{"gene":"IFT140","run_date":"2026-06-10T01:55:22","timeline":{"discoveries":[{"year":2012,"finding":"IFT140 is a component of intraflagellar transport complex A (IFT-A) required for retrograde protein transport in ciliated cells; loss of IFT140 function alters ciliary abundance and localization of anterograde IFT components in patient fibroblasts.","method":"Patient fibroblast analysis (immunocytochemistry of IFT components), Sanger sequencing","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cellular phenotyping in patient-derived fibroblasts with IFT localization readout, single lab, consistent with broader ciliopathy literature","pmids":["22503633"],"is_preprint":false},{"year":2014,"finding":"IFT140 (IFT-A complex) is required for opsin transport through the connecting cilium of photoreceptors: acute deletion of Ift140 causes opsin to accumulate in the plasma membrane of inner segments (not at the Golgi), distinguishing its role from IFT20 which mediates Golgi-to-cilium base transport.","method":"Conditional/acute knockout mouse model, immunofluorescence, epistasis comparison with Ift20 knockout","journal":"Cytoskeleton (Hoboken, N.J.)","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean conditional KO with specific subcellular phenotypic readout and epistatic comparison to a second IFT component in the same study, defining distinct pathway positions","pmids":["24619649"],"is_preprint":false},{"year":2013,"finding":"IFT140 is required for Hedgehog signaling downstream of primary cilia; Ift140 ENU mutant mouse embryos exhibit exencephaly, spina bifida, digit anomalies, and somite patterning defects attributable to altered Hedgehog signaling.","method":"ENU mutagenesis mouse model, embryo phenotyping, Hedgehog pathway analysis","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo loss-of-function model with defined Hedgehog signaling readout, single lab","pmids":["24009529"],"is_preprint":false},{"year":2018,"finding":"IFT140 is essential for male fertility and spermiogenesis: spermatocyte/spermatid-specific Ift140 knockout in mice produces severe sperm morphological defects (amorphous heads, short/bent flagella, swollen tail tips), and alters the localization (but not expression levels) of IFT-B components IFT27 and IFT88.","method":"Conditional knockout mice (spermatocyte/spermatid-specific), immunofluorescence localization of IFT components, electron microscopy, sperm motility/count assays","journal":"Cytoskeleton (Hoboken, N.J.)","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean conditional KO with multiple orthogonal readouts (morphology, IFT component localization, fertility), single lab but rigorous","pmids":["29236364"],"is_preprint":false},{"year":2018,"finding":"IFT140 loss-of-function causes accumulation of IFT-B component IFT88 at the ciliary tip in patient-derived urine renal epithelial cells (41% of cells), indicating impaired retrograde IFT; a patient missense mutation (p.Tyr923Asp) introduced into CRISPR/Cas9-derived Ift140 KO cells caused significantly greater IFT88 tip accumulation than wild-type IFT140 rescue.","method":"Patient-derived urine renal epithelial cells, immunocytochemistry, CRISPR/Cas9 KO cells, rescue transfection with mutant vs. wild-type IFT140 constructs","journal":"Cilia","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — functional rescue experiment with mutagenesis in isogenic KO cells plus patient-derived cells, two orthogonal cellular systems, single lab","pmids":["30479745"],"is_preprint":false},{"year":2016,"finding":"Missense mutations in IFT140 associated with nonsyndromic retinitis pigmentosa cause significantly reduced localization of IFT140 protein to the basal body in hTERT-RPE1 cells compared to wild-type, a phenotype shared with syndromic mutations.","method":"Transient plasmid transfection of hTERT-RPE1 cells, immunofluorescence for basal body co-localization","journal":"Investigative ophthalmology & visual science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cell-based functional assay comparing mutant vs. wild-type localization, single lab, two orthogonal mutations tested","pmids":["26968735"],"is_preprint":false},{"year":2017,"finding":"IFT140 is required for Sonic Hedgehog signaling in odontoblasts: conditional deletion of Ift140 in odontoblasts (Osx-Cre) causes loss of primary cilia, reduced SHH signaling molecules, impaired odontogenic differentiation in vitro, and defective reparative dentin formation in vivo.","method":"Conditional knockout mice (Osx-Cre), in vitro deletion of IFT140 in odontoblasts, SHH pathway analysis, tooth-drilling model for reparative dentin","journal":"Journal of dental research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with SHH pathway readout in both in vivo and in vitro systems, single lab","pmids":["29195058"],"is_preprint":false},{"year":2022,"finding":"ARL16 (an ARF-family GTPase) regulates trafficking of IFT140 from the Golgi to cilia: deletion of ARL16 in mouse embryonic fibroblasts causes accumulation of IFT140 (and INPP5E) at the Golgi, while other IFT proteins are unaffected, suggesting a specific Golgi-to-cilia export pathway for IFT140.","method":"ARL16 knockout MEFs, immunofluorescence for IFT140 and other IFT components, Golgi localization assay","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with specific subcellular localization phenotype for IFT140 vs. other IFT proteins as internal controls, single lab","pmids":["35196065"],"is_preprint":false},{"year":2017,"finding":"Homozygous IFT140 mutation (c.634G>A; p.Gly212Arg) causes