{"gene":"IFT22","run_date":"2026-06-10T01:55:22","timeline":{"discoveries":[{"year":2010,"finding":"IFT22 is a subunit of the ~500-kDa core of IFT complex B in Chlamydomonas reinhardtii, along with IFT88, IFT81 (x2), IFT74/72 (x2), IFT52, IFT46, IFT27, and IFT25. Chemical cross-linking provided evidence of an association between IFT27 and IFT81, placing IFT22 within a defined architectural context of IFT-B core.","method":"Biochemical fractionation, yeast two-hybrid, bacterial coexpression, chemical cross-linking","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal biochemical methods (fractionation, two-hybrid, coexpression, cross-linking) in a focused mechanistic study","pmids":["20435895"],"is_preprint":false},{"year":2012,"finding":"IFT22 (RABL5 homolog) in Chlamydomonas reinhardtii is a bona fide IFT-B subunit that controls the cellular pool size of both IFT complex A and B proteins; depletion of IFT22 reduces the cytoplasmic pool of IFT particles without reducing their flagellar distribution—instead causing accumulation of IFT particles in flagella. Overexpression of IFT22 also leads to flagellar IFT particle accumulation.","method":"RNAi/gene depletion, Western blotting, fluorescence microscopy, overexpression studies in C. reinhardtii","journal":"Cytoskeleton (Hoboken, N.J.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean loss-of-function and gain-of-function with quantitative protein measurements and imaging, single lab","pmids":["22076686"],"is_preprint":false},{"year":2018,"finding":"IFT22 knockout in mammalian cells causes no defects in ciliogenesis or ciliary protein trafficking, establishing that IFT22 is dispensable for these processes despite being an IFT-B subunit.","method":"CRISPR/Cas9 knockout, ciliogenesis assay, ciliary protein trafficking assay","journal":"Biology open","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype readout (negative result mechanistically informative), single lab","pmids":["29654116"],"is_preprint":false},{"year":2020,"finding":"IFT22 (RABL5) is an active GTPase with low intrinsic GTPase activity. Independent of its role in IFT-B1, IFT22 binds and stabilizes the Arf-like GTPase BBS3 (ARL6). When both IFT22 and BBS3 are in their GTP-bound states, they recruit the BBSome to the basal body for coupling with the IFT-B1 subcomplex and ciliary entry. IFT22 is not required for BBSome transport within cilia, indicating BBSome is transferred from IFT22 to IFT trains at the ciliary base.","method":"GTPase activity assays, co-immunoprecipitation/pulldown (biochemical), single-particle in vivo fluorescence imaging in Chlamydomonas, functional genetics (mutant rescue)","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro enzymatic assay, reciprocal biochemical interaction, in vivo single-particle imaging, and functional mutant analysis with multiple orthogonal methods in one study","pmids":["31953262"],"is_preprint":false},{"year":2014,"finding":"Knockdown of ift22 (anterograde IFT component) in zebrafish suppresses the bbs7-related retrograde intracellular melanosome transport delay, placing IFT22 functionally upstream in directional intracellular transport and demonstrating genetic interaction between anterograde IFT and BBS7-mediated retrograde transport.","method":"Morpholino knockdown in zebrafish, melanosome transport assay (in vivo imaging), epistasis analysis","journal":"Developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via double knockdown with defined transport phenotype readout, single lab","pmids":["24938409"],"is_preprint":false},{"year":2009,"finding":"The C. elegans RABL5/IFT22 ortholog IFTA-2 moves in an IFT-like manner along ciliary axonemes, associated with the IFT-B subcomplex, as established by GFP-tagged reporter imaging in C. elegans.","method":"GFP tagging, time-lapse in vivo fluorescence microscopy, IFT velocity measurements in C. elegans","journal":"Methods in cell biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single localization/motility observation in a methods chapter, no functional loss-of-function validation described for this protein specifically","pmids":["20409822"],"is_preprint":false}],"current_model":"IFT22 (RABL5) is a Rab-like small GTPase and IFT-B1 subunit that controls the cytoplasmic pool size of IFT particles and, in its GTP-bound state, cooperates with the GTPase BBS3/ARL6 to recruit the BBSome to the basal body for IFT-train-mediated ciliary entry; IFT22 is dispensable for ciliogenesis and ciliary protein trafficking per se, but is required for proper BBSome basal body targeting."