STRADA
gene geneOn this page
Also known as STLK5NY-BR-96LYK5StlkSTRAD
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 (top 8% of genes corpus-wide)
- GTEx eGene: eQTL in 28 tissues, sQTL in 33 (q < 0.05)
- Phenotypes (HPO): 50
- ChEMBL bioactivity: 5 clinical-phase molecules tested; no curated mechanism-of-action drug
- Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.65 (unconstrained)
- 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: 73 — 49 protein_coding, 11 nonsense_mediated_decay, 8 retained_intron, 5 protein_coding_CDS_not_defined
MANE Select: ENST00000336174
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 8, TSL 3: 5, TSL 4: 2, TSL 5: 34
ENST00000336174, ENST00000245865, 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, ENST00001044025, ENST00001044026, ENST00001044027, ENST00001059590, ENST00001059591, ENST00001059592, ENST00001059593, ENST00001059594, ENST00001059595, ENST00001126886, ENST00001139137
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.
Highest expression (Bgee): uterine tube, mucosa of stomach, testis, cortical plate, nerve.
Genetic regulation across tissues (GTEx eQTL / sQTL)
STRADA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 28 tissues and its splicing (sQTL) in 33 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
showing 20 of 61 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Cells Cultured fibroblasts | eqtl | 3.5e-19 | -0.31 | 17:63797521:AT:A |
| Nerve Tibial | eqtl | 7.4e-13 | -0.19 | 17:63711499:C:T |
| Cells Cultured fibroblasts | sqtl | 2.7e-11 | +0.52 | 17:63685848:A:G |
| Esophagus Muscularis | sqtl | 2.9e-11 | +0.63 | 17:63757269:G:T |
| Adipose Subcutaneous | eqtl | 9.1e-11 | -0.21 | 17:63885518:C:T |
| Colon Sigmoid | sqtl | 5.6e-09 | +0.64 | 17:63707888:G:A |
| Adrenal Gland | eqtl | 2.5e-08 | -0.28 | 17:63728941:CATT:C |
| Esophagus Muscularis | eqtl | 3.4e-08 | -0.16 | 17:63749477:G:A |
| Adipose Visceral Omentum | eqtl | 5.4e-08 | -0.20 | 17:63817218:T:C |
| Esophagus Mucosa | sqtl | 6.3e-08 | +0.48 | 17:63696844:C:CT |
| Artery Tibial | sqtl | 1.4e-07 | +0.49 | 17:63619677:T:C |
| Thyroid | sqtl | 8.6e-07 | +0.42 | 17:63599175:G:T |
| Nerve Tibial | sqtl | 1.8e-06 | +0.43 | 17:63677851:T:A |
| Whole Blood | eqtl | 7.8e-06 | +0.08 | 17:63846478:G:A |
| Esophagus Gastroesophageal Junction | sqtl | 8.8e-06 | +0.59 | 17:63628037:T:C |
| Colon Sigmoid | eqtl | 1.1e-05 | -0.14 | 17:63725765:G:A |
| Breast Mammary Tissue | sqtl | 1.3e-05 | -1.21 | 17:63513126:A:G |
| Skin Not Sun Exposed Suprapubic | sqtl | 1.4e-05 | +0.45 | 17:63568639:G:A |
| Esophagus Gastroesophageal Junction | eqtl | 3.5e-05 | -0.14 | 17:63728941:CATT:C |
| Brain Frontal Cortex BA9 | eqtl | 5.2e-05 | -0.19 | 17:63797521:AT:A |
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
showing 100 of 247 tissues 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 |
| left adrenal gland cortex | UBERON:0035825 | 93.22 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 93.09 | gold quality |
| left adrenal gland | UBERON:0001234 | 93.08 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 92.83 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 92.67 | gold quality |
| skin of abdomen | UBERON:0001416 | 92.61 | gold quality |
| right coronary artery | UBERON:0001625 | 92.60 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 92.56 | gold quality |
| left uterine tube | UBERON:0001303 | 92.53 | gold quality |
| skin of leg | UBERON:0001511 | 92.45 | gold quality |
| right atrium auricular region | UBERON:0006631 | 92.43 | gold quality |
| body of stomach | UBERON:0001161 | 92.41 | gold quality |
