STRADA

Summary

STRADA (STE20 related adaptor alpha, HGNC:30172) is a protein-coding gene on chromosome 17q23.3, encoding STE20-related kinase adapter protein alpha (Q7RTN6). Pseudokinase which, in complex with CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates STK11/LKB1.

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.

Source: NCBI Gene 92335 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polyhydramnios, megalencephaly, and symptomatic epilepsy (Definitive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 416 total — 16 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 50
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001003787

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30172
Approved symbol	STRADA
Name	STE20 related adaptor alpha
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	STLK5, NY-BR-96, LYK5, Stlk, STRAD
Ensembl gene	ENSG00000266173
Ensembl biotype	protein_coding
OMIM	608626
Entrez	92335

Gene structure

Transcript identifiers

Ensembl transcripts: 62 — 42 protein_coding, 8 retained_intron, 7 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000245865, ENST00000336174, ENST00000375840, ENST00000392950, ENST00000447001, ENST00000577375, ENST00000578008, ENST00000578507, ENST00000578801, ENST00000579318, ENST00000579340, ENST00000579350, ENST00000579549, ENST00000580039, ENST00000580288, ENST00000580338, ENST00000581243, ENST00000581505, ENST00000582026, ENST00000582030, ENST00000582137, ENST00000583085, ENST00000584110, ENST00000617949, ENST00000638193, ENST00000638276, ENST00000638309, ENST00000638578, ENST00000638698, ENST00000638702, ENST00000638708, ENST00000638718, ENST00000638888, ENST00000639135, ENST00000639164, ENST00000639192, ENST00000639521, ENST00000639603, ENST00000639778, ENST00000639816, ENST00000639835, ENST00000639940, ENST00000640086, ENST00000640174, ENST00000640183, ENST00000640397, ENST00000640679, ENST00000640707, ENST00000640741, ENST00000640827, ENST00000640870, ENST00000640924, ENST00000640979, ENST00000640999, ENST00000858962, ENST00000858963, ENST00000858964, ENST00000858965, ENST00000858966, ENST00000938501, ENST00000938502, ENST00000956276

RefSeq mRNA: 15 — MANE Select: NM_001003787 NM_001003786, NM_001003787, NM_001003788, NM_001165969, NM_001165970, NM_001363786, NM_001363787, NM_001363788, NM_001363789, NM_001363790, NM_001363791, NM_001411083, NM_001411084, NM_001411085, NM_153335

CCDS: CCDS11642, CCDS32703, CCDS42367, CCDS54156, CCDS58585, CCDS86625, CCDS86626, CCDS86630, CCDS86632, CCDS86633, CCDS92377, CCDS92378, CCDS92380

Canonical transcript exons

ENST00000336174 — 13 exons

Exon	Start	End
ENSE00003509662	63704341	63704582
ENSE00003540430	63713406	63713527
ENSE00003563897	63706635	63706739
ENSE00003579321	63714006	63714108
ENSE00003611414	63707247	63707418
ENSE00003611471	63728334	63728413
ENSE00003627172	63723298	63723326
ENSE00003644002	63704005	63704047
ENSE00003649404	63710728	63710836
ENSE00003651077	63710491	63710614
ENSE00003689688	63726638	63726695
ENSE00003802073	63741741	63741799
ENSE00003847734	63702832	63703751

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5235 / max 186.5970, expressed in 1817 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167480	17.8269	1817
167481	0.5198	282
167479	0.1767	77

Top tissues by expression

247 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.06	gold quality
mucosa of stomach	UBERON:0001199	95.46	gold quality
left testis	UBERON:0004533	95.20	gold quality
cortical plate	UBERON:0005343	95.04	gold quality
right testis	UBERON:0004534	95.02	gold quality
nerve	UBERON:0001021	94.96	gold quality
tibial nerve	UBERON:0001323	94.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.83	gold quality
right frontal lobe	UBERON:0002810	94.75	gold quality
ganglionic eminence	UBERON:0004023	94.60	gold quality
right ovary	UBERON:0002118	94.59	gold quality
cerebellar hemisphere	UBERON:0002245	94.47	gold quality
cerebellar cortex	UBERON:0002129	94.34	gold quality
metanephros cortex	UBERON:0010533	94.19	gold quality
body of uterus	UBERON:0009853	94.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.02	gold quality
left ovary	UBERON:0002119	94.00	gold quality
right adrenal gland cortex	UBERON:0035827	93.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.98	gold quality
endocervix	UBERON:0000458	93.91	gold quality
granulocyte	CL:0000094	93.88	gold quality
right adrenal gland	UBERON:0001233	93.80	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.65	gold quality
adenohypophysis	UBERON:0002196	93.45	gold quality
right lobe of thyroid gland	UBERON:0001119	93.42	gold quality
ectocervix	UBERON:0012249	93.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.39	gold quality
lower esophagus	UBERON:0013473	93.38	gold quality
sural nerve	UBERON:0015488	93.25	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.25	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

