{"gene":"RABL2B","run_date":"2026-04-28T19:45:45","timeline":{"discoveries":[{"year":2017,"finding":"CEP19 specifically captures GTP-bound RABL2B at the ciliary base; RABL2B is activated via its intrinsic nucleotide exchange, then captures and releases the IFT-B holocomplex from the large pool of pre-docked IFT-B complexes to initiate ciliary entry of IFT. CEP19 is recruited to the ciliary base by the centriolar CEP350/FOP complex.","method":"Affinity-purification mass spectrometry, Co-immunoprecipitation, biochemical reconstitution of GTP-binding and effector interactions","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods (AP-MS, Co-IP, nucleotide-binding assays) in a single rigorous study establishing the complete mechanistic pathway","pmids":["28625565"],"is_preprint":false},{"year":2019,"finding":"RABL2 (RABL2A/RABL2B) positively controls localization of ciliary GPCRs (GPR161 and HTR6) at the ciliary base; RABL2 recruitment to the mother centriole depends on distal appendage proteins CEP164 and CEP83; RABL2 physically associates with ciliary GPCRs; RABL2 controls GPR161 localization independently of TULP3; CEP19 and IFT-B, which interact with RABL2, are also required for GPR161 localization.","method":"siRNA knockdown, overexpression, Co-immunoprecipitation, immunofluorescence localization","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2-3 — clean KD/OE with defined ciliary trafficking phenotype and Co-IP for physical association, but paralogs RABL2A and RABL2B not fully distinguished","pmids":["30578315"],"is_preprint":false},{"year":1999,"finding":"RABL2B encodes a small GTPase of the RAB family, located at 22q13.3; it shares near-identical sequence with paralog RABL2A (differing by only 3 conservative amino acid changes over 228 residues); both are expressed ubiquitously with tissue-specific alternative splicing in the 3' UTR.","method":"cDNA cloning, Northern blot, chromosomal mapping","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 — original gene characterization by cloning and expression analysis; foundational identification of GTPase family membership","pmids":["10444334"],"is_preprint":false},{"year":2011,"finding":"RABL2B produces multiple splice isoforms at constant ratios in genetically diverse lymphoblastoid cell lines, independent of gene expression level, including splice events that create premature stop codons; subtle tandem acceptor splice site usage depends strongly on upstream donor sequence content.","method":"RT-PCR quantification across multiple genetically diverse cell lines, comparative analysis with chimpanzee cells","journal":"Genetics","confidence":"Medium","confidence_rationale":"Tier 2 — quantitative isoform analysis across multiple independent samples with mechanistic insight into splicing regulation","pmids":["21220357"],"is_preprint":false},{"year":2010,"finding":"Despite equal gene dosage, RABL2B is preferentially expressed over paralog RABL2A in human tissues and lymphoblastoid cell lines, with the difference most pronounced in brain and placenta, suggesting incomplete functional redundancy between the two paralogs.","method":"Pyrosequencing-based paralogous sequence quantification of genomic and transcriptional ratios","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 — quantitative high-throughput method across multiple tissues with direct comparison to chimpanzee","pmids":["20138207"],"is_preprint":false}],"current_model":"RABL2B is a GTP-binding small GTPase that, when activated by intrinsic nucleotide exchange and captured by CEP19 (itself recruited to the ciliary base via CEP350/FOP), binds and releases the IFT-B holocomplex to initiate intraflagellar transport and ciliary entry; it also physically associates with ciliary GPCRs (GPR161, HTR6) to control their trafficking to the ciliary membrane, acting upstream of IFT-B but independently of TULP3."},"narrative":{"teleology":[{"year":1999,"claim":"Molecular identity of RABL2B was established as a ubiquitously expressed small GTPase nearly identical to its paralog RABL2A, providing the foundational classification needed for functional studies.","evidence":"cDNA cloning, Northern blot, and chromosomal mapping in human tissues","pmids":["10444334"],"confidence":"Medium","gaps":["No functional role assigned beyond GTPase family membership","Whether RABL2A and RABL2B are functionally redundant was unknown"]},{"year":2010,"claim":"Demonstration that RABL2B is preferentially expressed over RABL2A across human tissues suggested incomplete functional redundancy and pointed to RABL2B as the dominant paralog.","evidence":"Pyrosequencing-based paralogous sequence quantification of genomic and transcriptional ratios across multiple human and chimpanzee tissues","pmids":["20138207"],"confidence":"Medium","gaps":["Protein-level expression differences between