{"gene":"SNTB1","run_date":"2026-06-10T07:46:37","timeline":{"discoveries":[{"year":2021,"finding":"SNTB1 (beta-1 syntrophin) positively regulates the Wnt/β-catenin signaling pathway in colorectal cancer cells; silencing SNTB1 decreased levels of β-catenin pathway components, suppressed tumor growth and cancer stemness in vitro, and reduced tumorigenesis in vivo, as assessed by luciferase reporter assay and agonist recovery experiments.","method":"siRNA knockdown, Western blot, luciferase reporter assay, agonist recovery assay, in vivo xenograft, flow cytometry (side population assay)","journal":"Annals of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD with defined cellular and in vivo phenotype, multiple orthogonal methods (luciferase, Western blot, xenograft) in single lab","pmids":["34277816"],"is_preprint":false},{"year":2023,"finding":"SNTB1 knockdown in colorectal cancer cells decreased levels of Wnt1, C-Jun, C-Myc, TCF7, and cyclin D1, inhibited EMT, suppressed proliferation, migration and invasion in vitro, and inhibited tumor growth and metastasis in vivo; mechanistically, SNTB1 positively regulated YAP1 expression, and YAP1 partially rescued the effects of SNTB1 knockdown on Wnt/β-catenin/MYC signaling and CRC cell phenotypes.","method":"siRNA knockdown, Western blot, colony formation assay, migration/invasion assay, nude mouse xenograft/metastasis model, YAP1 overexpression rescue experiment","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD with defined cellular and in vivo phenotypes plus rescue experiment placing SNTB1 upstream of YAP1 in Wnt/β-catenin signaling, single lab","pmids":["37592763"],"is_preprint":false},{"year":2024,"finding":"SNTB1 forms a physical complex with SRC kinase (demonstrated by co-immunoprecipitation), and SNTB1 overexpression activates the Hippo-YAP pathway in colon adenocarcinoma; overexpression of SNTB1 enhanced proliferation, migration and invasion of COAD cell lines and increased tumor metastasis to lung, liver and bone in nude mice; single-cell RNA-seq and CellphoneDB analysis indicated that SNTB1-high cancer cells communicate with enterocytes via TGF-β to promote EMT.","method":"Co-immunoprecipitation, Western blot, overexpression in cell lines, in vivo caudal vein injection metastasis model, scRNA-seq, CellphoneDB analysis","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal Co-IP establishing SNTB1-SRC complex plus in vivo functional data, but single lab with limited mechanistic dissection of how SNTB1 modulates SRC","pmids":["39548564"],"is_preprint":false},{"year":2025,"finding":"ZC3H13, an m6A methyltransferase component, mediates YTHDF1-dependent m6A modification of SNTB1 mRNA, leading to post-transcriptional upregulation of SNTB1 protein; elevated SNTB1 promotes EMT and progression of gastric cancer cells in vitro and in vivo.","method":"MeRIP-seq (m6A sequencing), RNA-seq, immunoprecipitation, in vivo and in vitro functional assays, multi-omics analysis","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MeRIP-seq plus immunoprecipitation identifying ZC3H13/YTHDF1 as writer/reader for m6A modification of SNTB1 mRNA, supported by functional rescue, single lab","pmids":["40774945"],"is_preprint":false}],"current_model":"SNTB1 (beta-1 syntrophin) functions as an intracellular scaffold protein that physically interacts with SRC kinase, positively regulates Wnt/β-catenin signaling and YAP1 expression to promote cell proliferation, EMT, and metastasis; its mRNA is subject to ZC3H13/YTHDF1-dependent m6A modification that post-transcriptionally upregulates SNTB1 protein levels."