{"gene":"DYNC2I2","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2007,"finding":"Chlamydomonas FAP133 (ortholog of WDR34/DYNC2I2) is a WD-repeat dynein intermediate chain that associates with the IFT dynein heavy chain DHC1b, the light intermediate chain D1bLIC, and the LC8 dynein light chain, forming part of the retrograde IFT dynein complex. FAP133 localizes to the peri-basal body region and in punctate structures along flagella. In the absence of DHC1b or D1bLIC, FAP133 fails to localize at the peri-basal body region and instead concentrates near the cell center, demonstrating its localization depends on the motor complex.","method":"Biochemical fractionation of flagellar matrix proteins, co-immunoprecipitation, immunofluorescence localization in IFT mutant strains","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-purification, localization experiments with functional consequence in multiple mutant backgrounds, foundational paper replicated by subsequent studies","pmids":["17895364"],"is_preprint":false},{"year":2013,"finding":"WDR34 (DYNC2I2) mutations cause Jeune asphyxiating thoracic dystrophy. WDR34 concentrates around centrioles and basal bodies in mammalian cells and also shows axonemal staining. WDR34 co-immunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, suggesting a potential link between cytoplasmic dynein-1 and IFT dynein-2 motors.","method":"Exome sequencing and targeted NGS for mutation identification; immunofluorescence for subcellular localization; co-immunoprecipitation for DYNLL1 interaction; 3D protein modeling","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct co-IP and localization experiments in mammalian cells, single lab, interaction with dynein-1 light chain based on single co-IP","pmids":["24183451"],"is_preprint":false},{"year":2014,"finding":"In Trypanosoma brucei, the DIC5 (FAP133/WDR34/DYNC2I2) ortholog is required for the localization of dynein heavy chains DHC2.1 and DHC2.2, and the light intermediate chain DLI1, to the base of the flagellum. In the absence of DIC5, these components fail to localize correctly, establishing DIC5 as essential for assembly of the IFT dynein complex at the flagellar base.","method":"RNAi knockdown of DIC5 in Trypanosoma brucei; immunofluorescence and western blot to assess localization of dynein complex components in knockdown cells","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with specific molecular phenotype (mislocalization of multiple dynein subunits), single organism/lab","pmids":["24989795"],"is_preprint":false},{"year":2022,"finding":"Disease-associated WDR34 (DYNC2I2) mutations in Jeune syndrome, short-rib polydactyly syndrome, and asphyxiating thoracic dysplasia lead to diverse impacts including altered dynein-2 complex assembly, defects in axoneme initiation and extension, mislocalization of IFT complex-B proteins, disruption of transition zone integrity, and impaired Hedgehog signalling. Different mutations produce distinct phenotypic spectra, revealing that WDR34 is required for multiple aspects of dynein-2 function and ciliary transport.","method":"Stable expression of WDR34 patient mutations in WDR34-knockout cells; quantitative proteomics; immunofluorescence for IFT-B localization and transition zone markers; Hedgehog signaling reporter assays","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — knockout complementation with patient alleles, quantitative proteomics, multiple orthogonal functional readouts in a single rigorous study","pmids":["36268591"],"is_preprint":false}],"current_model":"DYNC2I2 (WDR34) encodes a WD40-repeat dynein intermediate chain that is an integral subunit of the dynein-2 retrograde IFT motor complex, associating with the dynein heavy chain, light intermediate chain, and LC8 light chain; it is required for assembly and basal-body localization of the dynein-2 complex, for proper IFT-B protein distribution within cilia, transition zone integrity, axoneme extension, and Hedgehog signaling, with loss-of-function mutations causing skeletal ciliopathies including Jeune asphyxiating thoracic dystrophy."},"narrative":{"mechanistic_narrative":"DYNC2I2 (WDR34) encodes a WD40-repeat dynein intermediate chain that is an integral subunit of the dynein-2 retrograde intraflagellar transport (IFT) motor, where it associates with the IFT dynein heavy chain, the light intermediate chain, and the LC8 dynein light chain [PMID:17895364]. It concentrates around centrioles and basal bodies and shows axonemal staining, and its peri-basal-body localization depends on the intact motor complex, since loss of the heavy chain or light intermediate chain redistributes it away from the basal-body region [PMID:17895364, PMID:24183451]. Reciprocally, DYNC2I2 is itself required to assemble the dynein-2 complex at the ciliary base, organizing the recruitment of multiple dynein subunits there [PMID:24989795]. Through this assembly role, DYNC2I2 supports axoneme initiation and extension, proper distribution