{"gene":"GNAI3","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2012,"finding":"GNAI3 missense mutations in auriculocondylar syndrome (ACS) disrupt the catalytic/GDP-GTP binding site of the protein, and functional studies in cultured osteoblasts from ACS probands showed significant reduction in downstream DLX5 and DLX6 expression, placing GNAI3 as a core signaling molecule in the EDN1-DLX5/DLX6 pathway regulating mandibular specification.","method":"Exome sequencing identifying mutations, protein-structure modeling of catalytic sites, functional gene expression assays in cultured osteoblasts from probands","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — structural modeling plus functional downstream expression assay in patient cells, single lab, two orthogonal methods","pmids":["22560091"],"is_preprint":false},{"year":2014,"finding":"GNAI3 variants in ACS cluster in the GDP/GTP-binding region (G1 and G4 boxes), and structural modeling of all five reported ACS-associated GNAI3 residues indicates they all disrupt guanine nucleotide binding, consistent with a dominant negative mechanism.","method":"Sanger sequencing, protein structural modeling of GDP/GTP-binding motifs","journal":"European journal of human genetics : EJHG","confidence":"Low","confidence_rationale":"Tier 4 / Weak — structural modeling only, no in vitro biochemical validation of dominant negative effect","pmids":["25026904"],"is_preprint":false},{"year":2014,"finding":"GNAI3 inhibits hepatocellular carcinoma (HCC) cell migration and invasion, as demonstrated by transwell assays following GNAI3 manipulation; miR-222 directly binds the GNAI3 mRNA 3'UTR and decreases GNAI3 protein expression, providing a post-transcriptional regulatory mechanism.","method":"Transwell migration/invasion assays with GNAI3 overexpression/knockdown; miR-222 target prediction confirmed by experimental screening and mRNA binding","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — functional cell-based assays plus miRNA-target experimental screening, single lab, two methods","pmids":["25444921"],"is_preprint":false},{"year":2014,"finding":"GNAI3 (Gαi3) is required for zVAD-induced autophagy in L929 cells, and this autophagy is required for zVAD-induced TNF production; GNAI3 was identified as a partner of RGS19 (itself identified as a RIP3-interacting protein), and shRNA knockdown of GNAI3 suppressed zVAD-induced but not TNF-induced cell death.","method":"Co-immunoprecipitation identifying RGS19-RIP3 and RGS19-GNAI3 interactions; shRNA knockdown of GNAI3 with cell death and autophagy readouts","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus shRNA loss-of-function with defined cellular phenotype, single lab, two orthogonal methods","pmids":["24751948"],"is_preprint":false},{"year":2013,"finding":"Gαi3 (encoded by Gnai3), together with Gαi2, is required for B lymphocyte chemoattractant receptor signaling; B cells lacking both Gαi2 and Gαi3 are refractory to chemokine stimulation, fail to populate mucosal sites, splenic marginal zones, and lymph nodes, and cause disrupted lymphoid organ architecture with a hyper-IgM-like syndrome.","method":"Conditional knockout of Gnai2 and Gnai3 in B cells (mouse genetic model), flow cytometry, chemokine responsiveness assays","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean conditional double-knockout with multiple defined cellular and organismal phenotypes, flow cytometry, functional chemokine assays","pmids":["23977324"],"is_preprint":false},{"year":2019,"finding":"GNAI1 and GNAI3 suppress colitis-associated tumorigenesis by blocking IL6 signaling; in the absence of GNAI1/3, IL6 activates NF-κB via JAK2-TRAF6-TAK1-CHUK/IKKβ and STAT3 via JAK2, resulting in increased GNAI2, IL6ST (GP130), and NOS2 expression and MDSC expansion. Immunoprecipitation of colon tumor tissues and MDSCs demonstrated interactions of GNAI1 and GNAI3 with proteins in the IL6 signaling pathway.","method":"Double-knockout mouse model (GNAI1/3 DKO), immunoprecipitation, immunoblot, flow cytometry, anti-IL6 antibody rescue experiment","journal":"Gastroenterology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with rescue, Co-IP demonstrating protein interactions, multiple orthogonal methods across mouse and human tissues","pmids":["30836096"],"is_preprint":false},{"year":2017,"finding":"GATA4 directly binds the GNAI3 promoter and transcriptionally activates GNAI3 expression; GATA4 deletion reduces GNAI3 levels in dental papilla cells, and GNAI3 knockdown itself decreases odontogenic/osteogenic differentiation of stem cells of dental apical papilla (SCAPs).","method":"Dual-luciferase reporter assay and ChIP assay confirming GATA4 binding to GNAI3 promoter; shRNA knockdown of GNAI3 with osteogenic differentiation readouts in SCAPs; conditional knockout mouse model","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP plus luciferase assay confirming direct promoter binding, combined with loss-of-function differentiation assays, single lab","pmids":["28484278"],"is_preprint":false},{"year":2021,"finding":"Mir24-2-5p directly binds the Gnai3 3'UTR and negatively regulates Gnai3 expression; Gnai3 promotes osteoblast precursor cell