{"gene":"ITFG1","run_date":"2026-06-10T01:55:23","timeline":{"discoveries":[{"year":2014,"finding":"LINKIN (ITFG1/LNKN-1) is a conserved transmembrane protein with seven atypical FG-GAP domains in its extracellular domain that potentially fold into a β-propeller structure resembling the α-integrin ligand-binding domain. It localizes to the plasma membrane with apical and lateral bias in C. elegans gonadal cells and promotes adhesion between neighboring cells through its extracellular domain while regulating microtubule dynamics through RUVBL proteins at its intracellular domain.","method":"SILAC mass spectrometry interactome (human HEK293T cells), C. elegans genetic loss-of-function, immunofluorescence localization, domain analysis","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal IP-MS identification of interactors, validated by genetic epistasis in C. elegans, localization confirmed by imaging, replicated across two organisms","pmids":["25437307"],"is_preprint":false},{"year":2014,"finding":"ITFG1/LNKN-1 interacts with RUVBL1, RUVBL2, and α-tubulin as identified by immunoprecipitation-mass spectrometry in human HEK293T cells, and these interactions were functionally validated in C. elegans male gonad development.","method":"SILAC mass spectrometry co-immunoprecipitation (human HEK293T cells), C. elegans functional validation","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — IP-MS in human cells with orthogonal genetic validation in C. elegans, subsequently independently replicated in breast cancer cells","pmids":["25437307","28341484"],"is_preprint":false},{"year":2017,"finding":"RUVBL1 interacts with ITFG1 in the cytoplasm and at the plasma membrane of breast cancer cells, and this interaction is required for collective invasion; silencing either RUVBL1 or ITFG1 individually compromises collective invasion in vitro (transwell and microfluidic assays) and in vivo (xenograft and tail vein injection models).","method":"Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, transwell invasion assay, microfluidic invasion assay, xenograft mouse model","journal":"Biochimica et biophysica acta. General subjects","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with co-localization, multiple orthogonal functional assays (in vitro and in vivo), single lab","pmids":["28341484"],"is_preprint":false},{"year":2023,"finding":"Epitope-tagged ITFG1 localizes to the cell surface of MDA-MB-231 breast cancer cells. IP-MS identified new ITFG1 interactors including ATP9A, NME1, and ANAPC2; loss-of-function of their C. elegans orthologs (tat-5, ndk-1, apc-2) produced migratory detachment phenotypes similar to lnkn-1 loss, implicating membrane remodeling and chromosome biology in LINKIN-dependent cell adhesion.","method":"IP-MS (MDA-MB-231 cells), epitope-tag surface localization, C. elegans loss-of-function genetic analysis","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — IP-MS with orthogonal C. elegans genetic validation, single lab, preprint not yet peer-reviewed","pmids":["36798316"],"is_preprint":true},{"year":2012,"finding":"The ITFG1 gene resides in the 16q12.1 euchromatic band, and a chromosomal translocation breakpoint maps within ITFG1, causing position-effect silencing of a neighboring gene (NETO2/BTCL2), associated with a severe neurological phenotype; the breakpoint disruption of ITFG1's chromosomal context was established by FISH.","method":"FISH breakpoint mapping, real-time PCR expression analysis, chromatin immunoprecipitation, pyrosequencing","journal":"Molecular cytogenetics","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — FISH localization of breakpoint within ITFG1, but functional consequence attributed to position effect on neighboring genes, not to ITFG1 protein mechanism directly","pmids":["22475481"],"is_preprint":false}],"current_model":"ITFG1 (LINKIN/LNKN-1) is a conserved transmembrane protein with extracellular FG-GAP domains that mediate cell–cell adhesion, while its intracellular domain interacts with the AAA-ATPases RUVBL1 and RUVBL2 and α-tubulin to regulate microtubule dynamics; in breast cancer cells the RUVBL1–ITFG1 complex at the cytoplasm and plasma membrane is required for collective invasion, and additional interactors (ATP9A, NME1, ANAPC2) implicate membrane remodeling and chromosome biology in LINKIN-dependent tissue integrity during collective cell migration."