},"narrative":{"mechanistic_narrative":"SNTB1 (beta-1 syntrophin) is an intracellular scaffold protein that promotes gastrointestinal cancer proliferation, epithelial-mesenchymal transition (EMT), and metastasis by amplifying oncogenic signaling [PMID:34277816, PMID:39548564]. In colorectal cancer cells it acts as a positive regulator of Wnt/β-catenin signaling, with knockdown lowering β-catenin pathway components (Wnt1, C-Jun, C-Myc, TCF7, cyclin D1), suppressing cancer stemness, proliferation, migration, invasion, and in vivo tumor growth and metastasis [PMID:34277816, PMID:37592763]. SNTB1 operates upstream of YAP1, and YAP1 re-expression partially rescues the Wnt/β-catenin/MYC signaling and phenotypic defects caused by SNTB1 loss, linking SNTB1 to Hippo-YAP output [PMID:37592763, PMID:39548564]. SNTB1 forms a physical complex with SRC kinase and engages TGF-β-mediated communication with enterocytes to drive EMT [PMID:39548564]. Upstream, SNTB1 mRNA is subject to ZC3H13-mediated, YTHDF1-dependent m6A modification that post-transcriptionally elevates SNTB1 protein and promotes gastric cancer progression [PMID:40774945].","teleology":[{"year":2021,"claim":"Established SNTB1 as a positive regulator of Wnt/β-catenin signaling in cancer rather than a passive scaffold, defining a functional role in tumor growth and stemness.","evidence":"siRNA knockdown with luciferase reporter, Western blot, agonist recovery, and xenograft in colorectal cancer cells","pmids":["34277816"],"confidence":"Medium","gaps":["Molecular mechanism by which SNTB1 activates the pathway not defined","Direct binding partner within the Wnt cascade not identified","Single-lab finding"]},{"year":2023,"claim":"Placed SNTB1 upstream of YAP1 in driving Wnt/β-catenin/MYC signaling and EMT, identifying YAP1 as a downstream effector via rescue.","evidence":"siRNA knockdown plus YAP1 overexpression rescue, colony formation, migration/invasion, and xenograft/metastasis models in colorectal cancer cells","pmids":["37592763"],"confidence":"Medium","gaps":["How SNTB1 controls YAP1 expression is unresolved","YAP1 rescue is partial, implying additional effectors","Single-lab finding"]},{"year":2024,"claim":"Identified a direct physical partner (SRC kinase) and a Hippo-YAP/TGF-β cell-communication axis, connecting SNTB1 scaffolding to a defined signaling kinase.","evidence":"Reciprocal co-immunoprecipitation, overexpression, caudal-vein metastasis model, and scRNA-seq/CellphoneDB in colon adenocarcinoma","pmids":["39548564"],"confidence":"Medium","gaps":["Mechanism by which SNTB1 modulates SRC activity not dissected","Whether SRC binding mediates the YAP/Wnt effects untested","Single-lab finding"]},{"year":2025,"claim":"Defined how SNTB1 itself is upregulated, identifying m6A modification as a post-transcriptional control point.","evidence":"MeRIP-seq, immunoprecipitation, and functional rescue assays implicating ZC3H13 writer/YTHDF1 reader in gastric cancer","pmids":["40774945"],"confidence":"Medium","gaps":["Specific m6A sites on SNTB1 mRNA not mapped","Whether m6A control operates in colorectal/colon contexts unknown","Single-lab finding"]},{"year":null,"claim":"How SNTB1 mechanistically integrates SRC binding, Wnt/β-catenin activation, and YAP1 regulation into a single scaffold function remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of SNTB1 complexes","Causal ordering of SRC, YAP1, and β-catenin not established","Non-cancer physiological role not addressed in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2]}],"localization":[],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,1,2]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[0,1,2,3]}],"complexes":[],"partners":["SRC"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q13884","full_name":"Beta-1-syntrophin","aliases":["59 kDa dystrophin-associated protein A1 basic component 1","DAPA1B","BSYN2","Syntrophin-2","Tax interaction protein 43","TIP-43"],"length_aa":538,"mass_kda":58.1,"function":"Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex","subcellular_location":"Cell membrane, sarcolemma; Cell junction; Cytoplasm, cytoskeleton","url":"https://www.uniprot.org/uniprotkb/Q13884/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SNTB1","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"UTRN","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SNTB1","total_profiled":1310},"omim":[{"mim_id":"603563","title":"SPASTIC PARAPLEGIA 8, AUTOSOMAL DOMINANT; SPG8","url":"https://www.omim.org/entry/603563"},{"mim_id":"600026","title":"SYNTROPHIN, BETA-1; SNTB1","url":"https://www.omim.org/entry/600026"},{"mim_id":"102565","title":"FILAMIN