},"narrative":{"mechanistic_narrative":"IFT22 (RABL5) is a Rab-like small GTPase that functions as a subunit of the intraflagellar transport complex B (IFT-B) core, embedded among IFT88, IFT81, IFT74/72, IFT52, IFT46, IFT27, and IFT25 [PMID:20435895]. Beyond its structural role in IFT-B, IFT22 governs the cytoplasmic pool size of both IFT-A and IFT-B particles: its depletion reduces the cellular reservoir of IFT proteins and causes their abnormal accumulation within flagella, a phenotype mirrored by overexpression [PMID:22076686]. IFT22 is an active GTPase with low intrinsic activity that, in its GTP-bound state and together with the GTP-bound Arf-like GTPase BBS3/ARL6, recruits the BBSome to the basal body for coupling with the IFT-B1 subcomplex and ciliary entry; the BBSome is then handed off to IFT trains at the ciliary base, since IFT22 is not required for BBSome movement within cilia [PMID:31953262]. Consistent with this targeting role, IFT22 is dispensable for ciliogenesis and ciliary protein trafficking per se in mammalian cells [PMID:29654116]. No disease association is established within this corpus.","teleology":[{"year":2010,"claim":"Established that IFT22 is a defined architectural component of the IFT-B core rather than a peripheral associate, anchoring it within the conserved transport machinery.","evidence":"Biochemical fractionation, yeast two-hybrid, bacterial coexpression and chemical cross-linking of the IFT-B core in Chlamydomonas","pmids":["20435895"],"confidence":"High","gaps":["Did not define IFT22's direct binding partners within the core","No functional role assigned"]},{"year":2012,"claim":"Showed that IFT22 sets the cytoplasmic pool size of IFT particles, distinguishing a regulatory function from passive cargo transport.","evidence":"RNAi depletion, overexpression, Western blotting and fluorescence imaging in C. reinhardtii","pmids":["22076686"],"confidence":"Medium","gaps":["Mechanism linking pool-size control to GTPase activity not defined","Single lab, single organism"]},{"year":2014,"claim":"Placed IFT22 functionally upstream in directional intracellular transport via genetic interaction with BBS7-mediated retrograde melanosome movement.","evidence":"Morpholino double-knockdown epistasis with melanosome transport imaging in zebrafish","pmids":["24938409"],"confidence":"Medium","gaps":["Morpholino knockdown without genetic mutant confirmation","Molecular basis of the IFT22–BBS7 interaction not resolved"]},{"year":2018,"claim":"Demonstrated that IFT22 is dispensable for ciliogenesis and ciliary protein trafficking, refocusing its essential function away from core IFT delivery.","evidence":"CRISPR/Cas9 knockout with ciliogenesis and ciliary trafficking assays in mammalian cells","pmids":["29654116"],"confidence":"Medium","gaps":["Negative result does not identify the process that requires IFT22","Single cell-type readout"]},{"year":2020,"claim":"Resolved IFT22's specific function as a GTP-state-dependent BBSome-recruiting factor acting with BBS3/ARL6 at the basal body, unifying the prior structural and pool-size observations.","evidence":"In vitro GTPase assays, reciprocal pulldowns, single-particle in vivo imaging and mutant rescue in Chlamydomonas","pmids":["31953262"],"confidence":"High","gaps":["Structural basis of the IFT22–BBS3–BBSome assembly not determined","Nucleotide cycling regulators (GEF/GAP) for IFT22 unknown"]},{"year":null,"claim":"How IFT22 nucleotide state is regulated and how the IFT22/BBS3-bound BBSome is physically transferred onto IFT trains remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No GEF/GAP identified for IFT22","No structural model of the handoff to IFT-B1 trains","Mammalian relevance of the BBSome-recruitment mechanism not tested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003924","term_label":"GTPase activity","supporting_discovery_ids":[3]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[3,5]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[3]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[3]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0]}],"complexes":["IFT-B core","BBSome"],"partners":["BBS3","ARL6","IFT27","IFT81"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9H7X7","full_name":"Intraflagellar transport protein 22 homolog","aliases":["Rab-like protein 5"],"length_aa":185,"mass_kda":20.8,"function":"Small GTPase-like component of the intraflagellar transport (IFT) complex B","subcellular_location":"Cell projection, cilium","url":"https://www.uniprot.org/uniprotkb/Q9H7X7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/IFT22","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HSPB11","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/search/IFT22","total_profiled":1310},"omim":[{"mim_id":"620505","title":"INTRAFLAGELLAR