of IFT complex-B proteins within cilia, transition zone integrity, and Hedgehog signaling, and patient mutations that disrupt these functions cause skeletal ciliopathies including Jeune asphyxiating thoracic dystrophy and short-rib polydactyly syndrome [PMID:24183451, PMID:36268591].","teleology":[{"year":2007,"claim":"Established that the WDR34 ortholog is a bona fide intermediate chain of the retrograde IFT dynein motor rather than a free-standing protein, by defining its physical partners and showing its localization depends on the motor complex.","evidence":"Flagellar matrix fractionation, co-immunoprecipitation, and immunofluorescence in Chlamydomonas IFT dynein mutants","pmids":["17895364"],"confidence":"High","gaps":["Stoichiometry and structural arrangement within the dynein-2 complex not resolved","Direct binding interfaces between FAP133 and each subunit not mapped","Findings in alga; mammalian complex composition not yet tested here"]},{"year":2013,"claim":"Linked WDR34 to human disease and placed the mammalian protein at centrioles/basal bodies, while raising a possible bridge between cytoplasmic dynein-1 and IFT dynein-2 via a shared light chain.","evidence":"Exome/targeted sequencing of patients, immunofluorescence localization, and in vitro co-IP with DYNLL1 in mammalian cells","pmids":["24183451"],"confidence":"Medium","gaps":["DYNLL1 interaction rests on a single in vitro co-IP without reciprocal or functional validation","Functional significance of a dynein-1/dynein-2 link not established","Mutation-to-phenotype mechanism not yet defined"]},{"year":2014,"claim":"Demonstrated that WDR34 is causally required for assembling the IFT dynein complex at the flagellar base, by showing its loss mislocalizes the heavy chains and light intermediate chain.","evidence":"RNAi knockdown of the DIC5 ortholog in Trypanosoma brucei with immunofluorescence and western blot readouts of dynein subunit localization","pmids":["24989795"],"confidence":"Medium","gaps":["Single organism and lab","Whether the assembly role is direct or via complex stabilization unresolved","No biochemical reconstitution of the assembly step"]},{"year":2022,"claim":"Connected specific patient mutations to defined molecular defects, showing WDR34 is required for multiple aspects of dynein-2 function and that distinct alleles produce distinct phenotypic outcomes.","evidence":"Patient-allele complementation in WDR34-knockout cells with quantitative proteomics, IFT-B and transition-zone immunofluorescence, and Hedgehog reporter assays","pmids":["36268591"],"confidence":"High","gaps":["Mechanistic basis for allele-specific phenotypic differences not fully resolved","How transition zone integrity is mechanistically maintained by dynein-2 not defined","Structural consequences of individual mutations on complex assembly not directly visualized"]},{"year":null,"claim":"How the dynein-2 complex is assembled at the basal body at the molecular level and whether the dynein-1/dynein-2 link via a shared light chain is functionally meaningful remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of WDR34 within the assembled dynein-2 motor","Functional role of the DYNLL1 interaction untested in vivo","Mechanism coupling dynein-2 to transition zone integrity unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]},{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1,3]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,3]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[1,3]}],"complexes":["dynein-2 / IFT retrograde dynein complex"],"partners":["DYNC2H1","DYNLL1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96EX3","full_name":"Cytoplasmic dynein 2 intermediate chain 2","aliases":["Dynein 2 intermediate chain 2","WD repeat-containing protein 34"],"length_aa":536,"mass_kda":57.8,"function":"Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the intraflagellar transport (IFT) system (PubMed:25205765, PubMed:29742051). DYNC2I2 plays a major role in retrograde ciliary protein trafficking and in ciliogenesis (PubMed:29742051, PubMed:30320547, PubMed:30649997). Required also to maintain a functional transition zone (PubMed:30320547) Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Inhibits the MAP3K7-induced NF-kappa-B activation pathway. Inhibits MAP3K7 phosphorylation at 'Thr-184' and 'Thr-187' upon Il-1 beta stimulation","subcellular_location":"Cytoplasm; Cytoplasm, cytoskeleton, cilium basal body; Cytoplasm, cytoskeleton, cilium axoneme; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cell projection, cilium; Cell projection, filopodium","url":"https://www.uniprot.org/uniprotkb/Q96EX3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DYNC2I2","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DYNC2LI1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DYNC2I2","total_profiled":1310},"omim":[{"mim_id":"615633","title":"SHORT-RIB THORACIC DYSPLASIA 11 WITH OR WITHOUT