paralogs were not measured","Functional consequences of differential expression were not tested"]},{"year":2011,"claim":"Discovery of regulated alternative splicing of RABL2B—including isoforms with premature stop codons—revealed post-transcriptional complexity that could modulate functional protein output.","evidence":"RT-PCR isoform quantification across genetically diverse human and chimpanzee lymphoblastoid cell lines","pmids":["21220357"],"confidence":"Medium","gaps":["Whether alternative splice isoforms encode functional proteins was not determined","No link to ciliary biology was yet apparent"]},{"year":2017,"claim":"The core mechanism of RABL2B at the ciliary base was elucidated: GTP-bound RABL2B is captured by CEP19 (recruited via CEP350/FOP), then binds and releases the IFT-B holocomplex to initiate intraflagellar transport, resolving how IFT entry is triggered from pre-docked complexes.","evidence":"Affinity-purification mass spectrometry, co-immunoprecipitation, and biochemical reconstitution of GTP-binding and effector interactions","pmids":["28625565"],"confidence":"High","gaps":["Structural basis of the RABL2B–CEP19 and RABL2B–IFT-B interfaces was not resolved","Whether RABL2A can substitute for RABL2B in this pathway was not directly tested","GAP identity or regulation of GTP hydrolysis cycle was not identified"]},{"year":2019,"claim":"RABL2B's role was extended beyond IFT-B release to direct physical association with ciliary GPCRs (GPR161, HTR6) and TULP3-independent control of their ciliary trafficking, with recruitment depending on distal appendage proteins CEP164 and CEP83.","evidence":"siRNA knockdown, overexpression, co-immunoprecipitation, and immunofluorescence localization in mammalian cells","pmids":["30578315"],"confidence":"Medium","gaps":["RABL2A and RABL2B were not fully distinguished in functional assays","Whether RABL2B directly binds GPCRs or acts through an intermediary was not resolved","Cargo selectivity of RABL2B beyond GPR161 and HTR6 was not defined"]},{"year":null,"claim":"Key unresolved questions include the structural basis of RABL2B interactions with CEP19 and IFT-B, the identity of a GAP for RABL2B, the full range of ciliary cargo controlled by RABL2B, and whether RABL2A is functionally redundant in vivo.","evidence":"","pmids":[],"confidence":"High","gaps":["No GAP for RABL2B has been identified","No high-resolution structure of RABL2B in complex with its effectors exists","In vivo genetic distinction between RABL2A and RABL2B function is lacking"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003924","term_label":"GTPase activity","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,1]}],"complexes":[],"partners":["CEP19","CEP350","FOP","CEP164","CEP83","GPR161","HTR6"],"other_free_text":[]},"mechanistic_narrative":"RABL2B is a small GTPase of the RAB family that functions as a gatekeeper for intraflagellar transport (IFT) initiation at the ciliary base. Upon intrinsic nucleotide exchange to its GTP-bound state, RABL2B is captured by CEP19—itself recruited via the centriolar CEP350/FOP complex—and then binds and releases the IFT-B holocomplex from pre-docked pools to trigger ciliary entry [PMID:28625565]. RABL2B also physically associates with ciliary GPCRs such as GPR161 and HTR6, controlling their trafficking to the ciliary membrane independently of TULP3, with its recruitment to the mother centriole depending on distal appendage proteins CEP164 and CEP83 [PMID:30578315]. RABL2B is ubiquitously expressed and is the preferentially transcribed paralog over RABL2A in most human tissues [PMID:20138207]."},"prefetch_data":{"uniprot":{"accession":"Q9UNT1","full_name":"Rab-like protein 2B","aliases":[],"length_aa":228,"mass_kda":26.1,"function":"Small GTPase required for ciliation. Activated in a guanine nucleotide exchange factor (GEF)-independent manner via its intrinsic GDP for GTP nucleotide exchange ability (PubMed:28625565). Involved in ciliary assembly by binding the intraflagellar transport (IFT) complex B from the large pool pre-docked at the base of the cilium and thus triggers its entry into the cilia (PubMed:28428259, PubMed:28625565)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Cytoplasm, cytoskeleton, cilium basal body; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q9UNT1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RABL2B","classification":"Not Classified","n_dependent_lines":35,"n_total_lines":1165,"dependency_fraction":0.030042918454935622},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/RABL2B","total_profiled":1310},"omim":[{"mim_id":"617870","title":"CENTROSOMAL PROTEIN 350; CEP350","url":"https://www.omim.org/entry/617870"},{"mim_id":"615586","title":"CENTROSOMAL PROTEIN, 19-KD; CEP19","url":"https://www.omim.org/entry/615586"},{"mim_id":"606232","title":"PHELAN-MCDERMID