{"gene":"ARL2BP","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":2013,"finding":"ARL2BP is an effector protein of the small GTPases ARL2 and ARL3. In mouse retina, ARL2BP localizes to the basal body and cilium-associated centriole of photoreceptors and the periciliary extension of the inner segment. Depletion of ARL2, but not ARL3, caused displacement of ARL2BP from the basal body, establishing that ARL2 is required for recruiting or anchoring ARL2BP at the base of the cilium. The p.Met45Arg mutation reduced binding to ARL2 and caused loss of ARL2BP localization at the basal body in ciliated nasal epithelial cells. Depletion of ARL2BP caused cilia shortening.","method":"Homozygosity mapping, exome sequencing, blood RNA splicing analysis, immunolocalization in mouse retina, siRNA depletion in ciliated cells, binding assay with mutant protein","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization experiments with functional consequences, ARL2-dependence established by selective depletion (ARL2 vs ARL3), mutant protein binding assay, replicated across cell types","pmids":["23849777"],"is_preprint":false},{"year":2018,"finding":"ARL2BP is necessary for photoreceptor ciliary doublet microtubule formation and axoneme elongation, which is required for outer segment morphogenesis and vision. ARL2BP knockout mice display disorganization of the photoreceptor outer segment with vertically aligned disks, shortened axonemes, open B-tubule doublets, and loss of singlet microtubules, accompanied by an early and progressive reduction in visual response.","method":"Knockout mouse model, electron microscopy of ciliary ultrastructure, electroretinography, immunofluorescence","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO mouse with defined cellular phenotype, ultrastructural analysis by EM, functional readout by ERG, multiple orthogonal methods in one study","pmids":["29718757"],"is_preprint":false},{"year":2019,"finding":"ARL2BP is required for the structural maintenance of cilia and the sperm flagellum. In ARL2BP knockout mice, spermiogenesis is impaired, resulting in abnormally shaped sperm heads, shortened and mis-assembled sperm tails, and loss of axonemal doublets. Additional ciliopathy phenotypes included enlarged brain ventricles and situs inversus. Mouse embryonic fibroblasts from knockout animals showed delayed depolymerization of primary cilia.","method":"Knockout mouse model, sperm morphology analysis, electron microscopy, primary cilia depolymerization assay in MEFs","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO mouse with multiple defined cellular phenotypes, EM ultrastructural validation, functional cilia assay, multiple orthogonal methods","pmids":["31425546"],"is_preprint":false},{"year":2022,"finding":"Loss-of-function variant in ARL2BP in patient-derived fibroblasts resulted in reduced cell proliferation and reduced ciliary length, consistent with a role for ARL2BP in ciliogenesis.","method":"Patient-derived fibroblast analysis, ciliary length measurement, cell proliferation assay","journal":"Clinical genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single patient, patient-derived fibroblasts with direct measurements but single lab, no mechanistic follow-up","pmids":["36507858"],"is_preprint":false}],"current_model":"ARL2BP is a ciliary effector protein that binds the small GTPase ARL2 (but not ARL3); ARL2 is required to recruit/anchor ARL2BP to the basal body of cilia, where ARL2BP is necessary for doublet microtubule integrity, axoneme elongation, and outer segment morphogenesis in photoreceptors, and for structural maintenance of the sperm flagellum, with loss of function causing retinitis pigmentosa, situs inversus, and male infertility."},"narrative":{"mechanistic_narrative":"ARL2BP is a ciliary effector protein that links the small GTPase ARL2 to the structural integrity of microtubule-based cilia and flagella [PMID:23849777, PMID:29718757]. It acts as a selective effector of ARL2 rather than ARL3: depletion of ARL2, but not ARL3, displaces ARL2BP from the basal body, establishing that ARL2 recruits or anchors ARL2BP at the base of the cilium, while the disease-associated p.Met45Arg substitution reduces ARL2 binding and abolishes basal-body localization [PMID:23849777]. At the photoreceptor basal body and cilium-associated centriole, ARL2BP is required for ciliary doublet microtubule formation and axoneme elongation; its loss produces shortened axonemes, open B-tubule doublets, loss of singlet microtubules, and disorganized outer segments with impaired visual response [PMID:23849777, PMID:29718757]. The same activity supports structural maintenance of the sperm flagellum, where loss causes mis-assembled tails and loss of axonemal doublets, and underlies broader ciliopathy phenotypes including situs inversus [PMID:31425546]. Through these roles ARL2BP loss of