mis-splicing producing a majority transcript with premature termination codon; zebrafish in vivo complementation confirmed loss-of-function effect of the minority p.Gly212Arg missense allele.","method":"RT-PCR/sequencing from patient cells, zebrafish in vivo complementation assay","journal":"Human genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional validation combining patient cell splicing analysis and zebrafish complementation, single lab","pmids":["28724397"],"is_preprint":false},{"year":2019,"finding":"IFT140 protein is normally present at the neck and mid-piece of human spermatozoa; compound heterozygous IFT140 variants (p.Asp613Asn and p.Ser1416Asn) cause absence of IFT140 from these regions and produce sperm with head, nuclear, and tail morphological abnormalities in a human infertility patient.","method":"Immunofluorescence of patient sperm, transmission electron microscopy, whole-exome sequencing with family segregation","journal":"Molecular genetics & genomic medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization of IFT140 in human sperm with TEM, single case/lab","pmids":["31397098"],"is_preprint":false},{"year":2025,"finding":"IFT140 missense mutations reduce IFT140 interaction with the IFT-A complex in a domain-specific manner as quantified by AP-MS; 10 of 23 tested missense mutations significantly reduced IFT140-IFT-A complex formation. IFT140 KO abolishes cilia, but individual missense mutations show only mild cilia assembly defects, indicating the IFT-A system tolerates partial reduction in IFT140-complex interaction.","method":"Affinity purification coupled with mass spectrometry (AP-MS) of 23 missense mutant IFT140 proteins; IFT140 KO ciliogenesis assay; cilia assembly phenotyping for 4 selected mutations","journal":"Molecular & cellular proteomics : MCP","confidence":"High","confidence_rationale":"Tier 1 / Moderate — quantitative AP-MS with mutagenesis panel plus functional ciliogenesis assay, multiple orthogonal methods in single rigorous study","pmids":["39880085"],"is_preprint":false},{"year":2025,"finding":"IFT140 is required for motile cilia assembly: conditional deletion of Ift140 in FOXJ1+ cells (motile cilia-forming cells) causes short motile cilia in efferent ductules and airways with reduced beat frequency, abnormal central apparatus ultrastructure, and accumulation of particles within cilia, despite normal dynein arm localization; males are infertile with short sperm flagella.","method":"FOXJ1-Cre conditional KO mice, cilia length measurement, ciliary beat frequency, transmission electron microscopy, immunofluorescence for ciliary proteins","journal":"Cellular and molecular life sciences : CMLS","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean conditional KO with multiple orthogonal readouts (ultrastructure, beat frequency, protein localization), establishes specific role in motile cilia distinct from primary cilia","pmids":["40348912"],"is_preprint":false},{"year":2025,"finding":"IFT140 loss in zebrafish causes not only cilia defects but also non-ciliary phenotypes including disrupted cell polarity and aberrant cytoplasmic microtubule stabilization in kidney epithelial cells; inhibition of mTOR or ULK1 reversed both cilia-related and non-cilia-related abnormalities in ift140-deficient fish.","method":"Zebrafish ift140 mutants and MMEJ-based crispants, immunofluorescence for cell polarity and microtubule markers, genetic/pharmacological modifier screen with mTOR and ULK1 inhibitors","journal":"Journal of the American Society of Nephrology : JASN","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo genetic model with multiple cellular phenotype readouts and pharmacological rescue, single lab","pmids":["40924493"],"is_preprint":false},{"year":2025,"finding":"A novel conserved protein Pasovec (Psv) physically associates with IFT140 (a core IFT-A component) independently of Wg/Wnt-signaling activation; Psv contains a nuclear localization sequence required for its own nuclear localization and for nuclear translocation of β-catenin/Arm upon Wg/Wnt-signaling activation, placing IFT-A/IFT140 in the nuclear translocation step of canonical Wnt signaling.","method":"Co-immunoprecipitation (physical association of Psv with IFT140), Drosophila genetics (epistasis/mutant phenotypes resembling wg and arm mutants), NLS mutagenesis, subcellular localization assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus genetic epistasis and mutagenesis in Drosophila model, preprint not yet peer-reviewed","pmids":["bio_10.1101_2025.06.21.660855"],"is_preprint":true}],"current_model":"IFT140 is a core structural component of the intraflagellar transport complex A (IFT-A) that mediates retrograde ciliary trafficking; it is required for transit of cargo (including opsins and other membrane proteins) through the ciliary axoneme, for motile cilia assembly and beat function, for Hedgehog and Wnt/β-catenin signaling through primary cilia, and for spermiogenesis and sperm flagella formation, with specific ciliopathy-associated missense mutations reducing IFT140 integration into the IFT-A complex in a domain-specific manner while the system retains partial functional resilience."