proliferation, migration, osteogenic differentiation, and mineralization, and acts through activation of the JNK-p38 MAPK signaling axis. In zebrafish, gnai3 morpholino knockdown recapitulated mandibular/cartilage developmental defects, partially rescued by gnai3 mRNA injection.","method":"Dual-luciferase reporter assay for miRNA-target interaction; shRNA knockdown of Gnai3; Western blot for p-JNK and p-p38; zebrafish morpholino knockdown with phenotypic rescue; osteogenic differentiation assays","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase assay plus loss-of-function with pathway readouts, ortholog zebrafish rescue, single lab","pmids":["34803495"],"is_preprint":false},{"year":2016,"finding":"GNAI3 (Gαi3) is specifically activated by the OA1 G-protein coupled receptor in the retinal pigment epithelium and participates in the OA1 transduction pathway regulating melanosomal biogenesis.","method":"Functional signaling studies demonstrating Oa1-specific activation of Gαi3 (referenced as prior work); GNAI3 gene screening in OA patients by next-generation sequencing","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 3 / Weak — the mechanistic claim (Oa1 activates Gαi3) is cited as prior work in this paper without the primary experimental detail being provided in the abstract; NGS screening only in this study","pmids":["27607449"],"is_preprint":false},{"year":2014,"finding":"Lin28A stabilizes GNAI3 mRNA, as demonstrated by RIP assay confirming Lin28A binding to GNAI3 mRNA, and Lin28A knockdown reduced GNAI3 expression; GNAI3 overexpression suppresses LPS-induced NF-κB/NLRP3 inflammasome pathway activation, inflammation, and apoptosis in periodontal ligament stem cells, and promotes osteogenic differentiation.","method":"RIP assay for Lin28A-GNAI3 mRNA interaction; GNAI3 overexpression with Western blot for NF-κB/NLRP3 pathway proteins; ELISA for cytokines; ALP and ARS staining for osteogenic differentiation","journal":"Archives of oral biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — RIP assay plus functional overexpression experiments with pathway readouts, single lab, multiple assays","pmids":["38636252"],"is_preprint":false},{"year":2025,"finding":"RGS14 physically interacts with GNAI3 to coordinately regulate spermatogonial stem cell (SSC) proliferation and PLPP2 expression; RGS14 knockdown suppresses SSC proliferation and induces apoptosis, phenotypes that are linked to GNAI3 and the RGS14-GNAI3-PLPP2 axis through MAPK signaling.","method":"Protein-protein interaction assays and co-immunoprecipitation of RGS14-GNAI3; shRNA knockdown of RGS14; RNA-sequencing; PLPP2 overexpression rescue","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with functional rescue experiments, single lab, multiple orthogonal methods","pmids":["40352663"],"is_preprint":false},{"year":2021,"finding":"Gαi3 is expressed in B cells, T cells, macrophages, granulocytes, platelets, and in the inner ear (Deiter's cells and first row of Hensen's cells in the organ of Corti), as determined by a Gnai3-iresGFP reporter mouse using flow cytometry and immunofluorescence.","method":"Gnai3-iresGFP knock-in reporter mouse; flow cytometry with cell-type specific surface markers; immunofluorescence staining of inner ear","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct expression mapping by validated knock-in reporter with cell-type-specific markers, single lab, two orthogonal methods","pmids":["34253772"],"is_preprint":false}],"current_model":"GNAI3 encodes the Gαi3 subunit of inhibitory heterotrimeric G proteins, functioning as a GDP/GTP-binding signaling molecule that (1) transduces chemoattractant receptor signals in B lymphocytes to direct their compartmentalization in lymphoid organs, (2) suppresses IL6-driven NF-κB and STAT3 signaling to limit colitis-associated tumorigenesis, (3) acts downstream of the OA1 GPCR to regulate melanosomal biogenesis, (4) interacts with RGS proteins (RGS19, RGS14) to regulate autophagy and spermatogonial stem cell homeostasis, (5) promotes osteogenic/odontogenic differentiation via MAPK (JNK-p38) signaling downstream of GATA4-driven transcription, and (6) is transcriptionally regulated by GATA4 and post-transcriptionally repressed by miR-222 and miR-24-2-5p; loss-of-function mutations in the GDP/GTP-binding domain cause auriculocondylar syndrome through dominant negative disruption of EDN1-DLX5/6 pathway signaling."},"narrative":{"mechanistic_narrative":"GNAI3 encodes Gαi3, an inhibitory heterotrimeric G-protein α subunit that transduces G-protein-coupled receptor signals into the control of cell migration, differentiation, and inflammatory signaling [PMID:23977324, PMID:30836096]. In the immune system, Gαi3 acts redundantly with Gαi2 to relay chemoattractant receptor signals in B lymphocytes; loss of both subunits renders B cells refractory to chemokine stimulation and disrupts their compartmentalization in mucosal sites, splenic marginal zones, and lymph nodes [PMID:23977324]. Gαi3 also restrains inflammatory tumorigenesis: together with Gαi1 it blocks IL6-driven activation of NF-κB (via JAK2–TRAF6–TAK1–IKKβ) and STAT3, limiting myeloid-derived suppressor cell expansion in colitis-associated