function causes retinitis pigmentosa, situs inversus, and male infertility [PMID:23849777, PMID:29718757, PMID:31425546].","teleology":[{"year":2013,"claim":"Established that ARL2BP is a basal-body effector whose ciliary localization depends specifically on ARL2, defining the recruitment logic at the cilium base and linking it to human disease.","evidence":"Immunolocalization in mouse retina, selective siRNA depletion of ARL2 vs ARL3, mutant-protein binding assay, and homozygosity mapping/exome sequencing in patients","pmids":["23849777"],"confidence":"High","gaps":["Mechanism by which ARL2-GTP anchors ARL2BP at the basal body not resolved at structural level","How basal-body ARL2BP couples to microtubule assembly machinery not defined"]},{"year":2018,"claim":"Demonstrated that ARL2BP is required for photoreceptor doublet microtubule formation and axoneme elongation, connecting the basal-body localization to outer-segment morphogenesis and vision.","evidence":"ARL2BP knockout mouse with EM ultrastructure, electroretinography, and immunofluorescence","pmids":["29718757"],"confidence":"High","gaps":["Molecular partners through which ARL2BP promotes B-tubule and singlet microtubule integrity not identified","Whether the defect is in microtubule nucleation, stabilization, or transport not distinguished"]},{"year":2019,"claim":"Extended ARL2BP function to structural maintenance of the sperm flagellum and motile-cilia-dependent processes, showing the cilium/flagellum phenotype is general rather than photoreceptor-specific.","evidence":"Knockout mouse sperm morphology, EM of axonemal doublets, situs/ventricle phenotyping, and primary cilia depolymerization assay in MEFs","pmids":["31425546"],"confidence":"High","gaps":["Mechanism linking ARL2BP to delayed cilia depolymerization unknown","Tissue-specific requirements versus a single shared axonemal function not dissected"]},{"year":2022,"claim":"Confirmed in patient-derived cells that ARL2BP loss reduces ciliary length and proliferation, corroborating a ciliogenesis role in human tissue.","evidence":"Patient-derived fibroblasts with ciliary length and proliferation measurements","pmids":["36507858"],"confidence":"Medium","gaps":["Single patient, single lab, no mechanistic follow-up","Causal link between proliferation defect and ciliary defect not established"]},{"year":null,"claim":"The biochemical mechanism by which ARL2BP, downstream of ARL2, directs doublet microtubule assembly and axoneme integrity remains undefined.","evidence":"","pmids":[],"confidence":"High","gaps":["No identified molecular effectors or microtubule-associated partners of ARL2BP","No structural model of the ARL2-ARL2BP complex at the basal body","Whether ARL2BP has intrinsic biochemical activity beyond ARL2 binding is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,2]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1,2]}],"complexes":[],"partners":["ARL2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y2Y0","full_name":"ADP-ribosylation factor-like protein 2-binding protein","aliases":["Binder of ARF2 protein 1"],"length_aa":163,"mass_kda":18.8,"function":"Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. May play a role as an effector of ARL2","subcellular_location":"Cytoplasm; Mitochondrion intermembrane space; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Nucleus; Cytoplasm, cytoskeleton, spindle; Cytoplasm, cytoskeleton, cilium basal body","url":"https://www.uniprot.org/uniprotkb/Q9Y2Y0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ARL2BP","classification":"Not Classified","n_dependent_lines":24,"n_total_lines":1208,"dependency_fraction":0.019867549668874173},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000102931","cell_line_id":"CID000500","localizations":[{"compartment":"cytoplasmic","grade":3},{"compartment":"nucleoplasm","grade":3}],"interactors":[{"gene":"CFAP20","stoichiometry":10.0},{"gene":"YWHAB","stoichiometry":0.2},{"gene":"YWHAQ","stoichiometry":0.2},{"gene":"YWHAE","stoichiometry":0.2},{"gene":"YWHAZ","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000500","total_profiled":1310},"omim":[{"mim_id":"615434","title":"RETINITIS PIGMENTOSA 82 WITH OR WITHOUT SITUS INVERSUS; RP82","url":"https://www.omim.org/entry/615434"},{"mim_id":"615407","title":"ADP-RIBOSYLATION FACTOR-LIKE GTPase 2-BINDING PROTEIN; ARL2BP","url":"https://www.omim.org/entry/615407"},{"mim_id":"610812","title":"HYDIN AXONEMAL CENTRAL PAIR APPARATUS PROTEIN; HYDIN","url":"https://www.omim.org/entry/610812"},{"mim_id":"608647","title":"CILIARY DYSKINESIA, PRIMARY, 5; CILD5","url":"https://www.omim.org/entry/608647"},{"mim_id":"601175","title":"ADP-RIBOSYLATION FACTOR-LIKE GTPase 2; ARL2","url":"https://www.omim.org/entry/601175"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"},{"location":"Centrosome","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/ARL2BP"},"hgnc":{"alias_symbol":["BART1","BART"],"prev_symbol":["RP66"]},"alphafold":{"accession":"Q9Y2Y0","domains":[{"cath_id":"1.20.1520.10","chopping":"10-132","consensus_level":"high","plddt":88.0798,"start":10,"end":132}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y2Y0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y2Y0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y2Y0-F1-predicted_aligned_error_v6.png","plddt_mean":80.