},"narrative":{"mechanistic_narrative":"IFT140 is a core component of intraflagellar transport complex A (IFT-A) that mediates retrograde protein trafficking within cilia, and its loss perturbs the ciliary localization of anterograde IFT machinery [PMID:22503633]. In photoreceptors it is required to move opsin through the connecting cilium; acute Ift140 deletion strands opsin in the inner-segment plasma membrane, a defect distinct from the Golgi-to-cilium-base role of IFT20 [PMID:24619649]. The retrograde nature of IFT140 function is evidenced by accumulation of the IFT-B component IFT88 at the ciliary tip when IFT140 is lost or carries pathogenic missense alleles [PMID:30479745], and by mislocalization of IFT-B components IFT27 and IFT88 during spermiogenesis [PMID:29236364]. Through primary cilia, IFT140 is required for Hedgehog signaling, with loss producing neural tube, skeletal, and somite patterning defects in mouse embryos and impaired odontoblast differentiation and reparative dentin formation [PMID:24009529, PMID:29195058]. Beyond primary cilia, IFT140 is required for motile cilia assembly and beat function, with FOXJ1+ conditional deletion yielding short cilia, reduced beat frequency, and abnormal central-apparatus ultrastructure [PMID:40348912], and is essential for spermiogenesis and sperm flagellum formation, localizing to the neck and mid-piece of human sperm [PMID:29236364, PMID:31397098]. IFT140 is delivered from the Golgi to cilia via the ARF-family GTPase ARL16, whose loss traps IFT140 at the Golgi [PMID:35196065]. Pathogenic missense mutations reduce IFT140 integration into the IFT-A complex in a domain-specific manner, yet individual mutations cause only mild ciliogenesis defects while IFT140 knockout abolishes cilia, indicating the IFT-A system tolerates partial loss of IFT140 incorporation [PMID:39880085]. Mutations in IFT140 cause ciliopathy phenotypes including syndromic and nonsyndromic retinitis pigmentosa, with mutant protein showing reduced basal-body localization [PMID:26968735, PMID:28724397].","teleology":[{"year":2012,"claim":"Established IFT140 as an IFT-A component required for retrograde ciliary transport by linking patient mutations to disrupted ciliary IFT distribution.","evidence":"Immunocytochemistry of IFT components in patient fibroblasts plus Sanger sequencing","pmids":["22503633"],"confidence":"Medium","gaps":["Did not define which cargoes depend on IFT140","No reconstitution of IFT-A complex architecture"]},{"year":2013,"claim":"Connected IFT140 to Hedgehog-dependent developmental patterning, showing its ciliary role is required for a specific signaling output.","evidence":"ENU mutant mouse embryo phenotyping with Hedgehog pathway analysis","pmids":["24009529"],"confidence":"Medium","gaps":["Molecular step in Hedgehog transduction affected not resolved","Single mutant allele"]},{"year":2014,"claim":"Defined a specific cargo (opsin) and positioned IFT140 in the axonemal transit step, distinct from Golgi-to-base transport mediated by IFT20.","evidence":"Acute conditional Ift140 knockout mouse with immunofluorescence and epistatic comparison to Ift20 knockout","pmids":["24619649"],"confidence":"High","gaps":["Mechanism of opsin recognition by IFT-A not shown","Restricted to photoreceptor system"]},{"year":2016,"claim":"Showed that both nonsyndromic retinitis pigmentosa and syndromic IFT140 missense mutations impair basal-body localization, providing a shared cellular mechanism for allelic disease.","evidence":"Transient transfection of hTERT-RPE1 cells with mutant vs wild-type IFT140 and basal-body co-localization imaging","pmids":["26968735"],"confidence":"Medium","gaps":["Overexpression in transient assay may not reflect endogenous behavior","No quantitative link to IFT-A assembly"]},{"year":2017,"claim":"Extended IFT140's Hedgehog role to odontoblast differentiation and dentin repair, and validated a splicing/missense allele as loss-of-function in vivo.","evidence":"Osx-Cre conditional knockout mice with SHH readouts and tooth-drilling model; patient RT-PCR splicing analysis with zebrafish complementation","pmids":["29195058","28724397"],"confidence":"Medium","gaps":["Tissue-specific dependence on cilia not generalized","Splicing vs missense contribution to phenotype not separated"]},{"year":2018,"claim":"Demonstrated retrograde defect directly via IFT88 ciliary-tip accumulation and used isogenic rescue to assign causality to a specific missense allele, and established IFT140's role in spermiogenesis.","evidence":"Patient urine renal epithelial cells and CRISPR KO cells with mutant/WT rescue; spermatocyte/spermatid-specific conditional KO mice with EM, IFT localization, and fertility assays","pmids":["30479745","29236364"],"confidence":"High","gaps":["Why IFT-B components mislocalize without expression change not mechanistically resolved","Substrate selectivity of IFT-A in sperm undefined"]},{"year":2019,"claim":"Localized IFT140 to the neck and mid-piece of human sperm and tied biallelic variants to male infertility with structural sperm defects.","evidence":"Immunofluorescence and TEM of patient sperm with exome sequencing and family segregation","pmids":["31397098"],"confidence":"Medium","gaps":["Single case","Causal mechanism of structural defects not dissected"]},{"year":2022,"claim":"Identified ARL16 as a GTPase regulating a selective Golgi-to-cilia export route for IFT140, explaining how IFT140 reaches the cilium.","evidence":"ARL16 knockout MEFs with IFT140 vs other-IFT-protein Golgi localization imaging","pmids":["35196065"],"confidence":"Medium","gaps":["Direct ARL16-IFT140 interaction not shown","Vesicular carrier identity undefined"]},{"year":2025,"claim":"Quantified, domain-specifically, how missense mutations reduce IFT140 incorporation into IFT-A and revealed functional resilience to partial loss; separately established a dedicated requirement in