},"narrative":{"mechanistic_narrative":"ITFG1 (LINKIN/LNKN-1) is a conserved transmembrane protein that couples cell–cell adhesion to microtubule dynamics during collective cell migration [PMID:25437307]. Its extracellular region contains seven atypical FG-GAP domains predicted to fold into a β-propeller resembling the α-integrin ligand-binding domain, and it localizes to the plasma membrane to promote adhesion between neighboring cells [PMID:25437307]. Through its intracellular domain it engages the AAA-ATPases RUVBL1 and RUVBL2 together with α-tubulin, linking adhesion to microtubule regulation [PMID:25437307, PMID:28341484]. In breast cancer cells the RUVBL1–ITFG1 complex resides in the cytoplasm and at the plasma membrane and is required for collective invasion, as silencing either partner compromises invasion in vitro and in vivo [PMID:28341484]. Additional interactors implicating membrane remodeling and chromosome biology in LINKIN-dependent tissue integrity have been identified [PMID:36798316], but beyond these interaction and adhesion-migration roles no further enzymatic or structural mechanism has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Established ITFG1/LINKIN as a transmembrane adhesion molecule whose extracellular FG-GAP domains mediate cell–cell adhesion while its intracellular domain controls microtubule dynamics, defining a single protein that bridges adhesion and the cytoskeleton.","evidence":"SILAC IP-MS interactome in HEK293T cells, C. elegans genetic loss-of-function, immunofluorescence localization, and domain analysis","pmids":["25437307"],"confidence":"High","gaps":["β-propeller fold of the FG-GAP region is predicted, not structurally resolved","the adhesion ligand/binding partner on neighboring cells is not identified","no enzymatic activity assigned to ITFG1 itself"]},{"year":2014,"claim":"Identified the intracellular binding partners (RUVBL1, RUVBL2, α-tubulin) that mechanistically connect ITFG1 to microtubule regulation, answering how a surface adhesion protein influences the cytoskeleton.","evidence":"SILAC co-IP-MS in HEK293T cells with C. elegans male gonad functional validation","pmids":["25437307","28341484"],"confidence":"High","gaps":["the binding interface/domain on the ITFG1 cytoplasmic tail is not mapped","whether ITFG1 modulates RUVBL ATPase activity is unknown","stoichiometry of the ITFG1–RUVBL–tubulin assembly is undefined"]},{"year":2017,"claim":"Showed the RUVBL1–ITFG1 interaction is functionally required for collective cancer cell invasion, extending the adhesion/microtubule role into a disease-relevant migratory program.","evidence":"Reciprocal Co-IP, immunofluorescence co-localization, siRNA knockdown, transwell and microfluidic invasion assays, xenograft and tail-vein mouse models in breast cancer cells","pmids":["28341484"],"confidence":"High","gaps":["downstream effectors translating the complex into invasive behavior are not defined","single-lab finding","the contribution of the extracellular adhesion function versus intracellular RUVBL binding to invasion is not separated"]},{"year":2023,"claim":"Broadened the LINKIN interactome to ATP9A, NME1, and ANAPC2, implicating membrane remodeling and chromosome biology in ITFG1-dependent adhesion through cross-species phenotype concordance.","evidence":"IP-MS in MDA-MB-231 cells, epitope-tag surface localization, and C. elegans loss-of-function of orthologs tat-5, ndk-1, apc-2 (preprint)","pmids":["36798316"],"confidence":"Medium","gaps":["preprint, not yet peer-reviewed","direct physical versus indirect association of the new interactors not resolved","mechanistic link between membrane remodeling/chromosome biology and adhesion not established"]},{"year":2012,"claim":"Mapped a translocation breakpoint within ITFG1 that silences a neighboring gene by position effect, characterizing the genomic context rather than ITFG1 protein function.","evidence":"FISH breakpoint mapping, real-time PCR expression analysis, chromatin immunoprecipitation, and pyrosequencing","pmids":["22475481"],"confidence":"Medium","gaps":["phenotype attributed to position effect on NETO2/BTCL2, not to ITFG1 protein loss","no direct test of ITFG1 protein function","does not establish an ITFG1-intrinsic disease mechanism"]},{"year":null,"claim":"How ITFG1 transduces extracellular adhesion signals across the membrane to regulate RUVBL/tubulin-dependent microtubule dynamics, and what its true extracellular ligand is, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["no structure of the FG-GAP β-propeller or the cytoplasmic interaction interface","extracellular adhesion ligand unidentified","no biochemical reconstitution of the ITFG1–RUVBL–tubulin assembly"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[0]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,2,3]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-1474244","term_label":"Extracellular matrix organization","supporting_discovery_ids":[0]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[2]}],"complexes":[],"partners":["RUVBL1","RUVBL2","TUBA","ATP9A","NME1","ANAPC2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8TB96","full_name":"T-cell immunomodulatory protein","aliases":["Integrin-alpha FG-GAP repeat-containing protein 1","Linkin"],"length_aa":612,"mass_kda":68.1,"function":"Modulator of T-cell function. Has a protective effect in graft versus host disease model (By