cancer [PMID:30836096], and Gαi3 expression suppresses LPS-induced NF-κB/NLRP3 inflammasome signaling [PMID:38636252]. In skeletal and dental development, Gαi3 promotes osteoblast and odontoblast proliferation, migration, and osteogenic/odontogenic differentiation through the JNK–p38 MAPK axis [PMID:34803495], functioning as a transcriptional target directly activated by GATA4 [PMID:28484278] and post-transcriptionally repressed by miR-222, miR-24-2-5p, and stabilized by Lin28A [PMID:25444921, PMID:34803495, PMID:38636252]. Gαi3 cooperates with regulator-of-G-protein-signaling proteins, partnering with RGS19 to enable zVAD-induced autophagy [PMID:24751948] and with RGS14 to sustain spermatogonial stem cell proliferation via a PLPP2/MAPK axis [PMID:40352663]. Missense mutations in the GDP/GTP-binding region of GNAI3 cause auriculocondylar syndrome, acting through a dominant-negative mechanism that disrupts EDN1–DLX5/DLX6 signaling required for mandibular specification [PMID:22560091, PMID:25026904].","teleology":[{"year":2012,"claim":"Established GNAI3 as a disease gene by linking missense mutations to auriculocondylar syndrome and placing Gαi3 within the EDN1-DLX5/DLX6 craniofacial patterning pathway.","evidence":"Exome sequencing, protein-structure modeling of catalytic sites, and downstream expression assays in patient osteoblasts","pmids":["22560091"],"confidence":"Medium","gaps":["No in vitro biochemical demonstration of altered nucleotide binding","Dominant-negative mechanism inferred from modeling, not reconstituted"]},{"year":2013,"claim":"Defined a physiological role for Gαi3 in immune cell trafficking, showing it acts redundantly with Gαi2 to transduce chemoattractant signals required for B cell positioning.","evidence":"Conditional Gnai2/Gnai3 double-knockout mouse, flow cytometry, chemokine responsiveness assays","pmids":["23977324"],"confidence":"High","gaps":["Redundancy with Gαi2 obscures Gαi3-specific contribution","Receptor partners not individually mapped"]},{"year":2014,"claim":"Identified post-transcriptional and protein-interaction layers controlling Gαi3, linking it to cancer cell motility, autophagy, and a tumor-suppressive output.","evidence":"Transwell assays with miR-222 3'UTR targeting in HCC; Co-IP of RGS19-GNAI3 with shRNA autophagy/cell-death readouts in L929; RIP assay for Lin28A mRNA stabilization with osteogenic readouts","pmids":["25444921","24751948","38636252"],"confidence":"Medium","gaps":["Mechanism of Gαi3 in autophagy beyond RGS19 association unclear","Lin28A study published later; mRNA-regulation generality untested"]},{"year":2014,"claim":"Refined the structural basis of ACS variants, showing all reported residues cluster in G1/G4 nucleotide-binding boxes consistent with dominant-negative loss of GTP binding.","evidence":"Sanger sequencing and structural modeling of GDP/GTP-binding motifs","pmids":["25026904"],"confidence":"Low","gaps":["Structural modeling only, no biochemical validation of nucleotide-binding defect","Dominant-negative effect not functionally demonstrated"]},{"year":2016,"claim":"Connected Gαi3 to OA1 GPCR signaling in retinal pigment epithelium controlling melanosomal biogenesis.","evidence":"OA1-specific Gαi3 activation cited as prior work; GNAI3 NGS screening in ocular albinism patients","pmids":["27607449"],"confidence":"Low","gaps":["Primary OA1-Gαi3 activation data not provided in this study","No causative GNAI3 variant established in patients"]},{"year":2017,"claim":"Placed GNAI3 in a transcriptional circuit by showing GATA4 directly activates its promoter to drive odontogenic/osteogenic differentiation.","evidence":"Dual-luciferase reporter and ChIP for GATA4 promoter binding; shRNA GNAI3 knockdown in SCAPs; conditional knockout mouse","pmids":["28484278"],"confidence":"Medium","gaps":["Downstream effectors of Gαi3 in differentiation not defined here","Single-lab finding"]},{"year":2019,"claim":"Demonstrated a tumor-suppressive immunoregulatory function, with Gαi1/3 blocking IL6-driven NF-κB and STAT3 signaling to limit colitis-associated tumorigenesis.","evidence":"GNAI1/3 double-knockout mouse, immunoprecipitation, immunoblot, flow cytometry, anti-IL6 rescue","pmids":["30836096"],"confidence":"High","gaps":["Direct molecular target of Gαi3 within the IL6 cascade not pinpointed","Relative contributions of Gαi1 vs Gαi3 not separated"]},{"year":2021,"claim":"Mapped Gαi3 expression across immune and inner-ear cell types and confirmed its osteogenic role and miRNA control via a conserved zebrafish model.","evidence":"Gnai3-iresGFP reporter mouse with flow cytometry/immunofluorescence; dual-luciferase miR-24-2-5p targeting; JNK/p38 Western blot; zebrafish morpholino with mRNA rescue","pmids":["34253772","34803495"],"confidence":"Medium","gaps":["Functional role of inner-ear expression untested","Receptor upstream of JNK-p38 activation not identified"]},{"year":2025,"claim":"Extended Gαi3's RGS partnerships to reproductive biology, showing RGS14-Gαi3 interaction sustains spermatogonial stem cell proliferation through a PLPP2/MAPK axis.","evidence":"Reciprocal Co-IP of RGS14-GNAI3, shRNA knockdown, RNA-seq, PLPP2 overexpression