TRANSPORT 22; IFT22","url":"https://www.omim.org/entry/620505"},{"mim_id":"608845","title":"ADP-RIBOSYLATION FACTOR-LIKE GTPase 6; ARL6","url":"https://www.omim.org/entry/608845"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Microtubules","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Mitotic spindle","reliability":"Additional"},{"location":"Primary cilium","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"},{"location":"Flagellar centriole","reliability":"Additional"},{"location":"Mid piece","reliability":"Additional"},{"location":"Principal piece","reliability":"Additional"},{"location":"End piece","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"choroid plexus","ntpm":69.9}],"url":"https://www.proteinatlas.org/search/IFT22"},"hgnc":{"alias_symbol":["FLJ14117","FLJ13225","DKFZp761N0823","FAP9","CFAP9"],"prev_symbol":["RABL5"]},"alphafold":{"accession":"Q9H7X7","domains":[{"cath_id":"3.40.50.300","chopping":"1-183","consensus_level":"high","plddt":91.8236,"start":1,"end":183}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H7X7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H7X7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H7X7-F1-predicted_aligned_error_v6.png","plddt_mean":91.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=IFT22","jax_strain_url":"https://www.jax.org/strain/search?query=IFT22"},"sequence":{"accession":"Q9H7X7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H7X7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H7X7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H7X7"}},"corpus_meta":[{"pmid":"20435895","id":"PMC_20435895","title":"Direct interactions of intraflagellar transport complex B proteins IFT88, IFT52, and IFT46.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20435895","citation_count":68,"is_preprint":false},{"pmid":"29654116","id":"PMC_29654116","title":"Robust interaction of IFT70 with IFT52-IFT88 in the IFT-B complex is required for ciliogenesis.","date":"2018","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/29654116","citation_count":40,"is_preprint":false},{"pmid":"31953262","id":"PMC_31953262","title":"Intraflagellar transport protein RABL5/IFT22 recruits the BBSome to the basal body through the GTPase ARL6/BBS3.","date":"2020","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/31953262","citation_count":35,"is_preprint":false},{"pmid":"22076686","id":"PMC_22076686","title":"The RABL5 homolog IFT22 regulates the cellular pool size and the amount of IFT particles partitioned to the flagellar compartment in Chlamydomonas reinhardtii.","date":"2012","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/22076686","citation_count":24,"is_preprint":false},{"pmid":"34224160","id":"PMC_34224160","title":"Genetic basis of chicken plumage color in artificial population of complex epistasis.","date":"2021","source":"Animal genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34224160","citation_count":16,"is_preprint":false},{"pmid":"20409822","id":"PMC_20409822","title":"Functional genomics of intraflagellar transport-associated proteins in C. elegans.","date":"2009","source":"Methods in cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/20409822","citation_count":13,"is_preprint":false},{"pmid":"24938409","id":"PMC_24938409","title":"Functional characterization of Prickle2 and BBS7 identify overlapping phenotypes yet distinct mechanisms.","date":"2014","source":"Developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/24938409","citation_count":7,"is_preprint":false},{"pmid":"38641568","id":"PMC_38641568","title":"Identification of the principal neuropeptide MIP and its action pathway in larval settlement of the echiuran worm Urechis unicinctus.","date":"2024","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/38641568","citation_count":4,"is_preprint":false},{"pmid":"39417279","id":"PMC_39417279","title":"Autism Spectrum Disorder and Atypical Brain Connectivity: Novel Insights from Brain Connectivity-Associated Genes by Combining Random Forest and Support Vector Machine Algorithm.","date":"2024","source":"Omics : a journal of integrative biology","url":"https://pubmed.ncbi.nlm.nih.gov/39417279","citation_count":2,"is_preprint":false},{"pmid":"41412973","id":"PMC_41412973","title":"Design of a Pan-Tumor Fluorescence Imaging Cocktail for Fluorescence-Guided Surgery.","date":"2025","source":"Bioconjugate chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41412973","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7352,"output_tokens":1625,"usd":0.023216,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8322,"output_tokens":2043,"usd":0.046343,"stage2_stop_reason":"end_turn"},"total_usd":0.069559,"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\": 2010,\n      \"finding\": \"IFT22 is a subunit of the ~500-kDa core of IFT complex B in Chlamydomonas reinhardtii, along with IFT88, IFT81 (x2), IFT74/72 (x2), IFT52, IFT46, IFT27, and IFT25. Chemical cross-linking provided evidence of an association between IFT27 and IFT81, placing IFT22 within a defined architectural context of IFT-B core.