{"gene":"MKKS","run_date":"2026-04-28T18:30:28","timeline":{"discoveries":[{"year":2005,"finding":"MKKS/BBS6 is a divergent Group II chaperonin-like protein that does not oligomerize (unlike canonical chaperonins) and localizes predominantly to the pericentriolar material (PCM) surrounding centrioles; during interphase it is confined to the lateral surfaces of the PCM, but during mitosis it relocalizes throughout the PCM and to the intercellular bridge. Its predicted substrate-binding apical domain is sufficient for centrosomal association. Patient-derived mutations in this domain cause mislocalization. RNAi silencing of BBS6 leads to multinucleate, multicentrosomal cells with cytokinesis defects.","method":"Subcellular fractionation, live-cell imaging, RNAi knockdown, domain deletion/mutagenesis analysis, patient mutation functional testing","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (localization, RNAi phenotype, domain mapping, patient mutations) in a single rigorous study","pmids":["15731008"],"is_preprint":false},{"year":2007,"finding":"Disease-causing MKKS mutants are rapidly degraded via the ubiquitin-proteasome pathway in a manner dependent on CHIP (HSC70-interacting protein), a chaperone-dependent ubiquitin ligase. Wild-type MKKS shuttles dynamically between the centrosome and cytosol, whereas rapidly degraded mutants fail to localize to the centrosome. CHIP and partner chaperones HSP70/HSC70 and HSP90 preferentially recognize MKKS mutants, and CHIP knockdown by RNAi moderately inhibits mutant degradation. Proteasome inhibition causes MKKS mutants to form insoluble structures at the centrosome.","method":"Live-cell imaging (centrosome shuttling), co-immunoprecipitation, RNAi knockdown of CHIP, proteasome inhibition assays, ubiquitination assays","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (Co-IP, live imaging, RNAi, proteasome inhibition) establishing mechanism of mutant degradation","pmids":["18094050"],"is_preprint":false},{"year":2012,"finding":"The domain deleted in the CEP290rd16 allele directly interacts with MKKS; MKKS mutations identified in BBS patients disrupt this interaction. Combined subminimal knockdown of mkks and cep290 in zebrafish produced sensory defects, while combining Cep290rd16 and Mkks knockout alleles in mice paradoxically improved ciliogenesis and sensory function compared with either mutant alone, indicating that altered association of CEP290 and MKKS affects integrity of multiprotein complexes at the cilia transition zone and basal body.","method":"Co-immunoprecipitation (direct protein-protein interaction), zebrafish morpholino double knockdown epistasis, mouse double-mutant genetic epistasis, ciliogenesis assays","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 1–2 — reciprocal Co-IP plus genetic epistasis in two model organisms with functional readouts","pmids":["22446187"],"is_preprint":false},{"year":2017,"finding":"BBS6 is actively transported between the cytoplasm and nucleus; the McKusick-Kaufman syndrome allele (BBS6-H84Y;A242S) maintains cilia function but is defective in nuclear-cytoplasmic transport. BBS6 interacts with the SWI/SNF chromatin remodeling protein SMARCC1 (Smarcc1a in zebrafish), modulates its subcellular localization, and produces similar transcriptional changes as smarcc1a manipulation. This identifies a cilia-independent nuclear function of BBS6 underlying congenital heart defects.","method":"Nuclear-cytoplasmic fractionation, inducible transgenic zebrafish BBS6 pulldown, protein-protein interaction studies, transcriptional profiling, cilia functional assays","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (fractionation, Co-IP/pulldown, transcriptomics, functional cilia assays) in a single study establishing a new non-cilia mechanism","pmids":["28753627"],"is_preprint":false},{"year":2005,"finding":"Mkks knockout mice exhibit retinal degeneration via apoptosis, failure of spermatozoa flagella formation, elevated blood pressure, hyperphagia-driven obesity, and olfactory/social deficits, phenocopying other BBS mouse models (Bbs2−/− and Bbs4−/−), establishing that complete loss of Mkks function underlies the BBS phenotype.","method":"Knockout mouse model, histology, retinal apoptosis assay, blood pressure measurement, behavioral testing","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 — clean knockout model with multiple defined phenotypic readouts, phenotype confirmed across BBS model comparisons","pmids":["15772095"],"is_preprint":false},{"year":2000,"finding":"Loss-of-function mutations (frameshift, nonsense, missense) in the MKKS gene, which encodes a chaperonin-like protein, cause Bardet-Biedl syndrome; the data suggest that inability to fold a range of target proteins underlies the clinical manifestations.","method":"Positional cloning, mutation screening in patient pedigrees, linkage analysis","journal":"Nature genetics","confidence":"Medium","confidence_rationale":"Tier 2 — two independent groups identified causative mutations, but direct biochemical folding assay not performed; inference of chaperonin folding function is based on sequence homology","pmids":["10973251","10973238"],"is_preprint":false},{"year":2016,"finding":"The H395R mutation in MKKS/BBS6 decreases the interaction of MKKS/BBS6 with BBS12, as demonstrated by protein-protein interaction studies in HEK-293T and ARPE-19 cells, linking disrupted BBS6–BBS12 interaction to a limited RP/polydactyly phenotype.","method":"Co-immunoprecipitation / protein-protein interaction studies in HEK-293T and ARPE-19 cells","journal":"Molecular vision","confidence":"Medium","confidence_rationale":"Tier 3 — single lab, single method (Co-IP) with functional phenotypic correlation","pmids":["26900326"],"is_preprint":false},{"year":2003,"finding":"A BBS6 missense mutation introduced in mammalian cells causes dramatic mislocalization of the protein compared with wild-type, and heterozygous BBS6 mutations can act as a third allele to potentiate disease severity in patients already carrying two recessive mutations at another BBS locus, demonstrating oligogenic/epistatic interaction.","method":"Mammalian cell transfection with patient-derived missense allele (mislocalization assay), clinical genetic epistasis analysis in patient families","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2–3 — cell-based localization experiment plus genetic epistasis, but localization validation is single-lab","pmids":["12837689"],"is_preprint":false},{"year":2022,"finding":"BBS6 chaperonin-like protein is required for initial BBSome assembly in vitro; BBS6 together with BBS10 and BBS12 (all Group II chaperonin-like proteins) function as a chaperonin co-complex necessary for BBSome formation.","method":"In vitro BBSome assembly assay (reconstitution)","journal":"American journal of medical genetics. Part C, Seminars in medical genetics","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro reconstitution described, but this is a review citing prior work; primary experimental source not independently verifiable from this abstract alone","pmids":["35373910"],"is_preprint":false},{"year":2024,"finding":"BBS6 functions as part of a TRiC/CCT-BBS chaperonin co-complex required for the localization of the adhesion GPCR ADGRV1 to the base of primary cilia; knockdown of BBS6 results in reduced ciliated cells and shorter primary cilia, and in the absence of this co-complex ADGRV1 is depleted from the ciliary base and degraded via the proteasome.","method":"RNAi knockdown, ciliogenesis quantification, proteasome inhibition assay, large-scale protein interaction network (ciliary proteome)","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 — preprint, single lab, RNAi phenotype without direct biochemical reconstitution of complex","pmids":["bio_10.1101_2024.10.31.621306"],"is_preprint":true}],"current_model":"MKKS/BBS6 is a divergent Group II chaperonin-like protein that localizes to the pericentriolar material and dynamically shuttles between the centrosome and cytosol; it is required for cytokinesis and ciliogenesis, interacts with CEP290 at the cilia transition zone/basal body, interacts with BBS12 and is required for BBSome assembly, and undergoes CHIP-mediated ubiquitin-proteasome degradation when disease-causing mutations cause misfolding and centrosomal mislocalization; additionally, BBS6 shuttles between cytoplasm and nucleus where it binds the chromatin remodeler SMARCC1 to modulate gene expression, a cilia-independent function underlying congenital heart defects in McKusick-Kaufman syndrome."},"narrative":{"teleology":[{"year":2000,"claim":"Positional cloning established that loss-of-function mutations in MKKS, encoding a chaperonin-like protein, are causative for Bardet-Biedl syndrome, providing the first gene-disease link and suggesting a protein-folding role.","evidence":"Linkage analysis and mutation screening in BBS patient pedigrees by two independent groups","pmids":["10973251","10973238"],"confidence":"Medium","gaps":["Chaperonin folding function inferred from sequence homology only, not demonstrated biochemically","No target substrates identified","Subcellular localization unknown"]},{"year":2003,"claim":"Disease-associated BBS6 missense mutations cause dramatic protein mislocalization in mammalian cells, and heterozygous BBS6 alleles can modify disease severity at other BBS loci, establishing an oligogenic/epistatic mode of action.","evidence":"Mammalian cell transfection with patient allele and clinical genetic epistasis analysis","pmids":["12837689"],"confidence":"Medium","gaps":["Mislocalization validated only in a single lab","Mechanism of epistatic interaction with other BBS loci undefined","Correct localization site not yet identified"]},{"year":2005,"claim":"MKKS was shown to localize to the pericentriolar material via its apical domain, to redistribute during mitosis, and to be essential for cytokinesis — resolving where the protein acts and providing the first cellular function beyond sequence-based predictions.","evidence":"Subcellular fractionation, live-cell imaging, RNAi knockdown, domain deletion and patient mutation mapping","pmids":["15731008"],"confidence":"High","gaps":["No direct chaperonin activity demonstrated","Substrates at the centrosome unidentified","Mechanism linking centrosomal function to BBS disease phenotypes unclear"]},{"year":2005,"claim":"Mkks knockout mice phenocopied other BBS models — retinal degeneration, flagellar defects, obesity, and sensory deficits — confirming that complete MKKS loss underlies the full BBS phenotype in vivo.","evidence":"Knockout mouse with histology, retinal apoptosis, blood pressure, and behavioral assays","pmids":["15772095"],"confidence":"High","gaps":["Molecular mechanism underlying each organ-specific phenotype not resolved","Whether phenotypes are cilia-dependent or -independent not distinguished"]},{"year":2007,"claim":"The fate of disease-causing MKKS mutants was explained: CHIP-dependent ubiquitin-proteasome degradation removes misfolded mutants, preventing their centrosomal accumulation, while wild-type MKKS dynamically shuttles between the centrosome and cytosol.","evidence":"Co-immunoprecipitation with CHIP/HSP70/HSP90, RNAi of CHIP, proteasome inhibition, live-cell FRAP-style shuttling analysis","pmids":["18094050"],"confidence":"High","gaps":["Whether degradation of mutant protein is the primary pathogenic mechanism or loss of centrosomal function is not distinguished","No structural basis for mutant misfolding"]},{"year":2012,"claim":"MKKS was found to physically interact with CEP290 at the cilia transition zone/basal body, and genetic epistasis in zebrafish and mice showed their association governs multiprotein complex integrity and ciliogenesis — identifying a key protein partner and localizing MKKS function to the transition zone.","evidence":"Reciprocal Co-IP, zebrafish morpholino double knockdown, mouse double-mutant epistasis with ciliogenesis readouts","pmids":["22446187"],"confidence":"High","gaps":["Stoichiometry and composition of the transition zone complex not defined","Whether MKKS chaperonin activity is required for CEP290 folding or assembly is unknown"]},{"year":2016,"claim":"The H395R mutation was shown to specifically disrupt MKKS–BBS12 interaction, linking reduced binding between these two chaperonin-like proteins to a limited retinitis pigmentosa/polydactyly phenotype and refining genotype-phenotype correlations.","evidence":"Co-immunoprecipitation in HEK-293T and ARPE-19 cells","pmids":["26900326"],"confidence":"Medium","gaps":["Single method (Co-IP) without reciprocal validation or in vivo confirmation","Functional consequence of reduced BBS6–BBS12 binding on BBSome assembly not tested"]},{"year":2017,"claim":"A cilia-independent nuclear function was discovered: BBS6 shuttles into the nucleus, binds the SWI/SNF subunit SMARCC1, modulates its localization and downstream transcription, and the McKusick-Kaufman syndrome allele H84Y;A242S retains cilia function but is defective in nuclear transport — decoupling ciliopathy from cardiac defects.","evidence":"Nuclear-cytoplasmic fractionation, inducible transgenic zebrafish pulldown, transcriptional profiling, cilia functional assays","pmids":["28753627"],"confidence":"High","gaps":["Direct target genes regulated by BBS6–SMARCC1 interaction not fully defined","Whether nuclear BBS6 acts as a chaperone for SMARCC1 or as a transcriptional cofactor is unresolved","Relevance to non-cardiac BBS phenotypes unknown"]},{"year":2022,"claim":"In vitro reconstitution confirmed that BBS6, together with BBS10 and BBS12, forms a chaperonin co-complex required for initial BBSome assembly — establishing the biochemical function long predicted from sequence homology.","evidence":"In vitro BBSome assembly reconstitution assay (described in review of prior work)","pmids":["35373910"],"confidence":"Medium","gaps":["Primary experimental data cited indirectly via review","Individual contributions of BBS6 vs BBS10/BBS12 within the co-complex not delineated","No structural model of the co-complex"]},{"year":null,"claim":"Key unresolved questions include the structural basis for BBS6 chaperonin co-complex function, the full spectrum of substrates folded or assembled by BBS6, and how its dual centrosomal/nuclear roles are coordinately regulated.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of BBS6 alone or in the BBS chaperonin co-complex","Endogenous substrates beyond BBSome components and CEP290 not identified","Regulatory signals governing nuclear vs centrosomal partitioning unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[0,5,8]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[3]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,2,4]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[1,8]}],"complexes":["BBS chaperonin co-complex (BBS6/BBS10/BBS12)"],"partners":["CEP290","BBS12","SMARCC1","STUB1","HSPA8","HSP90AA1"],"other_free_text":[]},"mechanistic_narrative":"MKKS (BBS6) is a divergent Group II chaperonin-like protein that functions at the nexus of ciliogenesis, cytokinesis, and chromatin remodeling. It localizes to the pericentriolar material and dynamically shuttles between the centrosome and cytosol; its apical domain mediates centrosomal targeting, and RNAi depletion causes cytokinesis failure and ciliogenesis defects [PMID:15731008]. MKKS forms a chaperonin co-complex with BBS10 and BBS12 that is required for BBSome assembly, and it physically interacts with CEP290 at the cilia transition zone/basal body to maintain multiprotein complex integrity [PMID:22446187, PMID:35373910]. Disease-causing mutations lead to CHIP-dependent proteasomal degradation and centrosomal mislocalization [PMID:18094050]; independently, MKKS shuttles into the nucleus where it binds the SWI/SNF subunit SMARCC1 to regulate gene expression, a cilia-independent function linked to congenital heart defects in McKusick-Kaufman syndrome [PMID:28753627]. Loss-of-function mutations in MKKS cause Bardet-Biedl syndrome, with knockout mice exhibiting retinal degeneration, flagellar defects, obesity, and sensory deficits [PMID:10973251, PMID:15772095]."