rescue","pmids":["40352663"],"confidence":"Medium","gaps":["Direction of regulation between RGS14 and Gαi3 not fully resolved","PLPP2 regulatory link mechanistically incomplete"]},{"year":null,"claim":"How a single Gαi3 subunit is selectively coupled to distinct receptors and effectors across immune, skeletal, reproductive, and pigmentary contexts, and the biochemical basis of its dominant-negative disease variants, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconstituted biochemistry of ACS mutant nucleotide handling","Receptor-specific coupling determinants undefined","Distinction of Gαi3-specific vs redundant Gαi functions incomplete"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[4,5,8]},{"term_id":"GO:0003924","term_label":"GTPase activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[4,8]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[4,5,8]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[4,5]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[0,6,7]}],"complexes":[],"partners":["RGS19","RGS14","GNAI2","GNAI1","OA1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P08754","full_name":"Guanine nucleotide-binding protein G(i) subunit alpha-3","aliases":["G(i) alpha-3"],"length_aa":354,"mass_kda":40.5,"function":"Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (By similarity). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:18434541, PubMed:19478087, PubMed:8774883). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (PubMed:19478087). Stimulates the activity of receptor-regulated K(+) channels (PubMed:2535845). The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division (PubMed:17635935). The active GTP-bound form activates the calcium permeant TRPC5 ion channels (PubMed:37137991)","subcellular_location":"Cytoplasm; Cell membrane; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","url":"https://www.uniprot.org/uniprotkb/P08754/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GNAI3","classification":"Not Classified","n_dependent_lines":19,"n_total_lines":1208,"dependency_fraction":0.015728476821192054},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"GNB1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/GNAI3","total_profiled":1310},"omim":[{"mim_id":"619344","title":"PURKINJE CELL PROTEIN 2; PCP2","url":"https://www.omim.org/entry/619344"},{"mim_id":"616919","title":"FERM AND PDZ DOMAINS-CONTAINING PROTEIN 1; FRMPD1","url":"https://www.omim.org/entry/616919"},{"mim_id":"615706","title":"AURICULOCONDYLAR SYNDROME 3; ARCND3","url":"https://www.omim.org/entry/615706"},{"mim_id":"614669","title":"AURICULOCONDYLAR SYNDROME 2A; ARCND2A","url":"https://www.omim.org/entry/614669"},{"mim_id":"612798","title":"QUESTION MARK EARS, ISOLATED; QME","url":"https://www.omim.org/entry/612798"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Centrosome","reliability":"Supported"},{"location":"Principal piece","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Golgi apparatus","reliability":"Additional"},{"location":"Centriolar satellite","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GNAI3"},"hgnc":{"alias_symbol":["87U6"],"prev_symbol":[]},"alphafold":{"accession":"P08754","domains":[{"cath_id":"1.10.400.10","chopping":"62-174","consensus_level":"high","plddt":96.533,"start":62,"end":174},{"cath_id":"3.40.50.300","chopping":"215-340","consensus_level":"high","plddt":96.5248,"start":215,"end":340}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P08754","model_url":"https://alphafold.ebi.ac.uk/files/AF-P08754-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P08754-F1-predicted_aligned_error_v6.png","plddt_mean":93.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GNAI3","jax_strain_url":"https://www.jax.org/strain/search?query=GNAI3"},"sequence":{"accession":"P08754","fasta_url":"https://rest.uniprot.org/uniprotkb/P08754.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P08754/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P08754"}},"corpus_meta":[{"pmid":"30836096","id":"PMC_30836096","title":"GNAI1 and GNAI3 Reduce Colitis-Associated Tumorigenesis in Mice by Blocking IL6 Signaling and Down-regulating Expression of GNAI2.","date":"2019","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/30836096","citation_count":80,"is_preprint":false},{"pmid":"22560091","id":"PMC_22560091","title":"A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome.","date":"2012","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22560091","citation_count":77,"is_preprint":false},{"pmid":"25444921","id":"PMC_25444921","title":"GNAI3 inhibits tumor cell migration and invasion and is post-transcriptionally regulated by miR-222 in hepatocellular carcinoma.","date":"2014","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/25444921","citation_count":36,"is_preprint":false},{"pmid":"23977324","id":"PMC_23977324","title":"The loss of Gnai2 and Gnai3 in B cells eliminates B lymphocyte compartments and leads to a hyper-IgM like syndrome.