C; FLNC","url":"https://www.omim.org/entry/102565"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"liver","ntpm":83.5}],"url":"https://www.proteinatlas.org/search/SNTB1"},"hgnc":{"alias_symbol":["59-DAP","A1B","BSYN2","TIP-43","SNT2"],"prev_symbol":["SNT2B1"]},"alphafold":{"accession":"Q13884","domains":[{"cath_id":"2.30.42.10","chopping":"109-195","consensus_level":"high","plddt":86.5544,"start":109,"end":195},{"cath_id":"2.30.29.30","chopping":"251-387_396-438","consensus_level":"medium","plddt":88.3432,"start":251,"end":438},{"cath_id":"2.30.29.30","chopping":"442-535","consensus_level":"high","plddt":91.3021,"start":442,"end":535}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13884","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q13884-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q13884-F1-predicted_aligned_error_v6.png","plddt_mean":77.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SNTB1","jax_strain_url":"https://www.jax.org/strain/search?query=SNTB1"},"sequence":{"accession":"Q13884","fasta_url":"https://rest.uniprot.org/uniprotkb/Q13884.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q13884/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13884"}},"corpus_meta":[{"pmid":"8041722","id":"PMC_8041722","title":"The A1 and A1B proteins of heterogeneous nuclear ribonucleoparticles modulate 5' splice site selection in vivo.","date":"1994","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/8041722","citation_count":199,"is_preprint":false},{"pmid":"19409369","id":"PMC_19409369","title":"Protein-cofactor interactions in bioenergetic complexes: the role of the A1A and A1B phylloquinones in Photosystem I.","date":"2009","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/19409369","citation_count":103,"is_preprint":false},{"pmid":"23878396","id":"PMC_23878396","title":"The yeast Snt2 protein coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress.","date":"2013","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/23878396","citation_count":39,"is_preprint":false},{"pmid":"10843177","id":"PMC_10843177","title":"Spatio-temporal expression of the trans-acting splicing factors SF2/ASF and heterogeneous ribonuclear proteins A1/A1B in the myometrium of the pregnant human uterus: a molecular mechanism for regulating regional protein isoform expression in vivo.","date":"2000","source":"The Journal of clinical endocrinology and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/10843177","citation_count":27,"is_preprint":false},{"pmid":"24747069","id":"PMC_24747069","title":"Evidence that histidine forms a coordination bond to the A(0A) and A(0B) chlorophylls and a second H-bond to the A(1A) and A(1B) phylloquinones in M688H(PsaA) and M668H(PsaB) variants of Synechocystis sp. PCC 6803.","date":"2014","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/24747069","citation_count":27,"is_preprint":false},{"pmid":"31300455","id":"PMC_31300455","title":"Association of the ZC3H11B, ZFHX1B and SNTB1 genes with myopia of different severities.","date":"2019","source":"The British journal of ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/31300455","citation_count":26,"is_preprint":false},{"pmid":"17222873","id":"PMC_17222873","title":"Broad screening of the legume family for variability in seed insecticidal activities and for the occurrence of the A1b-like knottin peptide entomotoxins.","date":"2007","source":"Phytochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17222873","citation_count":25,"is_preprint":false},{"pmid":"21535351","id":"PMC_21535351","title":"Inactivation of Snt2, a BAH/PHD-containing transcription factor, impairs pathogenicity and increases autophagosome abundance in Fusarium oxysporum.","date":"2011","source":"Molecular plant pathology","url":"https://pubmed.ncbi.nlm.nih.gov/21535351","citation_count":24,"is_preprint":false},{"pmid":"3543208","id":"PMC_3543208","title":"Haemoprotein b-590 (Escherichia coli), a reducible catalase and peroxidase: evidence