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ARL2BP","jax_strain_url":"https://www.jax.org/strain/search?query=ARL2BP"},"sequence":{"accession":"Q9Y2Y0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y2Y0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y2Y0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y2Y0"}},"corpus_meta":[{"pmid":"26135619","id":"PMC_26135619","title":"Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.","date":"2015","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/26135619","citation_count":186,"is_preprint":false},{"pmid":"30557400","id":"PMC_30557400","title":"EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma.","date":"2018","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/30557400","citation_count":93,"is_preprint":false},{"pmid":"23849777","id":"PMC_23849777","title":"Mutations in ARL2BP, encoding ADP-ribosylation-factor-like 2 binding protein, cause autosomal-recessive retinitis pigmentosa.","date":"2013","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23849777","citation_count":59,"is_preprint":false},{"pmid":"23685147","id":"PMC_23685147","title":"EBV-miR-BART1 is involved in regulating metabolism-associated genes in nasopharyngeal carcinoma.","date":"2013","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/23685147","citation_count":58,"is_preprint":false},{"pmid":"26701721","id":"PMC_26701721","title":"Epstein-Barr virus mir-bart1-5p detection via nasopharyngeal brush sampling is effective for diagnosing nasopharyngeal carcinoma.","date":"2016","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/26701721","citation_count":35,"is_preprint":false},{"pmid":"32056716","id":"PMC_32056716","title":"MiR-BART1-5p targets core 2β-1,6-acetylglucosaminyltransferase GCNT3 to inhibit cell proliferation and migration in EBV-associated gastric cancer.","date":"2019","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/32056716","citation_count":30,"is_preprint":false},{"pmid":"32025216","id":"PMC_32025216","title":"Epstein-Barr virus miR-BART1-3p suppresses apoptosis and promotes migration of gastric carcinoma cells by targeting DAB2.","date":"2020","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32025216","citation_count":28,"is_preprint":false},{"pmid":"31425546","id":"PMC_31425546","title":"Mutations in ARL2BP, a protein required for ciliary microtubule structure, cause syndromic male infertility in humans and mice.","date":"2019","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31425546","citation_count":24,"is_preprint":false},{"pmid":"37097161","id":"PMC_37097161","title":"Targeting exosomes enveloped EBV-miR-BART1-5p-antagomiRs for NPC therapy through both anti-vasculogenic mimicry and anti-angiogenesis.","date":"2023","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/37097161","citation_count":19,"is_preprint":false},{"pmid":"29718757","id":"PMC_29718757","title":"ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure.","date":"2018","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/29718757","citation_count":18,"is_preprint":false},{"pmid":"34681596","id":"PMC_34681596","title":"Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34681596","citation_count":17,"is_preprint":false},{"pmid":"8639266","id":"PMC_8639266","title":"Isolation and characterization of BART-1: A novel balloon angioplasty responsive transcript in rat carotid arteries.","date":"1996","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/8639266","citation_count":13,"is_preprint":false},{"pmid":"30210231","id":"PMC_30210231","title":"Novel homozygous splicing mutations in ARL2BP cause autosomal recessive retinitis pigmentosa.","date":"2018","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/30210231","citation_count":10,"is_preprint":false},{"pmid":"27790702","id":"PMC_27790702","title":"ARL2BP mutations account for 0.1% of autosomal recessive rod-cone dystrophies with the report of a novel splice variant.","date":"2017","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27790702","citation_count":10,"is_preprint":false},{"pmid":"37345178","id":"PMC_37345178","title":"Effects of Co-Culture EBV-miR-BART1-3p on Proliferation and Invasion of Gastric Cancer Cells Based on Exosomes.","date":"2023","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/37345178","citation_count":6,"is_preprint":false},{"pmid":"33507707","id":"PMC_33507707","title":"As Evidence-Based Tumorigenic Role of Epstein-Barr Virus