STRADA

Chr 17AR

STE20 related adaptor alpha

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

The protein is a pseudokinase that forms a complex with CAB39 and activates STK11/LKB1, which is essential for STK11-induced cell cycle arrest and cellular energy sensing. Biallelic mutations cause polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome through an autosomal recessive inheritance pattern. Disease results from loss-of-function mutations that disrupt the protein's ability to activate STK11/LKB1.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.801 OMIM phenotype
Clinical SummarySTRADA
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 62 VUS of 200 total submissions
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Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — STRADA
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.000
Z-score 2.36
OE 0.50 (0.330.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.49Z-score
OE missense 0.74 (0.660.83)
190 obs / 257.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.330.80)
00.351.4
Missense OE0.74 (0.660.83)
00.61.4
Synonymous OE0.94
01.21.6
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.

References:PMID:19465912

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.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic3
VUS62
Likely Benign112
11
Pathogenic
3
Likely Pathogenic
62
VUS
112
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
2
0
11
Likely Pathogenic
3
0
0
0
3
VUS
2
57
3
0
62
Likely Benign
2
4
62
44
112
Benign
0
0
0
0
0
Total16616744188

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

View in ClinVar →

Protein Context — Lollipop Plot

STRADA · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Ganglioneuroblastoma, NodularNeuroblastoma

Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma

RECRUITING
NCT06172296Phase PHASE3National Cancer Institute (NCI)Started 2024-04-19
Biospecimen CollectionBone Marrow AspirationBone Marrow Biopsy
COVID-19 InfectionHematopoietic and Lymphatic System NeoplasmMalignant Solid Neoplasm

NCI COVID-19 in Cancer Patients, NCCAPS Study

ACTIVE NOT RECRUITING
NCT04387656National Cancer Institute (NCI)Started 2020-06-05
Biospecimen CollectionData CollectionQuality-of-Life Assessment
Adult Cystic NephromaAnaplastic Kidney Wilms TumorAngiolipoma

Study of Kidney Tumors in Younger Patients

ACTIVE NOT RECRUITING
NCT00898365Children's Oncology GroupStarted 2006-02-27
Cytology Specimen Collection ProcedureLaboratory Biomarker Analysis
Acute Myeloid Leukemia

A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations

RECRUITING
NCT04293562Phase PHASE3Children's Oncology GroupStarted 2020-07-21
Allogeneic Hematopoietic Stem Cell TransplantationAsparaginase Erwinia chrysanthemiBiospecimen Collection
GanglioneuroblastomaLocalized Resectable NeuroblastomaLocalized Unresectable Neuroblastoma

Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma

ACTIVE NOT RECRUITING
NCT00904241Children's Oncology GroupStarted 2000-11-06
Cytology Specimen Collection ProcedureLaboratory Biomarker Analysis
Desmoid FibromatosisRecurrent Desmoid FibromatosisUnresectable Desmoid Fibromatosis

A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery

ACTIVE NOT RECRUITING
NCT04195399Phase PHASE2Children's Oncology GroupStarted 2020-10-07
Biospecimen CollectionComputed TomographyEchocardiography Test
Clinical Literature
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