motile cilia.","evidence":"AP-MS panel of 23 missense mutants with ciliogenesis assays; FOXJ1-Cre conditional KO mice with beat-frequency and ultrastructure analysis","pmids":["39880085","40348912"],"confidence":"High","gaps":["Structural basis for domain-specific assembly loss not solved","How partial complex reduction is buffered not mechanistically defined"]},{"year":2025,"claim":"Uncovered non-ciliary roles in cell polarity and microtubule stabilization rescuable by mTOR/ULK1 inhibition, and a candidate physical partner (Psv) linking IFT-A to Wnt/β-catenin nuclear translocation.","evidence":"Zebrafish ift140 mutants/crispants with polarity and microtubule imaging and pharmacological modifiers; Drosophila Co-IP, NLS mutagenesis, and genetic epistasis (preprint)","pmids":["40924493","bio_10.1101_2025.06.21.660855"],"confidence":"Medium","gaps":["Whether non-ciliary phenotypes are independent of cilia loss unresolved","Psv-IFT140 interaction is a single Co-IP in Drosophila pending peer review","Human relevance of Wnt nuclear translocation role untested"]},{"year":null,"claim":"How IFT140 within IFT-A selects and hands off specific membrane and signaling cargoes, and the structural rules governing mutation-driven complex disassembly, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No high-resolution structure of mutant IFT-A assemblies in the corpus","Cargo-recognition mechanism undefined","Mechanistic basis of functional resilience to partial IFT140 loss unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[1,3,4]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,10]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1,4,11]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[5]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[7]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,6]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[1,4]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[11]}],"complexes":["IFT-A"],"partners":["IFT88","IFT27","IFT20","ARL16","INPP5E"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96RY7","full_name":"Intraflagellar transport protein 140 homolog","aliases":["WD and tetratricopeptide repeats protein 2"],"length_aa":1462,"mass_kda":165.2,"function":"Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs) (PubMed:20889716, PubMed:22503633). Plays a pivotal role in proper development and function of ciliated cells through its role in ciliogenesis and/or cilium maintenance (PubMed:22503633). Required for the development and maintenance of the outer segments of rod and cone photoreceptor cells. Plays a role in maintenance and the delivery of opsin to the outer segment of photoreceptor cells (By similarity)","subcellular_location":"Cytoplasm, cytoskeleton, cilium basal body; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cell projection, cilium","url":"https://www.uniprot.org/uniprotkb/Q96RY7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/IFT140","classification":"Not Classified","n_dependent_lines":11,"n_total_lines":1208,"dependency_fraction":0.009105960264900662},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/IFT140","total_profiled":1310},"omim":[{"mim_id":"621180","title":"CRANIOECTODERMAL DYSPLASIA 5; CED5","url":"https://www.omim.org/entry/621180"},{"mim_id":"621164","title":"POLYCYSTIC KIDNEY DISEASE 9, SUSCEPTIBILITY TO; PKD9","url":"https://www.omim.org/entry/621164"},{"mim_id":"617781","title":"RETINITIS PIGMENTOSA 80; RP80","url":"https://www.omim.org/entry/617781"},{"mim_id":"614620","title":"INTRAFLAGELLAR TRANSPORT 140; IFT140","url":"https://www.omim.org/entry/614620"},{"mim_id":"608671","title":"DAZ-INTERACTING ZINC FINGER PROTEIN 1; DZIP1","url":"https://www.omim.org/entry/608671"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Basal body","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Mitochondria","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/IFT140"},"hgnc":{"alias_symbol":["gs114","KIAA0590"],"prev_symbol":["WDTC2"]},"alphafold":{"accession":"Q96RY7","domains":[{"cath_id":"-","chopping":"801-871","consensus_level":"medium","plddt":82.149,"start":801,"end":871},{"cath_id":"-","chopping":"872-942","consensus_level":"medium","plddt":88.4313,"start":872,"end":942},{"cath_id":"4.10.810","chopping":"762-796","consensus_level":"medium","plddt":76.9554,"start":762,"end":796},{"cath_id":"1.25.40","chopping":"1047-1115","consensus_level":"medium","plddt":77.7523,"start":1047,"end":1115},{"cath_id":"1.25.40","chopping":"1340-1428","consensus_level":"medium","plddt":80.3445,"start":1340,"end":1428}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96RY7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96RY7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96RY7-F1-predicted_aligned_error_v6.png","plddt_mean":80.