similarity)","subcellular_location":"Secreted; Membrane","url":"https://www.uniprot.org/uniprotkb/Q8TB96/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ITFG1","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ITFG1","total_profiled":1310},"omim":[{"mim_id":"611803","title":"INTEGRIN-ALPHA FG-GAP REPEAT-CONTAINING PROTEIN 1; ITFG1","url":"https://www.omim.org/entry/611803"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Vesicles","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ITFG1"},"hgnc":{"alias_symbol":["CDA08","TIP","LNKN-1"],"prev_symbol":[]},"alphafold":{"accession":"Q8TB96","domains":[{"cath_id":"2.130.10.10","chopping":"35-432","consensus_level":"medium","plddt":94.4221,"start":35,"end":432},{"cath_id":"2.60.40","chopping":"438-561","consensus_level":"medium","plddt":90.2334,"start":438,"end":561}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TB96","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TB96-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TB96-F1-predicted_aligned_error_v6.png","plddt_mean":89.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ITFG1","jax_strain_url":"https://www.jax.org/strain/search?query=ITFG1"},"sequence":{"accession":"Q8TB96","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8TB96.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8TB96/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TB96"}},"corpus_meta":[{"pmid":"25972268","id":"PMC_25972268","title":"Toward the development of transcriptional biodosimetry for the identification of irradiated individuals and assessment of absorbed radiation dose.","date":"2015","source":"Radiation and environmental biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/25972268","citation_count":39,"is_preprint":false},{"pmid":"34683848","id":"PMC_34683848","title":"Multiomics Identification of Potential Targets for Alzheimer Disease and Antrocin as a Therapeutic Candidate.","date":"2021","source":"Pharmaceutics","url":"https://pubmed.ncbi.nlm.nih.gov/34683848","citation_count":26,"is_preprint":false},{"pmid":"33747210","id":"PMC_33747210","title":"Potential application of genomic profiling for the diagnosis and treatment of patients with sarcoma.","date":"2021","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/33747210","citation_count":22,"is_preprint":false},{"pmid":"22475481","id":"PMC_22475481","title":"Juxtaposition of heterochromatic and euchromatic regions by chromosomal translocation mediates a heterochromatic long-range position effect associated with a severe neurological phenotype.","date":"2012","source":"Molecular cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/22475481","citation_count":22,"is_preprint":false},{"pmid":"28341484","id":"PMC_28341484","title":"RUVBL1-ITFG1 interaction is required for collective invasion in breast cancer.","date":"2017","source":"Biochimica et biophysica acta. General subjects","url":"https://pubmed.ncbi.nlm.nih.gov/28341484","citation_count":20,"is_preprint":false},{"pmid":"21724286","id":"PMC_21724286","title":"Developing point of care and high-throughput biological assays for determining absorbed radiation dose.","date":"2011","source":"Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/21724286","citation_count":20,"is_preprint":false},{"pmid":"30341748","id":"PMC_30341748","title":"Identification of genes associated with survival of breast cancer patients.","date":"2018","source":"Breast cancer (Tokyo, Japan)","url":"https://pubmed.ncbi.nlm.nih.gov/30341748","citation_count":20,"is_preprint":false},{"pmid":"25437307","id":"PMC_25437307","title":"LINKIN, a new transmembrane protein necessary for cell adhesion.","date":"2014","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/25437307","citation_count":13,"is_preprint":false},{"pmid":"38471523","id":"PMC_38471523","title":"PUM1 and PGK1 are Favorable Housekeeping Genes over Established Biodosimetry-related Housekeeping Genes such as HPRT1, ITFG1, DPM1, MRPS5, 18S rRNA and Others after Radiation Exposure.","date":"2024","source":"Radiation research","url":"https://pubmed.ncbi.nlm.nih.gov/38471523","citation_count":2,"is_preprint":false},{"pmid":"36798316","id":"PMC_36798316","title":"LINKIN-associated proteins necessary for tissue integrity during collective cell migration.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/36798316","citation_count":0,"is_preprint":false},{"pmid":"41122296","id":"PMC_41122296","title":"Verification of Preferred Reference Genes for RT-qPCR Analysis of Radiosensitivity Gene in Human Peripheral Blood.","date":"2025","source":"Dose-response : a publication of International Hormesis Society","url":"https://pubmed.ncbi.nlm.nih.gov/41122296","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8669,"output_tokens":1463,"usd":0.023976,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8148,"output_tokens":2321,"usd":0.049383,"stage2_stop_reason":"end_turn"},"total_usd":0.073359,"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\": 2014,\n      \"finding\": \"LINKIN (ITFG1/LNKN-1) is a conserved transmembrane protein with seven atypical FG-GAP domains in its extracellular domain that potentially fold into a β-propeller structure resembling the α-integrin ligand-binding domain. It localizes to the plasma membrane with apical and lateral bias in C. elegans gonadal cells and promotes adhesion between neighboring cells through its extracellular domain while regulating microtubule dynamics through RUVBL proteins at its intracellular domain.