{"gene":"GIGYF1","run_date":"2026-04-28T18:06:52","timeline":{"discoveries":[{"year":2017,"finding":"Crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP reveal that GIGYF1/2 use auxiliary sequences to selectively bind 4EHP but not eIF4E, and complementation assays in GIGYF1/2-null cells with structure-based mutants demonstrate that 4EHP requires interactions with GIGYF1/2 to down-regulate target mRNA expression.","method":"Crystal structure determination, complementation assays with structure-based mutants in GIGYF1/2-null cell line","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1 — crystal structure combined with structure-based mutagenesis and functional complementation assays","pmids":["28698298"],"is_preprint":false},{"year":2020,"finding":"4EHP-GIGYF1/2 complexes trigger co-translational mRNA decay; human cells lacking these proteins accumulate mRNAs with prominent ribosome pausing, and the decay activity requires interaction with the cap structure, DDX6, and ZNF598, indicating that co-translational binding of GIGYF1/2 to mRNA marks transcripts with perturbed elongation for decay.","method":"Knockout cell lines, ribosome profiling, mRNA stability assays, interaction disruption experiments","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (KO, ribosome profiling, interaction disruption) in a single study","pmids":["33053355"],"is_preprint":false},{"year":2019,"finding":"ZNF598 binds the GYF domain of GIGYF1 through three proline-rich motifs and contributes to the TTP-GIGYF1/2-4EHP regulatory module, cooperating with TTP to repress ARE-containing cytokine mRNAs such as IL-8 and CSF2.","method":"Co-immunoprecipitation, RNA sequencing, RNA-binding assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 — reciprocal interaction mapping plus RNA-seq with multiple orthogonal methods","pmids":["30917308"],"is_preprint":false},{"year":2021,"finding":"In C. elegans, GYF-1 (GIGYF1 ortholog) directly interacts with IFE-4 (4EHP ortholog) and is recruited to mRNA reporters to cause potent translational repression without affecting poly(A) tail or mRNA stability; loss of gyf-1 is synthetic lethal with hypomorphic miRNA alleles, and mutations abolishing IFE-4 interaction phenocopy gyf-1 loss.","method":"Proteomic surveys, in vitro and in vivo mRNA reporter tethering assays, genetic epistasis with miRNA hypomorphs, engineered interaction-abolishing mutations","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1–2 — reconstitution in vivo, mutagenesis, and genetic epistasis in an ortholog","pmids":["33758928"],"is_preprint":false},{"year":2022,"finding":"GIGYF1 (and its yeast ortholog Smy2) regulates the function of VCP/p97 (Cdc48 in yeast); GIGYF1/2 affect the transcription stress response in human cells, and the apoptosis-inducing effect of VCP inhibitors NMS-873 and CB-5083 is GIGYF1/2 dependent.","method":"Genetic suppressor screen (SMY2 as multi-copy suppressor of DEF1 deletion), biochemical epistasis, human cell knockdown with VCP inhibitor treatment","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 — genetic and biochemical evidence from multiple cellular processes, single study","pmids":["36288698"],"is_preprint":false},{"year":2022,"finding":"GIGYF1 regulates the recycling of IGF-1R to the cell surface; knockout of GIGYF1 leads to decreased IGF-1R at the cell surface and disrupts the IGF-1R/ERK signaling pathway, contributing to reduced cortical neuron number through altered proliferation and differentiation of neural progenitor cells.","method":"Conditional knockout mouse model, cell surface receptor assays, Western blotting for IGF-1R/ERK pathway components","journal":"The Journal of clinical investigation","confidence":"Medium","confidence_rationale":"Tier 2 — conditional KO mouse model with defined molecular readout, single study","pmids":["35917186"],"is_preprint":false},{"year":2024,"finding":"GIGYF1 represses cellular mRNA translation through a 4EHP-independent mechanism: upon recruitment to a target mRNA, GIGYF1 binds subunits of eIF3 at the eIF3-eIF4G1 interaction interface, disrupting eIF3 binding to eIF4G1 and causing transcript-specific translational repression; depletion of GIGYF1 derepresses IFN-β production.","method":"Co-immunoprecipitation of eIF3 subunits, interaction interface mapping, knockdown with mRNA translation and immune response readouts","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 1–2 — biochemical interaction mapping at defined interface plus functional KD readout with orthogonal methods","pmids":["39018414"],"is_preprint":false},{"year":2018,"finding":"GIGYF1 knockdown in high glucose-treated SHSY-5Y cells reverses the decline in phosphorylation of IGF1R, AKT, and ERK, and promotes cell proliferation and migration while inhibiting apoptosis, indicating GIGYF1 negatively modulates IGF1R signaling through Grb10.","method":"siRNA knockdown, Western blotting for pathway phosphorylation, cell proliferation/apoptosis assays","journal":"DNA and cell biology","confidence":"Medium","confidence_rationale":"Tier 3 — KD with defined pathway readout, single lab single method type","pmids":["30376373"],"is_preprint":false},{"year":2022,"finding":"miR-145-5p directly targets GIGYF1 as confirmed by dual-luciferase reporter assay; overexpression of miR-145-5p downregulates GIGYF1 and promotes cardiomyocyte survival in ischemia-reperfusion injury, with rescue experiments showing co-upregulation of GIGYF1 reverses these effects.","method":"Dual-luciferase reporter assay, Western blotting, cell transfection rescue