49 targeting STRADA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4426	99.17	66.74	1949

Literature-anchored findings (GeneRIF, showing 12)

• Identification and characterization of an LKB1-specific adaptor protein and substrate, STRAD. Results imply that STRAD plays a key role in regulating the tumor suppressor activities of LKB1. (PMID:12805220)
• Several novel splice isoforms of STRADalpha that differentially affect the kinase activity, complex assembly, subcellular localization of LKB1 and the activation of the LKB1-dependent AMPK pathway were discovered. (PMID:17921699)
• identify a multifactored mechanism to control LKB1 localization, and they suggest that the STRADbeta-LKB1 complex might possess unique functions in the nucleus (PMID:18256292)
• LKB1 deacetylation is regulated by SIRT1 and that this in turn influences its intracellular localization, association with STRAD, kinase activity, and ability to activate AMPK. (PMID:18687677)
• STRADalpha.MO25alpha complexes containing LKB1 variants were equally effective at phosphorylating and activating AMPK, BRSK1, and BRSK2 (PMID:18854318)
• These data define a brush border induction pathway downstream of the Lkb1/Strad/Mo25 polarization complex, yet separate from other polarity events. (PMID:19386264)
• ATP and MO25alpha cooperate to maintain STRADalpha in an “active” closed conformation required for LKB1 activation. (PMID:19513107)
• study describes structure of the core heterotrimeric LKB1-STRADalpha-MO25alpha complex, revealing an unusual allosteric mechanism of LKB1 activation; structure also reveals how mutations in Peutz-Jeghers syndrome & sporadic cancers impair LKB1 function (PMID:19892943)
• aberrant nuclear accumulation of LKB1 caused by STRADalpha deficiency contributes to hyperactivation of mTORC1 signaling and disruption of neuronal lamination during corticogenesis (PMID:20424326)
• We identified for the first time a homozygous point mutation in STRADA causing PMSE. Additional bi-allelic mutations related to PMSE thus far have not been observed in Baylor approximately 6,000 consecutive clinical WES cases, supporting the rarity of this disorder. (PMID:27170158)
• Two further cases of polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome, caused by a truncating variant in STRADA. (PMID:33247513)
• Type II Binders Targeting the ““GLR-Out”” Conformation of the Pseudokinase STRADalpha. (PMID:33440120)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	strada	ENSDARG00000037929
mus_musculus	Strada	ENSMUSG00000069631
rattus_norvegicus	Strada	ENSRNOG00000008637

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), STK26 (ENSG00000134602), TAOK3 (ENSG00000135090), PAK6 (ENSG00000137843), MINK1 (ENSG00000141503), PAK1 (ENSG00000149269), TAOK2 (ENSG00000149930), TNIK (ENSG00000154310), TAOK1 (ENSG00000160551), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), MAP3K19 (ENSG00000176601), PAK2 (ENSG00000180370), SBK2 (ENSG00000187550), STK39 (ENSG00000198648)

Protein

Protein identifiers

STE20-related kinase adapter protein alpha — Q7RTN6 (reviewed: Q7RTN6)

Alternative names: STE20-related adapter protein, Serologically defined breast cancer antigen NY-BR-96

All UniProt accessions (31): A0A0G2JLH2, A0A1W2PNV1, A0A1W2PNV7, A0A1W2PP17, A0A1W2PP78, A0A1W2PPG2, A0A1W2PPI1, A0A1W2PPJ9, A0A1W2PPM8, A0A1W2PQ00, A0A1W2PQ20, A0A1W2PQE8, A0A1W2PQF1, A0A1W2PR00, A0A1W2PR44, A0A1W2PR65, A0A1W2PRI8, A0A1W2PRQ6, Q7RTN6, A0A1W2PRW9, A0A1W2PS04, J3KSA2, J3KSK5, J3QKR7, J3QKU4, J3QQS3, J3QR78, J3QRC1, J3QRH3, J3QS66, Q86YC8

UniProt curated annotations — full annotation on UniProt →

Function. Pseudokinase which, in complex with CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates STK11/LKB1. Adopts a closed conformation typical of active protein kinases and binds STK11/LKB1 as a pseudosubstrate, promoting conformational change of STK11/LKB1 in an active conformation.