POLYDACTYLY; SRTD11","url":"https://www.omim.org/entry/615633"},{"mim_id":"613363","title":"DYNEIN, CYTOPLASMIC 2, INTERMEDIATE CHAIN 2; DYNC2I2","url":"https://www.omim.org/entry/613363"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Centrosome","reliability":"Supported"},{"location":"Basal body","reliability":"Supported"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Nuclear bodies","reliability":"Additional"},{"location":"Primary cilium","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DYNC2I2"},"hgnc":{"alias_symbol":["DIC5","MGC20486","bA216B9.3","FAP133","CFAP133"],"prev_symbol":["WDR34"]},"alphafold":{"accession":"Q96EX3","domains":[{"cath_id":"2.130.10.10","chopping":"423-536","consensus_level":"medium","plddt":93.4741,"start":423,"end":536}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96EX3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96EX3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96EX3-F1-predicted_aligned_error_v6.png","plddt_mean":82.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DYNC2I2","jax_strain_url":"https://www.jax.org/strain/search?query=DYNC2I2"},"sequence":{"accession":"Q96EX3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96EX3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96EX3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96EX3"}},"corpus_meta":[{"pmid":"24183451","id":"PMC_24183451","title":"Mutations in the gene encoding IFT dynein complex component WDR34 cause Jeune asphyxiating thoracic dystrophy.","date":"2013","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24183451","citation_count":93,"is_preprint":false},{"pmid":"17895364","id":"PMC_17895364","title":"Chlamydomonas FAP133 is a dynein intermediate chain associated with the retrograde intraflagellar transport motor.","date":"2007","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/17895364","citation_count":82,"is_preprint":false},{"pmid":"9365836","id":"PMC_9365836","title":"dic(5;17): a recurring abnormality in malignant myeloid disorders associated with mutations of TP53.","date":"1997","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/9365836","citation_count":52,"is_preprint":false},{"pmid":"23864713","id":"PMC_23864713","title":"WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia.","date":"2013","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/23864713","citation_count":43,"is_preprint":false},{"pmid":"24989795","id":"PMC_24989795","title":"The intraflagellar transport dynein complex of trypanosomes is made of a heterodimer of dynein heavy chains and of light and intermediate chains of distinct functions.","date":"2014","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/24989795","citation_count":31,"is_preprint":false},{"pmid":"20637434","id":"PMC_20637434","title":"Malignant granular cell tumor: case report with a novel karyotype and review of the literature.","date":"2009","source":"Annals of diagnostic pathology","url":"https://pubmed.ncbi.nlm.nih.gov/20637434","citation_count":26,"is_preprint":false},{"pmid":"18792983","id":"PMC_18792983","title":"Further evidence for a relationship between the 5p15 chromosome region and the oculoauriculovertebral anomaly.","date":"2008","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/18792983","citation_count":26,"is_preprint":false},{"pmid":"7832190","id":"PMC_7832190","title":"Acute promyelocytic leukaemia (M3): relapse with acute myeloblastic leukaemia (M2) and dic(5;17) (q11;p11).","date":"1995","source":"American journal of hematology","url":"https://pubmed.ncbi.nlm.nih.gov/7832190","citation_count":24,"is_preprint":false},{"pmid":"8721684","id":"PMC_8721684","title":"Loss of the chromosomal region 5q11-q31 in the myeloid cell line HL-60: characterization by comparative genomic hybridization and fluorescence in situ hybridization.","date":"1996","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/8721684","citation_count":18,"is_preprint":false},{"pmid":"2162731","id":"PMC_2162731","title":"A cytogenetic study of male breast cancer.","date":"1990","source":"Cancer genetics and cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/2162731","citation_count":18,"is_preprint":false},{"pmid":"8143281","id":"PMC_8143281","title":"Cytogenetic triclonality in acute myeloid leukemia: a morphologic, immunologic and in situ hybridization study.","date":"1994","source":"Cancer genetics and cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/8143281","citation_count":15,"is_preprint":false},{"pmid":"11063806","id":"PMC_11063806","title":"Karyotypic findings in two cases of male breast cancer.","date":"2000","source":"Cancer genetics and cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/11063806","citation_count":14,"is_preprint":false},{"pmid":"36268591","id":"PMC_36268591","title":"Disease-associated mutations in WDR34 lead to diverse impacts on the assembly and function of dynein-2.","date":"2022","source":"Journal of cell 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presentation of a rare cytogenetic phenomenon.","date":"2023","source":"Clinical