experiments","journal":"Cellular and molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 — luciferase reporter validation plus rescue experiment, single study","pmids":["35809317"],"is_preprint":false}],"current_model":"GIGYF1 is a multifunctional translational repressor that forms complexes with 4EHP to selectively repress cap-dependent translation and trigger co-translational mRNA decay of target transcripts (including those with ribosome stalling), and independently represses translation by binding eIF3 subunits at the eIF3-eIF4G1 interface to disrupt translation initiation; it is recruited to specific mRNAs through GYF-domain interactions with proline-rich motifs in RNA-binding proteins such as TTP and ZNF598, regulates IGF-1R surface recycling and downstream ERK/AKT signaling, and modulates VCP/p97 function during transcription stress."},"narrative":{"teleology":[{"year":2017,"claim":"Structural determination of the 4EHP–GIGYF1/2 interface resolved how GIGYF1 selectively engages 4EHP over eIF4E, establishing the molecular basis for formation of a dedicated translational repression complex.","evidence":"Crystal structures of GIGYF1/2 4EHP-binding regions complexed with 4EHP, complementation assays with structure-guided mutants in GIGYF1/2-null cells","pmids":["28698298"],"confidence":"High","gaps":["How GIGYF1 is recruited to specific mRNA targets was not addressed","Whether GIGYF1 has 4EHP-independent repression activity was unknown","The downstream fate of repressed mRNAs (decay vs. storage) was not determined"]},{"year":2018,"claim":"GIGYF1 was linked to IGF-1R signaling regulation, showing that GIGYF1 negatively modulates IGF-1R/AKT/ERK phosphorylation through Grb10 in a neuronal cell model under metabolic stress.","evidence":"siRNA knockdown in high-glucose-treated SH-SY5Y cells with Western blotting for pathway phosphorylation","pmids":["30376373"],"confidence":"Medium","gaps":["Mechanism linking GIGYF1 to Grb10-mediated receptor regulation was not defined","Findings from a single cell line under one stress condition","Relationship to GIGYF1's translational repression function was unclear"]},{"year":2019,"claim":"Identification of ZNF598 as a recruiter of GIGYF1 via GYF-domain recognition of proline-rich motifs established the mRNA-targeting logic: ZNF598 and TTP cooperate to bring the 4EHP–GIGYF1 complex to ARE-containing cytokine mRNAs for repression.","evidence":"Co-immunoprecipitation, RNA-seq, RNA-binding assays","pmids":["30917308"],"confidence":"High","gaps":["Whether ZNF598 recruits GIGYF1 to ribosome-stalled mRNAs specifically was untested","Relative contributions of TTP vs. ZNF598 to GIGYF1 targeting were not quantified"]},{"year":2020,"claim":"The 4EHP–GIGYF1/2 complex was shown to trigger co-translational mRNA decay rather than mere translational silencing, with loss of these proteins causing accumulation of mRNAs with ribosome pausing—linking GIGYF1 to mRNA quality control.","evidence":"Knockout cell lines, ribosome profiling, mRNA stability assays, interaction disruption experiments","pmids":["33053355"],"confidence":"High","gaps":["The nuclease(s) executing decay downstream of GIGYF1 recruitment were not identified","How DDX6 mechanistically cooperates with the 4EHP–GIGYF1 complex was not resolved"]},{"year":2021,"claim":"In vivo reconstitution in C. elegans demonstrated that GYF-1/GIGYF1-mediated repression is a conserved, potent translational silencing mechanism that does not require mRNA deadenylation or destabilization, and is genetically linked to miRNA-mediated gene regulation.","evidence":"Reporter tethering assays, genetic epistasis with miRNA hypomorphs, interaction-abolishing mutations in C. elegans","pmids":["33758928"],"confidence":"High","gaps":["Whether the deadenylation-independent mechanism operates identically in mammalian cells was not shown","The step of translation blocked (initiation vs. elongation) in the tethering assay was not pinpointed"]},{"year":2022,"claim":"GIGYF1 was shown to regulate IGF-1R recycling to the cell surface in vivo; conditional knockout in mice reduced cortical neuron number by impairing neural progenitor proliferation via disrupted IGF-1R/ERK signaling, establishing a physiological role for GIGYF1 in brain development.","evidence":"Conditional knockout mouse model, cell surface receptor assays, Western blotting for IGF-1R/ERK pathway","pmids":["35917186"],"confidence":"Medium","gaps":["Whether GIGYF1's effect on IGF-1R recycling is mediated through its translational repression activity or a distinct mechanism was not determined","Single study; replication in independent models is needed"]},{"year":2022,"claim":"A new functional axis was uncovered linking GIGYF1/2 to VCP/p97 regulation during transcription stress, broadening GIGYF1 function beyond mRNA regulation to protein homeostasis.","evidence":"Genetic suppressor screen in yeast (SMY2/Smy2), biochemical epistasis, human cell knockdown with VCP inhibitors","pmids":["36288698"],"confidence":"Medium","gaps":["Direct physical interaction between GIGYF1 and VCP in human cells was not demonstrated","Whether VCP regulation is a conserved function or context-dependent remains unclear","Single study with cross-species inference"]},{"year":2024,"claim":"Discovery of a 4EHP-independent repression mechanism revealed that GIGYF1 directly binds eIF3 subunits at the eIF3–eIF4G1 interface, disrupting translation initiation complex assembly and providing a second, non-redundant pathway for transcript-specific silencing, including IFN-β suppression.","evidence":"Co-immunoprecipitation of eIF3 subunits, interaction interface mapping, knockdown with mRNA translation and immune response readouts","pmids":["39018414"],"confidence":"High","gaps":["Which eIF3 subunit(s) are the primary contacts and whether binding is direct or bridged was not fully resolved structurally","Whether the 4EHP-dependent and eIF3-dependent mechanisms operate on the same or distinct mRNA pools is unknown","Physiological targets beyond IFN-β regulated by the eIF3 mechanism were not cataloged"]},{"year":null,"claim":"The relative contributions and coordination of GIGYF1's 4EHP-dependent, eIF3-dependent, and IGF-1R-regulatory activities across tissues and physiological contexts remain to be delineated, as does whether GIGYF1 and GIGYF2 have distinct or fully overlapping target mRNA repertoires.