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=IFT140","jax_strain_url":"https://www.jax.org/strain/search?query=IFT140"},"sequence":{"accession":"Q96RY7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96RY7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96RY7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96RY7"}},"corpus_meta":[{"pmid":"22503633","id":"PMC_22503633","title":"Mainzer-Saldino 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Report.","date":"2024","source":"Case reports in nephrology and dialysis","url":"https://pubmed.ncbi.nlm.nih.gov/39015124","citation_count":4,"is_preprint":false},{"pmid":"39594267","id":"PMC_39594267","title":"Compound Heterozygous Variants in the IFT140 Gene Associated with Skeletal Ciliopathies.","date":"2024","source":"Diagnostics (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/39594267","citation_count":3,"is_preprint":false},{"pmid":"38465144","id":"PMC_38465144","title":"IFT140 Mutation and End-Stage Renal Disease in Mainzer-Saldino Syndrome: A Case Report.","date":"2024","source":"Cureus","url":"https://pubmed.ncbi.nlm.nih.gov/38465144","citation_count":3,"is_preprint":false},{"pmid":"40348912","id":"PMC_40348912","title":"Role of intraflagellar transport protein IFT140 in the formation and function of motile cilia in mammals.","date":"2025","source":"Cellular and molecular life sciences : 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Cases report and review of literature.","date":"2025","source":"Ophthalmic genetics","url":"https://pubmed.ncbi.nlm.nih.gov/39927556","citation_count":0,"is_preprint":false},{"pmid":"39803421","id":"PMC_39803421","title":"The ift140 -Deficient Zebrafish: A Model for Renal Cystogenesis and an F0-Based Screen to Identify Genetic Modifiers of Kidney Cysts.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39803421","citation_count":0,"is_preprint":false},{"pmid":"42021201","id":"PMC_42021201","title":"A novel mutation of IFT140 in a preschool child with Mainzer-Saldino syndrome accompanied by rare tumor blastic plasmacytoid dendritic cell neoplasm: a case report.","date":"2026","source":"BMC pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/42021201","citation_count":0,"is_preprint":false},{"pmid":"41994676","id":"PMC_41994676","title":"Clinical and Genetic Characterization of a Patient With SEC63-Related Autosomal Dominant Polycystic Liver Disease and an IFT140 Pathogenic Variant Associated With Polycystic Kidney Disease.","date":"2026","source":"Cureus","url":"https://pubmed.ncbi.nlm.nih.gov/41994676","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.21.660855","title":"A novel conserved protein associates with the IFT-A complex to mediate nuclear translocation of β-catenin in Wg/Wnt-signaling","date":"2025-06-23","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.21.660855","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.02.631132","title":"The  <i>ift140</i>  -Deficient Zebrafish: A Model for Renal Cystogenesis and an F0-Based Screen to Identify Genetic Modifiers of Kidney Cysts","date":"2025-01-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.02.631132","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":24835,"output_tokens":3590,"usd":0.064177,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11118,"output_tokens":3593,"usd":0.072707,"stage2_stop_reason":"end_turn"},"total_usd":0.136884,"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\": 2012,\n      \"finding\": \"IFT140 is a component of intraflagellar transport complex A (IFT-A) required for retrograde protein transport in ciliated cells; loss of IFT140 function alters ciliary abundance and localization of anterograde IFT components in patient fibroblasts.\",\n      \"method\": \"Patient fibroblast analysis (immunocytochemistry of IFT components), Sanger sequencing\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cellular phenotyping in patient-derived fibroblasts with IFT localization readout, single lab, consistent with broader ciliopathy literature\",\n      \"pmids\": [\"22503633\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"IFT140 (IFT-A complex) is required for opsin transport through the connecting cilium of photoreceptors: acute deletion of Ift140 causes opsin to accumulate in the plasma membrane of inner segments (not at the Golgi), distinguishing its role from IFT20 which mediates Golgi-to-cilium base transport.\",\n      \"method\": \"Conditional/acute knockout mouse model, immunofluorescence, epistasis comparison with Ift20 knockout\",\n      \"journal\": \"Cytoskeleton (Hoboken, N.J.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean conditional KO with specific subcellular phenotypic readout and epistatic comparison to a second IFT component in the same study, defining distinct pathway positions\",\n      \"pmids\": [\"24619649\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"IFT140 is required for Hedgehog signaling downstream of primary cilia; Ift140 ENU mutant mouse embryos exhibit exencephaly, spina bifida, digit anomalies, and somite patterning defects attributable to altered Hedgehog signaling.\",\n      \"method\": \"ENU mutagenesis mouse model, embryo phenotyping, Hedgehog pathway analysis\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo loss-of-function model with defined Hedgehog signaling readout, single lab\",\n      \"pmids\": [\"24009529\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"IFT140 is essential for male fertility and spermiogenesis: spermatocyte/spermatid-specific Ift140 knockout in mice produces severe sperm morphological defects (amorphous heads, short/bent flagella, swollen tail tips), and alters the localization (but not expression levels) of IFT-B components IFT27 and IFT88.\",\n      \"method\": \"Conditional knockout mice (spermatocyte/spermatid-specific), immunofluorescence localization of IFT components, electron microscopy, sperm motility/count assays\",\n      \"journal\": \"Cytoskeleton (Hoboken, N.J.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean conditional KO with multiple orthogonal readouts (morphology, IFT component localization, fertility), single lab but rigorous\",\n      \"pmids\": [\"29236364\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"IFT140 loss-of-function causes accumulation of IFT-B component IFT88 at the ciliary tip in patient-derived urine renal epithelial cells (41% of cells), indicating impaired retrograde IFT; a patient missense mutation (p.Tyr923Asp) introduced into CRISPR/Cas9-derived Ift140 KO cells caused significantly greater IFT88 tip accumulation than wild-type IFT140 rescue.