STRADB
Chr 2STE20 related adaptor beta
This gene encodes a pseudokinase that forms a complex with CAB39/MO25 to activate the master kinase STK11/LKB1, which regulates cell polarity and energy metabolism. Mutations cause Polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome, an autosomal recessive disorder characterized by fetal polyhydramnios, macrocephaly, and early-onset epilepsy. The gene is tolerant to loss-of-function variation (LOEUF 0.689), consistent with recessive inheritance requiring biallelic mutations for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
STRADB · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →No open access results found
External Resources
Links to major genomics databases and tools