\",\n      \"method\": \"Biochemical fractionation, yeast two-hybrid, bacterial coexpression, chemical cross-linking\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal biochemical methods (fractionation, two-hybrid, coexpression, cross-linking) in a focused mechanistic study\",\n      \"pmids\": [\"20435895\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"IFT22 (RABL5 homolog) in Chlamydomonas reinhardtii is a bona fide IFT-B subunit that controls the cellular pool size of both IFT complex A and B proteins; depletion of IFT22 reduces the cytoplasmic pool of IFT particles without reducing their flagellar distribution—instead causing accumulation of IFT particles in flagella. Overexpression of IFT22 also leads to flagellar IFT particle accumulation.\",\n      \"method\": \"RNAi/gene depletion, Western blotting, fluorescence microscopy, overexpression studies in C. reinhardtii\",\n      \"journal\": \"Cytoskeleton (Hoboken, N.J.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean loss-of-function and gain-of-function with quantitative protein measurements and imaging, single lab\",\n      \"pmids\": [\"22076686\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"IFT22 knockout in mammalian cells causes no defects in ciliogenesis or ciliary protein trafficking, establishing that IFT22 is dispensable for these processes despite being an IFT-B subunit.\",\n      \"method\": \"CRISPR/Cas9 knockout, ciliogenesis assay, ciliary protein trafficking assay\",\n      \"journal\": \"Biology open\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype readout (negative result mechanistically informative), single lab\",\n      \"pmids\": [\"29654116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"IFT22 (RABL5) is an active GTPase with low intrinsic GTPase activity. Independent of its role in IFT-B1, IFT22 binds and stabilizes the Arf-like GTPase BBS3 (ARL6). When both IFT22 and BBS3 are in their GTP-bound states, they recruit the BBSome to the basal body for coupling with the IFT-B1 subcomplex and ciliary entry. IFT22 is not required for BBSome transport within cilia, indicating BBSome is transferred from IFT22 to IFT trains at the ciliary base.\",\n      \"method\": \"GTPase activity assays, co-immunoprecipitation/pulldown (biochemical), single-particle in vivo fluorescence imaging in Chlamydomonas, functional genetics (mutant rescue)\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro enzymatic assay, reciprocal biochemical interaction, in vivo single-particle imaging, and functional mutant analysis with multiple orthogonal methods in one study\",\n      \"pmids\": [\"31953262\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Knockdown of ift22 (anterograde IFT component) in zebrafish suppresses the bbs7-related retrograde intracellular melanosome transport delay, placing IFT22 functionally upstream in directional intracellular transport and demonstrating genetic interaction between anterograde IFT and BBS7-mediated retrograde transport.\",\n      \"method\": \"Morpholino knockdown in zebrafish, melanosome transport assay (in vivo imaging), epistasis analysis\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via double knockdown with defined transport phenotype readout, single lab\",\n      \"pmids\": [\"24938409\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The C. elegans RABL5/IFT22 ortholog IFTA-2 moves in an IFT-like manner along ciliary axonemes, associated with the IFT-B subcomplex, as established by GFP-tagged reporter imaging in C. elegans.\",\n      \"method\": \"GFP tagging, time-lapse in vivo fluorescence microscopy, IFT velocity measurements in C. elegans\",\n      \"journal\": \"Methods in cell biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single localization/motility observation in a methods chapter, no functional loss-of-function validation described for this protein specifically\",\n      \"pmids\": [\"20409822\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"IFT22 (RABL5) is a Rab-like small GTPase and IFT-B1 subunit that controls the cytoplasmic pool size of IFT particles and, in its GTP-bound state, cooperates with the GTPase BBS3/ARL6 to recruit the BBSome to the basal body for IFT-train-mediated ciliary entry; IFT22 is dispensable for ciliogenesis and ciliary protein trafficking per se, but is required for proper BBSome basal body targeting.