\",\n      \"method\": \"Patient-derived urine renal epithelial cells, immunocytochemistry, CRISPR/Cas9 KO cells, rescue transfection with mutant vs. wild-type IFT140 constructs\",\n      \"journal\": \"Cilia\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — functional rescue experiment with mutagenesis in isogenic KO cells plus patient-derived cells, two orthogonal cellular systems, single lab\",\n      \"pmids\": [\"30479745\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Missense mutations in IFT140 associated with nonsyndromic retinitis pigmentosa cause significantly reduced localization of IFT140 protein to the basal body in hTERT-RPE1 cells compared to wild-type, a phenotype shared with syndromic mutations.\",\n      \"method\": \"Transient plasmid transfection of hTERT-RPE1 cells, immunofluorescence for basal body co-localization\",\n      \"journal\": \"Investigative ophthalmology & visual science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cell-based functional assay comparing mutant vs. wild-type localization, single lab, two orthogonal mutations tested\",\n      \"pmids\": [\"26968735\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"IFT140 is required for Sonic Hedgehog signaling in odontoblasts: conditional deletion of Ift140 in odontoblasts (Osx-Cre) causes loss of primary cilia, reduced SHH signaling molecules, impaired odontogenic differentiation in vitro, and defective reparative dentin formation in vivo.\",\n      \"method\": \"Conditional knockout mice (Osx-Cre), in vitro deletion of IFT140 in odontoblasts, SHH pathway analysis, tooth-drilling model for reparative dentin\",\n      \"journal\": \"Journal of dental research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with SHH pathway readout in both in vivo and in vitro systems, single lab\",\n      \"pmids\": [\"29195058\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"ARL16 (an ARF-family GTPase) regulates trafficking of IFT140 from the Golgi to cilia: deletion of ARL16 in mouse embryonic fibroblasts causes accumulation of IFT140 (and INPP5E) at the Golgi, while other IFT proteins are unaffected, suggesting a specific Golgi-to-cilia export pathway for IFT140.\",\n      \"method\": \"ARL16 knockout MEFs, immunofluorescence for IFT140 and other IFT components, Golgi localization assay\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with specific subcellular localization phenotype for IFT140 vs. other IFT proteins as internal controls, single lab\",\n      \"pmids\": [\"35196065\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Homozygous IFT140 mutation (c.634G>A; p.Gly212Arg) causes mis-splicing producing a majority transcript with premature termination codon; zebrafish in vivo complementation confirmed loss-of-function effect of the minority p.Gly212Arg missense allele.\",\n      \"method\": \"RT-PCR/sequencing from patient cells, zebrafish in vivo complementation assay\",\n      \"journal\": \"Human genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional validation combining patient cell splicing analysis and zebrafish complementation, single lab\",\n      \"pmids\": [\"28724397\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"IFT140 protein is normally present at the neck and mid-piece of human spermatozoa; compound heterozygous IFT140 variants (p.Asp613Asn and p.Ser1416Asn) cause absence of IFT140 from these regions and produce sperm with head, nuclear, and tail morphological abnormalities in a human infertility patient.\",\n      \"method\": \"Immunofluorescence of patient sperm, transmission electron microscopy, whole-exome sequencing with family segregation\",\n      \"journal\": \"Molecular genetics & genomic medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization of IFT140 in human sperm with TEM, single case/lab\",\n      \"pmids\": [\"31397098\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"IFT140 missense mutations reduce IFT140 interaction with the IFT-A complex in a domain-specific manner as quantified by AP-MS; 10 of 23 tested missense mutations significantly reduced IFT140-IFT-A complex formation. IFT140 KO abolishes cilia, but individual missense mutations show only mild cilia assembly defects, indicating the IFT-A system tolerates partial reduction in IFT140-complex interaction.\",\n      \"method\": \"Affinity purification coupled with mass spectrometry (AP-MS) of 23 missense mutant IFT140 proteins; IFT140 KO ciliogenesis assay; cilia assembly phenotyping for 4 selected mutations\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — quantitative AP-MS with mutagenesis panel plus functional ciliogenesis assay, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"39880085\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"IFT140 is required for motile cilia assembly: conditional deletion of Ift140 in FOXJ1+ cells (motile cilia-forming cells) causes short motile cilia in efferent ductules and airways with reduced beat frequency, abnormal central apparatus ultrastructure, and accumulation of particles within cilia, despite normal dynein arm localization; males are infertile with short sperm flagella.