STRADA

Chr 17AR

STE20 related adaptor alpha

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

NCBI Gene: 92335ENSG00000266173UniProt: Q7RTN6

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]

Primary Disease Associations & Inheritance

Polyhydramnios, megalencephaly, and symptomatic epilepsyMIM #611087
AR
448
ClinVar variants
35
Pathogenic / LP
0.00
pLI score
6
Active trials
Clinical Summary— STRADA
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 Pathogenic / Likely Pathogenic· 197 VUS of 448 total submissions
💊
Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.000
Z-score 2.36
OE 0.50 (0.33–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.49Z-score
OE missense 0.74 (0.66–0.83)
190 obs / 257.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.50 (0.33–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.66–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 13 / 26.0Missense obs/exp: 190 / 257.2Syn Z: 0.51

ClinVar Variant Classifications

448 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic6
VUS197
Likely Benign205
Benign5
Conflicting6
29
Pathogenic
6
Likely Pathogenic
197
VUS
205
Likely Benign
5
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
2
18
0
29
Likely Pathogenic
6
0
0
0
6
VUS
6
170
19
2
197
Likely Benign
0
9
95
101
205
Benign
0
1
4
0
5
Conflicting
—6
Total21182136103448

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.

Gene2Phenotype Curations

STRADA-related polyhydramnios, megalencephaly, and symptomatic epilepsy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Polyhydramnios, megalencephaly, and symptomatic epilepsy

MIM #611087

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — STRADA
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Whole exome sequencing identifies the first STRADA point mutation in a patient with polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE).
Bi W et al.·Am J Med Genet A
2016Review
Impact of clinical exomes in neurodevelopmental and neurometabolic disorders.
Evers C et al.·Mol Genet Metab
2017
Whole-exome sequencing and adrenocorticotropic hormone therapy in individuals with infantile spasms.
Demarest S et al.·Dev Med Child Neurol
2022
NHWD-870 suppresses tumor proliferation via the BRD4/STRADA/CCND1 axis in small cell lung cancer.
Ma L et al.·Lung Cancer
2025
Homozygous missense STRADA mutation in a patient with polyhydramnios, megalencephaly and symptomatic epilepsy syndrome.
Aerden M et al.·Clin Dysmorphol
2021Case report
Sleep apnea-related risk of motor vehicle accidents is reduced by continuous positive airway pressure: Swedish Traffic Accident Registry data.
Karimi M et al.·Sleep
2015
Two further cases of polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome, caused by a truncating variant in STRADA.
Alsaif HS et al.·Am J Med Genet A
2021Case report
Zebrafish models of developmental epileptic encephalopathy accurately reflect clinical electrographic biomarkers.
Whyte-Fagundes P et al.·Epilepsia
2026Functional
Identification of EWSR1 rearrangements in patients with immature hematopoietic neoplasms: A case series and review of literature.
Gagnon MF et al.·Ann Diagn Pathol
2022Review
STRADalpha deficiency results in aberrant mTORC1 signaling during corticogenesis in humans and mice.
Orlova KA et al.·J Clin Invest
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
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
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
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

External Resources

Links to major genomics databases and tools