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23977324","citation_count":26,"is_preprint":false},{"pmid":"28484278","id":"PMC_28484278","title":"Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28484278","citation_count":25,"is_preprint":false},{"pmid":"25026904","id":"PMC_25026904","title":"Novel variants in GNAI3 associated with auriculocondylar syndrome strengthen a common dominant negative effect.","date":"2014","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/25026904","citation_count":24,"is_preprint":false},{"pmid":"34803495","id":"PMC_34803495","title":"Mir24-2-5p suppresses the osteogenic differentiation with Gnai3 inhibition presenting a direct target via inactivating JNK-p38 MAPK signaling axis.","date":"2021","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34803495","citation_count":17,"is_preprint":false},{"pmid":"24751948","id":"PMC_24751948","title":"Regulator of G-protein signaling 19 (RGS19) and its partner Gα-inhibiting activity polypeptide 3 (GNAI3) are required for zVAD-induced autophagy and cell death in L929 cells.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24751948","citation_count":12,"is_preprint":false},{"pmid":"8662225","id":"PMC_8662225","title":"GNAI3, GNAT2, AMPD2, GSTM are clustered in 120 kb of Chinese hamster chromosome 1q.","date":"1996","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/8662225","citation_count":11,"is_preprint":false},{"pmid":"7698751","id":"PMC_7698751","title":"The highly conserved Chinese hamster GNAI3 gene maps less than 60 kb from the AMPD2 gene and lacks the intronic U6 snRNA present in its human counterpart.","date":"1994","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/7698751","citation_count":9,"is_preprint":false},{"pmid":"10075990","id":"PMC_10075990","title":"Initiation of DNA replication at the Chinese hamster origin oriGNAI3 relies on local sequences and/or chromatin structures, but not on transcription of the nearby GNAI3 gene.","date":"1999","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/10075990","citation_count":7,"is_preprint":false},{"pmid":"33723370","id":"PMC_33723370","title":"A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1.","date":"2021","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/33723370","citation_count":7,"is_preprint":false},{"pmid":"32032744","id":"PMC_32032744","title":"Novel CpG-SNPs in the gastric acid secretion pathway GNAI3 and susceptibility to gastric 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auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report.","date":"2024","source":"BMC oral health","url":"https://pubmed.ncbi.nlm.nih.gov/39014351","citation_count":1,"is_preprint":false},{"pmid":"41202710","id":"PMC_41202710","title":"LncRNA SNHG29 Suppresses Epithelial Ovarian Cancer Cell Invasion and Migration via miR-20b-3p/GNAI3 Axis Regulation.","date":"2025","source":"Cancer genetics","url":"https://pubmed.ncbi.nlm.nih.gov/41202710","citation_count":0,"is_preprint":false},{"pmid":"40352663","id":"PMC_40352663","title":"RGS14 binds to GNAI3 and regulates the proliferation and apoptosis of human spermatogonial stem cells by affecting PLPP2 expression and MAPK signaling.","date":"2025","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/40352663","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14101,"output_tokens":3327,"usd":0.046104,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10875,"output_tokens":3344,"usd":0.068987,"stage2_stop_reason":"end_turn"},"total_usd":0.115091,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"GNAI3 missense mutations in auriculocondylar syndrome (ACS) disrupt the catalytic/GDP-GTP binding site of the protein, and functional studies in cultured osteoblasts from ACS probands showed significant reduction in downstream DLX5 and DLX6 expression, placing GNAI3 as a core signaling molecule in the EDN1-DLX5/DLX6 pathway regulating mandibular specification.\",\n      \"method\": \"Exome sequencing identifying mutations, protein-structure modeling of catalytic sites, functional gene expression assays in cultured osteoblasts from probands\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — structural modeling plus functional downstream expression assay in patient cells, single lab, two orthogonal methods\",\n      \"pmids\": [\"22560091\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"GNAI3 variants in ACS cluster in the GDP/GTP-binding region (G1 and G4 boxes), and structural modeling of all five reported ACS-associated GNAI3 residues indicates they all disrupt guanine nucleotide binding, consistent with a dominant negative mechanism.\",\n      \"method\": \"Sanger sequencing, protein structural modeling of GDP/GTP-binding motifs\",\n      \"journal\": \"European journal of human genetics : EJHG\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — structural modeling only, no in vitro biochemical validation of dominant negative effect\",\n      \"pmids\": [\"25026904\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"GNAI3 inhibits hepatocellular carcinoma (HCC) cell migration and invasion, as demonstrated by transwell assays following GNAI3 manipulation; miR-222 directly binds the GNAI3 mRNA 3'UTR and decreases GNAI3 protein expression, providing a post-transcriptional regulatory mechanism.