for its close relationship to hydroperoxidase I and a 'cytochrome a1b' preparation.","date":"1986","source":"Journal of general microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/3543208","citation_count":23,"is_preprint":false},{"pmid":"28732529","id":"PMC_28732529","title":"Exiguobacterium sp. A1b/GX59 isolated from a patient with community-acquired pneumonia and bacteremia: genomic characterization and literature review.","date":"2017","source":"BMC infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/28732529","citation_count":22,"is_preprint":false},{"pmid":"22352450","id":"PMC_22352450","title":"Exploring the electron transfer pathways in photosystem I by high-time-resolution electron paramagnetic resonance: observation of the B-side radical pair P700(+)A1B(-) in whole cells of the deuterated green alga Chlamydomonas reinhardtii at cryogenic temperatures.","date":"2012","source":"Journal of the American Chemical Society","url":"https://pubmed.ncbi.nlm.nih.gov/22352450","citation_count":22,"is_preprint":false},{"pmid":"17845830","id":"PMC_17845830","title":"Toxicity, binding and internalization of the pea-A1b entomotoxin in Sf9 cells.","date":"2007","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/17845830","citation_count":16,"is_preprint":false},{"pmid":"6418000","id":"PMC_6418000","title":"The existence of atypical blood group galactosyltransferase which causes an expression of A2 character in A1B red blood cells.","date":"1983","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/6418000","citation_count":16,"is_preprint":false},{"pmid":"19639652","id":"PMC_19639652","title":"Inducible 70 kDa heat shock proteins protect embryos from teratogen-induced exencephaly: Analysis using Hspa1a/a1b knockout mice.","date":"2009","source":"Birth defects research. Part A, Clinical and molecular teratology","url":"https://pubmed.ncbi.nlm.nih.gov/19639652","citation_count":15,"is_preprint":false},{"pmid":"2944882","id":"PMC_2944882","title":"Limited tryptic digestion of Ca2+,Mg2+-adenosine triphosphatase of the sarcoplasmic reticulum: enzymatic properties of A1b + B complex.","date":"1986","source":"Journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2944882","citation_count":14,"is_preprint":false},{"pmid":"14692877","id":"PMC_14692877","title":"A new ephrin-A1 isoform (ephrin-A1b) with altered receptor binding properties abrogates the cleavage of ephrin-A1a.","date":"2004","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/14692877","citation_count":13,"is_preprint":false},{"pmid":"15485655","id":"PMC_15485655","title":"SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation.","date":"2004","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15485655","citation_count":12,"is_preprint":false},{"pmid":"3918362","id":"PMC_3918362","title":"The A1B genotype expressed as A2B on the red cells of individuals with strong B gene-specific transferases. Results from two paternity cases.","date":"1985","source":"Transfusion","url":"https://pubmed.ncbi.nlm.nih.gov/3918362","citation_count":11,"is_preprint":false},{"pmid":"37592763","id":"PMC_37592763","title":"SNTB1 regulates colorectal cancer cell proliferation and metastasis through YAP1 and the WNT/β-catenin pathway.","date":"2023","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/37592763","citation_count":10,"is_preprint":false},{"pmid":"34277816","id":"PMC_34277816","title":"Beta-1 syntrophin (SNTB1) regulates colorectal cancer progression and stemness via regulation of the Wnt/β-catenin signaling pathway.","date":"2021","source":"Annals of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34277816","citation_count":10,"is_preprint":false},{"pmid":"28848321","id":"PMC_28848321","title":"Association and interaction of myopia with SNP markers rs13382811 and rs6469937 at ZFHX1B and SNTB1 in Han Chinese and European populations.","date":"2017","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/28848321","citation_count":10,"is_preprint":false},{"pmid":"34630013","id":"PMC_34630013","title":"hnRNP A1B, a Splice Variant of