Subunit / interactions. Component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity.

Subcellular location. Nucleus. Cytoplasm.

Disease relevance. A homozygous 7-kb deletion involving STRADA is a cause of a syndrome characterized by polyhydramnios, megalencephaly and symptomatic epilepsy.

Domain organisation. The protein kinase domain is predicted to be catalytically inactive.

Similarity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
Q7RTN6-1	1	yes
Q7RTN6-2	2
Q7RTN6-3	3
Q7RTN6-4	4
Q7RTN6-5	5
Q7RTN6-6	6

RefSeq proteins (15): NP_001003786, NP_001003787, NP_001003788, NP_001159441, NP_001159442, NP_001350715, NP_001350716, NP_001350717, NP_001350718, NP_001350719, NP_001350720, NP_001398012, NP_001398013, NP_001398014, NP_699166 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR047173	STRAD_A/B-like	Family

Pfam: PF00069

UniProt features (60 total): helix 17, strand 8, splice variant 7, mutagenesis site 7, turn 6, sequence conflict 4, modified residue 4, sequence variant 3, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1UPK	X-RAY DIFFRACTION	1.85
3GNI	X-RAY DIFFRACTION	2.35
2WTK	X-RAY DIFFRACTION	2.65
8VSU	ELECTRON MICROSCOPY	2.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTN6-F1	80.46	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 2, 46, 329, 419

Mutagenesis-validated functional residues (7):

Position	Phenotype
185	suppresses stk11/lkb1 activation without affecting complex assembly.
231	inhibits interaction with stk11/lkb1; when associated with a-.
233	inhibits interaction with stk11/lkb1; when associated with a-.
241	inhibits interaction with stk11/lkb1.
251	inhibits interaction with stk11/lkb1.
329	loss of stk11/lkb1-mediated phosphorylation.
419	loss of stk11/lkb1-mediated phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-380972	Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-162582	Signal Transduction
R-HSA-165159	MTOR signalling

MSigDB gene sets: 240 (showing top): TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NUCLEAR_TRANSPORT, GOMF_KINASE_ACTIVATOR_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_NUCLEAR_EXPORT, GOBP_ACTIVATION_OF_PROTEIN_KINASE_ACTIVITY, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOBP_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS

GO Biological Process (4): protein export from nucleus (GO:0006611), activation of protein kinase activity (GO:0032147), G1 to G0 transition (GO:0070314), protein phosphorylation (GO:0006468)

GO Molecular Function (7): ATP binding (GO:0005524), kinase binding (GO:0019900), protein kinase activator activity (GO:0030295), protein serine/threonine kinase activator activity (GO:0043539), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), intracellular protein-containing complex (GO:0140535), serine/threonine protein kinase complex (GO:1902554), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
MTOR signalling	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular protein transport	1
nuclear export	1
positive regulation of protein kinase activity	1
cell cycle process	1
phosphorylation	1
protein modification process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
enzyme binding	1
protein kinase activity	1
kinase activator activity	1
protein kinase regulator activity	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
protein-containing complex	1
protein kinase complex	1
cellular_component	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STRADA	CAB39	Q9Y376	999
STRADA	STK11	Q15831	999
STRADA	CAB39L	Q9H9S4	928
STRADA	GOLGA2	Q08379	820
STRADA	STK25	O00506	764
STRADA	RELN	P78509	688
STRADA	GOLPH3	Q9H4A6	684
STRADA	STK11IP	Q8N1F8	665
STRADA	GORASP1	Q9BQQ3	583
STRADA	LRP8	Q14114	570
STRADA	STK24	Q9Y6E0	557
STRADA	USO1	O60763	549
STRADA	YWHAQ	P27348	530
STRADA	VLDLR	P98155	518
STRADA	SLCO6A1	Q86UG4	517

IntAct

45 interactions, top by confidence:

