{"gene":"IFT70A","run_date":"2026-06-10T01:55:22","timeline":{"discoveries":[{"year":2018,"finding":"IFT70A (TTC30A) is a peripheral subunit of the IFT-B complex that interacts with the IFT52-IFT88 dimer; deletion of the first TPR or the terminal α36 helix of IFT70A greatly reduces this interaction. IFT70A and IFT70B double-knockout cells fail to form cilia, while single knockouts do not, demonstrating redundant but essential roles. Exogenous IFT70A or IFT70B rescues ciliogenesis, confirming functional redundancy. Other IFT-B subunits still assemble at the ciliary base in IFT70-KO cells.","method":"CRISPR/Cas9 knockout cell lines (IFT70A/B double-KO), rescue with exogenous expression, deletion mutagenesis of TPR and α36 domains, ciliogenesis assay","journal":"Biology open","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — domain mutagenesis combined with KO rescue and interaction assays in a single focused study with multiple orthogonal methods","pmids":["29654116"],"is_preprint":false},{"year":2021,"finding":"Loss of Ttc30a (IFT70A ortholog) in Xenopus tropicalis impairs ciliogenesis and embryonic renal excretion, and is associated with altered posttranslational tubulin acetylation, glycylation, and defective axoneme compartmentalization, placing TTC30A/IFT70A as an essential node in ciliary chondrodysplasia and nephronophthisis-related disease networks.","method":"CRISPR/Cas9 mutagenesis in Xenopus tropicalis, immunofluorescence for tubulin modifications (acetylation, glycylation), phenotypic analysis of cilia and kidney","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function in a vertebrate model with defined molecular readouts (tubulin modifications), single lab","pmids":["34548398"],"is_preprint":false},{"year":2023,"finding":"TTC30A (IFT70A) has a paralog-specific interaction with PKA catalytic subunit α (PRKACA); a disease-associated TTC30A mutant inhibits ciliary localization of Smoothened independently of Patched1, and is associated with accumulation of phosphorylated PKA substrates upon forskolin treatment, resulting in downregulation of Sonic hedgehog signaling. Additionally, mutant TTC30A shows impaired interaction with IFT57 compared to wildtype, while TTC30B is less affected. These effects were observed without impact on cilia assembly.","method":"TTC30A/B single and double CRISPR/Cas9 knockout hTERT-RPE1 cells, rescue with wildtype or mutant constructs, mass spectrometry interactome analysis, immunofluorescence for Smoothened ciliary localization, PKA substrate phosphorylation assay with forskolin","journal":"Frontiers in molecular biosciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (MS, KO rescue, localization assay), single lab","pmids":["38074101"],"is_preprint":false},{"year":2019,"finding":"In men with bi-allelic TTC29 mutations, immunofluorescence of spermatozoa showed deficiency of TTC29 and markedly reduced staining of IFT-B-associated protein TTC30A (IFT70A), indicating TTC30A localizes to sperm flagella and its proper localization is dependent on TTC29.","method":"Immunofluorescence of human spermatozoa from TTC29 mutation carriers; Ttc29-mutant mouse model generated by CRISPR-Cas9","journal":"American journal of human genetics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single immunofluorescence observation in the context of a TTC29 study; TTC30A/IFT70A is a secondary finding","pmids":["31735294"],"is_preprint":false},{"year":2025,"finding":"IFT70A mislocalizes specifically in spermatozoa (but not testicular spermatids) of Tulp2-/- mice, indicating IFT70A localization in mature sperm is dependent on TULP2. Quantitative analyses also revealed significant dysregulation of IFT70A levels in Tulp2-/- mice.","method":"Localization analysis by immunofluorescence in Tulp2-knockout mouse spermatids and spermatozoa; quantitative protein analysis","journal":"Biology of reproduction","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization finding is secondary to the TULP2 study; single method, single lab","pmids":["40613306"],"is_preprint":false}],"current_model":"IFT70A (TTC30A) is a peripheral subunit of the IFT-B complex that binds the IFT52-IFT88 dimer via its TPR repeats and terminal α36 helix, and is functionally redundant with its paralog IFT70B for ciliogenesis; beyond its structural role in IFT-B, TTC30A has a paralog-specific interaction with PRKACA and IFT57 that modulates Sonic hedgehog signaling by regulating Smoothened ciliary entry, and loss of TTC30A alters posttranslational tubulin modifications (acetylation and glycylation) and axoneme compartmentalization."