\",\n      \"method\": \"Transwell migration/invasion assays with GNAI3 overexpression/knockdown; miR-222 target prediction confirmed by experimental screening and mRNA binding\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — functional cell-based assays plus miRNA-target experimental screening, single lab, two methods\",\n      \"pmids\": [\"25444921\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"GNAI3 (Gαi3) is required for zVAD-induced autophagy in L929 cells, and this autophagy is required for zVAD-induced TNF production; GNAI3 was identified as a partner of RGS19 (itself identified as a RIP3-interacting protein), and shRNA knockdown of GNAI3 suppressed zVAD-induced but not TNF-induced cell death.\",\n      \"method\": \"Co-immunoprecipitation identifying RGS19-RIP3 and RGS19-GNAI3 interactions; shRNA knockdown of GNAI3 with cell death and autophagy readouts\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus shRNA loss-of-function with defined cellular phenotype, single lab, two orthogonal methods\",\n      \"pmids\": [\"24751948\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Gαi3 (encoded by Gnai3), together with Gαi2, is required for B lymphocyte chemoattractant receptor signaling; B cells lacking both Gαi2 and Gαi3 are refractory to chemokine stimulation, fail to populate mucosal sites, splenic marginal zones, and lymph nodes, and cause disrupted lymphoid organ architecture with a hyper-IgM-like syndrome.\",\n      \"method\": \"Conditional knockout of Gnai2 and Gnai3 in B cells (mouse genetic model), flow cytometry, chemokine responsiveness assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean conditional double-knockout with multiple defined cellular and organismal phenotypes, flow cytometry, functional chemokine assays\",\n      \"pmids\": [\"23977324\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"GNAI1 and GNAI3 suppress colitis-associated tumorigenesis by blocking IL6 signaling; in the absence of GNAI1/3, IL6 activates NF-κB via JAK2-TRAF6-TAK1-CHUK/IKKβ and STAT3 via JAK2, resulting in increased GNAI2, IL6ST (GP130), and NOS2 expression and MDSC expansion. Immunoprecipitation of colon tumor tissues and MDSCs demonstrated interactions of GNAI1 and GNAI3 with proteins in the IL6 signaling pathway.\",\n      \"method\": \"Double-knockout mouse model (GNAI1/3 DKO), immunoprecipitation, immunoblot, flow cytometry, anti-IL6 antibody rescue experiment\",\n      \"journal\": \"Gastroenterology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with rescue, Co-IP demonstrating protein interactions, multiple orthogonal methods across mouse and human tissues\",\n      \"pmids\": [\"30836096\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"GATA4 directly binds the GNAI3 promoter and transcriptionally activates GNAI3 expression; GATA4 deletion reduces GNAI3 levels in dental papilla cells, and GNAI3 knockdown itself decreases odontogenic/osteogenic differentiation of stem cells of dental apical papilla (SCAPs).\",\n      \"method\": \"Dual-luciferase reporter assay and ChIP assay confirming GATA4 binding to GNAI3 promoter; shRNA knockdown of GNAI3 with osteogenic differentiation readouts in SCAPs; conditional knockout mouse model\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus luciferase assay confirming direct promoter binding, combined with loss-of-function differentiation assays, single lab\",\n      \"pmids\": [\"28484278\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Mir24-2-5p directly binds the Gnai3 3'UTR and negatively regulates Gnai3 expression; Gnai3 promotes osteoblast precursor cell proliferation, migration, osteogenic differentiation, and mineralization, and acts through activation of the JNK-p38 MAPK signaling axis. In zebrafish, gnai3 morpholino knockdown recapitulated mandibular/cartilage developmental defects, partially rescued by gnai3 mRNA injection.\",\n      \"method\": \"Dual-luciferase reporter assay for miRNA-target interaction; shRNA knockdown of Gnai3; Western blot for p-JNK and p-p38; zebrafish morpholino knockdown with phenotypic rescue; osteogenic differentiation assays\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase assay plus loss-of-function with pathway readouts, ortholog zebrafish rescue, single lab\",\n      \"pmids\": [\"34803495\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"GNAI3 (Gαi3) is specifically activated by the OA1 G-protein coupled receptor in the retinal pigment epithelium and participates in the OA1 transduction pathway regulating melanosomal biogenesis.\",\n      \"method\": \"Functional signaling studies demonstrating Oa1-specific activation of Gαi3 (referenced as prior work); GNAI3 gene screening in OA patients by next-generation sequencing\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — the mechanistic claim (Oa1 activates Gαi3) is cited as prior work in this paper without the primary experimental detail being provided in the abstract; NGS screening only in this study\",\n      \"pmids\": [\"27607449\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Lin28A stabilizes GNAI3 mRNA, as demonstrated by RIP assay confirming Lin28A binding to GNAI3 mRNA, and Lin28A knockdown reduced GNAI3 expression; GNAI3 overexpression suppresses LPS-induced NF-κB/NLRP3 inflammasome pathway activation, inflammation, and apoptosis in periodontal ligament stem cells, and promotes osteogenic differentiation.