HNRNPA1, Is Spatially and Temporally Regulated.","date":"2021","source":"Frontiers in neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/34630013","citation_count":9,"is_preprint":false},{"pmid":"30187493","id":"PMC_30187493","title":"Mango phenolics increase the serum apolipoprotein A1/B ratio in rats fed high cholesterol and sodium cholate diets.","date":"2018","source":"Journal of the science of food and agriculture","url":"https://pubmed.ncbi.nlm.nih.gov/30187493","citation_count":8,"is_preprint":false},{"pmid":"34898734","id":"PMC_34898734","title":"Plasma Apolipoproteins A1/B and OxLDL Levels in Patients with Covid-19 As Possible Markers of the Disease.","date":"2021","source":"Cytology and genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34898734","citation_count":6,"is_preprint":false},{"pmid":"19657725","id":"PMC_19657725","title":"A protocol comparison for the analysis of heat shock protein A1B +A1538G SNP.","date":"2009","source":"Cell stress & chaperones","url":"https://pubmed.ncbi.nlm.nih.gov/19657725","citation_count":6,"is_preprint":false},{"pmid":"26509826","id":"PMC_26509826","title":"Evaluation of group A1B erythrocytes converted to type as group O: studies of markers of function and compatibility.","date":"2015","source":"Blood transfusion = Trasfusione del sangue","url":"https://pubmed.ncbi.nlm.nih.gov/26509826","citation_count":5,"is_preprint":false},{"pmid":"32452213","id":"PMC_32452213","title":"Association of SNTB1 with High Myopia.","date":"2020","source":"Current eye research","url":"https://pubmed.ncbi.nlm.nih.gov/32452213","citation_count":4,"is_preprint":false},{"pmid":"34081189","id":"PMC_34081189","title":"A1B and BB blood group genotypes are risk factors for pulmonary embolism.","date":"2021","source":"Wiener klinische Wochenschrift","url":"https://pubmed.ncbi.nlm.nih.gov/34081189","citation_count":4,"is_preprint":false},{"pmid":"39189801","id":"PMC_39189801","title":"Developing a mouse model of human coronavirus NL63 infection: comparison with rhinovirus-A1B and effects of prior rhinovirus infection.","date":"2024","source":"American journal of physiology. Lung cellular and molecular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/39189801","citation_count":3,"is_preprint":false},{"pmid":"25756154","id":"PMC_25756154","title":"Co-segregation of Freiberg's infraction with a familial translocation t(5;7)(p13.3;p22.2) ascertained by a child with cri du chat syndrome and brachydactyly type A1B.","date":"2015","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/25756154","citation_count":3,"is_preprint":false},{"pmid":"37890754","id":"PMC_37890754","title":"The SNTB1 and ZFHX1B gene have susceptibility in northern Han Chinese populations with high myopia.","date":"2023","source":"Experimental eye research","url":"https://pubmed.ncbi.nlm.nih.gov/37890754","citation_count":2,"is_preprint":false},{"pmid":"35469752","id":"PMC_35469752","title":"Detection of anti-B antibodies in a patient with A1B blood group: A case report and literature review.","date":"2022","source":"Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis","url":"https://pubmed.ncbi.nlm.nih.gov/35469752","citation_count":2,"is_preprint":false},{"pmid":"26745065","id":"PMC_26745065","title":"Polymorphisms in Heat Shock Proteins A1B and A1L (HOM) as Risk Factors for Oesophageal Carcinoma in Northeast India.","date":"2015","source":"Asian Pacific journal of cancer prevention : APJCP","url":"https://pubmed.ncbi.nlm.nih.gov/26745065","citation_count":2,"is_preprint":false},{"pmid":"37796012","id":"PMC_37796012","title":"Full genome sequence of a human rhinovirus A1B, obtained in Kazakhstan.","date":"2023","source":"Microbiology resource announcements","url":"https://pubmed.ncbi.nlm.nih.gov/37796012","citation_count":2,"is_preprint":false},{"pmid":"6818134","id":"PMC_6818134","title":"Abnormal blood group galactosyltransferase in blood type A1B-subjects whose sera contain anti-B agglutinin.","date":"1982","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/6818134","citation_count":2,"is_preprint":false},{"pmid":"39548564","id":"PMC_39548564","title":"Modulation