SYNDROME; PHMDS","url":"https://www.omim.org/entry/606232"},{"mim_id":"606230","title":"SH3 AND MULTIPLE ANKYRIN REPEAT DOMAINS 3; SHANK3","url":"https://www.omim.org/entry/606230"},{"mim_id":"605413","title":"RAB, MEMBER OF RAS ONCOGENE FAMILY-LIKE 2B; RABL2B","url":"https://www.omim.org/entry/605413"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Centrosome","reliability":"Supported"},{"location":"Basal body","reliability":"Supported"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"epididymis","ntpm":84.8}],"url":"https://www.proteinatlas.org/search/RABL2B"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q9UNT1","domains":[{"cath_id":"3.40.50.300","chopping":"17-184","consensus_level":"high","plddt":88.0478,"start":17,"end":184}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UNT1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UNT1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UNT1-F1-predicted_aligned_error_v6.png","plddt_mean":79.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RABL2B","jax_strain_url":"https://www.jax.org/strain/search?query=RABL2B"},"sequence":{"accession":"Q9UNT1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UNT1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UNT1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UNT1"}},"corpus_meta":[{"pmid":"28625565","id":"PMC_28625565","title":"The CEP19-RABL2 GTPase Complex Binds IFT-B to Initiate Intraflagellar Transport at the Ciliary Base.","date":"2017","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/28625565","citation_count":94,"is_preprint":false},{"pmid":"12073014","id":"PMC_12073014","title":"FISH-mapping of a 100-kb terminal 22q13 deletion.","date":"2002","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/12073014","citation_count":65,"is_preprint":false},{"pmid":"32699331","id":"PMC_32699331","title":"Gene biomarker discovery at different stages of Alzheimer using gene co-expression network approach.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32699331","citation_count":46,"is_preprint":false},{"pmid":"19454329","id":"PMC_19454329","title":"Chromosome 22q13.3 deletion syndrome with a de novo interstitial 22q13.3 cryptic deletion disrupting SHANK3.","date":"2009","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/19454329","citation_count":43,"is_preprint":false},{"pmid":"10444334","id":"PMC_10444334","title":"Two novel human RAB genes with near identical sequence each map to a telomere-associated region: the subtelomeric region of 22q13.3 and the ancestral telomere band 2q13.","date":"1999","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/10444334","citation_count":33,"is_preprint":false},{"pmid":"30578315","id":"PMC_30578315","title":"RABL2 positively controls localization of GPCRs in mammalian primary cilia.","date":"2019","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/30578315","citation_count":25,"is_preprint":false},{"pmid":"28138870","id":"PMC_28138870","title":"The impact of RABL2B gene (rs144944885) on human male infertility in patients with oligoasthenoteratozoospermia and immotile short tail sperm defects.","date":"2017","source":"Journal of assisted reproduction and genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28138870","citation_count":18,"is_preprint":false},{"pmid":"20635403","id":"PMC_20635403","title":"Fulminant hepatic failure requiring liver transplantation in 22q13.3 deletion syndrome.","date":"2010","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/20635403","citation_count":11,"is_preprint":false},{"pmid":"21220357","id":"PMC_21220357","title":"Constant splice-isoform ratios in human lymphoblastoid cells support the concept of a splico-stat.","date":"2011","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21220357","citation_count":10,"is_preprint":false},{"pmid":"20138207","id":"PMC_20138207","title":"Analysis of relative gene dosage and expression differences of the paralogs RABL2A and RABL2B by Pyrosequencing.","date":"2010","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/20138207","citation_count":9,"is_preprint":false},{"pmid":"28553998","id":"PMC_28553998","title":"Splicing-related single nucleotide polymorphism of RAB, member of RAS oncogene family like 2B (RABL2B) jeopardises semen quality in Chinese Holstein bulls.","date":"2017","source":"Reproduction, fertility, and development","url":"https://pubmed.ncbi.nlm.nih.gov/28553998","citation_count":5,"is_preprint":false},{"pmid":"28018439","id":"PMC_28018439","title":"Phelan-McDermid syndrome presenting with developmental delays and facial dysmorphisms.","date":"2016","source":"Korean journal of pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/28018439","citation_count":4,"is_preprint":false},{"pmid":"41249621","id":"PMC_41249621","title":"Meta single-cell atlas and xQTL post-GWAS analysis