| ascending aorta | UBERON:0001496 | 92.33 | gold quality |
| thoracic aorta | UBERON:0001515 | 92.32 | gold quality |
| spleen | UBERON:0002106 | 92.20 | gold quality |
| left coronary artery | UBERON:0001626 | 92.07 | gold quality |
| ventricular zone | UBERON:0003053 | 91.99 | gold quality |
| tibial artery | UBERON:0007610 | 91.95 | gold quality |
| popliteal artery | UBERON:0002250 | 91.94 | gold quality |
| aorta | UBERON:0000947 | 91.90 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 91.89 | gold quality |
| apex of heart | UBERON:0002098 | 91.80 | gold quality |
| monocyte | CL:0000576 | 91.76 | gold quality |
| body of pancreas | UBERON:0001150 | 91.73 | gold quality |
| leukocyte | CL:0000738 | 91.72 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 91.64 | gold quality |
| cardiac atrium | UBERON:0002081 | 91.54 | gold quality |
| bone marrow cell | CL:0002092 | 91.42 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 91.41 | gold quality |
| hypothalamus | UBERON:0001898 | 91.31 | gold quality |
| minor salivary gland | UBERON:0001830 | 91.27 | gold quality |
| colonic epithelium | UBERON:0000397 | 91.25 | gold quality |
| cerebellum | UBERON:0002037 | 91.16 | gold quality |
| esophagus | UBERON:0001043 | 91.05 | gold quality |
| nucleus accumbens | UBERON:0001882 | 91.04 | gold quality |
| testis | UBERON:0000473 | 90.93 | gold quality |
| transverse colon | UBERON:0001157 | 90.93 | gold quality |
| adrenal cortex | UBERON:0001235 | 90.89 | gold quality |
| spinal cord | UBERON:0002240 | 90.70 | gold quality |
| thyroid gland | UBERON:0002046 | 90.68 | gold quality |
| right lung | UBERON:0002167 | 90.61 | gold quality |
| right lobe of liver | UBERON:0001114 | 90.58 | gold quality |
| adrenal gland | UBERON:0002369 | 90.54 | gold quality |
| putamen | UBERON:0001874 | 90.43 | gold quality |
| omental fat pad | UBERON:0010414 | 90.34 | gold quality |
| coronary artery | UBERON:0001621 | 90.32 | gold quality |
| peritoneum | UBERON:0002358 | 90.25 | gold quality |
| amygdala | UBERON:0001876 | 90.15 | gold quality |
| vermiform appendix | UBERON:0001154 | 90.11 | gold quality |
| stomach | UBERON:0000945 | 90.06 | gold quality |
| stromal cell of endometrium | CL:0002255 | 90.04 | gold quality |
| islet of Langerhans | UBERON:0000006 | 90.03 | gold quality |
| gall bladder | UBERON:0002110 | 89.87 | gold quality |
| prefrontal cortex | UBERON:0000451 | 89.78 | gold quality |
| caudate nucleus | UBERON:0001873 | 89.67 | gold quality |
| pituitary gland | UBERON:0000007 | 89.56 | gold quality |
| pancreas | UBERON:0001264 | 89.52 | gold quality |
| uterine cervix | UBERON:0000002 | 89.45 | gold quality |
| esophagus mucosa | UBERON:0002469 | 89.29 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 89.08 | gold quality |
| rectum | UBERON:0001052 | 88.93 | gold quality |
| small intestine | UBERON:0002108 | 88.30 | gold quality |
| upper lobe of lung | UBERON:0008948 | 88.19 | gold quality |
| adrenal tissue | UBERON:0018303 | 88.08 | gold quality |
| heart left ventricle | UBERON:0002084 | 87.92 | gold quality |
| calcaneal tendon | UBERON:0003701 | 87.87 | gold quality |
| lymph node | UBERON:0000029 | 87.82 | gold quality |
| gastrocnemius | UBERON:0001388 | 87.74 | gold quality |
| muscle of leg | UBERON:0001383 | 87.69 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 87.63 | 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 |
HPA expression
RNA tissue specificity: Low tissue specificity
showing 60 of 80 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Testis | tissue | 34.4 | high |
| Postcentral gyrus | tissue | 31.5 | |
| Hippocampus | tissue | 26.8 | medium |