},"narrative":{"mechanistic_narrative":"IFT70A (TTC30A) is a peripheral subunit of the intraflagellar transport IFT-B complex required for ciliogenesis [PMID:29654116]. It engages the IFT-B core through its TPR repeats and terminal α36 helix, binding the IFT52-IFT88 dimer; removing the first TPR or the α36 helix abrogates this interaction [PMID:29654116]. IFT70A acts redundantly with its paralog IFT70B—single knockouts assemble cilia normally and other IFT-B subunits still localize to the ciliary base, but loss of both abolishes ciliogenesis, and either paralog rescues the defect [PMID:29654116]. Beyond this structural role, loss of the IFT70A ortholog in Xenopus impairs ciliogenesis and renal excretion and alters posttranslational tubulin acetylation and glycylation with defective axoneme compartmentalization [PMID:34548398]. A paralog-specific function distinguishes IFT70A from IFT70B: it interacts with the PKA catalytic subunit PRKACA and with IFT57, and a disease-associated mutant blocks ciliary entry of Smoothened independently of Patched1, leading to accumulation of phosphorylated PKA substrates and downregulation of Sonic hedgehog signaling without affecting cilium assembly [PMID:38074101].","teleology":[{"year":2018,"claim":"Established how IFT70A docks into the IFT-B complex and whether it is individually essential, resolving its structural role in ciliogenesis.","evidence":"CRISPR/Cas9 IFT70A/B double-knockout cells with rescue, TPR and α36 deletion mutagenesis, and interaction/ciliogenesis assays","pmids":["29654116"],"confidence":"High","gaps":["Does not define functional differences between IFT70A and IFT70B given full redundancy here","No structural model of the IFT52-IFT88-IFT70A interface","Mechanism of how IFT70A loss blocks ciliogenesis at the molecular level not resolved"]},{"year":2019,"claim":"Showed IFT70A localizes to sperm flagella and that its localization depends on TTC29, extending its role beyond primary cilia.","evidence":"Immunofluorescence of human spermatozoa from biallelic TTC29 mutation carriers and a Ttc29-mutant mouse","pmids":["31735294"],"confidence":"Low","gaps":["Single immunofluorescence observation secondary to a TTC29-focused study; not independently validated","Whether TTC29 and IFT70A interact directly is unknown","No functional consequence of altered IFT70A flagellar localization defined"]},{"year":2021,"claim":"Connected IFT70A loss to altered tubulin posttranslational modifications and axoneme compartmentalization in a vertebrate, linking it to ciliopathy phenotypes.","evidence":"CRISPR/Cas9 mutagenesis in Xenopus tropicalis with immunofluorescence for tubulin acetylation/glycylation and analysis of cilia and kidney","pmids":["34548398"],"confidence":"Medium","gaps":["Whether tubulin modification changes are direct or downstream of impaired transport is unresolved","Single lab, single model organism","No mechanism linking IFT70A to the modifying enzymes"]},{"year":2023,"claim":"Defined a paralog-specific role for IFT70A in Hedgehog signaling distinct from its structural IFT-B function, via PRKACA and IFT57 interactions and Smoothened regulation.","evidence":"TTC30A/B knockout RPE1 cells with wildtype/mutant rescue, mass spectrometry interactome, Smoothened localization, and forskolin PKA-substrate phosphorylation assays","pmids":["38074101"],"confidence":"Medium","gaps":["Direct vs indirect nature of the PRKACA interaction not biochemically resolved","Mechanism by which the mutant blocks Smoothened ciliary entry independent of Patched1 unknown","Single lab; disease relevance of the mutant beyond cell models not established"]},{"year":2025,"claim":"Showed IFT70A mature-sperm localization and abundance depend on TULP2, further defining flagellar regulation of IFT70A.","evidence":"Immunofluorescence localization and quantitative protein analysis in Tulp2-knockout mouse spermatids and spermatozoa","pmids":["40613306"],"confidence":"Low","gaps":["Localization finding is secondary to a TULP2-focused study; single method","Whether TULP2 acts directly on IFT70A is unknown","Stage specificity (spermatozoa but not spermatids) is unexplained mechanistically"]},{"year":null,"claim":"How IFT70A-specific interactions are partitioned from its redundant IFT-B structural role, and the molecular basis of its Hedgehog-modulating and tubulin-modification effects, remain open.