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"IFT22 (RABL5) is a Rab-like small GTPase that functions as a subunit of the intraflagellar transport complex B (IFT-B) core, embedded among IFT88, IFT81, IFT74/72, IFT52, IFT46, IFT27, and IFT25 [#0]. Beyond its structural role in IFT-B, IFT22 governs the cytoplasmic pool size of both IFT-A and IFT-B particles: its depletion reduces the cellular reservoir of IFT proteins and causes their abnormal accumulation within flagella, a phenotype mirrored by overexpression [#1]. IFT22 is an active GTPase with low intrinsic activity that, in its GTP-bound state and together with the GTP-bound Arf-like GTPase BBS3/ARL6, recruits the BBSome to the basal body for coupling with the IFT-B1 subcomplex and ciliary entry; the BBSome is then handed off to IFT trains at the ciliary base, since IFT22 is not required for BBSome movement within cilia [#3]. Consistent with this targeting role, IFT22 is dispensable for ciliogenesis and ciliary protein trafficking per se in mammalian cells [#2]. No disease association is established within this corpus.\"\n,\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Established that IFT22 is a defined architectural component of the IFT-B core rather than a peripheral associate, anchoring it within the conserved transport machinery.\",\n      \"evidence\": \"Biochemical fractionation, yeast two-hybrid, bacterial coexpression and chemical cross-linking of the IFT-B core in Chlamydomonas\",\n      \"pmids\": [\"20435895\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define IFT22's direct binding partners within the core\", \"No functional role assigned\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Showed that IFT22 sets the cytoplasmic pool size of IFT particles, distinguishing a regulatory function from passive cargo transport.\",\n      \"evidence\": \"RNAi depletion, overexpression, Western blotting and fluorescence imaging in C. reinhardtii\",\n      \"pmids\": [\"22076686\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking pool-size control to GTPase activity not defined\", \"Single lab, single organism\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Placed IFT22 functionally upstream in directional intracellular transport via genetic interaction with BBS7-mediated retrograde melanosome movement.\",\n      \"evidence\": \"Morpholino double-knockdown epistasis with melanosome transport imaging in zebrafish\",\n      \"pmids\": [\"24938409\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Morpholino knockdown without genetic mutant confirmation\", \"Molecular basis of the IFT22\\u2013BBS7 interaction not resolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrated that IFT22 is dispensable for ciliogenesis and ciliary protein trafficking, refocusing its essential function away from core IFT delivery.\",\n      \"evidence\": \"CRISPR/Cas9 knockout with ciliogenesis and ciliary trafficking assays in mammalian cells\",\n      \"pmids\": [\"29654116\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Negative result does not identify the process that requires IFT22\", \"Single cell-type readout\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolved IFT22's specific function as a GTP-state-dependent BBSome-recruiting factor acting with BBS3/ARL6 at the basal body, unifying the prior structural and pool-size observations.\",\n      \"evidence\": \"In vitro GTPase assays, reciprocal pulldowns, single-particle in vivo imaging and mutant rescue in Chlamydomonas\",\n      \"pmids\": [\"31953262\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the IFT22\\u2013BBS3\\u2013BBSome assembly not determined\", \"Nucleotide cycling regulators (GEF/GAP) for IFT22 unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How IFT22 nucleotide state is regulated and how the IFT22/BBS3-bound BBSome is physically transferred onto IFT trains remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No GEF/GAP identified for IFT22\", \"No structural model of the handoff to IFT-B1 trains\", \"Mammalian relevance of the BBSome-recruitment mechanism not tested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [3, 5]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"IFT-B core\", \"BBSome\"],\n    \"partners\": [\"BBS3\", \"ARL6\", \"IFT27\", \"IFT81\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}