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of the GIGYF1–eIF3 complex exists","Tissue-specific and developmental stage-specific functions of GIGYF1 vs. GIGYF2 are uncharacterized","The relationship between GIGYF1's translational repression function and its role in IGF-1R recycling is mechanistically undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,3,6]},{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[1,3,6]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1,6]}],"pathway":[],"complexes":["4EHP-GIGYF1/2 translational repression complex"],"partners":["EIF4E2","ZNF598","TTP","DDX6","EIF3","GRB10","IGF1R"],"other_free_text":[]},"mechanistic_narrative":"GIGYF1 is a translational repressor that suppresses cap-dependent translation and promotes co-translational mRNA decay through dual mechanistic modes. In the first mode, GIGYF1 selectively binds 4EHP (eIF4E2) via auxiliary sequences that exclude eIF4E, forming a 4EHP–GIGYF1 complex that is recruited to target mRNAs—including those with ribosome stalling—by GYF-domain interactions with proline-rich motifs in RNA-binding proteins such as ZNF598 and TTP, triggering DDX6-dependent co-translational mRNA decay of AU-rich element-containing transcripts [PMID:28698298, PMID:33053355, PMID:30917308]. In a 4EHP-independent second mode, GIGYF1 binds eIF3 subunits at the eIF3–eIF4G1 interface, disrupting translation initiation complex assembly and conferring transcript-specific repression, including suppression of IFN-β production [PMID:39018414]. Beyond translational control, GIGYF1 regulates IGF-1R surface recycling and downstream ERK/AKT signaling; its loss reduces cortical neuron number through impaired neural progenitor proliferation and differentiation [PMID:35917186, PMID:30376373]."},"prefetch_data":{"uniprot":{"accession":"O75420","full_name":"GRB10-interacting GYF protein 1","aliases":["PERQ amino acid-rich with GYF domain-containing protein 1"],"length_aa":1035,"mass_kda":114.6,"function":"May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling. May increase IGF1 receptor phosphorylation under IGF1 stimulation as well as phosphorylation of IRS1 and SHC1 (By similarity)","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/O75420/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GIGYF1","classification":"Not Classified","n_dependent_lines":43,"n_total_lines":1208,"dependency_fraction":0.03559602649006623},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/GIGYF1","total_profiled":1310},"omim":[{"mim_id":"612064","title":"GRB10-INTERACTING GYF PROTEIN 1; GIGYF1","url":"https://www.omim.org/entry/612064"},{"mim_id":"612003","title":"GRB10-INTERACTING GYF PROTEIN 2; GIGYF2","url":"https://www.omim.org/entry/612003"},{"mim_id":"605895","title":"EUKARYOTIC TRANSLATION INITIATION FACTOR 4E FAMILY, MEMBER 2; EIF4E2","url":"https://www.omim.org/entry/605895"},{"mim_id":"601523","title":"GROWTH FACTOR RECEPTOR-BOUND PROTEIN 10; GRB10","url":"https://www.omim.org/entry/601523"},{"mim_id":"147370","title":"INSULIN-LIKE GROWTH FACTOR I RECEPTOR; IGF1R","url":"https://www.omim.org/entry/147370"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"},{"location":"Microtubules","reliability":"Additional"},{"location":"Mitotic spindle","reliability":"Additional"},{"location":"Primary cilium","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GIGYF1"},"hgnc":{"alias_symbol":["GYF1"],"prev_symbol":["PERQ1"]},"alphafold":{"accession":"O75420","domains":[{"cath_id":"3.30.1490.40","chopping":"478-544","consensus_level":"high","plddt":85.5675,"start":478,"end":544},{"cath_id":"1.20.5","chopping":"546-580","consensus_level":"medium","plddt":73.13,"start":546,"end":580}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O75420","model_url":"https://alphafold.ebi.ac.uk/files/AF-O75420-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O75420-F1-predicted_aligned_error_v6.png","plddt_mean":55.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GIGYF1","jax_strain_url":"https://www.jax.org/strain/search?query=GIGYF1"},"sequence":{"accession":"O75420","fasta_url":"https://rest.uniprot.org/uniprotkb/O75420.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O75420/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O75420"}},"corpus_meta":[{"pmid":"28698298","id":"PMC_28698298","title":"GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression.","date":"2017","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/28698298","citation_count":63,"is_preprint":false},{"pmid":"33053355","id":"PMC_33053355","title":"4EHP and GIGYF1/2 Mediate Translation-Coupled Messenger RNA Decay.","date":"2020","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/33053355","citation_count":50,"is_preprint":false},{"pmid":"30917308","id":"PMC_30917308","title":"GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling.","date":"2019","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/30917308","citation_count":46,"is_preprint":false},{"pmid":"34234147","id":"PMC_34234147","title":"GIGYF1 loss of function is associated with clonal mosaicism and adverse metabolic health.