| Pituitary gland | tissue | 26.5 | |
| Locus coeruleus | tissue | 25.6 | |
| Nucleus accumbens | tissue | 25.0 | |
| Choroid plexus | tissue | 23.1 | |
| Vagina | tissue | 19.4 | medium |
| Hippocampal formation | tissue | 19.2 | |
| Spinal cord | tissue | 19.1 | |
| Tonsil | tissue | 19.1 | high |
| Lymph node | tissue | 19.0 | high |
| Thymus | tissue | 18.8 | |
| Superior colliculi | tissue | 18.3 | |
| Medulla oblongata | tissue | 18.2 | |
| Pons | tissue | 18.0 | |
| Parathyroid gland | tissue | 17.9 | high |
| Skin 1 | tissue | 17.8 | medium |
| Substantia nigra | tissue | 17.7 | |
| Cerebellum | tissue | 17.5 | high |
| Thalamus | tissue | 17.4 | |
| Fallopian tube | tissue | 17.4 | high |
| Bone marrow | tissue | 17.3 | high |
| Epididymis | tissue | 17.2 | medium |
| Hypothalamus | tissue | 17.2 | |
| Periaqueductal gray | tissue | 17.1 | |
| Cerebral cortex | tissue | 17.0 | medium |
| Somatosensory cortex | tissue | 17.0 | |
| Frontal cortex | tissue | 16.8 | |
| Midbrain | tissue | 16.8 | |
| Corpus callosum | tissue | 16.5 | |
| Basal ganglia | tissue | 16.2 | medium |
| Olfactory bulb | tissue | 16.1 | |
| Occipital cortex | tissue | 16.1 | |
| Smooth muscle | tissue | 16.0 | low |
| Septum | tissue | 16.0 | |
| Spleen | tissue | 15.6 | medium |
| Prefrontal cortex | tissue | 15.4 | |
| Ventral forebrain | tissue | 15.2 | |
| Putamen | tissue | 15.0 | |
| Amygdala | tissue | 14.9 | |
| Retrosplenial and cingulate cortex | tissue | 14.7 | |
| Ovary | tissue | 14.5 | not detected |
| Caudate putamen | tissue | 14.5 | |
| Motor cortex | tissue | 14.4 | |
| Insular cortex | tissue | 14.2 | |
| Retrosplenial cortex | tissue | 14.1 | |
| Entorhinal cortex | tissue | 13.9 | |
| Temporal cortex | tissue | 13.9 | |
| Heart muscle | tissue | 13.5 | high |
| Seminal vesicle | tissue | 13.4 | medium |
| Adrenal gland | tissue | 13.0 | high |
| Retina | tissue | 12.9 | |
| Endometrium 1 | tissue | 12.5 | high |
| Placenta | tissue | 12.5 | high |
| Gallbladder | tissue | 12.5 | high |
| Cervix | tissue | 12.1 | high |
| Lung | tissue | 12.1 | medium |
| Kidney | tissue | 12.1 | high |
| Esophagus | tissue | 12.0 | high |
Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Nucleus ambiguus (32.3), Precentral gyrus (31.6), Precentral gyrus, middle (29.8), Paracentral lobule, anterior (29.2), Perirhinal gyrus (28.8).
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): TAL1
miRNA regulators (miRDB)
Targeting STRADA by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).
showing 30 of 49 miRNAs:
| 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 |
Functional genomics
gnomAD constraint: pLI 0.00788, LOEUF 0.649, missense Z 1.92 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD RMC): no regional variation along ENST00000336174 — one region, missense o/e 0.81.
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)
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:1919399) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| cleft palate | 1 |
| malocclusion | 1 |
| domed cranium | 1 |
| tremors | 1 |
| decreased body size | 1 |
| decreased locomotor activity | 1 |
| abnormal suckling behavior | 1 |
| reduced female fertility | 1 |
| abnormal body wall morphology | 1 |
| hypotonia | 1 |
| long incisors | 1 |
| increased brain size | 1 |
| abnormal neuronal migration | 1 |
| protruding tongue | 1 |
| postnatal lethality, incomplete penetrance | 1 |
| preweaning lethality, complete penetrance | 1 |
| enlarged brain ventricles | 1 |
| ectopic neuron | 1 |
Additional cross-species homologs
Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.