},"prefetch_data":{"uniprot":{"accession":"Q9NPJ1","full_name":"Molecular chaperone MKKS","aliases":["Bardet-Biedl syndrome 6 protein","McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin"],"length_aa":570,"mass_kda":62.3,"function":"Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis (PubMed:20080638). Plays a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). May play a role in protein processing in limb, cardiac and reproductive system development. May play a role in cytokinesis (PubMed:28753627)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytosol; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9NPJ1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MKKS","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MKKS","total_profiled":1310},"omim":[{"mim_id":"617088","title":"SHORT-RIB THORACIC DYSPLASIA 15 WITH POLYDACTYLY; SRTD15","url":"https://www.omim.org/entry/617088"},{"mim_id":"615983","title":"BARDET-BIEDL SYNDROME 5; BBS5","url":"https://www.omim.org/entry/615983"},{"mim_id":"615586","title":"CENTROSOMAL PROTEIN, 19-KD; CEP19","url":"https://www.omim.org/entry/615586"},{"mim_id":"610162","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 28B; CCDC28B","url":"https://www.omim.org/entry/610162"},{"mim_id":"610148","title":"BBS10 GENE; BBS10","url":"https://www.omim.org/entry/610148"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MKKS"},"hgnc":{"alias_symbol":[],"prev_symbol":["BBS6"]},"alphafold":{"accession":"Q9NPJ1","domains":[{"cath_id":"1.10.560.10","chopping":"12-139_409-568","consensus_level":"medium","plddt":88.325,"start":12,"end":568},{"cath_id":"-","chopping":"144-209_379-404","consensus_level":"high","plddt":92.7108,"start":144,"end":404},{"cath_id":"3.50.7.10","chopping":"219-368","consensus_level":"high","plddt":88.6172,"start":219,"end":368}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NPJ1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NPJ1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NPJ1-F1-predicted_aligned_error_v6.png","plddt_mean":88.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MKKS","jax_strain_url":"https://www.jax.org/strain/search?query=MKKS"},"sequence":{"accession":"Q9NPJ1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NPJ1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NPJ1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NPJ1"}},"corpus_meta":[{"pmid":"10973251","id":"PMC_10973251","title":"Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.","date":"2000","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/10973251","citation_count":241,"is_preprint":false},{"pmid":"10973238","id":"PMC_10973238","title":"Mutations in MKKS cause Bardet-Biedl syndrome.","date":"2000","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/10973238","citation_count":209,"is_preprint":false},{"pmid":"15772095","id":"PMC_15772095","title":"Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome.","date":"2005","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/15772095","citation_count":161,"is_preprint":false},{"pmid":"12837689","id":"PMC_12837689","title":"Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus.","date":"2003","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/12837689","citation_count":153,"is_preprint":false},{"pmid":"15731008","id":"PMC_15731008","title":"MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity disorder Bardet-Biedl syndrome, is a novel centrosomal component required for cytokinesis.","date":"2005","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/15731008","citation_count":137,"is_preprint":false},{"pmid":"22446187","id":"PMC_22446187","title":"Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.","date":"2012","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/22446187","citation_count":67,"is_preprint":false},{"pmid":"11179009","id":"PMC_11179009","title":"Genetic and mutational analyses of a large multiethnic Bardet-Biedl cohort reveal a minor involvement of BBS6 and delineate the critical intervals of other loci.","date":"2001","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/11179009","citation_count":60,"is_preprint":false},{"pmid":"12107442","id":"PMC_12107442","title":"Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients.","date":"2002","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/12107442","citation_count":49,"is_preprint":false},{"pmid":"20173330","id":"PMC_20173330","title":"LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins.","date":"2010","source":"Neuro-degenerative diseases","url":"https://pubmed.ncbi.nlm.nih.gov/20173330","citation_count":46,"is_preprint":false},{"pmid":"21044901","id":"PMC_21044901","title":"Molecular diagnosis reveals genetic heterogeneity for the overlapping MKKS and BBS phenotypes.","date":"2010","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21044901","citation_count":34,"is_preprint":false},{"pmid":"28753627","id":"PMC_28753627","title":"Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein.","date":"2017","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28753627","citation_count":28,"is_preprint":false},{"pmid":"31156213","id":"PMC_31156213","title":"Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages.","date":"2019","source":"Medical science monitor : international medical journal of experimental and clinical research","url":"https://pubmed.ncbi.nlm.nih.gov/31156213","citation_count":25,"is_preprint":false},{"pmid":"18094050","id":"PMC_18094050","title":"MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination.","date":"2007","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/18094050","citation_count":21,"is_preprint":false},{"pmid":"35373910","id":"PMC_35373910","title":"Bardet-Biedl syndrome: The pleiotropic role of the chaperonin-like BBS6, 10, and 12 proteins.","date":"2022","source":"American journal of medical genetics. 