\",\n      \"method\": \"SILAC mass spectrometry interactome (human HEK293T cells), C. elegans genetic loss-of-function, immunofluorescence localization, domain analysis\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal IP-MS identification of interactors, validated by genetic epistasis in C. elegans, localization confirmed by imaging, replicated across two organisms\",\n      \"pmids\": [\"25437307\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ITFG1/LNKN-1 interacts with RUVBL1, RUVBL2, and α-tubulin as identified by immunoprecipitation-mass spectrometry in human HEK293T cells, and these interactions were functionally validated in C. elegans male gonad development.\",\n      \"method\": \"SILAC mass spectrometry co-immunoprecipitation (human HEK293T cells), C. elegans functional validation\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — IP-MS in human cells with orthogonal genetic validation in C. elegans, subsequently independently replicated in breast cancer cells\",\n      \"pmids\": [\"25437307\", \"28341484\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RUVBL1 interacts with ITFG1 in the cytoplasm and at the plasma membrane of breast cancer cells, and this interaction is required for collective invasion; silencing either RUVBL1 or ITFG1 individually compromises collective invasion in vitro (transwell and microfluidic assays) and in vivo (xenograft and tail vein injection models).\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, transwell invasion assay, microfluidic invasion assay, xenograft mouse model\",\n      \"journal\": \"Biochimica et biophysica acta. General subjects\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with co-localization, multiple orthogonal functional assays (in vitro and in vivo), single lab\",\n      \"pmids\": [\"28341484\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Epitope-tagged ITFG1 localizes to the cell surface of MDA-MB-231 breast cancer cells. IP-MS identified new ITFG1 interactors including ATP9A, NME1, and ANAPC2; loss-of-function of their C. elegans orthologs (tat-5, ndk-1, apc-2) produced migratory detachment phenotypes similar to lnkn-1 loss, implicating membrane remodeling and chromosome biology in LINKIN-dependent cell adhesion.\",\n      \"method\": \"IP-MS (MDA-MB-231 cells), epitope-tag surface localization, C. elegans loss-of-function genetic analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — IP-MS with orthogonal C. elegans genetic validation, single lab, preprint not yet peer-reviewed\",\n      \"pmids\": [\"36798316\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The ITFG1 gene resides in the 16q12.1 euchromatic band, and a chromosomal translocation breakpoint maps within ITFG1, causing position-effect silencing of a neighboring gene (NETO2/BTCL2), associated with a severe neurological phenotype; the breakpoint disruption of ITFG1's chromosomal context was established by FISH.\",\n      \"method\": \"FISH breakpoint mapping, real-time PCR expression analysis, chromatin immunoprecipitation, pyrosequencing\",\n      \"journal\": \"Molecular cytogenetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — FISH localization of breakpoint within ITFG1, but functional consequence attributed to position effect on neighboring genes, not to ITFG1 protein mechanism directly\",\n      \"pmids\": [\"22475481\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ITFG1 (LINKIN/LNKN-1) is a conserved transmembrane protein with extracellular FG-GAP domains that mediate cell–cell adhesion, while its intracellular domain interacts with the AAA-ATPases RUVBL1 and RUVBL2 and α-tubulin to regulate microtubule dynamics; in breast cancer cells the RUVBL1–ITFG1 complex at the cytoplasm and plasma membrane is required for collective invasion, and additional interactors (ATP9A, NME1, ANAPC2) implicate membrane remodeling and chromosome biology in LINKIN-dependent tissue integrity during collective cell migration.