miR-BART1-3p in Neurological Tumors.","date":"2021","source":"Asian Pacific journal of cancer prevention : APJCP","url":"https://pubmed.ncbi.nlm.nih.gov/33507707","citation_count":5,"is_preprint":false},{"pmid":"32339206","id":"PMC_32339206","title":"Correction: EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma.","date":"2020","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/32339206","citation_count":5,"is_preprint":false},{"pmid":"37535140","id":"PMC_37535140","title":"MiR-BART1-3p and BART18-5p inhibit cell migration, proliferation and activate autophagy in Epstein-Barr virus-associated gastric cancer by targeting erythropoietin-producing human hepatocellular 2.","date":"2023","source":"Virus genes","url":"https://pubmed.ncbi.nlm.nih.gov/37535140","citation_count":3,"is_preprint":false},{"pmid":"36507858","id":"PMC_36507858","title":"Novel homozygous variant in ARL2BP associated with retinitis pigmentosa, situs inversus, and male infertility in a Chinese patient.","date":"2022","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36507858","citation_count":2,"is_preprint":false},{"pmid":"38649918","id":"PMC_38649918","title":"A novel homozygous splice site variant in ARL2BP causes a syndromic autosomal recessive rod-cone dystrophy with situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts.","date":"2024","source":"BMC medical genomics","url":"https://pubmed.ncbi.nlm.nih.gov/38649918","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11779,"output_tokens":1159,"usd":0.026361,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7776,"output_tokens":1892,"usd":0.04309,"stage2_stop_reason":"end_turn"},"total_usd":0.069451,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"ARL2BP is an effector protein of the small GTPases ARL2 and ARL3. In mouse retina, ARL2BP localizes to the basal body and cilium-associated centriole of photoreceptors and the periciliary extension of the inner segment. Depletion of ARL2, but not ARL3, caused displacement of ARL2BP from the basal body, establishing that ARL2 is required for recruiting or anchoring ARL2BP at the base of the cilium. The p.Met45Arg mutation reduced binding to ARL2 and caused loss of ARL2BP localization at the basal body in ciliated nasal epithelial cells. Depletion of ARL2BP caused cilia shortening.\",\n      \"method\": \"Homozygosity mapping, exome sequencing, blood RNA splicing analysis, immunolocalization in mouse retina, siRNA depletion in ciliated cells, binding assay with mutant protein\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization experiments with functional consequences, ARL2-dependence established by selective depletion (ARL2 vs ARL3), mutant protein binding assay, replicated across cell types\",\n      \"pmids\": [\"23849777\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"ARL2BP is necessary for photoreceptor ciliary doublet microtubule formation and axoneme elongation, which is required for outer segment morphogenesis and vision. ARL2BP knockout mice display disorganization of the photoreceptor outer segment with vertically aligned disks, shortened axonemes, open B-tubule doublets, and loss of singlet microtubules, accompanied by an early and progressive reduction in visual response.\",\n      \"method\": \"Knockout mouse model, electron microscopy of ciliary ultrastructure, electroretinography, immunofluorescence\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO mouse with defined cellular phenotype, ultrastructural analysis by EM, functional readout by ERG, multiple orthogonal methods in one study\",\n      \"pmids\": [\"29718757\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ARL2BP is required for the structural maintenance of cilia and the sperm flagellum. In ARL2BP knockout mice, spermiogenesis is impaired, resulting in abnormally shaped sperm heads, shortened and mis-assembled sperm tails, and loss of axonemal doublets. Additional ciliopathy phenotypes included enlarged brain ventricles and situs inversus. Mouse embryonic fibroblasts from knockout animals showed delayed depolymerization of primary cilia.\",\n      \"method\": \"Knockout mouse model, sperm morphology analysis, electron microscopy, primary cilia depolymerization assay in MEFs\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO mouse with multiple defined cellular phenotypes, EM ultrastructural validation, functional cilia assay, multiple orthogonal methods\",\n      \"pmids\": [\"31425546\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Loss-of-function variant in ARL2BP in patient-derived fibroblasts resulted in reduced cell proliferation and reduced ciliary length, consistent with a role for ARL2BP in ciliogenesis.