of SRC by SNTB1 activates the Hippo-YAP pathway during colon adenocarcinoma metastasis.","date":"2024","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39548564","citation_count":1,"is_preprint":false},{"pmid":"39587668","id":"PMC_39587668","title":"Transient receptor potential a1b regulates primordial germ cell numbers and sex differentiation in developing zebrafish.","date":"2024","source":"Journal of fish biology","url":"https://pubmed.ncbi.nlm.nih.gov/39587668","citation_count":1,"is_preprint":false},{"pmid":"41867379","id":"PMC_41867379","title":"SNTB1 gene polymorphisms and risk of high myopia: meta-analysis and single-center validation.","date":"2025","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/41867379","citation_count":0,"is_preprint":false},{"pmid":"40774945","id":"PMC_40774945","title":"ZC3H13 mediates N6-methyladenosine modification of SNTB1 to promote epithelial-mesenchymal transition in gastric cancer.","date":"2025","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/40774945","citation_count":0,"is_preprint":false},{"pmid":"6542041","id":"PMC_6542041","title":"[Population genetics of taiga hunters and reindeer breeders in central Siberia. The biochemical markers of genes Hp, Tf, Gc, A1b, GLO1, PGM1, AcP and EsD].","date":"1984","source":"Genetika","url":"https://pubmed.ncbi.nlm.nih.gov/6542041","citation_count":0,"is_preprint":false},{"pmid":"754172","id":"PMC_754172","title":"[Some aspects of the allelic interaction in family studies of normal A1B and A2B subjects (author's transl)].","date":"1978","source":"Nouvelle revue francaise d'hematologie","url":"https://pubmed.ncbi.nlm.nih.gov/754172","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.05.28.655990","title":"Genetic regulation of fatty acid content in adipose tissue","date":"2025-05-29","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.28.655990","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":24155,"output_tokens":2202,"usd":0.052748,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7903,"output_tokens":1842,"usd":0.042783,"stage2_stop_reason":"end_turn"},"total_usd":0.095531,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully classify each paper to determine which ones are about the canonical SNTB1 protein (syntrophin beta-1, also known as beta-1 syntrophin, SNT2, SNT2B1, BSYN2, TIP-43, 59-DAP).\n\nLooking through the papers:\n\n- Papers 1, 4, 22: About hnRNP A1/A1B (different gene - HNRNPA1) — EXCLUDE\n- Papers 2, 5, 11: About Photosystem I A1B cofactors — EXCLUDE (plant/cyanobacterial, symbol collision)\n- Paper 3: About yeast Snt2 (transcription factor with BAH/PHD domains) — This is a yeast gene but functions completely differently from mammalian SNTB1 (syntrophin scaffold protein). EXCLUDE as collision.\n- Paper 7: Pea albumin A1b — EXCLUDE (plant peptide)\n- Paper 8: Fusarium Snt2 — EXCLUDE (fungal, different protein)\n- Paper 9: Bacterial haemoprotein — EXCLUDE\n- Paper 10: Exiguobacterium A1b — EXCLUDE\n- Paper 12: Pea A1b entomotoxin — EXCLUDE (plant peptide)\n- Paper 13, 18, 26, 28, 32, 35, 41: Blood group A1B — EXCLUDE\n- Paper 14: Hspa1a/A1b heat shock proteins — EXCLUDE (HSPA1B, different gene)\n- Paper 15: SR ATPase A1b fragment — EXCLUDE (different protein)\n- Paper 16: Ephrin-A1b isoform — EXCLUDE (EFNA1, different gene)\n- Paper 17: SNT-2/FRS2beta interacts with ERK2 — This is about SNT-2 (FRS2beta/FRS2B). The alias \"SNT2\" is listed for SNTB1 in the query. However, SNT-2/FRS2beta is actually FRS2B (fibroblast growth factor receptor substrate 2 beta), a membrane-anchored docking protein — this is NOT the same as SNTB1 (syntrophin beta-1). The SNT-2 in paper 17 is described as \"suc1-binding neurotrophic target\" related to FRS2alpha — this is FRS2B, not SNTB1. EXCLUDE as alias collision.