revealed the pathogenic features of thyroid cancer for target therapy: A multi-omics study.","date":"2025","source":"Cancer gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/41249621","citation_count":0,"is_preprint":false},{"pmid":"38927965","id":"PMC_38927965","title":"Transcript-Level Biomarkers of Early Lung Carcinogenesis in Bronchial Lesions.","date":"2024","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/38927965","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8023,"output_tokens":1243,"usd":0.021357},"stage2":{"model":"claude-opus-4-6","input_tokens":4461,"output_tokens":1652,"usd":0.095408},"total_usd":0.116765,"stage1_batch_id":"msgbatch_01SUR8NDzVrNmyszWyJeCct7","stage2_batch_id":"msgbatch_01G7Yfutko3cDWzejrwH5AMx","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"CEP19 specifically captures GTP-bound RABL2B at the ciliary base; RABL2B is activated via its intrinsic nucleotide exchange, then captures and releases the IFT-B holocomplex from the large pool of pre-docked IFT-B complexes to initiate ciliary entry of IFT. CEP19 is recruited to the ciliary base by the centriolar CEP350/FOP complex.\",\n      \"method\": \"Affinity-purification mass spectrometry, Co-immunoprecipitation, biochemical reconstitution of GTP-binding and effector interactions\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods (AP-MS, Co-IP, nucleotide-binding assays) in a single rigorous study establishing the complete mechanistic pathway\",\n      \"pmids\": [\"28625565\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"RABL2 (RABL2A/RABL2B) positively controls localization of ciliary GPCRs (GPR161 and HTR6) at the ciliary base; RABL2 recruitment to the mother centriole depends on distal appendage proteins CEP164 and CEP83; RABL2 physically associates with ciliary GPCRs; RABL2 controls GPR161 localization independently of TULP3; CEP19 and IFT-B, which interact with RABL2, are also required for GPR161 localization.\",\n      \"method\": \"siRNA knockdown, overexpression, Co-immunoprecipitation, immunofluorescence localization\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — clean KD/OE with defined ciliary trafficking phenotype and Co-IP for physical association, but paralogs RABL2A and RABL2B not fully distinguished\",\n      \"pmids\": [\"30578315\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"RABL2B encodes a small GTPase of the RAB family, located at 22q13.3; it shares near-identical sequence with paralog RABL2A (differing by only 3 conservative amino acid changes over 228 residues); both are expressed ubiquitously with tissue-specific alternative splicing in the 3' UTR.\",\n      \"method\": \"cDNA cloning, Northern blot, chromosomal mapping\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — original gene characterization by cloning and expression analysis; foundational identification of GTPase family membership\",\n      \"pmids\": [\"10444334\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"RABL2B produces multiple splice isoforms at constant ratios in genetically diverse lymphoblastoid cell lines, independent of gene expression level, including splice events that create premature stop codons; subtle tandem acceptor splice site usage depends strongly on upstream donor sequence content.\",\n      \"method\": \"RT-PCR quantification across multiple genetically diverse cell lines, comparative analysis with chimpanzee cells\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — quantitative isoform analysis across multiple independent samples with mechanistic insight into splicing regulation\",\n      \"pmids\": [\"21220357\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Despite equal gene dosage, RABL2B is preferentially expressed over paralog RABL2A in human tissues and lymphoblastoid cell lines, with the difference most pronounced in brain and placenta, suggesting incomplete functional redundancy between the two paralogs.\",\n      \"method\": \"Pyrosequencing-based paralogous sequence quantification of genomic and transcriptional ratios\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — quantitative high-throughput method across multiple tissues with direct comparison to chimpanzee\",\n      \"pmids\": [\"20138207\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RABL2B is a GTP-binding small GTPase that, when activated by intrinsic nucleotide exchange and captured by CEP19 (itself recruited to the ciliary base via CEP350/FOP), binds and releases the IFT-B holocomplex to initiate intraflagellar transport and ciliary entry; it also physically associates with ciliary GPCRs (GPR161, HTR6) to control their trafficking to the ciliary membrane, acting upstream of IFT-B but independently of TULP3.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"RABL2B is a small GTPase of the RAB family that functions as a gatekeeper for intraflagellar transport (IFT) initiation at the ciliary base. Upon intrinsic nucleotide exchange to its GTP-bound state, RABL2B is captured by CEP19—itself recruited via the centriolar CEP350/FOP complex—and then binds and releases the IFT-B holocomplex from pre-docked pools to trigger ciliary entry [PMID:28625565]. RABL2B also physically associates with ciliary GPCRs such as GPR161 and HTR6, controlling their trafficking to the ciliary membrane independently of TULP3, with its recruitment to the mother centriole depending on distal appendage proteins CEP164 and CEP83 [PMID:30578315]. RABL2B is ubiquitously expressed and is the preferentially transcribed paralog over RABL2A in most human tissues [PMID:20138207].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Molecular identity of RABL2B was established as a ubiquitously expressed small GTPase nearly identical to its paralog RABL2A, providing the foundational classification needed for functional studies.\",\n      \"evidence\": \"cDNA cloning, Northern blot, and chromosomal mapping in human tissues\",\n      \"pmids\": [\"10444334\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional role assigned beyond GTPase family membership\",\n        \"Whether RABL2A and RABL2B are functionally redundant was unknown\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstration that RABL2B is preferentially expressed over RABL2A across human tissues suggested incomplete functional redundancy and pointed to RABL2B as the dominant paralog.\",\n      \"evidence\": \"Pyrosequencing-based paralogous sequence quantification of genomic and transcriptional ratios across multiple human and chimpanzee tissues\",\n      \"pmids\": [\"20138207\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Protein-level expression differences between paralogs were not measured\",\n        \"Functional consequences of differential expression were not tested\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Discovery of regulated alternative splicing of RABL2B—including isoforms with premature stop codons—revealed post-transcriptional complexity that could modulate functional protein output.\",\n      \"evidence\": \"RT-PCR isoform quantification across genetically diverse human and chimpanzee lymphoblastoid cell lines\",\n      \"pmids\": [\"21220357\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether alternative splice isoforms encode functional proteins was not determined\",\n        \"No link to ciliary biology was yet apparent\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The core mechanism of RABL2B at the ciliary base was elucidated: GTP-bound RABL2B is captured by CEP19 (recruited via CEP350/FOP), then binds and releases the IFT-B holocomplex to initiate intraflagellar transport, resolving how IFT entry is triggered from pre-docked complexes.\",\n      \"evidence\": \"Affinity-purification mass spectrometry, co-immunoprecipitation, and biochemical reconstitution of GTP-binding and effector interactions\",\n      \"pmids\": [\"28625565\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the RABL2B–CEP19 and RABL2B–IFT-B interfaces was not resolved\",\n        \"Whether RABL2A can substitute for RABL2B in this pathway was not directly tested\",\n        \"GAP identity or regulation of GTP hydrolysis cycle was not identified\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"RABL2B's role was extended beyond IFT-B release to direct physical association with ciliary GPCRs (GPR161, HTR6) and TULP3-independent control of their ciliary trafficking, with recruitment depending on distal appendage proteins CEP164 and CEP83.\",\n      \"evidence\": \"siRNA knockdown, overexpression, co-immunoprecipitation, and immunofluorescence localization in mammalian cells\",\n      \"pmids\": [\"30578315\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"RABL2A and RABL2B were not fully distinguished in functional assays\",\n        \"Whether RABL2B directly binds GPCRs or acts through an intermediary was not resolved\",\n        \"Cargo selectivity of RABL2B beyond GPR161 and HTR6 was not defined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis of RABL2B interactions with CEP19 and IFT-B, the identity of a GAP for RABL2B, the full range of ciliary cargo controlled by RABL2B, and whether RABL2A is functionally redundant in vivo.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No GAP for RABL2B has been identified\",\n        \"No high-resolution structure of RABL2B in complex with its effectors exists\",\n        \"In vivo genetic distinction between RABL2A and RABL2B function is lacking\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"CEP19\",\n      \"CEP350\",\n      \"FOP\",\n      \"CEP164\",\n      \"CEP83\",\n      \"GPR161\",\n      \"HTR6\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}