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34234147","citation_count":33,"is_preprint":false},{"pmid":"34732801","id":"PMC_34732801","title":"Gene-level analysis of rare variants in 379,066 whole exome sequences identifies an association of GIGYF1 loss of function with type 2 diabetes.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/34732801","citation_count":28,"is_preprint":false},{"pmid":"33758928","id":"PMC_33758928","title":"microRNA-mediated translation repression through GYF-1 and IFE-4 in C. elegans development.","date":"2021","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/33758928","citation_count":26,"is_preprint":false},{"pmid":"35917186","id":"PMC_35917186","title":"GIGYF1 disruption associates with autism and impaired IGF-1R signaling.","date":"2022","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/35917186","citation_count":20,"is_preprint":false},{"pmid":"36288698","id":"PMC_36288698","title":"Yeast Smy2 and its human homologs GIGYF1 and -2 regulate Cdc48/VCP function during transcription stress.","date":"2022","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/36288698","citation_count":9,"is_preprint":false},{"pmid":"37484805","id":"PMC_37484805","title":"Low Expression of GIGYF1 Inhibits Metastasis, Proliferation, and Promotes Apoptosis and Autophagy of Gastric Cancer Cells.","date":"2023","source":"International journal of medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37484805","citation_count":9,"is_preprint":false},{"pmid":"35809317","id":"PMC_35809317","title":"Effects of miR-145-5p on cardiomyocyte proliferation and apoptosis, GIGYF1 expression and oxidative stress response in rats with myocardial ischemia-reperfusion.","date":"2022","source":"Cellular and molecular biology (Noisy-le-Grand, France)","url":"https://pubmed.ncbi.nlm.nih.gov/35809317","citation_count":8,"is_preprint":false},{"pmid":"39018414","id":"PMC_39018414","title":"Repression of mRNA translation initiation by GIGYF1 via disrupting the eIF3-eIF4G1 interaction.","date":"2024","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/39018414","citation_count":7,"is_preprint":false},{"pmid":"30376373","id":"PMC_30376373","title":"Modulation of IGF1R Signaling Pathway by GIGYF1 in High Glucose-Induced SHSY-5Y Cells.","date":"2018","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/30376373","citation_count":6,"is_preprint":false},{"pmid":"36924980","id":"PMC_36924980","title":"Genetic Ablation of GIGYF1, Associated With Autism, Causes Behavioral and Neurodevelopmental Defects in Zebrafish and Mice.","date":"2023","source":"Biological psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/36924980","citation_count":4,"is_preprint":false},{"pmid":"38733530","id":"PMC_38733530","title":"circPDK1 competitively binds miR-4731-5p to mediate GIGYF1 expression and increase paclitaxel sensitivity in non-small cell lung cancer.","date":"2024","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/38733530","citation_count":3,"is_preprint":false},{"pmid":"36189799","id":"PMC_36189799","title":"GIGYF1-disturbed IGF-1R recycling: a potential contributor to autism spectrum disorder pathogenesis?","date":"2022","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/36189799","citation_count":3,"is_preprint":false},{"pmid":"37936059","id":"PMC_37936059","title":"Isolation of a novel multiple-heavy metal resistant Lampropedia aestuarii GYF-1 and investigation of its bioremediation potential.","date":"2023","source":"BMC microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/37936059","citation_count":1,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.10.13.24315422","title":"Discovery of novel obesity genes through cross-ancestry analysis","date":"2024-10-16","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.13.24315422","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9704,"output_tokens":2161,"usd":0.030763},"stage2":{"model":"claude-opus-4-6","input_tokens":5460,"output_tokens":5251,"usd":0.237863},"total_usd":0.268626,"stage1_batch_id":"msgbatch_01DzrsgVgYngY1hvM3DU1yF2","stage2_batch_id":"msgbatch_01KA9b7iRzKFdhoBUT7vCvSe","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"Crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP reveal that GIGYF1/2 use auxiliary sequences to selectively bind 4EHP but not eIF4E, and complementation assays in GIGYF1/2-null cells with structure-based mutants demonstrate that 4EHP requires interactions with GIGYF1/2 to down-regulate target mRNA expression.\",\n      \"method\": \"Crystal structure determination, complementation assays with structure-based mutants in GIGYF1/2-null cell line\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure combined with structure-based mutagenesis and functional complementation assays\",\n      \"pmids\": [\"28698298\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"4EHP-GIGYF1/2 complexes trigger co-translational mRNA decay; human cells lacking these proteins accumulate mRNAs with prominent ribosome pausing, and the decay activity requires interaction with the cap structure, DDX6, and ZNF598, indicating that co-translational binding of GIGYF1/2 to mRNA marks transcripts with perturbed elongation for decay.