A	B	Type	Score
STRADA	STK11	psi-mi:“MI:0915”(physical association)	0.960
STK11	STRADA	psi-mi:“MI:0217”(phosphorylation reaction)	0.960
STRADA	STK11	psi-mi:“MI:0403”(colocalization)	0.960
STK11	STRADA	psi-mi:“MI:0914”(association)	0.960
STK11	STRADA	psi-mi:“MI:2364”(proximity)	0.960
STK11	STRADA	psi-mi:“MI:0915”(physical association)	0.960
STK11	FKBP5	psi-mi:“MI:0914”(association)	0.910
STK11	HSP90AA1	psi-mi:“MI:0914”(association)	0.740
STK11	KDM4A	psi-mi:“MI:0914”(association)	0.640
CAB39	STRADA	psi-mi:“MI:0915”(physical association)	0.560
STRADA	CAB39	psi-mi:“MI:0915”(physical association)	0.560
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
C5orf24	MEIS1	psi-mi:“MI:0914”(association)	0.530
STRADA	BIRC6	psi-mi:“MI:0915”(physical association)	0.400
CFTR	STRADA	psi-mi:“MI:0915”(physical association)	0.370
STK11	H2AX	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350

BioGRID (61): STRADA (Affinity Capture-RNA), STRADA (Affinity Capture-MS), STRADA (Affinity Capture-MS), STRADA (Affinity Capture-MS), STRADA (Co-localization), STRADA (Affinity Capture-MS), STRADA (Affinity Capture-MS), STRADA (Affinity Capture-MS), STRADA (Affinity Capture-MS), STRADA (Affinity Capture-MS), STRADA (Affinity Capture-Western), STRADA (Co-crystal Structure), STRADA (Affinity Capture-Western), STRADA (Reconstituted Complex), STRADA (Biochemical Activity)

ESM2 similar proteins: A7E3S4, F1QGZ6, O19004, O42565, O54785, P04049, P04627, P05625, P09560, P10398, P11345, P11346, P14056, P27966, P34152, P53351, P53666, P53667, P53668, P53669, P53670, P53671, P62205, Q00944, Q13163, Q14680, Q28GW8, Q32L23, Q3UUJ4, Q4R6X5, Q5E9J9, Q5R4L1, Q5R5M7, Q5RBJ6, Q5ZK47, Q61083, Q61084, Q61846, Q62862, Q7RTN6

Diamond homologs: A0A509AKL0, A5K0N4, F1M5M3, G5ECN5, O23304, O34507, O43930, O54784, O61122, O74426, O88764, P13186, P15442, P15735, P23437, P23647, P28926, P30290, P32516, P32562, P34103, P83098, P84390, P92937, Q03306, Q0D4B2, Q10SC8, Q17850, Q2KJ16, Q3UUJ4, Q4R6X5, Q4WTN5, Q5AP97, Q5E9J9, Q5RBJ6, Q5ZK47, Q66HE5, Q69Q47, Q6L5D4, Q6ZLP5

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
STRADA	“up-regulates activity”	STK11	binding
STK11	“up-regulates activity”	STRADA	phosphorylation
STRADA	“up-regulates quantity”	STK11	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

416 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	5
Uncertain significance	185
Likely benign	185
Benign	4

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
2074680	NM_001003787.4(STRADA):c.207C>G (p.Tyr69Ter)	Pathogenic
254243	NM_001003787.4(STRADA):c.842dup (p.Asp281fs)	Pathogenic
2700850	NM_001003787.4(STRADA):c.101del (p.Pro34fs)	Pathogenic
2704723	NM_001003787.4(STRADA):c.156del (p.Phe53fs)	Pathogenic
2749405	NM_001003787.4(STRADA):c.630C>G (p.Tyr210Ter)	Pathogenic
2790856	NM_001003787.4(STRADA):c.751C>T (p.Gln251Ter)	Pathogenic
3243064	NC_000017.10:g.(?61805674)(61805729_?)del	Pathogenic
3644079	NM_001003787.4(STRADA):c.828_853del (p.Val277fs)	Pathogenic
3649917	NM_001003787.4(STRADA):c.54del (p.Lys18fs)	Pathogenic
4282368	NM_001003787.4(STRADA):c.891dup (p.Cys298fs)	Pathogenic
433133	NM_001003787.4(STRADA):c.403G>A (p.Ala135Thr)	Pathogenic
433134	NM_001003787.4(STRADA):c.190C>T (p.Pro64Ser)	Pathogenic
536756	NM_001003787.4(STRADA):c.1036C>T (p.Arg346Ter)	Pathogenic
842228	NM_001003787.4(STRADA):c.682C>T (p.Arg228Ter)	Pathogenic
856509	NM_001003787.4(STRADA):c.254_255del (p.Val85fs)	Pathogenic
952543	NM_001003787.4(STRADA):c.28C>T (p.Arg10Ter)	Pathogenic
1068097	NM_001003787.4(STRADA):c.36+1G>A	Likely pathogenic
3689518	NM_001003787.4(STRADA):c.457+1G>T	Likely pathogenic
4772793	NM_001003787.4(STRADA):c.95-2A>C	Likely pathogenic
663375	NM_001003787.4(STRADA):c.37-1G>C	Likely pathogenic
800960	NM_001003787.4(STRADA):c.1101-1G>C	Likely pathogenic