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Part A","url":"https://pubmed.ncbi.nlm.nih.gov/16104012","citation_count":12,"is_preprint":false},{"pmid":"30305582","id":"PMC_30305582","title":"Novel ASK1 Inhibitor AGI-1067 Attenuates AGE-Induced Fibrotic Response by Suppressing the MKKs/p38 MAPK Pathway in Human Coronary Arterial Smooth Muscle Cells.","date":"2018","source":"International heart journal","url":"https://pubmed.ncbi.nlm.nih.gov/30305582","citation_count":10,"is_preprint":false},{"pmid":"18813213","id":"PMC_18813213","title":"Association between BBS6/MKKS gene polymorphisms, obesity and metabolic syndrome in the Greek population.","date":"2008","source":"International journal of obesity (2005)","url":"https://pubmed.ncbi.nlm.nih.gov/18813213","citation_count":10,"is_preprint":false},{"pmid":"28694440","id":"PMC_28694440","title":"Phylogenomic analysis of MKKs and MAPKs from 16 legumes and detection of interacting pairs in chickpea divulge MAPK signalling modules.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28694440","citation_count":9,"is_preprint":false},{"pmid":"30633955","id":"PMC_30633955","title":"Two novel MKKs (MKK4 and MKK7) from Ctenopharyngodon idella are involved in the intestinal immune response to bacterial muramyl dipeptide challenge.","date":"2019","source":"Developmental and comparative immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30633955","citation_count":7,"is_preprint":false},{"pmid":"33520300","id":"PMC_33520300","title":"Novel Compound Heterozygous BBS2 and Homozygous MKKS Variants Detected in Chinese Families with Bardet-Biedl Syndrome.","date":"2021","source":"Journal of ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/33520300","citation_count":7,"is_preprint":false},{"pmid":"30186746","id":"PMC_30186746","title":"Novel ASK1 inhibitor AGI-1067 improves AGE-induced cardiac dysfunction by inhibiting MKKs/p38 MAPK and NF-κB apoptotic signaling.","date":"2018","source":"FEBS open bio","url":"https://pubmed.ncbi.nlm.nih.gov/30186746","citation_count":7,"is_preprint":false},{"pmid":"36498834","id":"PMC_36498834","title":"Behavioral Phenotyping of Bbs6 and Bbs8 Knockout Mice Reveals Major Alterations in Communication and Anxiety.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36498834","citation_count":6,"is_preprint":false},{"pmid":"35912300","id":"PMC_35912300","title":"Novel Mutations in the MKKS, BBS7, and ALMS1 Genes in Iranian Children with Clinically Suspected Bardet-Biedl Syndrome.","date":"2022","source":"Case reports in ophthalmological medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35912300","citation_count":6,"is_preprint":false},{"pmid":"33363891","id":"PMC_33363891","title":"Legg-Calvé-Perthes disease in a patient with Bardet-Biedl syndrome: A case report of a novel MKKS/BBS6 mutation.","date":"2020","source":"Clinical case reports","url":"https://pubmed.ncbi.nlm.nih.gov/33363891","citation_count":3,"is_preprint":false},{"pmid":"35810436","id":"PMC_35810436","title":"[Genetic analysis of novel MKKS variants in a Chinese patient with Bardet-Biedl syndrome].","date":"2022","source":"Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35810436","citation_count":2,"is_preprint":false},{"pmid":"31989739","id":"PMC_31989739","title":"Novel mutation in MKKS/BBS6 linked with arRP and polydactyly in a family of North Indian origin.","date":"2020","source":"Clinical & experimental ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/31989739","citation_count":1,"is_preprint":false},{"pmid":"41418239","id":"PMC_41418239","title":"Assessment of genetic variation(s) in BBS10, BBS6, and BBS12 in a family from Sindh, Pakistan diagnosed with Bardet-Biedl Syndrome.","date":"2025","source":"JPMA. The Journal of the Pakistan Medical Association","url":"https://pubmed.ncbi.nlm.nih.gov/41418239","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.16.682843","title":"Loss of ciliary proteins IFT20 and IFT88 results in defective phagocytosis and metabolism in the RPE","date":"2025-10-17","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.16.682843","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.31.621306","title":"The BBS/CCT chaperonin complex ensures the localization of the adhesion G protein-coupled receptor ADGRV1 to primary cilia","date":"2024-11-03","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.31.621306","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16121,"output_tokens":2702,"usd":0.044446},"stage2":{"model":"claude-opus-4-6","input_tokens":6030,"output_tokens":2546,"usd":0.1407},"total_usd":0.185146,"stage1_batch_id":"msgbatch_01Mgbec4vM6c9vXht7JVJzss","stage2_batch_id":"msgbatch_01JkuuH5RB2BdJNsgnhjbC6s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"MKKS/BBS6 is a divergent Group II chaperonin-like protein that does not oligomerize (unlike canonical chaperonins) and localizes predominantly to the pericentriolar material (PCM) surrounding centrioles; during interphase it is confined to the lateral surfaces of the PCM, but during mitosis it relocalizes throughout the PCM and to the intercellular bridge. Its predicted substrate-binding apical domain is sufficient for centrosomal association. Patient-derived mutations in this domain cause mislocalization. RNAi silencing of BBS6 leads to multinucleate, multicentrosomal cells with cytokinesis defects.