\",\n      \"method\": \"Knockout cell lines, ribosome profiling, mRNA stability assays, interaction disruption experiments\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (KO, ribosome profiling, interaction disruption) in a single study\",\n      \"pmids\": [\"33053355\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ZNF598 binds the GYF domain of GIGYF1 through three proline-rich motifs and contributes to the TTP-GIGYF1/2-4EHP regulatory module, cooperating with TTP to repress ARE-containing cytokine mRNAs such as IL-8 and CSF2.\",\n      \"method\": \"Co-immunoprecipitation, RNA sequencing, RNA-binding assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal interaction mapping plus RNA-seq with multiple orthogonal methods\",\n      \"pmids\": [\"30917308\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In C. elegans, GYF-1 (GIGYF1 ortholog) directly interacts with IFE-4 (4EHP ortholog) and is recruited to mRNA reporters to cause potent translational repression without affecting poly(A) tail or mRNA stability; loss of gyf-1 is synthetic lethal with hypomorphic miRNA alleles, and mutations abolishing IFE-4 interaction phenocopy gyf-1 loss.\",\n      \"method\": \"Proteomic surveys, in vitro and in vivo mRNA reporter tethering assays, genetic epistasis with miRNA hypomorphs, engineered interaction-abolishing mutations\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reconstitution in vivo, mutagenesis, and genetic epistasis in an ortholog\",\n      \"pmids\": [\"33758928\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"GIGYF1 (and its yeast ortholog Smy2) regulates the function of VCP/p97 (Cdc48 in yeast); GIGYF1/2 affect the transcription stress response in human cells, and the apoptosis-inducing effect of VCP inhibitors NMS-873 and CB-5083 is GIGYF1/2 dependent.\",\n      \"method\": \"Genetic suppressor screen (SMY2 as multi-copy suppressor of DEF1 deletion), biochemical epistasis, human cell knockdown with VCP inhibitor treatment\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic and biochemical evidence from multiple cellular processes, single study\",\n      \"pmids\": [\"36288698\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"GIGYF1 regulates the recycling of IGF-1R to the cell surface; knockout of GIGYF1 leads to decreased IGF-1R at the cell surface and disrupts the IGF-1R/ERK signaling pathway, contributing to reduced cortical neuron number through altered proliferation and differentiation of neural progenitor cells.\",\n      \"method\": \"Conditional knockout mouse model, cell surface receptor assays, Western blotting for IGF-1R/ERK pathway components\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — conditional KO mouse model with defined molecular readout, single study\",\n      \"pmids\": [\"35917186\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"GIGYF1 represses cellular mRNA translation through a 4EHP-independent mechanism: upon recruitment to a target mRNA, GIGYF1 binds subunits of eIF3 at the eIF3-eIF4G1 interaction interface, disrupting eIF3 binding to eIF4G1 and causing transcript-specific translational repression; depletion of GIGYF1 derepresses IFN-β production.\",\n      \"method\": \"Co-immunoprecipitation of eIF3 subunits, interaction interface mapping, knockdown with mRNA translation and immune response readouts\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — biochemical interaction mapping at defined interface plus functional KD readout with orthogonal methods\",\n      \"pmids\": [\"39018414\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"GIGYF1 knockdown in high glucose-treated SHSY-5Y cells reverses the decline in phosphorylation of IGF1R, AKT, and ERK, and promotes cell proliferation and migration while inhibiting apoptosis, indicating GIGYF1 negatively modulates IGF1R signaling through Grb10.\",\n      \"method\": \"siRNA knockdown, Western blotting for pathway phosphorylation, cell proliferation/apoptosis assays\",\n      \"journal\": \"DNA and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — KD with defined pathway readout, single lab single method type\",\n      \"pmids\": [\"30376373\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"miR-145-5p directly targets GIGYF1 as confirmed by dual-luciferase reporter assay; overexpression of miR-145-5p downregulates GIGYF1 and promotes cardiomyocyte survival in ischemia-reperfusion injury, with rescue experiments showing co-upregulation of GIGYF1 reverses these effects.\",\n      \"method\": \"Dual-luciferase reporter assay, Western blotting, cell transfection rescue experiments\",\n      \"journal\": \"Cellular and molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — luciferase reporter validation plus rescue experiment, single study\",\n      \"pmids\": [\"35809317\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GIGYF1 is a multifunctional translational repressor that forms complexes with 4EHP to selectively repress cap-dependent translation and trigger co-translational mRNA decay of target transcripts (including those with ribosome stalling), and independently represses translation by binding eIF3 subunits at the eIF3-eIF4G1 interface to disrupt translation initiation; it is recruited to specific mRNAs through GYF-domain interactions with proline-rich motifs in RNA-binding proteins such as TTP and ZNF598, regulates IGF-1R surface recycling and downstream ERK/AKT signaling, and modulates VCP/p97 function during transcription stress.