| Organism | UniProt | Identity | Method |
|---|---|---|---|
| Pongo abelii | Q5RBJ6 | 99.1% | Diamond |
| Macaca fascicularis | Q4R6X5 | 98.7% | Diamond |
| Bos taurus | Q5E9J9 | 95.4% | Diamond |
| Gallus gallus | Q5ZK47 | 86.0% | Diamond |
| Drosophila melanogaster | P83098 | 37.5% | Diamond |
| Caenorhabditis elegans | G5ECN5 | 35.4% | Diamond |
Genomic neighbors (locus context)
Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).
| Symbol | Type | Entrez |
|---|---|---|
| MAP3K3 | protein-coding | 4215 |
| LIMD2 | protein-coding | 80774 |
| FTSJ3 | protein-coding | 117246 |
| CCDC47 | protein-coding | 57003 |
| PSMC5 | protein-coding | 5705 |
| SMARCD2 | protein-coding | 6603 |
| DDX42 | protein-coding | 11325 |
| TACO1 | protein-coding | 51204 |
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): Q7RTN6, A0A0G2JLH2, A0A1W2PNV1, A0A1W2PNV7, A0A1W2PP17, A0A1W2PP78, A0A1W2PPG2, A0A1W2PPI1, A0A1W2PPJ9, A0A1W2PPM8, A0A1W2PQ00, A0A1W2PQ20, A0A1W2PQE8, A0A1W2PQF1, A0A1W2PR00, A0A1W2PR44, A0A1W2PR65, A0A1W2PRI8, A0A1W2PRQ6, 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 (64 total): helix 20, strand 8, splice variant 7, mutagenesis site 7, turn 7, 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 by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 1UPK | Crystal structure of MO25 in complex with a C-terminal peptide of STRAD | X-RAY DIFFRACTION | 1.85 |
| 3GNI | Structure of STRAD and MO25 | X-RAY DIFFRACTION | 2.35 |
| 2WTK | Structure of the heterotrimeric LKB1-STRADalpha-MO25alpha complex | X-RAY DIFFRACTION | 2.65 |
| 8VSU | Cryo-EM structure of LKB1-STRADalpha-MO25alpha heterocomplex | ELECTRON MICROSCOPY | 2.86 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q7RTN6-F1 | 80.46 | 0.64 |
Human Protein Atlas
Protein class: Enzymes, Kinases, STE Ser/Thr protein kinases, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system
Protein evidence: Evidence at protein level
Subcellular location (HPA, imaging): cytosol; nucleoplasm
Antibody reliability (HPA): IH approved · IF supported
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)
| Type | Positions |
|---|---|
| Phosphoserine | 2, 46 |
| Phosphothreonine | 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
1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
3 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | curated |
| R-HSA-165159 | MTOR signalling | — |
| R-HSA-162582 | Signal Transduction | — |
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
2 top-level categories:
| Category | Pathways |
|---|---|
| MTOR signalling | 1 |
| Signal Transduction | 1 |
GO top-level categories
29 GO namespaces:
| 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 |
| anion 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 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).
11 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| G1 to G0 transition | BP | physical interaction |
| activation of protein kinase activity | BP | direct assay |
| protein export from nucleus | BP | direct assay |
| cytoplasm | CC | direct assay |
| cytosol | CC | direct assay |
| intracellular protein-containing complex | CC | direct assay |
| nucleoplasm | CC | direct assay |
| nucleus | CC | direct assay |
| kinase binding | MF | physical interaction |
| protein kinase activator activity | MF | direct assay |
| protein serine/threonine kinase activator activity | MF | direct assay |
Protein interactions and networks
STRING
showing 15 of 596 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| STRADA | CAB39 | Q9Y376 | 979 |
| STRADA | STK11 | Q15831 | 944 |
| STRADA | CAB39L | Q9H9S4 | 845 |
| STRADA | GOLGA2 | Q08379 | 813 |
| STRADA | RELN | P78509 | 717 |
| STRADA | GOLPH3 | Q9H4A6 | 691 |
| STRADA | STK11IP | Q8N1F8 | 623 |
| STRADA | GORASP1 | Q9BQQ3 | 614 |
| STRADA | TSC2 | P49815 | 601 |
| STRADA | MTOR | P42345 | 587 |
| STRADA | LRP8 | Q14114 | 564 |
| STRADA | USO1 | O60763 | 552 |
| STRADA | YWHAQ | P27348 | 526 |