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of IFT70A within an assembled IFT-B train","Direct enzymatic or adaptor mechanism for tubulin modification changes unknown","Biochemical basis of paralog-specific PRKACA/IFT57 engagement not defined"]}],"mechanism_profile":{"molecular_activity":[{"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":[0,2]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1,2]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0]}],"complexes":["IFT-B"],"partners":["IFT52","IFT88","IFT70B","PRKACA","IFT57"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q86WT1","full_name":"Intraflagellar transport protein 70A","aliases":["Tetratricopeptide repeat protein 30A","TPR repeat protein 30A"],"length_aa":665,"mass_kda":76.1,"function":"Required for polyglutamylation of axonemal tubulin. Plays a role in anterograde intraflagellar transport (IFT), the process by which cilia precursors are transported from the base of the cilium to the site of their incorporation at the tip","subcellular_location":"Cell projection, cilium","url":"https://www.uniprot.org/uniprotkb/Q86WT1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/IFT70A","classification":"Not Classified","n_dependent_lines":10,"n_total_lines":1165,"dependency_fraction":0.008583690987124463},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/IFT70A","total_profiled":1310},"omim":[{"mim_id":"620742","title":"INTRAFLAGELLAR TRANSPORT 70B; IFT70B","url":"https://www.omim.org/entry/620742"},{"mim_id":"620741","title":"INTRAFLAGELLAR TRANSPORT 70A; IFT70A","url":"https://www.omim.org/entry/620741"}],"hpa":{"profiled":true,"resolved_as":"TTC30A","reliability":"Approved","locations":[{"location":"Primary cilium","reliability":"Approved"},{"location":"Centrosome","reliability":"Approved"},{"location":"Basal body","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Primary cilium tip","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TTC30A"},"hgnc":{"alias_symbol":["FLJ13946","FAP259","CFAP259"],"prev_symbol":["TTC30A"]},"alphafold":{"accession":"Q86WT1","domains":[{"cath_id":"1.25.40.10","chopping":"14-127","consensus_level":"medium","plddt":94.3579,"start":14,"end":127},{"cath_id":"-","chopping":"187-229_237-286","consensus_level":"medium","plddt":95.2841,"start":187,"end":286},{"cath_id":"1.25.40","chopping":"473-539","consensus_level":"medium","plddt":95.2473,"start":473,"end":539},{"cath_id":"1.20.58","chopping":"557-665","consensus_level":"medium","plddt":92.6985,"start":557,"end":665}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86WT1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86WT1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86WT1-F1-predicted_aligned_error_v6.png","plddt_mean":92.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=IFT70A","jax_strain_url":"https://www.jax.org/strain/search?query=IFT70A"},"sequence":{"accession":"Q86WT1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86WT1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86WT1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86WT1"}},"corpus_meta":[{"pmid":"31735294","id":"PMC_31735294","title":"Bi-allelic Mutations in TTC29 Cause Male Subfertility with Asthenoteratospermia in Humans and Mice.","date":"2019","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31735294","citation_count":75,"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":"34548398","id":"PMC_34548398","title":"Ttc30a affects tubulin modifications in a model for ciliary chondrodysplasia with polycystic kidney disease.","date":"2021","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/34548398","citation_count":11,"is_preprint":false},{"pmid":"38074101","id":"PMC_38074101","title":"Paralog-specific TTC30 regulation of Sonic hedgehog signaling.","date":"2023","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/38074101","citation_count":3,"is_preprint":false},{"pmid":"40150870","id":"PMC_40150870","title":"Genome-Wide Analysis of Genetic Predispositions Linked to Damaged Membranes and Impaired Fertility as Indicators of Compromised Sperm-Egg Interaction Mechanisms in Frozen-Thawed Rooster Semen.","date":"2025","source":"Frontiers in bioscience (Scholar edition)","url":"https://pubmed.ncbi.nlm.nih.gov/40150870","citation_count":2,"is_preprint":false},{"pmid":"40613306","id":"PMC_40613306","title":"TUB-like protein 2, a substrate of CCT8, is essential for the intraflagellar transport during spermiogenesis in mice†.","date":"2025","source":"Biology of reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/40613306","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5881,"output_tokens":1567,"usd":0.020574,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8259,"output_tokens":2323,"usd":0.049685,"stage2_stop_reason":"end_turn"},"total_usd":0.070259,"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\": 2018,\n      \"finding\": \"IFT70A (TTC30A) is a peripheral subunit of the IFT-B complex that interacts with the IFT52-IFT88 dimer; deletion of the first TPR or the terminal α36 helix of IFT70A greatly reduces this interaction. IFT70A and IFT70B double-knockout cells fail to form cilia, while single knockouts do not, demonstrating redundant but essential roles. Exogenous IFT70A or IFT70B rescues ciliogenesis, confirming functional redundancy. Other IFT-B subunits still assemble at the ciliary base in IFT70-KO cells.