case reports","url":"https://pubmed.ncbi.nlm.nih.gov/37529133","citation_count":1,"is_preprint":false},{"pmid":"41503593","id":"PMC_41503593","title":"A Rare Case of Prenatal Short-Rib Thoracic Dysplasia 11 Subtype With Compound Heterozygous Variants in the DYNC2I2 Gene: Presenting Polydactyly and Shortened Limbs.","date":"2026","source":"Clinical case reports","url":"https://pubmed.ncbi.nlm.nih.gov/41503593","citation_count":0,"is_preprint":false},{"pmid":"42098777","id":"PMC_42098777","title":"3D-printed dictamni-calcium silicate scaffolds modulate the osteoimmune microenvironment and enhance macrophage-derived exosomal miR-21 signaling in vascularized bone regeneration.","date":"2026","source":"Journal of nanobiotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/42098777","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11425,"output_tokens":1341,"usd":0.027195,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7950,"output_tokens":2093,"usd":0.046038,"stage2_stop_reason":"end_turn"},"total_usd":0.073233,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"Chlamydomonas FAP133 (ortholog of WDR34/DYNC2I2) is a WD-repeat dynein intermediate chain that associates with the IFT dynein heavy chain DHC1b, the light intermediate chain D1bLIC, and the LC8 dynein light chain, forming part of the retrograde IFT dynein complex. FAP133 localizes to the peri-basal body region and in punctate structures along flagella. In the absence of DHC1b or D1bLIC, FAP133 fails to localize at the peri-basal body region and instead concentrates near the cell center, demonstrating its localization depends on the motor complex.\",\n      \"method\": \"Biochemical fractionation of flagellar matrix proteins, co-immunoprecipitation, immunofluorescence localization in IFT mutant strains\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-purification, localization experiments with functional consequence in multiple mutant backgrounds, foundational paper replicated by subsequent studies\",\n      \"pmids\": [\"17895364\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"WDR34 (DYNC2I2) mutations cause Jeune asphyxiating thoracic dystrophy. WDR34 concentrates around centrioles and basal bodies in mammalian cells and also shows axonemal staining. WDR34 co-immunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, suggesting a potential link between cytoplasmic dynein-1 and IFT dynein-2 motors.\",\n      \"method\": \"Exome sequencing and targeted NGS for mutation identification; immunofluorescence for subcellular localization; co-immunoprecipitation for DYNLL1 interaction; 3D protein modeling\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct co-IP and localization experiments in mammalian cells, single lab, interaction with dynein-1 light chain based on single co-IP\",\n      \"pmids\": [\"24183451\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In Trypanosoma brucei, the DIC5 (FAP133/WDR34/DYNC2I2) ortholog is required for the localization of dynein heavy chains DHC2.1 and DHC2.2, and the light intermediate chain DLI1, to the base of the flagellum. In the absence of DIC5, these components fail to localize correctly, establishing DIC5 as essential for assembly of the IFT dynein complex at the flagellar base.\",\n      \"method\": \"RNAi knockdown of DIC5 in Trypanosoma brucei; immunofluorescence and western blot to assess localization of dynein complex components in knockdown cells\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with specific molecular phenotype (mislocalization of multiple dynein subunits), single organism/lab\",\n      \"pmids\": [\"24989795\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Disease-associated WDR34 (DYNC2I2) mutations in Jeune syndrome, short-rib polydactyly syndrome, and asphyxiating thoracic dysplasia lead to diverse impacts including altered dynein-2 complex assembly, defects in axoneme initiation and extension, mislocalization of IFT complex-B proteins, disruption of transition zone integrity, and impaired Hedgehog signalling. Different mutations produce distinct phenotypic spectra, revealing that WDR34 is required for multiple aspects of dynein-2 function and ciliary transport.\",\n      \"method\": \"Stable expression of WDR34 patient mutations in WDR34-knockout cells; quantitative proteomics; immunofluorescence for IFT-B localization and transition zone markers; Hedgehog signaling reporter assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — knockout complementation with patient alleles, quantitative proteomics, multiple orthogonal functional readouts in a single rigorous study\",\n      \"pmids\": [\"36268591\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DYNC2I2 (WDR34) encodes a WD40-repeat dynein intermediate chain that is an integral subunit of the dynein-2 retrograde IFT motor complex, associating with the dynein heavy chain, light intermediate chain, and LC8 light chain; it is required for assembly and basal-body localization of the dynein-2 complex, for proper IFT-B protein distribution within cilia, transition zone integrity, axoneme extension, and Hedgehog signaling, with loss-of-function mutations causing skeletal ciliopathies including Jeune asphyxiating thoracic dystrophy.