\",\n      \"method\": \"Patient-derived fibroblast analysis, ciliary length measurement, cell proliferation assay\",\n      \"journal\": \"Clinical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single patient, patient-derived fibroblasts with direct measurements but single lab, no mechanistic follow-up\",\n      \"pmids\": [\"36507858\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ARL2BP is a ciliary effector protein that binds the small GTPase ARL2 (but not ARL3); ARL2 is required to recruit/anchor ARL2BP to the basal body of cilia, where ARL2BP is necessary for doublet microtubule integrity, axoneme elongation, and outer segment morphogenesis in photoreceptors, and for structural maintenance of the sperm flagellum, with loss of function causing retinitis pigmentosa, situs inversus, and male infertility.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ARL2BP is a ciliary effector protein that links the small GTPase ARL2 to the structural integrity of microtubule-based cilia and flagella [#0, #1]. It acts as a selective effector of ARL2 rather than ARL3: depletion of ARL2, but not ARL3, displaces ARL2BP from the basal body, establishing that ARL2 recruits or anchors ARL2BP at the base of the cilium, while the disease-associated p.Met45Arg substitution reduces ARL2 binding and abolishes basal-body localization [#0]. At the photoreceptor basal body and cilium-associated centriole, ARL2BP is required for ciliary doublet microtubule formation and axoneme elongation; its loss produces shortened axonemes, open B-tubule doublets, loss of singlet microtubules, and disorganized outer segments with impaired visual response [#0, #1]. The same activity supports structural maintenance of the sperm flagellum, where loss causes mis-assembled tails and loss of axonemal doublets, and underlies broader ciliopathy phenotypes including situs inversus [#2]. Through these roles ARL2BP loss of function causes retinitis pigmentosa, situs inversus, and male infertility [#0, #1, #2].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Established that ARL2BP is a basal-body effector whose ciliary localization depends specifically on ARL2, defining the recruitment logic at the cilium base and linking it to human disease.\",\n      \"evidence\": \"Immunolocalization in mouse retina, selective siRNA depletion of ARL2 vs ARL3, mutant-protein binding assay, and homozygosity mapping/exome sequencing in patients\",\n      \"pmids\": [\"23849777\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which ARL2-GTP anchors ARL2BP at the basal body not resolved at structural level\",\n        \"How basal-body ARL2BP couples to microtubule assembly machinery not defined\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrated that ARL2BP is required for photoreceptor doublet microtubule formation and axoneme elongation, connecting the basal-body localization to outer-segment morphogenesis and vision.\",\n      \"evidence\": \"ARL2BP knockout mouse with EM ultrastructure, electroretinography, and immunofluorescence\",\n      \"pmids\": [\"29718757\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular partners through which ARL2BP promotes B-tubule and singlet microtubule integrity not identified\",\n        \"Whether the defect is in microtubule nucleation, stabilization, or transport not distinguished\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Extended ARL2BP function to structural maintenance of the sperm flagellum and motile-cilia-dependent processes, showing the cilium/flagellum phenotype is general rather than photoreceptor-specific.\",\n      \"evidence\": \"Knockout mouse sperm morphology, EM of axonemal doublets, situs/ventricle phenotyping, and primary cilia depolymerization assay in MEFs\",\n      \"pmids\": [\"31425546\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism linking ARL2BP to delayed cilia depolymerization unknown\",\n        \"Tissue-specific requirements versus a single shared axonemal function not dissected\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Confirmed in patient-derived cells that ARL2BP loss reduces ciliary length and proliferation, corroborating a ciliogenesis role in human tissue.\",\n      \"evidence\": \"Patient-derived fibroblasts with ciliary length and proliferation measurements\",\n      \"pmids\": [\"36507858\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single patient, single lab, no mechanistic follow-up\",\n        \"Causal link between proliferation defect and ciliary defect not established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism by which ARL2BP, downstream of ARL2, directs doublet microtubule assembly and axoneme integrity remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No identified molecular effectors or microtubule-associated partners of ARL2BP\",\n        \"No structural model of the ARL2-ARL2BP complex at the basal body\",\n        \"Whether ARL2BP has intrinsic biochemical activity beyond ARL2 binding is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ARL2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}