Network
Click a node to explore
STRADASTK25STK11IPPRKAA1PRKAA2PRKAB1PRKAB2
PROTEIN STRUCTURE
Preparing viewer…
PDB1UPK Β· 1.85 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.65LoF Tolerant
pLIβ“˜
0.01Tolerant
Observed/Expected LoF0.47 [0.34–0.65]
RankingsWhere STRADA stands among ~20K protein-coding genes
  • #8,618of 20,598
    Most Researched52
  • #2,022of 5,498
    Most Pathogenic Variants24
  • #4,701of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedSTRADA
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Plasticenta: First evidence of microplastics in human placenta.
PMID: 33395930
Environ Int Β· 2021
1.00
2
Redox Regulation of STAT1 and STAT3 Signaling.
PMID: 32987855
Int J Mol Sci Β· 2020
0.90
3
Where vision begins.
PMID: 34245377
Pflugers Arch Β· 2021
0.80
4
STRADA-mutant human cortical organoids model megalencephaly and exhibit delayed neuronal differentiation.
PMID: 33619909
Dev Neurobiol Β· 2021
0.70
5
LKB1-dependent signaling pathways.
PMID: 16756488
Annu Rev Biochem Β· 2006
0.60