SpliceAI

4148 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63688525:A:AG	acceptor_gain	1.0000
17:63688526:G:GG	acceptor_gain	1.0000
17:63688526:GCCC:G	acceptor_gain	1.0000
17:63688594:GGTG:G	donor_loss	1.0000
17:63688595:G:GG	donor_gain	1.0000
17:63688595:GT:G	donor_loss	1.0000
17:63688785:TCAG:T	acceptor_loss	1.0000
17:63688786:CAG:C	acceptor_loss	1.0000
17:63688787:A:AG	acceptor_gain	1.0000
17:63688788:G:GG	acceptor_gain	1.0000
17:63688878:GATG:G	donor_gain	1.0000
17:63688881:GGT:G	donor_loss	1.0000
17:63688882:G:GG	donor_gain	1.0000
17:63688882:G:T	donor_loss	1.0000
17:63688883:T:G	donor_loss	1.0000
17:63689719:G:GT	donor_gain	1.0000
17:63689720:A:T	donor_gain	1.0000
17:63689734:GT:G	donor_gain	1.0000
17:63690258:CTGTA:C	acceptor_gain	1.0000
17:63690259:TGTA:T	acceptor_loss	1.0000
17:63690259:TGTAG:T	acceptor_gain	1.0000
17:63690261:TAGC:T	acceptor_gain	1.0000
17:63690262:A:AG	acceptor_gain	1.0000
17:63690263:G:GG	acceptor_gain	1.0000
17:63690263:GC:G	acceptor_gain	1.0000
17:63690263:GCT:G	acceptor_gain	1.0000
17:63690263:GCTC:G	acceptor_gain	1.0000
17:63690263:GCTCC:G	acceptor_gain	1.0000
17:63690408:GCAAG:G	donor_gain	1.0000
17:63690409:CAAGG:C	donor_loss	1.0000

AlphaMissense

2840 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:63704341:C:A	R367M	1.000
17:63704341:C:G	R367T	1.000
17:63704578:A:G	L288P	1.000
17:63706656:A:C	F279L	1.000
17:63706656:A:T	F279L	1.000
17:63706658:A:G	F279L	1.000
17:63706658:A:T	F279I	1.000
17:63706675:G:T	A273D	1.000
17:63706678:A:G	L272P	1.000
17:63706696:C:T	G266E	1.000
17:63706697:C:G	G266R	1.000
17:63706697:C:T	G266R	1.000
17:63706701:A:C	S264R	1.000
17:63706701:A:T	S264R	1.000
17:63706703:T:G	S264R	1.000
17:63706711:T:A	D261V	1.000
17:63706712:C:A	D261Y	1.000
17:63706712:C:G	D261H	1.000
17:63707254:A:G	L249P	1.000
17:63707265:G:C	S245R	1.000
17:63707265:G:T	S245R	1.000
17:63707267:T:G	S245R	1.000
17:63707273:A:G	W243R	1.000
17:63707273:A:T	W243R	1.000
17:63707413:A:T	V196D	1.000
17:63704030:A:G	L373P	0.999
17:63704047:C:A	R367S	0.999
17:63704047:C:G	R367S	0.999
17:63704362:A:G	L360P	0.999
17:63704364:G:C	C359W	0.999

dbSNP variants (sampled 300 via entrez): RS1000046317 (17:63724837 A>G), RS1000048620 (17:63711621 C>T), RS1000318365 (17:63717219 A>G), RS1000334951 (17:63710411 C>A), RS1000376529 (17:63717230 T>C), RS1000430301 (17:63716925 A>C,G), RS1000670398 (17:63717475 G>GT,GTTTT), RS1000703126 (17:63725026 G>A,C), RS1000763251 (17:63715325 C>A), RS1000903651 (17:63736770 A>AT), RS1000904324 (17:63736692 G>A), RS1000908088 (17:63703862 T>C), RS1001014537 (17:63731071 G>A), RS1001041220 (17:63723153 C>T), RS1001094946 (17:63722801 C>T)