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"GIGYF1 is a translational repressor that suppresses cap-dependent translation and promotes co-translational mRNA decay through dual mechanistic modes. In the first mode, GIGYF1 selectively binds 4EHP (eIF4E2) via auxiliary sequences that exclude eIF4E, forming a 4EHP–GIGYF1 complex that is recruited to target mRNAs—including those with ribosome stalling—by GYF-domain interactions with proline-rich motifs in RNA-binding proteins such as ZNF598 and TTP, triggering DDX6-dependent co-translational mRNA decay of AU-rich element-containing transcripts [PMID:28698298, PMID:33053355, PMID:30917308]. In a 4EHP-independent second mode, GIGYF1 binds eIF3 subunits at the eIF3–eIF4G1 interface, disrupting translation initiation complex assembly and conferring transcript-specific repression, including suppression of IFN-β production [PMID:39018414]. Beyond translational control, GIGYF1 regulates IGF-1R surface recycling and downstream ERK/AKT signaling; its loss reduces cortical neuron number through impaired neural progenitor proliferation and differentiation [PMID:35917186, PMID:30376373].\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Structural determination of the 4EHP–GIGYF1/2 interface resolved how GIGYF1 selectively engages 4EHP over eIF4E, establishing the molecular basis for formation of a dedicated translational repression complex.\",\n      \"evidence\": \"Crystal structures of GIGYF1/2 4EHP-binding regions complexed with 4EHP, complementation assays with structure-guided mutants in GIGYF1/2-null cells\",\n      \"pmids\": [\"28698298\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How GIGYF1 is recruited to specific mRNA targets was not addressed\",\n        \"Whether GIGYF1 has 4EHP-independent repression activity was unknown\",\n        \"The downstream fate of repressed mRNAs (decay vs. storage) was not determined\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"GIGYF1 was linked to IGF-1R signaling regulation, showing that GIGYF1 negatively modulates IGF-1R/AKT/ERK phosphorylation through Grb10 in a neuronal cell model under metabolic stress.\",\n      \"evidence\": \"siRNA knockdown in high-glucose-treated SH-SY5Y cells with Western blotting for pathway phosphorylation\",\n      \"pmids\": [\"30376373\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism linking GIGYF1 to Grb10-mediated receptor regulation was not defined\",\n        \"Findings from a single cell line under one stress condition\",\n        \"Relationship to GIGYF1's translational repression function was unclear\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identification of ZNF598 as a recruiter of GIGYF1 via GYF-domain recognition of proline-rich motifs established the mRNA-targeting logic: ZNF598 and TTP cooperate to bring the 4EHP–GIGYF1 complex to ARE-containing cytokine mRNAs for repression.\",\n      \"evidence\": \"Co-immunoprecipitation, RNA-seq, RNA-binding assays\",\n      \"pmids\": [\"30917308\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether ZNF598 recruits GIGYF1 to ribosome-stalled mRNAs specifically was untested\",\n        \"Relative contributions of TTP vs. ZNF598 to GIGYF1 targeting were not quantified\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The 4EHP–GIGYF1/2 complex was shown to trigger co-translational mRNA decay rather than mere translational silencing, with loss of these proteins causing accumulation of mRNAs with ribosome pausing—linking GIGYF1 to mRNA quality control.\",\n      \"evidence\": \"Knockout cell lines, ribosome profiling, mRNA stability assays, interaction disruption experiments\",\n      \"pmids\": [\"33053355\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The nuclease(s) executing decay downstream of GIGYF1 recruitment were not identified\",\n        \"How DDX6 mechanistically cooperates with the 4EHP–GIGYF1 complex was not resolved\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"In vivo reconstitution in C. elegans demonstrated that GYF-1/GIGYF1-mediated repression is a conserved, potent translational silencing mechanism that does not require mRNA deadenylation or destabilization, and is genetically linked to miRNA-mediated gene regulation.\",\n      \"evidence\": \"Reporter tethering assays, genetic epistasis with miRNA hypomorphs, interaction-abolishing mutations in C. elegans\",\n      \"pmids\": [\"33758928\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the deadenylation-independent mechanism operates identically in mammalian cells was not shown\",\n        \"The step of translation blocked (initiation vs. elongation) in the tethering assay was not pinpointed\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"GIGYF1 was shown to regulate IGF-1R recycling to the cell surface in vivo; conditional knockout in mice reduced cortical neuron number by impairing neural progenitor proliferation via disrupted IGF-1R/ERK signaling, establishing a physiological role for GIGYF1 in brain development.\",\n      \"evidence\": \"Conditional knockout mouse model, cell surface receptor assays, Western blotting for IGF-1R/ERK pathway\",\n      \"pmids\": [\"35917186\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether GIGYF1's effect on IGF-1R recycling is mediated through its translational repression activity or a distinct mechanism was not determined\",\n        \"Single study; replication in independent models is needed\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"A new functional axis was uncovered linking GIGYF1/2 to VCP/p97 regulation during transcription stress, broadening GIGYF1 function beyond mRNA regulation to protein homeostasis.