\",\n      \"method\": \"FOXJ1-Cre conditional KO mice, cilia length measurement, ciliary beat frequency, transmission electron microscopy, immunofluorescence for ciliary proteins\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean conditional KO with multiple orthogonal readouts (ultrastructure, beat frequency, protein localization), establishes specific role in motile cilia distinct from primary cilia\",\n      \"pmids\": [\"40348912\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"IFT140 loss in zebrafish causes not only cilia defects but also non-ciliary phenotypes including disrupted cell polarity and aberrant cytoplasmic microtubule stabilization in kidney epithelial cells; inhibition of mTOR or ULK1 reversed both cilia-related and non-cilia-related abnormalities in ift140-deficient fish.\",\n      \"method\": \"Zebrafish ift140 mutants and MMEJ-based crispants, immunofluorescence for cell polarity and microtubule markers, genetic/pharmacological modifier screen with mTOR and ULK1 inhibitors\",\n      \"journal\": \"Journal of the American Society of Nephrology : JASN\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo genetic model with multiple cellular phenotype readouts and pharmacological rescue, single lab\",\n      \"pmids\": [\"40924493\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A novel conserved protein Pasovec (Psv) physically associates with IFT140 (a core IFT-A component) independently of Wg/Wnt-signaling activation; Psv contains a nuclear localization sequence required for its own nuclear localization and for nuclear translocation of β-catenin/Arm upon Wg/Wnt-signaling activation, placing IFT-A/IFT140 in the nuclear translocation step of canonical Wnt signaling.\",\n      \"method\": \"Co-immunoprecipitation (physical association of Psv with IFT140), Drosophila genetics (epistasis/mutant phenotypes resembling wg and arm mutants), NLS mutagenesis, subcellular localization assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus genetic epistasis and mutagenesis in Drosophila model, preprint not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.06.21.660855\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"IFT140 is a core structural component of the intraflagellar transport complex A (IFT-A) that mediates retrograde ciliary trafficking; it is required for transit of cargo (including opsins and other membrane proteins) through the ciliary axoneme, for motile cilia assembly and beat function, for Hedgehog and Wnt/β-catenin signaling through primary cilia, and for spermiogenesis and sperm flagella formation, with specific ciliopathy-associated missense mutations reducing IFT140 integration into the IFT-A complex in a domain-specific manner while the system retains partial functional resilience.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"IFT140 is a core component of intraflagellar transport complex A (IFT-A) that mediates retrograde protein trafficking within cilia, and its loss perturbs the ciliary localization of anterograde IFT machinery [#0]. In photoreceptors it is required to move opsin through the connecting cilium; acute Ift140 deletion strands opsin in the inner-segment plasma membrane, a defect distinct from the Golgi-to-cilium-base role of IFT20 [#1]. The retrograde nature of IFT140 function is evidenced by accumulation of the IFT-B component IFT88 at the ciliary tip when IFT140 is lost or carries pathogenic missense alleles [#4], and by mislocalization of IFT-B components IFT27 and IFT88 during spermiogenesis [#3]. Through primary cilia, IFT140 is required for Hedgehog signaling, with loss producing neural tube, skeletal, and somite patterning defects in mouse embryos and impaired odontoblast differentiation and reparative dentin formation [#2, #6]. Beyond primary cilia, IFT140 is required for motile cilia assembly and beat function, with FOXJ1+ conditional deletion yielding short cilia, reduced beat frequency, and abnormal central-apparatus ultrastructure [#11], and is essential for spermiogenesis and sperm flagellum formation, localizing to the neck and mid-piece of human sperm [#3, #9]. IFT140 is delivered from the Golgi to cilia via the ARF-family GTPase ARL16, whose loss traps IFT140 at the Golgi [#7]. Pathogenic missense mutations reduce IFT140 integration into the IFT-A complex in a domain-specific manner, yet individual mutations cause only mild ciliogenesis defects while IFT140 knockout abolishes cilia, indicating the IFT-A system tolerates partial loss of IFT140 incorporation [#10]. Mutations in IFT140 cause ciliopathy phenotypes including syndromic and nonsyndromic retinitis pigmentosa, with mutant protein showing reduced basal-body localization [#5, #8].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established IFT140 as an IFT-A component required for retrograde ciliary transport by linking patient mutations to disrupted ciliary IFT distribution.\",\n      \"evidence\": \"Immunocytochemistry of IFT components in patient fibroblasts plus Sanger sequencing\",\n      \"pmids\": [\"22503633\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define which cargoes depend on IFT140\", \"No reconstitution of IFT-A complex architecture\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Connected IFT140 to Hedgehog-dependent developmental patterning, showing its ciliary role is required for a specific signaling output.\",\n      \"evidence\": \"ENU mutant mouse embryo phenotyping with Hedgehog pathway analysis\",\n      \"pmids\": [\"24009529\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular step in Hedgehog transduction affected not resolved\", \"Single mutant allele\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined a specific cargo (opsin) and positioned IFT140 in the axonemal transit step, distinct from Golgi-to-base transport mediated by IFT20.