\",\n      \"method\": \"CRISPR/Cas9 knockout cell lines (IFT70A/B double-KO), rescue with exogenous expression, deletion mutagenesis of TPR and α36 domains, ciliogenesis assay\",\n      \"journal\": \"Biology open\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — domain mutagenesis combined with KO rescue and interaction assays in a single focused study with multiple orthogonal methods\",\n      \"pmids\": [\"29654116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Loss of Ttc30a (IFT70A ortholog) in Xenopus tropicalis impairs ciliogenesis and embryonic renal excretion, and is associated with altered posttranslational tubulin acetylation, glycylation, and defective axoneme compartmentalization, placing TTC30A/IFT70A as an essential node in ciliary chondrodysplasia and nephronophthisis-related disease networks.\",\n      \"method\": \"CRISPR/Cas9 mutagenesis in Xenopus tropicalis, immunofluorescence for tubulin modifications (acetylation, glycylation), phenotypic analysis of cilia and kidney\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function in a vertebrate model with defined molecular readouts (tubulin modifications), single lab\",\n      \"pmids\": [\"34548398\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TTC30A (IFT70A) has a paralog-specific interaction with PKA catalytic subunit α (PRKACA); a disease-associated TTC30A mutant inhibits ciliary localization of Smoothened independently of Patched1, and is associated with accumulation of phosphorylated PKA substrates upon forskolin treatment, resulting in downregulation of Sonic hedgehog signaling. Additionally, mutant TTC30A shows impaired interaction with IFT57 compared to wildtype, while TTC30B is less affected. These effects were observed without impact on cilia assembly.\",\n      \"method\": \"TTC30A/B single and double CRISPR/Cas9 knockout hTERT-RPE1 cells, rescue with wildtype or mutant constructs, mass spectrometry interactome analysis, immunofluorescence for Smoothened ciliary localization, PKA substrate phosphorylation assay with forskolin\",\n      \"journal\": \"Frontiers in molecular biosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (MS, KO rescue, localization assay), single lab\",\n      \"pmids\": [\"38074101\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In men with bi-allelic TTC29 mutations, immunofluorescence of spermatozoa showed deficiency of TTC29 and markedly reduced staining of IFT-B-associated protein TTC30A (IFT70A), indicating TTC30A localizes to sperm flagella and its proper localization is dependent on TTC29.\",\n      \"method\": \"Immunofluorescence of human spermatozoa from TTC29 mutation carriers; Ttc29-mutant mouse model generated by CRISPR-Cas9\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single immunofluorescence observation in the context of a TTC29 study; TTC30A/IFT70A is a secondary finding\",\n      \"pmids\": [\"31735294\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"IFT70A mislocalizes specifically in spermatozoa (but not testicular spermatids) of Tulp2-/- mice, indicating IFT70A localization in mature sperm is dependent on TULP2. Quantitative analyses also revealed significant dysregulation of IFT70A levels in Tulp2-/- mice.\",\n      \"method\": \"Localization analysis by immunofluorescence in Tulp2-knockout mouse spermatids and spermatozoa; quantitative protein analysis\",\n      \"journal\": \"Biology of reproduction\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization finding is secondary to the TULP2 study; single method, single lab\",\n      \"pmids\": [\"40613306\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"IFT70A (TTC30A) is a peripheral subunit of the IFT-B complex that binds the IFT52-IFT88 dimer via its TPR repeats and terminal α36 helix, and is functionally redundant with its paralog IFT70B for ciliogenesis; beyond its structural role in IFT-B, TTC30A has a paralog-specific interaction with PRKACA and IFT57 that modulates Sonic hedgehog signaling by regulating Smoothened ciliary entry, and loss of TTC30A alters posttranslational tubulin modifications (acetylation and glycylation) and axoneme compartmentalization.