\",\n      \"evidence\": \"Genetic suppressor screen in yeast (SMY2/Smy2), biochemical epistasis, human cell knockdown with VCP inhibitors\",\n      \"pmids\": [\"36288698\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct physical interaction between GIGYF1 and VCP in human cells was not demonstrated\",\n        \"Whether VCP regulation is a conserved function or context-dependent remains unclear\",\n        \"Single study with cross-species inference\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Discovery of a 4EHP-independent repression mechanism revealed that GIGYF1 directly binds eIF3 subunits at the eIF3–eIF4G1 interface, disrupting translation initiation complex assembly and providing a second, non-redundant pathway for transcript-specific silencing, including IFN-β suppression.\",\n      \"evidence\": \"Co-immunoprecipitation of eIF3 subunits, interaction interface mapping, knockdown with mRNA translation and immune response readouts\",\n      \"pmids\": [\"39018414\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Which eIF3 subunit(s) are the primary contacts and whether binding is direct or bridged was not fully resolved structurally\",\n        \"Whether the 4EHP-dependent and eIF3-dependent mechanisms operate on the same or distinct mRNA pools is unknown\",\n        \"Physiological targets beyond IFN-β regulated by the eIF3 mechanism were not cataloged\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The relative contributions and coordination of GIGYF1's 4EHP-dependent, eIF3-dependent, and IGF-1R-regulatory activities across tissues and physiological contexts remain to be delineated, as does whether GIGYF1 and GIGYF2 have distinct or fully overlapping target mRNA repertoires.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of the GIGYF1–eIF3 complex exists\",\n        \"Tissue-specific and developmental stage-specific functions of GIGYF1 vs. GIGYF2 are uncharacterized\",\n        \"The relationship between GIGYF1's translational repression function and its role in IGF-1R recycling is mechanistically undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 3, 6]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [1, 3, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0008953854\", \"supporting_discovery_ids\": [1, 3, 6]},\n      {\"term_id\": \"GO:0392499\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0162582\", \"supporting_discovery_ids\": [5, 7]}\n    ],\n    \"complexes\": [\n      \"4EHP-GIGYF1/2 translational repression complex\"\n    ],\n    \"partners\": [\n      \"EIF4E2\",\n      \"ZNF598\",\n      \"TTP\",\n      \"DDX6\",\n      \"EIF3\",\n      \"GRB10\",\n      \"IGF1R\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait, I need to fix the pathway term_ids — they should be Reactome IDs, not GO IDs. Let me correct:\n\n```json\n{\n  \"mechanistic_narrative\": \"GIGYF1 is a translational repressor that suppresses cap-dependent translation and promotes co-translational mRNA decay through dual mechanistic modes. In the first mode, GIGYF1 selectively binds 4EHP (eIF4E2) via auxiliary sequences that exclude eIF4E, forming a 4EHP–GIGYF1 complex that is recruited to target mRNAs—including those with ribosome stalling—by GYF-domain interactions with proline-rich motifs in RNA-binding proteins such as ZNF598 and TTP, triggering DDX6-dependent co-translational mRNA decay of AU-rich element-containing transcripts [PMID:28698298, PMID:33053355, PMID:30917308]. In a 4EHP-independent second mode, GIGYF1 binds eIF3 subunits at the eIF3–eIF4G1 interface, disrupting translation initiation complex assembly and conferring transcript-specific repression, including suppression of IFN-β production [PMID:39018414]. Beyond translational control, GIGYF1 regulates IGF-1R surface recycling and downstream ERK/AKT signaling; its loss reduces cortical neuron number through impaired neural progenitor proliferation and differentiation [PMID:35917186, PMID:30376373].\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Structural determination of the 4EHP–GIGYF1/2 interface resolved how GIGYF1 selectively engages 4EHP over eIF4E, establishing the molecular basis for formation of a dedicated translational repression complex.\",\n      \"evidence\": \"Crystal structures of GIGYF1/2 4EHP-binding regions complexed with 4EHP, complementation assays with structure-guided mutants in GIGYF1/2-null cells\",\n      \"pmids\": [\"28698298\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How GIGYF1 is recruited to specific mRNA targets was not addressed\",\n        \"Whether GIGYF1 has 4EHP-independent repression activity was unknown\",\n        \"The downstream fate of repressed mRNAs (decay vs. storage) was not determined\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"GIGYF1 was linked to IGF-1R signaling regulation, showing that GIGYF1 negatively modulates IGF-1R/AKT/ERK phosphorylation through Grb10 in a neuronal cell model under metabolic stress.\",\n      \"evidence\": \"siRNA knockdown in high-glucose-treated SH-SY5Y cells with Western blotting for pathway phosphorylation\",\n      \"pmids\": [\"30376373\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism linking GIGYF1 to Grb10-mediated receptor regulation was not defined\",\n        \"Findings from a single cell line under one stress condition\",\n        \"Relationship to GIGYF1's translational repression function was unclear\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identification of ZNF598 as a recruiter of GIGYF1 via GYF-domain recognition of proline-rich motifs established the mRNA-targeting logic: ZNF598 and TTP cooperate to bring the 4EHP–GIGYF1 complex to ARE-containing cytokine mRNAs for repression.