\",\n      \"method\": \"Subcellular fractionation, live-cell imaging, RNAi knockdown, domain deletion/mutagenesis analysis, patient mutation functional testing\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (localization, RNAi phenotype, domain mapping, patient mutations) in a single rigorous study\",\n      \"pmids\": [\"15731008\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Disease-causing MKKS mutants are rapidly degraded via the ubiquitin-proteasome pathway in a manner dependent on CHIP (HSC70-interacting protein), a chaperone-dependent ubiquitin ligase. Wild-type MKKS shuttles dynamically between the centrosome and cytosol, whereas rapidly degraded mutants fail to localize to the centrosome. CHIP and partner chaperones HSP70/HSC70 and HSP90 preferentially recognize MKKS mutants, and CHIP knockdown by RNAi moderately inhibits mutant degradation. Proteasome inhibition causes MKKS mutants to form insoluble structures at the centrosome.\",\n      \"method\": \"Live-cell imaging (centrosome shuttling), co-immunoprecipitation, RNAi knockdown of CHIP, proteasome inhibition assays, ubiquitination assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (Co-IP, live imaging, RNAi, proteasome inhibition) establishing mechanism of mutant degradation\",\n      \"pmids\": [\"18094050\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The domain deleted in the CEP290rd16 allele directly interacts with MKKS; MKKS mutations identified in BBS patients disrupt this interaction. Combined subminimal knockdown of mkks and cep290 in zebrafish produced sensory defects, while combining Cep290rd16 and Mkks knockout alleles in mice paradoxically improved ciliogenesis and sensory function compared with either mutant alone, indicating that altered association of CEP290 and MKKS affects integrity of multiprotein complexes at the cilia transition zone and basal body.\",\n      \"method\": \"Co-immunoprecipitation (direct protein-protein interaction), zebrafish morpholino double knockdown epistasis, mouse double-mutant genetic epistasis, ciliogenesis assays\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reciprocal Co-IP plus genetic epistasis in two model organisms with functional readouts\",\n      \"pmids\": [\"22446187\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"BBS6 is actively transported between the cytoplasm and nucleus; the McKusick-Kaufman syndrome allele (BBS6-H84Y;A242S) maintains cilia function but is defective in nuclear-cytoplasmic transport. BBS6 interacts with the SWI/SNF chromatin remodeling protein SMARCC1 (Smarcc1a in zebrafish), modulates its subcellular localization, and produces similar transcriptional changes as smarcc1a manipulation. This identifies a cilia-independent nuclear function of BBS6 underlying congenital heart defects.\",\n      \"method\": \"Nuclear-cytoplasmic fractionation, inducible transgenic zebrafish BBS6 pulldown, protein-protein interaction studies, transcriptional profiling, cilia functional assays\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (fractionation, Co-IP/pulldown, transcriptomics, functional cilia assays) in a single study establishing a new non-cilia mechanism\",\n      \"pmids\": [\"28753627\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Mkks knockout mice exhibit retinal degeneration via apoptosis, failure of spermatozoa flagella formation, elevated blood pressure, hyperphagia-driven obesity, and olfactory/social deficits, phenocopying other BBS mouse models (Bbs2−/− and Bbs4−/−), establishing that complete loss of Mkks function underlies the BBS phenotype.\",\n      \"method\": \"Knockout mouse model, histology, retinal apoptosis assay, blood pressure measurement, behavioral testing\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean knockout model with multiple defined phenotypic readouts, phenotype confirmed across BBS model comparisons\",\n      \"pmids\": [\"15772095\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Loss-of-function mutations (frameshift, nonsense, missense) in the MKKS gene, which encodes a chaperonin-like protein, cause Bardet-Biedl syndrome; the data suggest that inability to fold a range of target proteins underlies the clinical manifestations.\",\n      \"method\": \"Positional cloning, mutation screening in patient pedigrees, linkage analysis\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — two independent groups identified causative mutations, but direct biochemical folding assay not performed; inference of chaperonin folding function is based on sequence homology\",\n      \"pmids\": [\"10973251\", \"10973238\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The H395R mutation in MKKS/BBS6 decreases the interaction of MKKS/BBS6 with BBS12, as demonstrated by protein-protein interaction studies in HEK-293T and ARPE-19 cells, linking disrupted BBS6–BBS12 interaction to a limited RP/polydactyly phenotype.\",\n      \"method\": \"Co-immunoprecipitation / protein-protein interaction studies in HEK-293T and ARPE-19 cells\",\n      \"journal\": \"Molecular vision\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single method (Co-IP) with functional phenotypic correlation\",\n      \"pmids\": [\"26900326\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"A BBS6 missense mutation introduced in mammalian cells causes dramatic mislocalization of the protein compared with wild-type, and heterozygous BBS6 mutations can act as a third allele to potentiate disease severity in patients already carrying two recessive mutations at another BBS locus, demonstrating oligogenic/epistatic interaction.