| STRADA | VLDLR | P98155 | 516 |
| STRADA | NPRL3 | Q12980 | 496 |
IntAct
Human interaction partners of STRADA in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
4 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| STK11 | physical association | 0.960 | 12 |
| CAB39 | physical association | 0.560 | 3 |
| BIRC6 | physical association | 0.400 | 1 |
| CFTR | physical association | 0.370 | 1 |
BioGRID (61 interactions; top human partners by supporting records): STK11 (Affinity Capture-MS; 20 records), CAB39 (Co-crystal Structure; 4 records), CAB39L (Affinity Capture-MS; 3 records), C5orf24 (Affinity Capture-MS; 2 records), LBHD1 (Affinity Capture-MS; 2 records), PIP4K2A (Affinity Capture-MS; 2 records), XPO1 (Affinity Capture-MS; 2 records), AHSG (Affinity Capture-MS), AMY1A (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CFTR (PCA), CLASP2 (Affinity Capture-MS), DCAF10 (Proximity Label-MS), DDX58 (Affinity Capture-RNA)
SIGNOR signaling
showing 3 of 4 signaling interactions:
| A | Effect | B | Mechanism |
|---|---|---|---|
| STRADA | “up-regulates activity” | STK11 | binding |
| STK11 | “up-regulates activity” | STRADA | phosphorylation |
| STRADA | “up-regulates quantity” | STK11 | phosphorylation |
Protein complexes (CORUM) (1)
Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).
1 complexes by size:
| Complex | Subunits | Members |
|---|---|---|
| LKB1-STRAD-MO25 complex | 3 | CAB39, STK11, STRADA |
Disease & clinical
Genetic variants
Variant evidence for STRADA: 416 ClinVar records (21 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.
ClinVar
416 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 16 |
| Likely pathogenic | 5 |
| Uncertain significance | 187 |
| Likely benign | 184 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (15)
Showing the 15 best-reviewed of 21 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.
| Variant ID | HGVS | Classification | Review | Submitters |
|---|---|---|---|---|
| 842228 | NM_001003787.4(STRADA):c.682C>T (p.Arg228Ter) | Pathogenic | criteria provided, multiple submitters, no conflicts | 2 |
| 663375 | NM_001003787.4(STRADA):c.37-1G>C | Likely pathogenic | criteria provided, multiple submitters, no conflicts | 2 |
| 1068097 | NM_001003787.4(STRADA):c.36+1G>A | Likely pathogenic | criteria provided, multiple submitters, no conflicts | 2 |
| 536756 | NM_001003787.4(STRADA):c.1036C>T (p.Arg346Ter) | Pathogenic | criteria provided, single submitter | 1 |
| 856509 | NM_001003787.4(STRADA):c.254_255del (p.Val85fs) | Pathogenic | criteria provided, single submitter | 1 |
| 952543 | NM_001003787.4(STRADA):c.28C>T (p.Arg10Ter) | Pathogenic | criteria provided, single submitter | 1 |
| 2074680 | NM_001003787.4(STRADA):c.207C>G (p.Tyr69Ter) | Pathogenic | criteria provided, single submitter | 1 |
| 2700850 | NM_001003787.4(STRADA):c.101del (p.Pro34fs) | Pathogenic | criteria provided, single submitter | 1 |
| 2704723 | NM_001003787.4(STRADA):c.156del (p.Phe53fs) | Pathogenic | criteria provided, single submitter | 1 |
| 2749405 | NM_001003787.4(STRADA):c.630C>G (p.Tyr210Ter) | Pathogenic | criteria provided, single submitter | 1 |
| 2790856 | NM_001003787.4(STRADA):c.751C>T (p.Gln251Ter) | Pathogenic | criteria provided, single submitter | 1 |
| 3644079 | NM_001003787.4(STRADA):c.828_853del (p.Val277fs) | Pathogenic | criteria provided, single submitter | 1 |
| 3649917 | NM_001003787.4(STRADA):c.54del (p.Lys18fs) | Pathogenic | criteria provided, single submitter | 1 |
| 4282368 | NM_001003787.4(STRADA):c.891dup (p.Cys298fs) | Pathogenic | criteria provided, single submitter | 1 |
| 3689518 | NM_001003787.4(STRADA):c.457+1G>T | Likely pathogenic | criteria provided, single submitter | 1 |
Per-variant reference — Sugi Variant
Explore STRADA’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 935):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 17:63706633–63706634 | donor_loss | 1.0000 | 4 |
| 17:63706740–63706741 | acceptor_loss | 1.0000 | 5 |