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DYNC2I2 (WDR34) encodes a WD40-repeat dynein intermediate chain that is an integral subunit of the dynein-2 retrograde intraflagellar transport (IFT) motor, where it associates with the IFT dynein heavy chain, the light intermediate chain, and the LC8 dynein light chain [#0]. It concentrates around centrioles and basal bodies and shows axonemal staining, and its peri-basal-body localization depends on the intact motor complex, since loss of the heavy chain or light intermediate chain redistributes it away from the basal-body region [#0, #1]. Reciprocally, DYNC2I2 is itself required to assemble the dynein-2 complex at the ciliary base, organizing the recruitment of multiple dynein subunits there [#2]. Through this assembly role, DYNC2I2 supports axoneme initiation and extension, proper distribution of IFT complex-B proteins within cilia, transition zone integrity, and Hedgehog signaling, and patient mutations that disrupt these functions cause skeletal ciliopathies including Jeune asphyxiating thoracic dystrophy and short-rib polydactyly syndrome [#1, #3].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established that the WDR34 ortholog is a bona fide intermediate chain of the retrograde IFT dynein motor rather than a free-standing protein, by defining its physical partners and showing its localization depends on the motor complex.\",\n      \"evidence\": \"Flagellar matrix fractionation, co-immunoprecipitation, and immunofluorescence in Chlamydomonas IFT dynein mutants\",\n      \"pmids\": [\"17895364\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Stoichiometry and structural arrangement within the dynein-2 complex not resolved\",\n        \"Direct binding interfaces between FAP133 and each subunit not mapped\",\n        \"Findings in alga; mammalian complex composition not yet tested here\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Linked WDR34 to human disease and placed the mammalian protein at centrioles/basal bodies, while raising a possible bridge between cytoplasmic dynein-1 and IFT dynein-2 via a shared light chain.\",\n      \"evidence\": \"Exome/targeted sequencing of patients, immunofluorescence localization, and in vitro co-IP with DYNLL1 in mammalian cells\",\n      \"pmids\": [\"24183451\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"DYNLL1 interaction rests on a single in vitro co-IP without reciprocal or functional validation\",\n        \"Functional significance of a dynein-1/dynein-2 link not established\",\n        \"Mutation-to-phenotype mechanism not yet defined\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrated that WDR34 is causally required for assembling the IFT dynein complex at the flagellar base, by showing its loss mislocalizes the heavy chains and light intermediate chain.\",\n      \"evidence\": \"RNAi knockdown of the DIC5 ortholog in Trypanosoma brucei with immunofluorescence and western blot readouts of dynein subunit localization\",\n      \"pmids\": [\"24989795\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single organism and lab\",\n        \"Whether the assembly role is direct or via complex stabilization unresolved\",\n        \"No biochemical reconstitution of the assembly step\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connected specific patient mutations to defined molecular defects, showing WDR34 is required for multiple aspects of dynein-2 function and that distinct alleles produce distinct phenotypic outcomes.\",\n      \"evidence\": \"Patient-allele complementation in WDR34-knockout cells with quantitative proteomics, IFT-B and transition-zone immunofluorescence, and Hedgehog reporter assays\",\n      \"pmids\": [\"36268591\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanistic basis for allele-specific phenotypic differences not fully resolved\",\n        \"How transition zone integrity is mechanistically maintained by dynein-2 not defined\",\n        \"Structural consequences of individual mutations on complex assembly not directly visualized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the dynein-2 complex is assembled at the basal body at the molecular level and whether the dynein-1/dynein-2 link via a shared light chain is functionally meaningful remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of WDR34 within the assembled dynein-2 motor\",\n        \"Functional role of the DYNLL1 interaction untested in vivo\",\n        \"Mechanism coupling dynein-2 to transition zone integrity unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"complexes\": [\"dynein-2 / IFT retrograde dynein complex\"],\n    \"partners\": [\"DYNC2H1\", \"DYNLL1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}