\",\n      \"method\": \"Mammalian cell transfection with patient-derived missense allele (mislocalization assay), clinical genetic epistasis analysis in patient families\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — cell-based localization experiment plus genetic epistasis, but localization validation is single-lab\",\n      \"pmids\": [\"12837689\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"BBS6 chaperonin-like protein is required for initial BBSome assembly in vitro; BBS6 together with BBS10 and BBS12 (all Group II chaperonin-like proteins) function as a chaperonin co-complex necessary for BBSome formation.\",\n      \"method\": \"In vitro BBSome assembly assay (reconstitution)\",\n      \"journal\": \"American journal of medical genetics. Part C, Seminars in medical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution described, but this is a review citing prior work; primary experimental source not independently verifiable from this abstract alone\",\n      \"pmids\": [\"35373910\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"BBS6 functions as part of a TRiC/CCT-BBS chaperonin co-complex required for the localization of the adhesion GPCR ADGRV1 to the base of primary cilia; knockdown of BBS6 results in reduced ciliated cells and shorter primary cilia, and in the absence of this co-complex ADGRV1 is depleted from the ciliary base and degraded via the proteasome.\",\n      \"method\": \"RNAi knockdown, ciliogenesis quantification, proteasome inhibition assay, large-scale protein interaction network (ciliary proteome)\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — preprint, single lab, RNAi phenotype without direct biochemical reconstitution of complex\",\n      \"pmids\": [\"bio_10.1101_2024.10.31.621306\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"MKKS/BBS6 is a divergent Group II chaperonin-like protein that localizes to the pericentriolar material and dynamically shuttles between the centrosome and cytosol; it is required for cytokinesis and ciliogenesis, interacts with CEP290 at the cilia transition zone/basal body, interacts with BBS12 and is required for BBSome assembly, and undergoes CHIP-mediated ubiquitin-proteasome degradation when disease-causing mutations cause misfolding and centrosomal mislocalization; additionally, BBS6 shuttles between cytoplasm and nucleus where it binds the chromatin remodeler SMARCC1 to modulate gene expression, a cilia-independent function underlying congenital heart defects in McKusick-Kaufman syndrome.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MKKS (BBS6) is a divergent Group II chaperonin-like protein that functions at the nexus of ciliogenesis, cytokinesis, and chromatin remodeling. It localizes to the pericentriolar material and dynamically shuttles between the centrosome and cytosol; its apical domain mediates centrosomal targeting, and RNAi depletion causes cytokinesis failure and ciliogenesis defects [PMID:15731008]. MKKS forms a chaperonin co-complex with BBS10 and BBS12 that is required for BBSome assembly, and it physically interacts with CEP290 at the cilia transition zone/basal body to maintain multiprotein complex integrity [PMID:22446187, PMID:35373910]. Disease-causing mutations lead to CHIP-dependent proteasomal degradation and centrosomal mislocalization [PMID:18094050]; independently, MKKS shuttles into the nucleus where it binds the SWI/SNF subunit SMARCC1 to regulate gene expression, a cilia-independent function linked to congenital heart defects in McKusick-Kaufman syndrome [PMID:28753627]. Loss-of-function mutations in MKKS cause Bardet-Biedl syndrome, with knockout mice exhibiting retinal degeneration, flagellar defects, obesity, and sensory deficits [PMID:10973251, PMID:15772095].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Positional cloning established that loss-of-function mutations in MKKS, encoding a chaperonin-like protein, are causative for Bardet-Biedl syndrome, providing the first gene-disease link and suggesting a protein-folding role.\",\n      \"evidence\": \"Linkage analysis and mutation screening in BBS patient pedigrees by two independent groups\",\n      \"pmids\": [\"10973251\", \"10973238\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Chaperonin folding function inferred from sequence homology only, not demonstrated biochemically\", \"No target substrates identified\", \"Subcellular localization unknown\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Disease-associated BBS6 missense mutations cause dramatic protein mislocalization in mammalian cells, and heterozygous BBS6 alleles can modify disease severity at other BBS loci, establishing an oligogenic/epistatic mode of action.\",\n      \"evidence\": \"Mammalian cell transfection with patient allele and clinical genetic epistasis analysis\",\n      \"pmids\": [\"12837689\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mislocalization validated only in a single lab\", \"Mechanism of epistatic interaction with other BBS loci undefined\", \"Correct localization site not yet identified\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"MKKS was shown to localize to the pericentriolar material via its apical domain, to redistribute during mitosis, and to be essential for cytokinesis — resolving where the protein acts and providing the first cellular function beyond sequence-based predictions.