| 17:63706746–63706747 | acceptor_gain | 1.0000 | 2 |
| 17:63710489–63710490 | donor_loss | 1.0000 | 5 |
| 17:63710502 | donor_gain | 1.0000 | |
| 17:63710615–63710616 | acceptor_loss | 1.0000 | 5 |
| 17:63710726 | donor_loss | 1.0000 | |
| 17:63710837–63710838 | acceptor_loss | 1.0000 | 5 |
| 17:63713404–63713405 | donor_loss | 1.0000 | 3 |
| 17:63713528–63713529 | acceptor_loss | 1.0000 | 6 |
AlphaMissense
1,162 missense substitutions predicted likely pathogenic (of 2,840 scored), across 276 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:
| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
|---|---|---|---|
| M287 | 9 | 0.937 | 0.997 |
| M282 | 9 | 0.855 | 0.975 |
| D261 | 8 | 0.999 | 1.000 |
| D301 | 8 | 0.995 | 0.999 |
| H193 | 8 | 0.991 | 0.998 |
| H187 | 8 | 0.986 | 0.997 |
| F279 | 8 | 0.982 | 1.000 |
| S245 | 8 | 0.980 | 1.000 |
| H200 | 8 | 0.974 | 0.997 |
| S264 | 8 | 0.961 | 1.000 |
| F233 | 8 | 0.937 | 0.996 |
| H353 | 8 | 0.930 | 0.991 |
| H127 | 8 | 0.929 | 0.992 |
| N274 | 8 | 0.929 | 0.998 |
| F352 | 8 | 0.929 | 0.996 |
| F378 | 8 | 0.927 | 0.995 |
| F348 | 8 | 0.920 | 0.996 |
| F137 | 8 | 0.915 | 0.994 |
| F125 | 8 | 0.895 | 0.987 |
| D157 | 8 | 0.873 | 0.940 |
HPA cancer prognostics
RNA cancer specificity: Low cancer specificity
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
2 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Kidney Renal Clear Cell Carcinoma (TCGA) | unfavorable | 3.03e-05 |
| Liver Hepatocellular Carcinoma (TCGA) | unfavorable | 0.000426 |
Disease associations
OMIM: gene MIM:608626 | disease phenotypes: MIM:611087, MIM:117100
GenCC curated gene-disease
1 curated gene-disease records:
| Disease | Classification | Inheritance | Records |
|---|---|---|---|
| polyhydramnios, megalencephaly, and symptomatic epilepsy | Definitive | Autosomal recessive | 5 |
Genomics England panels (PanelApp)
Clinical diagnostic gene panels including this gene (11 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.
11 panels:
| Panel | Rating |
|---|---|
| DDG2P | green |
| Early onset or syndromic epilepsy | green |
| Fetal anomalies | green |
| Hydrocephalus | green |
| Hypotonic infant | green |
| Intellectual disability | green |
| Leukodystrophy, childhood onset | green |
| Nephrocalcinosis or nephrolithiasis | green |
| Paediatric disorders | green |
| Unexplained death in infancy and sudden unexplained death in childhood | green |
| Unexplained young onset end-stage renal disease | green |
Mondo (2): polyhydramnios, megalencephaly, and symptomatic epilepsy (MONDO:0012611), 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 phenotypes (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 |
| HP:0001999 | Abnormal facial shape |
| HP:0002003 | Large forehead |
| HP:0002119 | Ventriculomegaly |
| HP:0002133 | Status epilepticus |
| HP:0002307 | Drooling |
| HP:0002384 | Focal impaired awareness seizure |
| HP:0002446 | Astrocytosis |
| HP:0002540 | Inability to walk |
| HP:0002553 | Highly arched eyebrow |
| HP:0003199 | Decreased muscle mass |
| HP:0006829 | Severe muscular hypotonia |
| HP:0010804 | Tented upper lip vermilion |
| HP:0011182 | Interictal epileptiform activity |
| HP:0011344 | Severe global developmental delay |
| HP:0011968 | Feeding difficulties |
| HP:0012371 | Hyperplasia of midface |
| HP:0012430 | Cerebral white matter hypoplasia |
| HP:0012469 | Infantile spasms |
| HP:0030680 | Abnormal cardiovascular system morphology |
| HP:0030891 | Periventricular white matter hyperintensities |
GWAS associations
2 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST90002403_80 | Red blood cell count | 2e-12 |
| GCST000175_10 | Height | 7e-7 |
EFO canonical traits (from GWAS)
1 canonical traits:
| EFO ID | Trait name |
|---|---|
| EFO:0004305 | erythrocyte count |
MeSH disease descriptors
1 disease descriptors:
| Descriptor | Name | Tree numbers |
|---|---|---|
| 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
Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 18,430 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
5 molecules by phase:
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL1789941 | RUXOLITINIB | 4 | 12,161 |
| CHEMBL377300 | BRIVANIB | 3 | 1,784 |
| CHEMBL1231124 | AZD-1480 | 2 | 1,632 |
| CHEMBL1088751 | PH-797804 | 2 | 726 |
| CHEMBL296468 | BMS-387032 | 1 | 2,127 |
PharmGKB: 1 entry (CPIC guideline: no)
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 287 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 | increases expression, decreases response to substance, affects cotreatment | 2 |
| Ozone | affects cotreatment, increases expression, increases oxidation, increases abundance | 2 |
| GSK-J4 | decreases expression | 1 |
| alpha-pinene | affects cotreatment, increases expression, increases oxidation, increases abundance | 1 |
| beta-lapachone | increases expression | 1 |
| afimoxifene | decreases expression, decreases reaction | 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)
Via MONDO — disease-level, not drug-specific.
showing 60 of 300 trials:
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00004637 | Phase 4 | COMPLETED | Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy |
| NCT00043914 | Phase 4 | COMPLETED | Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy |
| NCT00132223 | Phase 4 | 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 | Phase 4 | UNKNOWN | Study to Improve the Treatment of Epilepsy (SITE) |
| NCT00137709 | Phase 4 | UNKNOWN | Hormone Profiles in Adults With Newly Diagnosed Epilepsy |
| NCT00154076 | Phase 4 | COMPLETED | A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies |
| NCT00165828 | Phase 4 | TERMINATED | Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization |
| NCT00181116 | Phase 4 | COMPLETED | Levetiracetam for Benign Rolandic Epilepsy |
| NCT00207935 | Phase 4 | COMPLETED | Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population |
| NCT00215592 | Phase 4 | COMPLETED | Open Label, Zonegran (Zonisamide) In Partial Onset Seizures |
| NCT00266604 | Phase 4 | COMPLETED | A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy |
| NCT00288639 | Phase 4 | COMPLETED | Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER). |
| NCT00312676 | Phase 4 | UNKNOWN | Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote |
| NCT00323947 | Phase 4 | COMPLETED | Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy |
| NCT00385411 | Phase 4 | COMPLETED | Study of Valproate in Young Patients Suffering From Epilepsy |
| NCT00522418 | Phase 4 | TERMINATED | Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients |
| NCT00537940 | Phase 4 | COMPLETED | Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures |
| NCT00552526 | Phase 4 | UNKNOWN | Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy |
| NCT00564915 | Phase 4 | COMPLETED | RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy |
| NCT00571155 | Phase 4 | COMPLETED | Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery |
| NCT00572195 | Phase 4 | COMPLETED | RNS® System LTT Study |
| NCT00610532 | Phase 4 | TERMINATED | Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy |
| NCT00630357 | Phase 4 | COMPLETED | Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy |
| NCT00630630 | Phase 4 | COMPLETED | Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy |
| NCT00630968 | Phase 4 | COMPLETED | S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy |
| NCT00631150 | Phase 4 | COMPLETED | A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy |
| NCT00659958 | Phase 4 | COMPLETED | ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs |
| NCT00713622 | Phase 4 | COMPLETED | Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate |
| NCT00807989 | Phase 4 | COMPLETED | The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy |
| NCT00832884 | Phase 4 | COMPLETED | The Safety of Intravenous Lacosamide |
| NCT00869622 | Phase 4 | COMPLETED | Antiepileptic Drugs and Osteoporotic Prevention Trial |