\n- Paper 19: SNTB1 in colorectal cancer — INCLUDE\n- Paper 20: SNTB1 in colorectal cancer — INCLUDE\n- Paper 21, 6, 27, 31, 38: SNTB1 SNP associations with myopia — These are GWAS/association studies, EXCLUDE mechanistic content\n- Paper 25: HSPA1B SNP — EXCLUDE (different gene)\n- Paper 29: Rhinovirus A1B — EXCLUDE (viral)\n- Paper 30: BDA1B chromosomal — EXCLUDE (different context)\n- Paper 33: HSPA1B polymorphisms — EXCLUDE\n- Paper 34: Rhinovirus genome — EXCLUDE\n- Paper 36: SNTB1 and SRC/Hippo-YAP in colon cancer — INCLUDE\n- Paper 37: Zebrafish Trpa1b — EXCLUDE (different gene, zebrafish ion channel)\n- Paper 39: ZC3H13 m6A modification of SNTB1 in gastric cancer — INCLUDE\n- Paper 40: Population genetics Alb markers — EXCLUDE\n- Paper 42: GWAS preprint mentioning SNTB1 locus — EXCLUDE (no mechanistic data)\n\nNow extracting from papers 19, 20, 36, 39:\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"SNTB1 (beta-1 syntrophin) positively regulates the Wnt/β-catenin signaling pathway in colorectal cancer cells; silencing SNTB1 decreased levels of β-catenin pathway components, suppressed tumor growth and cancer stemness in vitro, and reduced tumorigenesis in vivo, as assessed by luciferase reporter assay and agonist recovery experiments.\",\n      \"method\": \"siRNA knockdown, Western blot, luciferase reporter assay, agonist recovery assay, in vivo xenograft, flow cytometry (side population assay)\",\n      \"journal\": \"Annals of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD with defined cellular and in vivo phenotype, multiple orthogonal methods (luciferase, Western blot, xenograft) in single lab\",\n      \"pmids\": [\"34277816\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SNTB1 knockdown in colorectal cancer cells decreased levels of Wnt1, C-Jun, C-Myc, TCF7, and cyclin D1, inhibited EMT, suppressed proliferation, migration and invasion in vitro, and inhibited tumor growth and metastasis in vivo; mechanistically, SNTB1 positively regulated YAP1 expression, and YAP1 partially rescued the effects of SNTB1 knockdown on Wnt/β-catenin/MYC signaling and CRC cell phenotypes.\",\n      \"method\": \"siRNA knockdown, Western blot, colony formation assay, migration/invasion assay, nude mouse xenograft/metastasis model, YAP1 overexpression rescue experiment\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD with defined cellular and in vivo phenotypes plus rescue experiment placing SNTB1 upstream of YAP1 in Wnt/β-catenin signaling, single lab\",\n      \"pmids\": [\"37592763\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SNTB1 forms a physical complex with SRC kinase (demonstrated by co-immunoprecipitation), and SNTB1 overexpression activates the Hippo-YAP pathway in colon adenocarcinoma; overexpression of SNTB1 enhanced proliferation, migration and invasion of COAD cell lines and increased tumor metastasis to lung, liver and bone in nude mice; single-cell RNA-seq and CellphoneDB analysis indicated that SNTB1-high cancer cells communicate with enterocytes via TGF-β to promote EMT.\",\n      \"method\": \"Co-immunoprecipitation, Western blot, overexpression in cell lines, in vivo caudal vein injection metastasis model, scRNA-seq, CellphoneDB analysis\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal Co-IP establishing SNTB1-SRC complex plus in vivo functional data, but single lab with limited mechanistic dissection of how SNTB1 modulates SRC\",\n      \"pmids\": [\"39548564\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ZC3H13, an m6A methyltransferase component, mediates YTHDF1-dependent m6A modification of SNTB1 mRNA, leading to post-transcriptional upregulation of SNTB1 protein; elevated SNTB1 promotes EMT and progression of gastric cancer cells in vitro and in vivo.\",\n      \"method\": \"MeRIP-seq (m6A sequencing), RNA-seq, immunoprecipitation, in vivo and in vitro functional assays, multi-omics analysis\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MeRIP-seq plus immunoprecipitation identifying ZC3H13/YTHDF1 as writer/reader for m6A modification of SNTB1 mRNA, supported by functional rescue, single lab\",\n      \"pmids\": [\"40774945\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNTB1 (beta-1 syntrophin) functions as an intracellular scaffold protein that physically interacts with SRC kinase, positively regulates Wnt/β-catenin signaling and YAP1 expression to promote cell proliferation, EMT, and metastasis; its mRNA is subject to ZC3H13/YTHDF1-dependent m6A modification that post-transcriptionally upregulates SNTB1 protein levels.