\",\n      \"method\": \"RIP assay for Lin28A-GNAI3 mRNA interaction; GNAI3 overexpression with Western blot for NF-κB/NLRP3 pathway proteins; ELISA for cytokines; ALP and ARS staining for osteogenic differentiation\",\n      \"journal\": \"Archives of oral biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — RIP assay plus functional overexpression experiments with pathway readouts, single lab, multiple assays\",\n      \"pmids\": [\"38636252\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RGS14 physically interacts with GNAI3 to coordinately regulate spermatogonial stem cell (SSC) proliferation and PLPP2 expression; RGS14 knockdown suppresses SSC proliferation and induces apoptosis, phenotypes that are linked to GNAI3 and the RGS14-GNAI3-PLPP2 axis through MAPK signaling.\",\n      \"method\": \"Protein-protein interaction assays and co-immunoprecipitation of RGS14-GNAI3; shRNA knockdown of RGS14; RNA-sequencing; PLPP2 overexpression rescue\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with functional rescue experiments, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"40352663\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Gαi3 is expressed in B cells, T cells, macrophages, granulocytes, platelets, and in the inner ear (Deiter's cells and first row of Hensen's cells in the organ of Corti), as determined by a Gnai3-iresGFP reporter mouse using flow cytometry and immunofluorescence.\",\n      \"method\": \"Gnai3-iresGFP knock-in reporter mouse; flow cytometry with cell-type specific surface markers; immunofluorescence staining of inner ear\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct expression mapping by validated knock-in reporter with cell-type-specific markers, single lab, two orthogonal methods\",\n      \"pmids\": [\"34253772\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GNAI3 encodes the Gαi3 subunit of inhibitory heterotrimeric G proteins, functioning as a GDP/GTP-binding signaling molecule that (1) transduces chemoattractant receptor signals in B lymphocytes to direct their compartmentalization in lymphoid organs, (2) suppresses IL6-driven NF-κB and STAT3 signaling to limit colitis-associated tumorigenesis, (3) acts downstream of the OA1 GPCR to regulate melanosomal biogenesis, (4) interacts with RGS proteins (RGS19, RGS14) to regulate autophagy and spermatogonial stem cell homeostasis, (5) promotes osteogenic/odontogenic differentiation via MAPK (JNK-p38) signaling downstream of GATA4-driven transcription, and (6) is transcriptionally regulated by GATA4 and post-transcriptionally repressed by miR-222 and miR-24-2-5p; loss-of-function mutations in the GDP/GTP-binding domain cause auriculocondylar syndrome through dominant negative disruption of EDN1-DLX5/6 pathway signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GNAI3 encodes Gαi3, an inhibitory heterotrimeric G-protein α subunit that transduces G-protein-coupled receptor signals into the control of cell migration, differentiation, and inflammatory signaling [#4, #5]. In the immune system, Gαi3 acts redundantly with Gαi2 to relay chemoattractant receptor signals in B lymphocytes; loss of both subunits renders B cells refractory to chemokine stimulation and disrupts their compartmentalization in mucosal sites, splenic marginal zones, and lymph nodes [#4]. Gαi3 also restrains inflammatory tumorigenesis: together with Gαi1 it blocks IL6-driven activation of NF-κB (via JAK2–TRAF6–TAK1–IKKβ) and STAT3, limiting myeloid-derived suppressor cell expansion in colitis-associated cancer [#5], and Gαi3 expression suppresses LPS-induced NF-κB/NLRP3 inflammasome signaling [#9]. In skeletal and dental development, Gαi3 promotes osteoblast and odontoblast proliferation, migration, and osteogenic/odontogenic differentiation through the JNK–p38 MAPK axis [#7], functioning as a transcriptional target directly activated by GATA4 [#6] and post-transcriptionally repressed by miR-222, miR-24-2-5p, and stabilized by Lin28A [#2, #7, #9]. Gαi3 cooperates with regulator-of-G-protein-signaling proteins, partnering with RGS19 to enable zVAD-induced autophagy [#3] and with RGS14 to sustain spermatogonial stem cell proliferation via a PLPP2/MAPK axis [#10]. Missense mutations in the GDP/GTP-binding region of GNAI3 cause auriculocondylar syndrome, acting through a dominant-negative mechanism that disrupts EDN1–DLX5/DLX6 signaling required for mandibular specification [#0, #1].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established GNAI3 as a disease gene by linking missense mutations to auriculocondylar syndrome and placing Gαi3 within the EDN1-DLX5/DLX6 craniofacial patterning pathway.\",\n      \"evidence\": \"Exome sequencing, protein-structure modeling of catalytic sites, and downstream expression assays in patient osteoblasts\",\n      \"pmids\": [\"22560091\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in vitro biochemical demonstration of altered nucleotide binding\", \"Dominant-negative mechanism inferred from modeling, not reconstituted\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined a physiological role for Gαi3 in immune cell trafficking, showing it acts redundantly with Gαi2 to transduce chemoattractant signals required for B cell positioning.