\",\n      \"evidence\": \"Acute conditional Ift140 knockout mouse with immunofluorescence and epistatic comparison to Ift20 knockout\",\n      \"pmids\": [\"24619649\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of opsin recognition by IFT-A not shown\", \"Restricted to photoreceptor system\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Showed that both nonsyndromic retinitis pigmentosa and syndromic IFT140 missense mutations impair basal-body localization, providing a shared cellular mechanism for allelic disease.\",\n      \"evidence\": \"Transient transfection of hTERT-RPE1 cells with mutant vs wild-type IFT140 and basal-body co-localization imaging\",\n      \"pmids\": [\"26968735\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Overexpression in transient assay may not reflect endogenous behavior\", \"No quantitative link to IFT-A assembly\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Extended IFT140's Hedgehog role to odontoblast differentiation and dentin repair, and validated a splicing/missense allele as loss-of-function in vivo.\",\n      \"evidence\": \"Osx-Cre conditional knockout mice with SHH readouts and tooth-drilling model; patient RT-PCR splicing analysis with zebrafish complementation\",\n      \"pmids\": [\"29195058\", \"28724397\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Tissue-specific dependence on cilia not generalized\", \"Splicing vs missense contribution to phenotype not separated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrated retrograde defect directly via IFT88 ciliary-tip accumulation and used isogenic rescue to assign causality to a specific missense allele, and established IFT140's role in spermiogenesis.\",\n      \"evidence\": \"Patient urine renal epithelial cells and CRISPR KO cells with mutant/WT rescue; spermatocyte/spermatid-specific conditional KO mice with EM, IFT localization, and fertility assays\",\n      \"pmids\": [\"30479745\", \"29236364\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why IFT-B components mislocalize without expression change not mechanistically resolved\", \"Substrate selectivity of IFT-A in sperm undefined\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Localized IFT140 to the neck and mid-piece of human sperm and tied biallelic variants to male infertility with structural sperm defects.\",\n      \"evidence\": \"Immunofluorescence and TEM of patient sperm with exome sequencing and family segregation\",\n      \"pmids\": [\"31397098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single case\", \"Causal mechanism of structural defects not dissected\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified ARL16 as a GTPase regulating a selective Golgi-to-cilia export route for IFT140, explaining how IFT140 reaches the cilium.\",\n      \"evidence\": \"ARL16 knockout MEFs with IFT140 vs other-IFT-protein Golgi localization imaging\",\n      \"pmids\": [\"35196065\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct ARL16-IFT140 interaction not shown\", \"Vesicular carrier identity undefined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Quantified, domain-specifically, how missense mutations reduce IFT140 incorporation into IFT-A and revealed functional resilience to partial loss; separately established a dedicated requirement in motile cilia.\",\n      \"evidence\": \"AP-MS panel of 23 missense mutants with ciliogenesis assays; FOXJ1-Cre conditional KO mice with beat-frequency and ultrastructure analysis\",\n      \"pmids\": [\"39880085\", \"40348912\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis for domain-specific assembly loss not solved\", \"How partial complex reduction is buffered not mechanistically defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Uncovered non-ciliary roles in cell polarity and microtubule stabilization rescuable by mTOR/ULK1 inhibition, and a candidate physical partner (Psv) linking IFT-A to Wnt/β-catenin nuclear translocation.\",\n      \"evidence\": \"Zebrafish ift140 mutants/crispants with polarity and microtubule imaging and pharmacological modifiers; Drosophila Co-IP, NLS mutagenesis, and genetic epistasis (preprint)\",\n      \"pmids\": [\"40924493\", \"bio_10.1101_2025.06.21.660855\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether non-ciliary phenotypes are independent of cilia loss unresolved\", \"Psv-IFT140 interaction is a single Co-IP in Drosophila pending peer review\", \"Human relevance of Wnt nuclear translocation role untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How IFT140 within IFT-A selects and hands off specific membrane and signaling cargoes, and the structural rules governing mutation-driven complex disassembly, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No high-resolution structure of mutant IFT-A assemblies in the corpus\", \"Cargo-recognition mechanism undefined\", \"Mechanistic basis of functional resilience to partial IFT140 loss unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [1, 3, 4]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 4, 11]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0009536\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 6]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"complexes\": [\"IFT-A\"],\n    \"partners\": [\"IFT88\", \"IFT27\", \"IFT20\", \"ARL16\", \"INPP5E\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}