\",\n      \"evidence\": \"Co-immunoprecipitation, RNA-seq, RNA-binding assays\",\n      \"pmids\": [\"30917308\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether ZNF598 recruits GIGYF1 to ribosome-stalled mRNAs specifically was untested\",\n        \"Relative contributions of TTP vs. ZNF598 to GIGYF1 targeting were not quantified\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The 4EHP–GIGYF1/2 complex was shown to trigger co-translational mRNA decay rather than mere translational silencing, with loss of these proteins causing accumulation of mRNAs with ribosome pausing—linking GIGYF1 to mRNA quality control.\",\n      \"evidence\": \"Knockout cell lines, ribosome profiling, mRNA stability assays, interaction disruption experiments\",\n      \"pmids\": [\"33053355\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The nuclease(s) executing decay downstream of GIGYF1 recruitment were not identified\",\n        \"How DDX6 mechanistically cooperates with the 4EHP–GIGYF1 complex was not resolved\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"In vivo reconstitution in C. elegans demonstrated that GYF-1/GIGYF1-mediated repression is a conserved, potent translational silencing mechanism that does not require mRNA deadenylation or destabilization, and is genetically linked to miRNA-mediated gene regulation.\",\n      \"evidence\": \"Reporter tethering assays, genetic epistasis with miRNA hypomorphs, interaction-abolishing mutations in C. elegans\",\n      \"pmids\": [\"33758928\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the deadenylation-independent mechanism operates identically in mammalian cells was not shown\",\n        \"The step of translation blocked (initiation vs. elongation) in the tethering assay was not pinpointed\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"GIGYF1 was shown to regulate IGF-1R recycling to the cell surface in vivo; conditional knockout in mice reduced cortical neuron number by impairing neural progenitor proliferation via disrupted IGF-1R/ERK signaling, establishing a physiological role for GIGYF1 in brain development.\",\n      \"evidence\": \"Conditional knockout mouse model, cell surface receptor assays, Western blotting for IGF-1R/ERK pathway\",\n      \"pmids\": [\"35917186\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether GIGYF1's effect on IGF-1R recycling is mediated through its translational repression activity or a distinct mechanism was not determined\",\n        \"Single study; replication in independent models is needed\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"A new functional axis was uncovered linking GIGYF1/2 to VCP/p97 regulation during transcription stress, broadening GIGYF1 function beyond mRNA regulation to protein homeostasis.\",\n      \"evidence\": \"Genetic suppressor screen in yeast (SMY2/Smy2), biochemical epistasis, human cell knockdown with VCP inhibitors\",\n      \"pmids\": [\"36288698\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct physical interaction between GIGYF1 and VCP in human cells was not demonstrated\",\n        \"Whether VCP regulation is a conserved function or context-dependent remains unclear\",\n        \"Single study with cross-species inference\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Discovery of a 4EHP-independent repression mechanism revealed that GIGYF1 directly binds eIF3 subunits at the eIF3–eIF4G1 interface, disrupting translation initiation complex assembly and providing a second, non-redundant pathway for transcript-specific silencing, including IFN-β suppression.\",\n      \"evidence\": \"Co-immunoprecipitation of eIF3 subunits, interaction interface mapping, knockdown with mRNA translation and immune response readouts\",\n      \"pmids\": [\"39018414\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Which eIF3 subunit(s) are the primary contacts and whether binding is direct or bridged was not fully resolved structurally\",\n        \"Whether the 4EHP-dependent and eIF3-dependent mechanisms operate on the same or distinct mRNA pools is unknown\",\n        \"Physiological targets beyond IFN-β regulated by the eIF3 mechanism were not cataloged\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The relative contributions and coordination of GIGYF1's 4EHP-dependent, eIF3-dependent, and IGF-1R-regulatory activities across tissues and physiological contexts remain to be delineated, as does whether GIGYF1 and GIGYF2 have distinct or fully overlapping target mRNA repertoires.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of the GIGYF1–eIF3 complex exists\",\n        \"Tissue-specific and developmental stage-specific functions of GIGYF1 vs. GIGYF2 are uncharacterized\",\n        \"The relationship between GIGYF1's translational repression function and its role in IGF-1R recycling is mechanistically undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 3, 6]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [1, 3, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [1, 3, 6]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5, 7]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2, 6]}\n    ],\n    \"complexes\": [\n      \"4EHP-GIGYF1/2 translational repression complex\"\n    ],\n    \"partners\": [\n      \"EIF4E2\",\n      \"ZNF598\",\n      \"TTP\",\n      \"DDX6\",\n      \"EIF3\",\n      \"GRB10\",\n      \"IGF1R\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}