\",\n      \"evidence\": \"Conditional Gnai2/Gnai3 double-knockout mouse, flow cytometry, chemokine responsiveness assays\",\n      \"pmids\": [\"23977324\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Redundancy with Gαi2 obscures Gαi3-specific contribution\", \"Receptor partners not individually mapped\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified post-transcriptional and protein-interaction layers controlling Gαi3, linking it to cancer cell motility, autophagy, and a tumor-suppressive output.\",\n      \"evidence\": \"Transwell assays with miR-222 3'UTR targeting in HCC; Co-IP of RGS19-GNAI3 with shRNA autophagy/cell-death readouts in L929; RIP assay for Lin28A mRNA stabilization with osteogenic readouts\",\n      \"pmids\": [\"25444921\", \"24751948\", \"38636252\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of Gαi3 in autophagy beyond RGS19 association unclear\", \"Lin28A study published later; mRNA-regulation generality untested\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Refined the structural basis of ACS variants, showing all reported residues cluster in G1/G4 nucleotide-binding boxes consistent with dominant-negative loss of GTP binding.\",\n      \"evidence\": \"Sanger sequencing and structural modeling of GDP/GTP-binding motifs\",\n      \"pmids\": [\"25026904\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Structural modeling only, no biochemical validation of nucleotide-binding defect\", \"Dominant-negative effect not functionally demonstrated\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Connected Gαi3 to OA1 GPCR signaling in retinal pigment epithelium controlling melanosomal biogenesis.\",\n      \"evidence\": \"OA1-specific Gαi3 activation cited as prior work; GNAI3 NGS screening in ocular albinism patients\",\n      \"pmids\": [\"27607449\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Primary OA1-Gαi3 activation data not provided in this study\", \"No causative GNAI3 variant established in patients\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Placed GNAI3 in a transcriptional circuit by showing GATA4 directly activates its promoter to drive odontogenic/osteogenic differentiation.\",\n      \"evidence\": \"Dual-luciferase reporter and ChIP for GATA4 promoter binding; shRNA GNAI3 knockdown in SCAPs; conditional knockout mouse\",\n      \"pmids\": [\"28484278\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream effectors of Gαi3 in differentiation not defined here\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Demonstrated a tumor-suppressive immunoregulatory function, with Gαi1/3 blocking IL6-driven NF-κB and STAT3 signaling to limit colitis-associated tumorigenesis.\",\n      \"evidence\": \"GNAI1/3 double-knockout mouse, immunoprecipitation, immunoblot, flow cytometry, anti-IL6 rescue\",\n      \"pmids\": [\"30836096\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct molecular target of Gαi3 within the IL6 cascade not pinpointed\", \"Relative contributions of Gαi1 vs Gαi3 not separated\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Mapped Gαi3 expression across immune and inner-ear cell types and confirmed its osteogenic role and miRNA control via a conserved zebrafish model.\",\n      \"evidence\": \"Gnai3-iresGFP reporter mouse with flow cytometry/immunofluorescence; dual-luciferase miR-24-2-5p targeting; JNK/p38 Western blot; zebrafish morpholino with mRNA rescue\",\n      \"pmids\": [\"34253772\", \"34803495\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional role of inner-ear expression untested\", \"Receptor upstream of JNK-p38 activation not identified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended Gαi3's RGS partnerships to reproductive biology, showing RGS14-Gαi3 interaction sustains spermatogonial stem cell proliferation through a PLPP2/MAPK axis.\",\n      \"evidence\": \"Reciprocal Co-IP of RGS14-GNAI3, shRNA knockdown, RNA-seq, PLPP2 overexpression rescue\",\n      \"pmids\": [\"40352663\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direction of regulation between RGS14 and Gαi3 not fully resolved\", \"PLPP2 regulatory link mechanistically incomplete\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single Gαi3 subunit is selectively coupled to distinct receptors and effectors across immune, skeletal, reproductive, and pigmentary contexts, and the biochemical basis of its dominant-negative disease variants, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reconstituted biochemistry of ACS mutant nucleotide handling\", \"Receptor-specific coupling determinants undefined\", \"Distinction of Gαi3-specific vs redundant Gαi functions incomplete\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [4, 5, 8]},\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [4, 8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4, 5, 8]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [4, 5]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [0, 6, 7]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"RGS19\", \"RGS14\", \"GNAI2\", \"GNAI1\", \"OA1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}