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SNTB1 (beta-1 syntrophin) is an intracellular scaffold protein that promotes gastrointestinal cancer proliferation, epithelial-mesenchymal transition (EMT), and metastasis by amplifying oncogenic signaling [#0, #2]. In colorectal cancer cells it acts as a positive regulator of Wnt/\\u03b2-catenin signaling, with knockdown lowering \\u03b2-catenin pathway components (Wnt1, C-Jun, C-Myc, TCF7, cyclin D1), suppressing cancer stemness, proliferation, migration, invasion, and in vivo tumor growth and metastasis [#0, #1]. SNTB1 operates upstream of YAP1, and YAP1 re-expression partially rescues the Wnt/\\u03b2-catenin/MYC signaling and phenotypic defects caused by SNTB1 loss, linking SNTB1 to Hippo-YAP output [#1, #2]. SNTB1 forms a physical complex with SRC kinase and engages TGF-\\u03b2-mediated communication with enterocytes to drive EMT [#2]. Upstream, SNTB1 mRNA is subject to ZC3H13-mediated, YTHDF1-dependent m6A modification that post-transcriptionally elevates SNTB1 protein and promotes gastric cancer progression [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Established SNTB1 as a positive regulator of Wnt/\\u03b2-catenin signaling in cancer rather than a passive scaffold, defining a functional role in tumor growth and stemness.\",\n      \"evidence\": \"siRNA knockdown with luciferase reporter, Western blot, agonist recovery, and xenograft in colorectal cancer cells\",\n      \"pmids\": [\"34277816\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism by which SNTB1 activates the pathway not defined\", \"Direct binding partner within the Wnt cascade not identified\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Placed SNTB1 upstream of YAP1 in driving Wnt/\\u03b2-catenin/MYC signaling and EMT, identifying YAP1 as a downstream effector via rescue.\",\n      \"evidence\": \"siRNA knockdown plus YAP1 overexpression rescue, colony formation, migration/invasion, and xenograft/metastasis models in colorectal cancer cells\",\n      \"pmids\": [\"37592763\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How SNTB1 controls YAP1 expression is unresolved\", \"YAP1 rescue is partial, implying additional effectors\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified a direct physical partner (SRC kinase) and a Hippo-YAP/TGF-\\u03b2 cell-communication axis, connecting SNTB1 scaffolding to a defined signaling kinase.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, overexpression, caudal-vein metastasis model, and scRNA-seq/CellphoneDB in colon adenocarcinoma\",\n      \"pmids\": [\"39548564\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which SNTB1 modulates SRC activity not dissected\", \"Whether SRC binding mediates the YAP/Wnt effects untested\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined how SNTB1 itself is upregulated, identifying m6A modification as a post-transcriptional control point.\",\n      \"evidence\": \"MeRIP-seq, immunoprecipitation, and functional rescue assays implicating ZC3H13 writer/YTHDF1 reader in gastric cancer\",\n      \"pmids\": [\"40774945\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific m6A sites on SNTB1 mRNA not mapped\", \"Whether m6A control operates in colorectal/colon contexts unknown\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SNTB1 mechanistically integrates SRC binding, Wnt/\\u03b2-catenin activation, and YAP1 regulation into a single scaffold function remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of SNTB1 complexes\", \"Causal ordering of SRC, YAP1, and \\u03b2-catenin not established\", \"Non-cancer physiological role not addressed in the corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [0, 1, 2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SRC\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}