| NCT00896987 | Phase 4 | COMPLETED | Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies |
| NCT00952081 | Phase 4 | COMPLETED | A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients |
| NCT01118455 | Phase 4 | TERMINATED | Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures |
| NCT01127165 | Phase 4 | COMPLETED | Low and High Dose Zonisamide in Children as Monotherapy |
| NCT01127256 | Phase 4 | COMPLETED | Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation |
| NCT01140867 | Phase 4 | COMPLETED | Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy |
| NCT01175954 | Phase 4 | COMPLETED | Cognitive and Behavioral Effects of Lacosamide |
| NCT01229735 | Phase 4 | COMPLETED | Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures |
| NCT01244724 | Phase 4 | TERMINATED | Lexapro for Major Depression in Patients With Epilepsy |
| NCT01309074 | Phase 4 | WITHDRAWN | Does Pregabalin Improve Symptoms of Anxiety in Patients With Epilepsy? A Comparison With Sertraline |
| NCT01318408 | Phase 4 | COMPLETED | Levetiracetam: The Anti-Convulsant of Choice for Elderly Patients With Dementia |
| NCT01498822 | Phase 4 | COMPLETED | Levetiracetam Versus Oxcarbazepine as Monotherapy to Evaluate Efficacy and Safety in Subjects With Newly or Recently Diagnosed Partial Epilepsy |
| NCT01546688 | Phase 4 | TERMINATED | A Study to Evaluate the Safety and Tolerability and Explore the Efficacy of Zonisamide as add-on Therapy in Elderly Patients With Refractory Partial Seizures |
| NCT01607346 | Phase 4 | TERMINATED | An Open Label Study to Evaluate the Effects of Ezogabine/Retigabine Added to Existing Anti-epileptic Drug(s) on Urinary Voiding Function in Subjects With Partial Onset Seizures |
| NCT01627860 | Phase 4 | COMPLETED | First Add-on vs. Mono-therapy Study of Topiramate in Neuro-Surgical Patients |
| NCT01689649 | Phase 4 | COMPLETED | A Study to Assess Tolerability and Efficacy of Topiramate Monotherapy in Recently Diagnosed Patients With Epilepsy |
| NCT01713777 | Phase 4 | COMPLETED | Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy: Chronic-Dose 4-Period Replicate Design |
| NCT01733394 | Phase 4 | COMPLETED | Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy: Single-Dose 6-Period Replicate Design (EQUIGEN Single-Dose Study) |
| NCT01804322 | Phase 4 | COMPLETED | Standardized Educational Plan for Epilepsy Patients With Comorbidities |
| NCT01932502 | Phase 4 | UNKNOWN | Evaluation of Onfi Conversion Therapy Replacing Clonazepam in Patients With Medically Refractory Epilepsy |
| NCT01995825 | Phase 4 | COMPLETED | Lamotrigine Bioequivalence |
| NCT02100644 | Phase 4 | COMPLETED | Valproate Dose Reduction and Its Clinical Evaluation by Introducing Lamotrigine in Japanese Women With Epilepsy - Single Arm, Multicenter, and Open-label Study |
| NCT02178995 | Phase 4 | COMPLETED | Methylphenidate Treatment of Attention Deficits in Epilepsy |
| NCT02205931 | Phase 4 | UNKNOWN | Ketogenic Diet in Infants With Epilepsy (KIWE) |
| NCT02362373 | Phase 4 | COMPLETED | Women With Epilepsy: a Pilot Study of PK and PD Anti-epileptic Drug Effects in Levonorgestrel Intrauterine System Users |
| NCT02404168 | Phase 4 | COMPLETED | BEEP Follow Up: Evaluation of Repeatability of Lamotrigine Pharmacokinetics in Epileptic Patients |
| NCT02429596 | Phase 4 | UNKNOWN | A Trial of Generic Substitution of Antiepileptic Drugs |
| NCT02633241 | Phase 4 | COMPLETED | A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging |
| NCT02645279 | Phase 4 | UNKNOWN | Comparison of Oral 30 % Dextrose and iv Midazolam Sedation During MRI in Neonates |
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for STRADA across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
- Associated diseases: polyhydramnios, megalencephaly, and symptomatic epilepsy
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): polyhydramnios, polyhydramnios, megalencephaly, and symptomatic epilepsy, self-limited epilepsy with centrotemporal spikes