STRADA

Chr 17AR

STE20 related adaptor alpha

Also known as: LYK5, NY-BR-96, PMSE, STLK5, STRAD, STRAD alpha, Stlk

NCBI Gene: 92335ENSG00000266173UniProt: Q7RTN6OMIM: 608626

The protein encoded by this gene contains a STE20-like kinase domain, but lacks several residues that are critical for catalytic activity, so it is termed a 'pseudokinase'. The protein forms a heterotrimeric complex with serine/threonine kinase 11 (STK11, also known as LKB1) and the scaffolding protein calcium binding protein 39 (CAB39, also known as MO25). The protein activates STK11 leading to the phosphorylation of both proteins and excluding STK11 from the nucleus. The protein is necessary for STK11-induced G1 cell cycle arrest. A mutation in this gene has been shown to result in polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described but their full-length nature is not known. [provided by RefSeq, Sep 2009]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.801 OMIM phenotype
Clinical Summary— STRADA
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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 195 VUS of 448 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — STRADA
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.80LOEUF
pLI 0.000
Z-score 2.36
OE 0.50 (0.33–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.49Z-score
OE missense 0.74 (0.66–0.83)
190 obs / 257.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.50 (0.33–0.80)
0≤0.351.4
Missense OE?0.74 (0.66–0.83)
0≤0.61.4
Synonymous OE?0.94
0≤1.21.6
LoF obs/exp: 13 / 26.0Missense obs/exp: 190 / 257.2Syn Z: 0.51
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSTRADA-related polyhydramnios, megalencephaly, and symptomatic epilepsyLOFAR
Mechanism Note (expert annotation)
LOF

Biallelic LOF causes polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE). LOF disrupts LKB1-AMPK-mTOR signaling. GOF prediction is incorrect.1

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6743th %ile
GOF
0.7125th %ile
LOF
0.3746th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

  1. 1.PMID 19465912 ↗

ClinVar Variant Classifications

448 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic6
VUS195
Likely Benign206
Benign4
Conflicting6
19
Pathogenic
6
Likely Pathogenic
195
VUS
206
Likely Benign
4
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
2
2
0
19
Likely Pathogenic
6
0
0
0
6
VUS
8
173
12
2
195
Likely Benign
2
10
94
100
206
Benign
0
0
4
0
4
Conflicting
—6
Total31185112102436

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

10 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap STRADA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

STRADA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients