{"gene":"STRN","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":1998,"finding":"Human STRN encodes a 780-amino-acid calmodulin-binding protein belonging to the WD-repeat family, is preferentially expressed in brain, maps to chromosome 2p22-p21, and localizes to the somato-dendritic compartment of neurons (mainly in spines), suggesting a role in dendritic Ca2+ signaling.","method":"cDNA cloning, sequencing, chromosomal mapping by fluorescence in situ hybridization, northern blot expression analysis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cloning and characterization with chromosomal localization, single lab but multiple orthogonal methods (sequencing, FISH, expression analysis)","pmids":["9693043"],"is_preprint":false},{"year":2014,"finding":"The STRN-ALK fusion protein causes constitutive activation of ALK kinase via dimerization mediated by the coiled-coil domain of STRN (exon 3), leading to thyroid-stimulating hormone-independent proliferation of thyroid cells, transformation in vitro, and tumor formation in nude mice; ALK kinase activity is required for these effects.","method":"RNA sequencing to identify fusion, functional cell assays (proliferation, transformation), nude mouse xenograft, ALK inhibitor treatment (crizotinib, TAE684), mutagenesis/domain analysis of coiled-coil","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — constitutive kinase activation demonstrated by in vitro assays and in vivo tumor formation, mechanism (coiled-coil dimerization) established, replicated by independent group (PMID:24475247), multiple orthogonal methods","pmids":["24613930","24475247"],"is_preprint":false},{"year":2014,"finding":"The STRN-ALK fusion transcript consists of exon 3 of STRN fused to exon 20 of ALK, confirmed by array-CGH, RT-PCR, and Sanger sequencing, and the fusion is detected in papillary thyroid carcinoma.","method":"High-resolution array-CGH, RT-PCR, Sanger sequencing","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal molecular methods (array-CGH, RT-PCR, sequencing) in a single lab confirming fusion junction","pmids":["24475247"],"is_preprint":false},{"year":2018,"finding":"Thyroid-specific expression of STRN-ALK in transgenic mice drives development of poorly differentiated thyroid carcinomas with decreased thyroglobulin expression and loss of E-cadherin, establishing STRN-ALK as sufficient to cause thyroid cancer dedifferentiation in vivo.","method":"Transgenic mouse model (thyroglobulin promoter-driven STRN-ALK), histology, immunohistochemistry, goitrogen treatment","journal":"The American journal of pathology","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo transgenic model with rigorous histological and IHC characterization, replicated and extended in a subsequent study (PMID:31298630)","pmids":["30125543"],"is_preprint":false},{"year":2019,"finding":"Combined STRN-ALK expression and p53 loss in transgenic mice drives stepwise thyroid cancer progression from well-differentiated PTC to poorly differentiated and anaplastic thyroid carcinoma with lung metastases, demonstrating genetic epistasis between STRN-ALK and p53 in tumor progression.","method":"Compound transgenic mouse model, ultrasound imaging, histology, immunohistochemistry, RNA-seq, quantitative RT-PCR","journal":"Thyroid : official journal of the American Thyroid Association","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis established in vivo with multiple orthogonal readouts (imaging, histology, transcriptomics), builds on prior transgenic model","pmids":["31298630"],"is_preprint":false},{"year":2023,"finding":"Acute STRN-ALK expression in normal thyroid cells activates MAPK, JAK/STAT3, and PI3K/AKT/mTOR signaling, downregulates thyroid differentiation and iodine metabolism genes (including Slc5a5/NIS, Foxe1, Tg, Duox1/2), causes NIS loss from the cell membrane, and reduces NIS-mediated radioiodine uptake by fourfold; these effects are reversed by ALK inhibitors (crizotinib, ceritinib) or MEK inhibitor selumetinib.","method":"Doxycycline-inducible STRN-ALK expression in PCCL3 thyroid cells, qRT-PCR, Western blot, immunofluorescence, RNA sequencing, 131I uptake assay, ALK/MEK/JAK inhibitor treatments","journal":"Thyroid : official journal of the American Thyroid Association","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — inducible system with multiple orthogonal methods (transcriptomics, protein, functional iodine uptake, pharmacological rescue), mechanistic pathway dissection in a single rigorous study","pmids":["36585857"],"is_preprint":false},{"year":2022,"finding":"STK25 interacts with STRN (striatin), and STRN can reverse lipid metabolism changes caused by STK25 deficiency in hepatocellular carcinoma cells, placing STRN downstream of STK25 in the STK25/STRN/AMPK/ACC1 pathway regulating lipid synthesis and EMT.","method":"Co-immunoprecipitation, Western blot, wound healing assay, Transwell invasion assay, xenograft mouse model, STRING database interaction prediction","journal":"Cancer cell international","confidence":"Low","confidence_rationale":"Tier 3 / Weak — STK25-STRN interaction supported by Co-IP but pathway placement relies partly on database prediction and rescue experiments in a single lab without detailed mechanistic follow-up","pmids":["34986838"],"is_preprint":false},{"year":2020,"finding":"STRN overexpression in HCC cells (Huh7) promotes cell invasion and migration but does not affect proliferation or apoptosis; modulation of STRN expression alters cell morphology and changes EMT markers E-cadherin (negatively correlated) and Vimentin (positively correlated), establishing STRN as a regulator of EMT in hepatocellular carcinoma.","method":"siRNA knockdown and overexpression in Huh7 cells, migration and invasion assays, Western blot for EMT markers, IHC in human tissue","journal":"BioMed research international","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, KD/OE with cellular phenotype but no upstream/downstream pathway mechanism established beyond EMT marker correlation","pmids":["32280692"],"is_preprint":false},{"year":2017,"finding":"The STRN-ALK fusion retains the coiled-coil domain of STRN (exon 3) fused to the kinase domain of ALK (exon 20), and this fusion is functional and sensitive to crizotinib inhibition in lung adenocarcinoma, confirmed by RT-PCR and Sanger sequencing.","method":"NGS-based ctDNA profiling, RT-PCR, Sanger sequencing, clinical response to crizotinib","journal":"Mayo Clinic proceedings. Innovations, quality & outcomes","confidence":"Low","confidence_rationale":"Tier 3 / Weak — molecular confirmation of fusion structure and ALK dependence in a single clinical case, no dedicated functional experiments beyond drug response","pmids":["30225407"],"is_preprint":false},{"year":2025,"finding":"STRN functions as a multifunctional scaffold protein that modulates kinases, phosphatases, and calcium-dependent pathways; is involved in vascular reactivity, blood pressure regulation, and vascular remodeling in cardiovascular disease; and STRN polymorphisms are linked to salt sensitivity of blood pressure.","method":"Review synthesizing published experimental findings (no new primary experiments reported in this abstract)","journal":"Biomedicine & pharmacotherapy","confidence":"Low","confidence_rationale":"Tier 4 / Weak — review paper, no new primary experimental data described in the abstract; included for completeness of scaffold/phosphatase regulatory function attribution","pmids":["40752421"],"is_preprint":false}],"current_model":"STRN (striatin) is a calmodulin-binding WD-repeat scaffold protein that localizes to dendritic spines in neurons and functions as a scaffold modulating kinase, phosphatase, and calcium-dependent signaling; when fused to ALK via chromosomal rearrangement (most commonly exon 3 of STRN joined to exon 20 of ALK), the coiled-coil domain of STRN drives constitutive ALK kinase dimerization and activation, triggering MAPK, JAK/STAT3, and PI3K/AKT/mTOR pathways, downregulating thyroid differentiation genes including NIS/SLC5A5, and driving oncogenesis and dedifferentiation in thyroid, lung, and other cancers that are sensitive to ALK tyrosine kinase inhibitors."},"narrative":{"mechanistic_narrative":"STRN (striatin) is a brain-enriched, calmodulin-binding WD-repeat protein that localizes to the somato-dendritic compartment and dendritic spines of neurons, where its features point to a role as a scaffold in dendritic Ca2+ signaling [PMID:9693043]. Its most extensively characterized activity, however, is as the 5' partner in the oncogenic STRN-ALK fusion: a chromosomal rearrangement joins STRN exon 3 to ALK exon 20, retaining the STRN coiled-coil domain that drives constitutive ALK kinase dimerization and activation independent of upstream stimuli [PMID:24613930, PMID:24475247, PMID:30225407]. This fusion is sufficient to transform thyroid cells, conferring thyroid-stimulating hormone-independent proliferation and tumor formation in xenografts, with all effects dependent on ALK kinase activity [PMID:24613930, PMID:24475247]. In transgenic mice, thyroid-specific STRN-ALK expression produces poorly differentiated thyroid carcinoma with loss of thyroglobulin and E-cadherin, and combined p53 loss drives stepwise progression to anaplastic carcinoma with lung metastases [PMID:30125543, PMID:31298630]. Mechanistically, STRN-ALK activates MAPK, JAK/STAT3, and PI3K/AKT/mTOR signaling and downregulates thyroid differentiation and iodine-metabolism genes including Slc5a5/NIS, Foxe1, Tg, and Duox1/2, causing loss of membrane NIS and reduced radioiodine uptake that is reversed by ALK or MEK inhibition [PMID:36585857]. Outside the fusion context, STRN has been implicated as a regulator of epithelial-mesenchymal transition in hepatocellular carcinoma [PMID:32280692].","teleology":[{"year":1998,"claim":"Established the identity and basic properties of STRN, defining it as a calmodulin-binding WD-repeat protein with neuronal, dendritic localization—framing it as a candidate scaffold in dendritic calcium signaling.","evidence":"cDNA cloning, sequencing, FISH chromosomal mapping, and northern blot expression analysis","pmids":["9693043"],"confidence":"Medium","gaps":["No direct demonstration of the calcium-signaling function inferred from localization","Scaffold binding partners not identified in this work","No structural model of the WD-repeat or coiled-coil regions"]},{"year":2014,"claim":"Identified the STRN-ALK fusion and showed that the STRN coiled-coil domain mediates constitutive ALK dimerization and kinase activation, answering how a non-kinase scaffold becomes oncogenic.","evidence":"RNA-seq fusion discovery, proliferation/transformation assays, nude mouse xenografts, coiled-coil mutagenesis, and ALK inhibitor treatment; fusion junction confirmed by array-CGH, RT-PCR, and Sanger sequencing","pmids":["24613930","24475247"],"confidence":"High","gaps":["Does not address whether wild-type STRN function contributes to oncogenesis","Downstream effector pathways not dissected in this study"]},{"year":2018,"claim":"Demonstrated in vivo that STRN-ALK alone is sufficient to initiate thyroid carcinogenesis and dedifferentiation, moving beyond cell-based transformation to organismal causation.","evidence":"Thyroglobulin promoter-driven STRN-ALK transgenic mice with histology, IHC, and goitrogen treatment","pmids":["30125543"],"confidence":"High","gaps":["Tumors remained poorly differentiated rather than fully anaplastic, indicating cooperating events were unresolved","Molecular pathway downstream of the fusion not mapped here"]},{"year":2019,"claim":"Established genetic epistasis between STRN-ALK and p53 loss in driving progression to anaplastic carcinoma with metastasis, defining the cooperating event needed for full malignancy.","evidence":"Compound transgenic mice with ultrasound imaging, histology, IHC, RNA-seq, and qRT-PCR","pmids":["31298630"],"confidence":"High","gaps":["Does not establish which transcriptional programs mediate the progression","Therapeutic vulnerability of advanced tumors not tested"]},{"year":2023,"claim":"Dissected the signaling consequences of STRN-ALK, linking fusion activity to MAPK/JAK-STAT3/PI3K-AKT-mTOR activation and to loss of NIS-mediated radioiodine uptake reversible by kinase inhibition—explaining the dedifferentiation and radioiodine resistance phenotype.","evidence":"Doxycycline-inducible STRN-ALK in PCCL3 cells with transcriptomics, Western blot, immunofluorescence, 131I uptake assay, and ALK/MEK/JAK inhibitor rescue","pmids":["36585857"],"confidence":"High","gaps":["Which pathway predominantly drives NIS loss not fully resolved among the three activated arms","Findings in rat thyroid cell line require validation in human disease context"]},{"year":2022,"claim":"Proposed a non-fusion role for STRN as a downstream node of STK25 regulating hepatic lipid metabolism and EMT, extending STRN function into metabolic regulation.","evidence":"Co-IP, Western blot, wound healing/Transwell assays, xenografts, and STRING interaction prediction in HCC cells","pmids":["34986838"],"confidence":"Low","gaps":["Pathway placement relies partly on database prediction rather than direct mechanism","STK25-STRN interaction not validated reciprocally or by structural methods","Single lab without mechanistic follow-up"]},{"year":2020,"claim":"Implicated wild-type STRN as a regulator of EMT in hepatocellular carcinoma, suggesting a scaffold function in tumor invasion independent of ALK fusion.","evidence":"siRNA knockdown and overexpression in Huh7 cells with migration/invasion assays, EMT-marker Western blots, and tissue IHC","pmids":["32280692"],"confidence":"Low","gaps":["No upstream or downstream molecular mechanism beyond EMT-marker correlation","Single cell line and single lab","Effect on proliferation/apoptosis was absent, limiting interpretation"]},{"year":2025,"claim":"Synthesized evidence positioning STRN as a multifunctional scaffold modulating kinases, phosphatases, and calcium pathways with links to vascular reactivity and salt-sensitive blood pressure.","evidence":"Review synthesizing prior experimental findings (no new primary data)","pmids":["40752421"],"confidence":"Low","gaps":["No new primary experimental data","Cardiovascular and phosphatase-scaffold roles not mechanistically resolved within this corpus"]},{"year":null,"claim":"The normal physiological function of wild-type STRN as a calmodulin-binding scaffold—its phosphatase/kinase partners and its role in dendritic calcium signaling—remains uncharacterized at the mechanistic level in this corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No reconstituted scaffold complex or defined enzymatic partners in the timeline","Neuronal calcium-signaling role inferred from localization but not functionally tested","Link between native scaffold function and oncogenic fusion biology unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1,5]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[1,3,4]}],"complexes":[],"partners":["ALK","STK25","CALMODULIN"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O43815","full_name":"Striatin","aliases":[],"length_aa":780,"mass_kda":86.1,"function":"Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:18782753). STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (Probable)","subcellular_location":"Cytoplasm; Membrane; Cell projection, dendritic spine","url":"https://www.uniprot.org/uniprotkb/O43815/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/STRN","classification":"Not Classified","n_dependent_lines":6,"n_total_lines":1208,"dependency_fraction":0.004966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"STK26","stoichiometry":10.0},{"gene":"DYNLL2","stoichiometry":4.0},{"gene":"PPP2CA","stoichiometry":4.0},{"gene":"STK24","stoichiometry":4.0},{"gene":"CALD1","stoichiometry":0.2},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"CTTN","stoichiometry":0.2},{"gene":"DYNLL1","stoichiometry":0.2},{"gene":"MAP4K4","stoichiometry":0.2},{"gene":"PPP2CB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/STRN","total_profiled":1310},"omim":[{"mim_id":"618649","title":"HECT DOMAIN E3 UBIQUITIN PROTEIN LIGASE 1; HECTD1","url":"https://www.omim.org/entry/618649"},{"mim_id":"617919","title":"STRIATIN-INTERACTING PROTEIN 2; STRIP2","url":"https://www.omim.org/entry/617919"},{"mim_id":"617918","title":"STRIATIN-INTERACTING PROTEIN 1; STRIP1","url":"https://www.omim.org/entry/617918"},{"mim_id":"615100","title":"CTTNBP2 N TERMINUS-LIKE PROTEIN; CTTNBP2NL","url":"https://www.omim.org/entry/615100"},{"mim_id":"614767","title":"STRIATIN, CALMODULIN-BINDING PROTEIN 4; STRN4","url":"https://www.omim.org/entry/614767"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/STRN"},"hgnc":{"alias_symbol":["PPP2R6A","STRN1"],"prev_symbol":[]},"alphafold":{"accession":"O43815","domains":[{"cath_id":"2.130.10.10","chopping":"456-657_664-780","consensus_level":"high","plddt":93.081,"start":456,"end":780},{"cath_id":"1.20.5","chopping":"74-122","consensus_level":"medium","plddt":86.932,"start":74,"end":122}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O43815","model_url":"https://alphafold.ebi.ac.uk/files/AF-O43815-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O43815-F1-predicted_aligned_error_v6.png","plddt_mean":67.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=STRN","jax_strain_url":"https://www.jax.org/strain/search?query=STRN"},"sequence":{"accession":"O43815","fasta_url":"https://rest.uniprot.org/uniprotkb/O43815.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O43815/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O43815"}},"corpus_meta":[{"pmid":"24613930","id":"PMC_24613930","title":"Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer.","date":"2014","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24613930","citation_count":212,"is_preprint":false},{"pmid":"26848800","id":"PMC_26848800","title":"Two Cases of Renal Cell Carcinoma Harboring a Novel STRN-ALK Fusion Gene.","date":"2016","source":"The American journal of surgical pathology","url":"https://pubmed.ncbi.nlm.nih.gov/26848800","citation_count":72,"is_preprint":false},{"pmid":"24475247","id":"PMC_24475247","title":"Identification of a recurrent STRN/ALK fusion in thyroid carcinomas.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24475247","citation_count":68,"is_preprint":false},{"pmid":"29046324","id":"PMC_29046324","title":"ETV6-NTRK3 and STRN-ALK kinase fusions are recurrent events in papillary thyroid cancer of adult population.","date":"2017","source":"European journal of endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/29046324","citation_count":47,"is_preprint":false},{"pmid":"31298630","id":"PMC_31298630","title":"Mouse Model of Thyroid Cancer Progression and Dedifferentiation Driven by STRN-ALK Expression and Loss of p53: Evidence for the Existence of Two Types of Poorly Differentiated Carcinoma.","date":"2019","source":"Thyroid : official journal of the American Thyroid Association","url":"https://pubmed.ncbi.nlm.nih.gov/31298630","citation_count":34,"is_preprint":false},{"pmid":"32661669","id":"PMC_32661669","title":"Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion.","date":"2020","source":"Head and neck pathology","url":"https://pubmed.ncbi.nlm.nih.gov/32661669","citation_count":33,"is_preprint":false},{"pmid":"30225407","id":"PMC_30225407","title":"A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation Sequencing-Based Circulating Tumor DNA Profiling Exhibits Excellent Response to Crizotinib.","date":"2017","source":"Mayo Clinic proceedings. 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Functional testing of 527 cancer drugs in patient-derived cancer cells.","date":"2021","source":"Translational oncology","url":"https://pubmed.ncbi.nlm.nih.gov/33530027","citation_count":15,"is_preprint":false},{"pmid":"33555117","id":"PMC_33555117","title":"A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review.","date":"2021","source":"The oncologist","url":"https://pubmed.ncbi.nlm.nih.gov/33555117","citation_count":14,"is_preprint":false},{"pmid":"32280692","id":"PMC_32280692","title":"High STRN Expression Promotes HCC Invasion and Migration but Not Cell Proliferation or Apoptosis through Facilitating Epithelial-Mesenchymal Transition.","date":"2020","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/32280692","citation_count":13,"is_preprint":false},{"pmid":"34232939","id":"PMC_34232939","title":"Coexistence of a secondary STRN-ALK, EML4-ALK double-fusion variant in a lung adenocarcinoma patient with EGFR mutation: a case report.","date":"2021","source":"Anti-cancer drugs","url":"https://pubmed.ncbi.nlm.nih.gov/34232939","citation_count":12,"is_preprint":false},{"pmid":"33960639","id":"PMC_33960639","title":"Primary resistance to alectinib in a patient with STRN-ALK-positive non-small cell lung cancer: A case report.","date":"2021","source":"Thoracic cancer","url":"https://pubmed.ncbi.nlm.nih.gov/33960639","citation_count":12,"is_preprint":false},{"pmid":"31821324","id":"PMC_31821324","title":"RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease.","date":"2019","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/31821324","citation_count":9,"is_preprint":false},{"pmid":"38928438","id":"PMC_38928438","title":"Antineoplastic Effect of ALK Inhibitor Crizotinib in Primary Human Anaplastic Thyroid Cancer Cells with STRN-ALK Fusion In Vitro.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38928438","citation_count":9,"is_preprint":false},{"pmid":"36290807","id":"PMC_36290807","title":"STRN-ALK Fusion in Lung Adenocarcinoma with Brain Metastasis Responded Well to Ensartinib: A Case Report.","date":"2022","source":"Current oncology (Toronto, Ont.)","url":"https://pubmed.ncbi.nlm.nih.gov/36290807","citation_count":8,"is_preprint":false},{"pmid":"37869075","id":"PMC_37869075","title":"Case Report: Ensartinib for gastric epithelioid inflammatory myofibrosarcoma with STRN-ALK fusion.","date":"2023","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/37869075","citation_count":8,"is_preprint":false},{"pmid":"36524450","id":"PMC_36524450","title":"CircTNPO3 promotes hepatocellular carcinoma progression by sponging miR-199b-5p and regulating STRN expression.","date":"2022","source":"The Kaohsiung journal of medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36524450","citation_count":7,"is_preprint":false},{"pmid":"37865792","id":"PMC_37865792","title":"Identification of dual STRN-NTRK2 rearrangements in a high grade sarcoma, with good clinical response to first-line larotrectinib therapy.","date":"2023","source":"Diagnostic pathology","url":"https://pubmed.ncbi.nlm.nih.gov/37865792","citation_count":7,"is_preprint":false},{"pmid":"39721296","id":"PMC_39721296","title":"Alectinib for the treatment of papillary thyroid carcinoma harbouring STRN - ALK fusion.","date":"2024","source":"European journal of cancer (Oxford, England : 1990)","url":"https://pubmed.ncbi.nlm.nih.gov/39721296","citation_count":6,"is_preprint":false},{"pmid":"16144968","id":"PMC_16144968","title":"Downregulation of AQP2 expression in the kidney of polydipsic STR/N mice.","date":"2005","source":"American journal of physiology. Renal physiology","url":"https://pubmed.ncbi.nlm.nih.gov/16144968","citation_count":6,"is_preprint":false},{"pmid":"37810968","id":"PMC_37810968","title":"Case Report: A rare case of non-small cell lung cancer with STRN-ALK fusion in a patient in very poor condition treated with first-line ensartinib.","date":"2023","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/37810968","citation_count":4,"is_preprint":false},{"pmid":"38321754","id":"PMC_38321754","title":"Ciliated Muconodular Papillary Tumors of the Lung Harboring STRN::ALK Fusion: Case Report and Review of the Literature.","date":"2024","source":"International journal of surgical pathology","url":"https://pubmed.ncbi.nlm.nih.gov/38321754","citation_count":3,"is_preprint":false},{"pmid":"37152028","id":"PMC_37152028","title":"Coexistence of a novel STRN-ALK, NBEA-ALK double-fusion in an ovarian malignant mesothelioma patient: a case report and review.","date":"2023","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/37152028","citation_count":3,"is_preprint":false},{"pmid":"39830770","id":"PMC_39830770","title":"A rationale for the poor response to alectinib in a patient with adenocarcinoma of the lung harbouring a STRN-ALK fusion by artificial intelligence and molecular modelling: a case report.","date":"2024","source":"Translational lung cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/39830770","citation_count":3,"is_preprint":false},{"pmid":"37077094","id":"PMC_37077094","title":"STRN-ALK rearranged malignant peritoneal mesothelioma-Presenting with bilateral extensive pelvic masses in a young woman: Mimicking low-grade serous ovarian carcinoma.","date":"2023","source":"Indian journal of pathology & microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/37077094","citation_count":2,"is_preprint":false},{"pmid":"10794493","id":"PMC_10794493","title":"Reduced interleukin-1 responsiveness in immune system and central nervous system of inbred polydipsic (STR/N) mice.","date":"2000","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/10794493","citation_count":2,"is_preprint":false},{"pmid":"38526831","id":"PMC_38526831","title":"Reticular Myxoid Odontogenic Neoplasm with Novel STRN::ALK Fusion: Report of 2 Cases in 3-Year-Old Males.","date":"2024","source":"Head and neck pathology","url":"https://pubmed.ncbi.nlm.nih.gov/38526831","citation_count":1,"is_preprint":false},{"pmid":"40752421","id":"PMC_40752421","title":"Striatin (STRN): A multifunctional protein in cardiovascular health and cancer progression.","date":"2025","source":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/40752421","citation_count":0,"is_preprint":false},{"pmid":"39284095","id":"PMC_39284095","title":"STRN-ALK Fusion in Advanced Salivary Gland Carcinoma With Response to Anaplastic Lymphoma Kinase Inhibition: Case Report and Literature Review.","date":"2024","source":"WMJ : official publication of the State Medical Society of Wisconsin","url":"https://pubmed.ncbi.nlm.nih.gov/39284095","citation_count":0,"is_preprint":false},{"pmid":"42086841","id":"PMC_42086841","title":"STRN::NTRK3-fused neoplasm with \"monster cells\" in the pelvis of a young adult female: expanding the clinicopathologic spectrum of NTRK-rearranged neoplasms.","date":"2026","source":"Virchows Archiv : an international journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/42086841","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.15.670616","title":"Structural variants are enriched in deleterious visible phenotypes in  <i>Drosophila</i>","date":"2025-08-21","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.15.670616","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":19575,"output_tokens":2944,"usd":0.051443,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9900,"output_tokens":3045,"usd":0.062812,"stage2_stop_reason":"end_turn"},"total_usd":0.114255,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify papers about the canonical STRN protein (striatin, a calmodulin-binding WD-repeat scaffold protein). Let me classify each paper:\n\n- Papers 1-7, 9-17, 19-24, 26-35: About STRN-ALK fusion or STRN protein function — INCLUDE (relevant to STRN mechanism)\n- Paper 8: About human STRN cloning and characterization — INCLUDE\n- Paper 11: STK25/STRN interaction in HCC — INCLUDE\n- Paper 15: STRN role in EMT/HCC — INCLUDE\n- Paper 22: circTNPO3/miR-199b-5p/STRN axis — this is about a circRNA regulating STRN expression, not STRN protein mechanism directly — EXCLUDE (circRNA paper)\n- Papers 25, 31: About STR/N mouse strain (polydipsic mice) — EXCLUDE (different entity, mouse strain not the STRN gene)\n- Paper 29: AI/molecular modeling of STRN-ALK dimerization — computational only, EXCLUDE from high-confidence but review\n- Paper 36: Drosophila Strn-Mlck — different gene (Strn-Mlck = stretchin-MLCK), EXCLUDE\n\nNow extracting mechanistic discoveries:\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"Human STRN encodes a 780-amino-acid calmodulin-binding protein belonging to the WD-repeat family, is preferentially expressed in brain, maps to chromosome 2p22-p21, and localizes to the somato-dendritic compartment of neurons (mainly in spines), suggesting a role in dendritic Ca2+ signaling.\",\n      \"method\": \"cDNA cloning, sequencing, chromosomal mapping by fluorescence in situ hybridization, northern blot expression analysis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cloning and characterization with chromosomal localization, single lab but multiple orthogonal methods (sequencing, FISH, expression analysis)\",\n      \"pmids\": [\"9693043\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The STRN-ALK fusion protein causes constitutive activation of ALK kinase via dimerization mediated by the coiled-coil domain of STRN (exon 3), leading to thyroid-stimulating hormone-independent proliferation of thyroid cells, transformation in vitro, and tumor formation in nude mice; ALK kinase activity is required for these effects.\",\n      \"method\": \"RNA sequencing to identify fusion, functional cell assays (proliferation, transformation), nude mouse xenograft, ALK inhibitor treatment (crizotinib, TAE684), mutagenesis/domain analysis of coiled-coil\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — constitutive kinase activation demonstrated by in vitro assays and in vivo tumor formation, mechanism (coiled-coil dimerization) established, replicated by independent group (PMID:24475247), multiple orthogonal methods\",\n      \"pmids\": [\"24613930\", \"24475247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The STRN-ALK fusion transcript consists of exon 3 of STRN fused to exon 20 of ALK, confirmed by array-CGH, RT-PCR, and Sanger sequencing, and the fusion is detected in papillary thyroid carcinoma.\",\n      \"method\": \"High-resolution array-CGH, RT-PCR, Sanger sequencing\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal molecular methods (array-CGH, RT-PCR, sequencing) in a single lab confirming fusion junction\",\n      \"pmids\": [\"24475247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Thyroid-specific expression of STRN-ALK in transgenic mice drives development of poorly differentiated thyroid carcinomas with decreased thyroglobulin expression and loss of E-cadherin, establishing STRN-ALK as sufficient to cause thyroid cancer dedifferentiation in vivo.\",\n      \"method\": \"Transgenic mouse model (thyroglobulin promoter-driven STRN-ALK), histology, immunohistochemistry, goitrogen treatment\",\n      \"journal\": \"The American journal of pathology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo transgenic model with rigorous histological and IHC characterization, replicated and extended in a subsequent study (PMID:31298630)\",\n      \"pmids\": [\"30125543\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Combined STRN-ALK expression and p53 loss in transgenic mice drives stepwise thyroid cancer progression from well-differentiated PTC to poorly differentiated and anaplastic thyroid carcinoma with lung metastases, demonstrating genetic epistasis between STRN-ALK and p53 in tumor progression.\",\n      \"method\": \"Compound transgenic mouse model, ultrasound imaging, histology, immunohistochemistry, RNA-seq, quantitative RT-PCR\",\n      \"journal\": \"Thyroid : official journal of the American Thyroid Association\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis established in vivo with multiple orthogonal readouts (imaging, histology, transcriptomics), builds on prior transgenic model\",\n      \"pmids\": [\"31298630\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Acute STRN-ALK expression in normal thyroid cells activates MAPK, JAK/STAT3, and PI3K/AKT/mTOR signaling, downregulates thyroid differentiation and iodine metabolism genes (including Slc5a5/NIS, Foxe1, Tg, Duox1/2), causes NIS loss from the cell membrane, and reduces NIS-mediated radioiodine uptake by fourfold; these effects are reversed by ALK inhibitors (crizotinib, ceritinib) or MEK inhibitor selumetinib.\",\n      \"method\": \"Doxycycline-inducible STRN-ALK expression in PCCL3 thyroid cells, qRT-PCR, Western blot, immunofluorescence, RNA sequencing, 131I uptake assay, ALK/MEK/JAK inhibitor treatments\",\n      \"journal\": \"Thyroid : official journal of the American Thyroid Association\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — inducible system with multiple orthogonal methods (transcriptomics, protein, functional iodine uptake, pharmacological rescue), mechanistic pathway dissection in a single rigorous study\",\n      \"pmids\": [\"36585857\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"STK25 interacts with STRN (striatin), and STRN can reverse lipid metabolism changes caused by STK25 deficiency in hepatocellular carcinoma cells, placing STRN downstream of STK25 in the STK25/STRN/AMPK/ACC1 pathway regulating lipid synthesis and EMT.\",\n      \"method\": \"Co-immunoprecipitation, Western blot, wound healing assay, Transwell invasion assay, xenograft mouse model, STRING database interaction prediction\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — STK25-STRN interaction supported by Co-IP but pathway placement relies partly on database prediction and rescue experiments in a single lab without detailed mechanistic follow-up\",\n      \"pmids\": [\"34986838\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"STRN overexpression in HCC cells (Huh7) promotes cell invasion and migration but does not affect proliferation or apoptosis; modulation of STRN expression alters cell morphology and changes EMT markers E-cadherin (negatively correlated) and Vimentin (positively correlated), establishing STRN as a regulator of EMT in hepatocellular carcinoma.\",\n      \"method\": \"siRNA knockdown and overexpression in Huh7 cells, migration and invasion assays, Western blot for EMT markers, IHC in human tissue\",\n      \"journal\": \"BioMed research international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, KD/OE with cellular phenotype but no upstream/downstream pathway mechanism established beyond EMT marker correlation\",\n      \"pmids\": [\"32280692\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The STRN-ALK fusion retains the coiled-coil domain of STRN (exon 3) fused to the kinase domain of ALK (exon 20), and this fusion is functional and sensitive to crizotinib inhibition in lung adenocarcinoma, confirmed by RT-PCR and Sanger sequencing.\",\n      \"method\": \"NGS-based ctDNA profiling, RT-PCR, Sanger sequencing, clinical response to crizotinib\",\n      \"journal\": \"Mayo Clinic proceedings. Innovations, quality & outcomes\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — molecular confirmation of fusion structure and ALK dependence in a single clinical case, no dedicated functional experiments beyond drug response\",\n      \"pmids\": [\"30225407\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"STRN functions as a multifunctional scaffold protein that modulates kinases, phosphatases, and calcium-dependent pathways; is involved in vascular reactivity, blood pressure regulation, and vascular remodeling in cardiovascular disease; and STRN polymorphisms are linked to salt sensitivity of blood pressure.\",\n      \"method\": \"Review synthesizing published experimental findings (no new primary experiments reported in this abstract)\",\n      \"journal\": \"Biomedicine & pharmacotherapy\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — review paper, no new primary experimental data described in the abstract; included for completeness of scaffold/phosphatase regulatory function attribution\",\n      \"pmids\": [\"40752421\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"STRN (striatin) is a calmodulin-binding WD-repeat scaffold protein that localizes to dendritic spines in neurons and functions as a scaffold modulating kinase, phosphatase, and calcium-dependent signaling; when fused to ALK via chromosomal rearrangement (most commonly exon 3 of STRN joined to exon 20 of ALK), the coiled-coil domain of STRN drives constitutive ALK kinase dimerization and activation, triggering MAPK, JAK/STAT3, and PI3K/AKT/mTOR pathways, downregulating thyroid differentiation genes including NIS/SLC5A5, and driving oncogenesis and dedifferentiation in thyroid, lung, and other cancers that are sensitive to ALK tyrosine kinase inhibitors.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"STRN (striatin) is a brain-enriched, calmodulin-binding WD-repeat protein that localizes to the somato-dendritic compartment and dendritic spines of neurons, where its features point to a role as a scaffold in dendritic Ca2+ signaling [#0]. Its most extensively characterized activity, however, is as the 5' partner in the oncogenic STRN-ALK fusion: a chromosomal rearrangement joins STRN exon 3 to ALK exon 20, retaining the STRN coiled-coil domain that drives constitutive ALK kinase dimerization and activation independent of upstream stimuli [#1, #2, #8]. This fusion is sufficient to transform thyroid cells, conferring thyroid-stimulating hormone-independent proliferation and tumor formation in xenografts, with all effects dependent on ALK kinase activity [#1]. In transgenic mice, thyroid-specific STRN-ALK expression produces poorly differentiated thyroid carcinoma with loss of thyroglobulin and E-cadherin, and combined p53 loss drives stepwise progression to anaplastic carcinoma with lung metastases [#3, #4]. Mechanistically, STRN-ALK activates MAPK, JAK/STAT3, and PI3K/AKT/mTOR signaling and downregulates thyroid differentiation and iodine-metabolism genes including Slc5a5/NIS, Foxe1, Tg, and Duox1/2, causing loss of membrane NIS and reduced radioiodine uptake that is reversed by ALK or MEK inhibition [#5]. Outside the fusion context, STRN has been implicated as a regulator of epithelial-mesenchymal transition in hepatocellular carcinoma [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established the identity and basic properties of STRN, defining it as a calmodulin-binding WD-repeat protein with neuronal, dendritic localization—framing it as a candidate scaffold in dendritic calcium signaling.\",\n      \"evidence\": \"cDNA cloning, sequencing, FISH chromosomal mapping, and northern blot expression analysis\",\n      \"pmids\": [\"9693043\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct demonstration of the calcium-signaling function inferred from localization\", \"Scaffold binding partners not identified in this work\", \"No structural model of the WD-repeat or coiled-coil regions\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified the STRN-ALK fusion and showed that the STRN coiled-coil domain mediates constitutive ALK dimerization and kinase activation, answering how a non-kinase scaffold becomes oncogenic.\",\n      \"evidence\": \"RNA-seq fusion discovery, proliferation/transformation assays, nude mouse xenografts, coiled-coil mutagenesis, and ALK inhibitor treatment; fusion junction confirmed by array-CGH, RT-PCR, and Sanger sequencing\",\n      \"pmids\": [\"24613930\", \"24475247\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not address whether wild-type STRN function contributes to oncogenesis\", \"Downstream effector pathways not dissected in this study\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrated in vivo that STRN-ALK alone is sufficient to initiate thyroid carcinogenesis and dedifferentiation, moving beyond cell-based transformation to organismal causation.\",\n      \"evidence\": \"Thyroglobulin promoter-driven STRN-ALK transgenic mice with histology, IHC, and goitrogen treatment\",\n      \"pmids\": [\"30125543\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Tumors remained poorly differentiated rather than fully anaplastic, indicating cooperating events were unresolved\", \"Molecular pathway downstream of the fusion not mapped here\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Established genetic epistasis between STRN-ALK and p53 loss in driving progression to anaplastic carcinoma with metastasis, defining the cooperating event needed for full malignancy.\",\n      \"evidence\": \"Compound transgenic mice with ultrasound imaging, histology, IHC, RNA-seq, and qRT-PCR\",\n      \"pmids\": [\"31298630\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not establish which transcriptional programs mediate the progression\", \"Therapeutic vulnerability of advanced tumors not tested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Dissected the signaling consequences of STRN-ALK, linking fusion activity to MAPK/JAK-STAT3/PI3K-AKT-mTOR activation and to loss of NIS-mediated radioiodine uptake reversible by kinase inhibition—explaining the dedifferentiation and radioiodine resistance phenotype.\",\n      \"evidence\": \"Doxycycline-inducible STRN-ALK in PCCL3 cells with transcriptomics, Western blot, immunofluorescence, 131I uptake assay, and ALK/MEK/JAK inhibitor rescue\",\n      \"pmids\": [\"36585857\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Which pathway predominantly drives NIS loss not fully resolved among the three activated arms\", \"Findings in rat thyroid cell line require validation in human disease context\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Proposed a non-fusion role for STRN as a downstream node of STK25 regulating hepatic lipid metabolism and EMT, extending STRN function into metabolic regulation.\",\n      \"evidence\": \"Co-IP, Western blot, wound healing/Transwell assays, xenografts, and STRING interaction prediction in HCC cells\",\n      \"pmids\": [\"34986838\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Pathway placement relies partly on database prediction rather than direct mechanism\", \"STK25-STRN interaction not validated reciprocally or by structural methods\", \"Single lab without mechanistic follow-up\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Implicated wild-type STRN as a regulator of EMT in hepatocellular carcinoma, suggesting a scaffold function in tumor invasion independent of ALK fusion.\",\n      \"evidence\": \"siRNA knockdown and overexpression in Huh7 cells with migration/invasion assays, EMT-marker Western blots, and tissue IHC\",\n      \"pmids\": [\"32280692\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No upstream or downstream molecular mechanism beyond EMT-marker correlation\", \"Single cell line and single lab\", \"Effect on proliferation/apoptosis was absent, limiting interpretation\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Synthesized evidence positioning STRN as a multifunctional scaffold modulating kinases, phosphatases, and calcium pathways with links to vascular reactivity and salt-sensitive blood pressure.\",\n      \"evidence\": \"Review synthesizing prior experimental findings (no new primary data)\",\n      \"pmids\": [\"40752421\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No new primary experimental data\", \"Cardiovascular and phosphatase-scaffold roles not mechanistically resolved within this corpus\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The normal physiological function of wild-type STRN as a calmodulin-binding scaffold—its phosphatase/kinase partners and its role in dendritic calcium signaling—remains uncharacterized at the mechanistic level in this corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No reconstituted scaffold complex or defined enzymatic partners in the timeline\", \"Neuronal calcium-signaling role inferred from localization but not functionally tested\", \"Link between native scaffold function and oncogenic fusion biology unexplored\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 5]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [1, 3, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ALK\", \"STK25\", \"calmodulin\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":6,"faith_total":6,"faith_pct":100.0}}