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"IFT70A (TTC30A) is a peripheral subunit of the intraflagellar transport IFT-B complex required for ciliogenesis [#0]. It engages the IFT-B core through its TPR repeats and terminal α36 helix, binding the IFT52-IFT88 dimer; removing the first TPR or the α36 helix abrogates this interaction [#0]. IFT70A acts redundantly with its paralog IFT70B—single knockouts assemble cilia normally and other IFT-B subunits still localize to the ciliary base, but loss of both abolishes ciliogenesis, and either paralog rescues the defect [#0]. Beyond this structural role, loss of the IFT70A ortholog in Xenopus impairs ciliogenesis and renal excretion and alters posttranslational tubulin acetylation and glycylation with defective axoneme compartmentalization [#1]. A paralog-specific function distinguishes IFT70A from IFT70B: it interacts with the PKA catalytic subunit PRKACA and with IFT57, and a disease-associated mutant blocks ciliary entry of Smoothened independently of Patched1, leading to accumulation of phosphorylated PKA substrates and downregulation of Sonic hedgehog signaling without affecting cilium assembly [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Established how IFT70A docks into the IFT-B complex and whether it is individually essential, resolving its structural role in ciliogenesis.\",\n      \"evidence\": \"CRISPR/Cas9 IFT70A/B double-knockout cells with rescue, TPR and α36 deletion mutagenesis, and interaction/ciliogenesis assays\",\n      \"pmids\": [\"29654116\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not define functional differences between IFT70A and IFT70B given full redundancy here\",\n        \"No structural model of the IFT52-IFT88-IFT70A interface\",\n        \"Mechanism of how IFT70A loss blocks ciliogenesis at the molecular level not resolved\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showed IFT70A localizes to sperm flagella and that its localization depends on TTC29, extending its role beyond primary cilia.\",\n      \"evidence\": \"Immunofluorescence of human spermatozoa from biallelic TTC29 mutation carriers and a Ttc29-mutant mouse\",\n      \"pmids\": [\"31735294\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single immunofluorescence observation secondary to a TTC29-focused study; not independently validated\",\n        \"Whether TTC29 and IFT70A interact directly is unknown\",\n        \"No functional consequence of altered IFT70A flagellar localization defined\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Connected IFT70A loss to altered tubulin posttranslational modifications and axoneme compartmentalization in a vertebrate, linking it to ciliopathy phenotypes.\",\n      \"evidence\": \"CRISPR/Cas9 mutagenesis in Xenopus tropicalis with immunofluorescence for tubulin acetylation/glycylation and analysis of cilia and kidney\",\n      \"pmids\": [\"34548398\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether tubulin modification changes are direct or downstream of impaired transport is unresolved\",\n        \"Single lab, single model organism\",\n        \"No mechanism linking IFT70A to the modifying enzymes\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined a paralog-specific role for IFT70A in Hedgehog signaling distinct from its structural IFT-B function, via PRKACA and IFT57 interactions and Smoothened regulation.\",\n      \"evidence\": \"TTC30A/B knockout RPE1 cells with wildtype/mutant rescue, mass spectrometry interactome, Smoothened localization, and forskolin PKA-substrate phosphorylation assays\",\n      \"pmids\": [\"38074101\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct vs indirect nature of the PRKACA interaction not biochemically resolved\",\n        \"Mechanism by which the mutant blocks Smoothened ciliary entry independent of Patched1 unknown\",\n        \"Single lab; disease relevance of the mutant beyond cell models not established\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed IFT70A mature-sperm localization and abundance depend on TULP2, further defining flagellar regulation of IFT70A.\",\n      \"evidence\": \"Immunofluorescence localization and quantitative protein analysis in Tulp2-knockout mouse spermatids and spermatozoa\",\n      \"pmids\": [\"40613306\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Localization finding is secondary to a TULP2-focused study; single method\",\n        \"Whether TULP2 acts directly on IFT70A is unknown\",\n        \"Stage specificity (spermatozoa but not spermatids) is unexplained mechanistically\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How IFT70A-specific interactions are partitioned from its redundant IFT-B structural role, and the molecular basis of its Hedgehog-modulating and tubulin-modification effects, remain open.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of IFT70A within an assembled IFT-B train\",\n        \"Direct enzymatic or adaptor mechanism for tubulin modification changes unknown\",\n        \"Biochemical basis of paralog-specific PRKACA/IFT57 engagement not defined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"IFT-B\"\n    ],\n    \"partners\": [\n      \"IFT52\",\n      \"IFT88\",\n      \"IFT70B\",\n      \"PRKACA\",\n      \"IFT57\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":5,"faith_pct":80.0}}