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ITFG1 (LINKIN/LNKN-1) is a conserved transmembrane protein that couples cell–cell adhesion to microtubule dynamics during collective cell migration [#0]. Its extracellular region contains seven atypical FG-GAP domains predicted to fold into a β-propeller resembling the α-integrin ligand-binding domain, and it localizes to the plasma membrane to promote adhesion between neighboring cells [#0]. Through its intracellular domain it engages the AAA-ATPases RUVBL1 and RUVBL2 together with α-tubulin, linking adhesion to microtubule regulation [#0, #1]. In breast cancer cells the RUVBL1–ITFG1 complex resides in the cytoplasm and at the plasma membrane and is required for collective invasion, as silencing either partner compromises invasion in vitro and in vivo [#2]. Additional interactors implicating membrane remodeling and chromosome biology in LINKIN-dependent tissue integrity have been identified [#3], but beyond these interaction and adhesion-migration roles no further enzymatic or structural mechanism has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Established ITFG1/LINKIN as a transmembrane adhesion molecule whose extracellular FG-GAP domains mediate cell–cell adhesion while its intracellular domain controls microtubule dynamics, defining a single protein that bridges adhesion and the cytoskeleton.\",\n      \"evidence\": \"SILAC IP-MS interactome in HEK293T cells, C. elegans genetic loss-of-function, immunofluorescence localization, and domain analysis\",\n      \"pmids\": [\"25437307\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"β-propeller fold of the FG-GAP region is predicted, not structurally resolved\", \"the adhesion ligand/binding partner on neighboring cells is not identified\", \"no enzymatic activity assigned to ITFG1 itself\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified the intracellular binding partners (RUVBL1, RUVBL2, α-tubulin) that mechanistically connect ITFG1 to microtubule regulation, answering how a surface adhesion protein influences the cytoskeleton.\",\n      \"evidence\": \"SILAC co-IP-MS in HEK293T cells with C. elegans male gonad functional validation\",\n      \"pmids\": [\"25437307\", \"28341484\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"the binding interface/domain on the ITFG1 cytoplasmic tail is not mapped\", \"whether ITFG1 modulates RUVBL ATPase activity is unknown\", \"stoichiometry of the ITFG1–RUVBL–tubulin assembly is undefined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Showed the RUVBL1–ITFG1 interaction is functionally required for collective cancer cell invasion, extending the adhesion/microtubule role into a disease-relevant migratory program.\",\n      \"evidence\": \"Reciprocal Co-IP, immunofluorescence co-localization, siRNA knockdown, transwell and microfluidic invasion assays, xenograft and tail-vein mouse models in breast cancer cells\",\n      \"pmids\": [\"28341484\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"downstream effectors translating the complex into invasive behavior are not defined\", \"single-lab finding\", \"the contribution of the extracellular adhesion function versus intracellular RUVBL binding to invasion is not separated\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Broadened the LINKIN interactome to ATP9A, NME1, and ANAPC2, implicating membrane remodeling and chromosome biology in ITFG1-dependent adhesion through cross-species phenotype concordance.\",\n      \"evidence\": \"IP-MS in MDA-MB-231 cells, epitope-tag surface localization, and C. elegans loss-of-function of orthologs tat-5, ndk-1, apc-2 (preprint)\",\n      \"pmids\": [\"36798316\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"preprint, not yet peer-reviewed\", \"direct physical versus indirect association of the new interactors not resolved\", \"mechanistic link between membrane remodeling/chromosome biology and adhesion not established\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Mapped a translocation breakpoint within ITFG1 that silences a neighboring gene by position effect, characterizing the genomic context rather than ITFG1 protein function.\",\n      \"evidence\": \"FISH breakpoint mapping, real-time PCR expression analysis, chromatin immunoprecipitation, and pyrosequencing\",\n      \"pmids\": [\"22475481\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"phenotype attributed to position effect on NETO2/BTCL2, not to ITFG1 protein loss\", \"no direct test of ITFG1 protein function\", \"does not establish an ITFG1-intrinsic disease mechanism\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ITFG1 transduces extracellular adhesion signals across the membrane to regulate RUVBL/tubulin-dependent microtubule dynamics, and what its true extracellular ligand is, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"no structure of the FG-GAP β-propeller or the cytoplasmic interaction interface\", \"extracellular adhesion ligand unidentified\", \"no biochemical reconstitution of the ITFG1–RUVBL–tubulin assembly\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474244\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"RUVBL1\", \"RUVBL2\", \"TUBA\", \"ATP9A\", \"NME1\", \"ANAPC2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}