\",\n      \"evidence\": \"Subcellular fractionation, live-cell imaging, RNAi knockdown, domain deletion and patient mutation mapping\",\n      \"pmids\": [\"15731008\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No direct chaperonin activity demonstrated\", \"Substrates at the centrosome unidentified\", \"Mechanism linking centrosomal function to BBS disease phenotypes unclear\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Mkks knockout mice phenocopied other BBS models — retinal degeneration, flagellar defects, obesity, and sensory deficits — confirming that complete MKKS loss underlies the full BBS phenotype in vivo.\",\n      \"evidence\": \"Knockout mouse with histology, retinal apoptosis, blood pressure, and behavioral assays\",\n      \"pmids\": [\"15772095\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism underlying each organ-specific phenotype not resolved\", \"Whether phenotypes are cilia-dependent or -independent not distinguished\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"The fate of disease-causing MKKS mutants was explained: CHIP-dependent ubiquitin-proteasome degradation removes misfolded mutants, preventing their centrosomal accumulation, while wild-type MKKS dynamically shuttles between the centrosome and cytosol.\",\n      \"evidence\": \"Co-immunoprecipitation with CHIP/HSP70/HSP90, RNAi of CHIP, proteasome inhibition, live-cell FRAP-style shuttling analysis\",\n      \"pmids\": [\"18094050\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether degradation of mutant protein is the primary pathogenic mechanism or loss of centrosomal function is not distinguished\", \"No structural basis for mutant misfolding\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"MKKS was found to physically interact with CEP290 at the cilia transition zone/basal body, and genetic epistasis in zebrafish and mice showed their association governs multiprotein complex integrity and ciliogenesis — identifying a key protein partner and localizing MKKS function to the transition zone.\",\n      \"evidence\": \"Reciprocal Co-IP, zebrafish morpholino double knockdown, mouse double-mutant epistasis with ciliogenesis readouts\",\n      \"pmids\": [\"22446187\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and composition of the transition zone complex not defined\", \"Whether MKKS chaperonin activity is required for CEP290 folding or assembly is unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The H395R mutation was shown to specifically disrupt MKKS–BBS12 interaction, linking reduced binding between these two chaperonin-like proteins to a limited retinitis pigmentosa/polydactyly phenotype and refining genotype-phenotype correlations.\",\n      \"evidence\": \"Co-immunoprecipitation in HEK-293T and ARPE-19 cells\",\n      \"pmids\": [\"26900326\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single method (Co-IP) without reciprocal validation or in vivo confirmation\", \"Functional consequence of reduced BBS6–BBS12 binding on BBSome assembly not tested\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"A cilia-independent nuclear function was discovered: BBS6 shuttles into the nucleus, binds the SWI/SNF subunit SMARCC1, modulates its localization and downstream transcription, and the McKusick-Kaufman syndrome allele H84Y;A242S retains cilia function but is defective in nuclear transport — decoupling ciliopathy from cardiac defects.\",\n      \"evidence\": \"Nuclear-cytoplasmic fractionation, inducible transgenic zebrafish pulldown, transcriptional profiling, cilia functional assays\",\n      \"pmids\": [\"28753627\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct target genes regulated by BBS6–SMARCC1 interaction not fully defined\", \"Whether nuclear BBS6 acts as a chaperone for SMARCC1 or as a transcriptional cofactor is unresolved\", \"Relevance to non-cardiac BBS phenotypes unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"In vitro reconstitution confirmed that BBS6, together with BBS10 and BBS12, forms a chaperonin co-complex required for initial BBSome assembly — establishing the biochemical function long predicted from sequence homology.\",\n      \"evidence\": \"In vitro BBSome assembly reconstitution assay (described in review of prior work)\",\n      \"pmids\": [\"35373910\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Primary experimental data cited indirectly via review\", \"Individual contributions of BBS6 vs BBS10/BBS12 within the co-complex not delineated\", \"No structural model of the co-complex\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis for BBS6 chaperonin co-complex function, the full spectrum of substrates folded or assembled by BBS6, and how its dual centrosomal/nuclear roles are coordinately regulated.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No high-resolution structure of BBS6 alone or in the BBS chaperonin co-complex\", \"Endogenous substrates beyond BBSome components and CEP290 not identified\", \"Regulatory signals governing nuclear vs centrosomal partitioning unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [0, 5, 8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 2, 4]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1, 8]}\n    ],\n    \"complexes\": [\n      \"BBS chaperonin co-complex (BBS6/BBS10/BBS12)\"\n    ],\n    \"partners\": [\n      \"CEP290\",\n      \"BBS12\",\n      \"SMARCC1\",\n      \"STUB1\",\n      \"HSPA8\",\n      \"HSP90AA1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}