Disease associations

OMIM: gene MIM:608626 | disease phenotypes: MIM:611087, MIM:117100

GenCC curated gene-disease

Disease	Classification	Inheritance
polyhydramnios, megalencephaly, and symptomatic epilepsy	Definitive	Autosomal recessive

Mondo (4): polyhydramnios, megalencephaly, and symptomatic epilepsy (MONDO:0012611), polyhydramnios (MONDO:0004585), epilepsy (MONDO:0005027), self-limited epilepsy with centrotemporal spikes (MONDO:0007295)

Orphanet (2): Polyhydramnios-megalencephaly-symptomatic epilepsy syndrome (Orphanet:500533), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000121	Nephrocalcinosis
HP:0000154	Wide mouth
HP:0000179	Thick lower lip vermilion
HP:0000194	Open mouth
HP:0000215	Thick upper lip vermilion
HP:0000256	Macrocephaly
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000297	Facial hypotonia
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000431	Wide nasal bridge
HP:0000486	Strabismus
HP:0000873	Diabetes insipidus
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001344	Absent speech
HP:0001355	Megalencephaly
HP:0001382	Joint hypermobility
HP:0001508	Failure to thrive
HP:0001533	Slender build
HP:0001561	Polyhydramnios
HP:0001622	Premature birth
HP:0001631	Atrial septal defect
HP:0001635	Congestive heart failure

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000175_9	Height	7.000000e-07
GCST90002403_368	Red blood cell count	2.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D006831	Polyhydramnios	C12.050.703.610
C567020	Polyhydramnios, Megalencephaly, And Symptomatic Epilepsy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1795198 (SINGLE PROTEIN), CHEMBL3885534 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 17,619 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL377300	BRIVANIB	3	1,721
CHEMBL1088751	PH-797804	2	700
CHEMBL1231124	AZD-1480	2	1,576
CHEMBL296468	BMS-387032	1	2,075

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — STLK subfamily

ChEMBL bioactivities

10 potent at pChembl≥5 of 10 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	Kd	19.76	nM	CHEMBL3752910
7.70	ED50	19.76	nM	CHEMBL3752910
6.50	Kd	316	nM	AZD-1480
6.17	Kd	672	nM	PH-797804
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.94	Kd	1137	nM	BRIVANIB
5.55	Kd	2807	nM	BMS-387032
5.43	Kd	3672	nM	RUXOLITINIB

PubChem BioAssay actives

6 with measured affinity, of 276 total; 6 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149947: Binding affinity to human STRADA incubated for 45 mins by Kinobead based pull down assay	kd	0.0198	uM
5-chloro-2-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-N-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine	1425186: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3160	uM
3-[3-bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxo-1-pyridinyl]-N,4-dimethylbenzamide	1425186: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.6720	uM
(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-ol	1425186: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1370	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	1425186: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.8070	uM
Ruxolitinib	1425186: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	3.6720	uM

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Cisplatin	affects cotreatment, increases expression, decreases response to substance	2
Ozone	increases abundance, affects cotreatment, increases expression, increases oxidation	2
GSK-J4	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
beta-lapachone	increases expression	1
afimoxifene	decreases reaction, decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cannabidiol	decreases expression	1
Coumestrol	increases expression	1
Estrogens	decreases expression, decreases reaction	1
Ethyl Methanesulfonate	increases expression	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Gold Compounds	increases expression	1

ChEMBL screening assays

47 unique, capped per target: 47 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1838322	Binding	Inhibition of human STLK5 in HL60 cells lysate at 10 uM using post probe-labeling by LC-MS/MS analysis relative to control	Synthesis and structure-activity relationship of 4-quinolone-3-carboxylic acid based inhibitors of glycogen synthase kinase-3β. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TQ98	HAP1 STRADA (-) 1	Cancer cell line	Male
CVCL_TQ99	HAP1 STRADA (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy