{"gene":"MKKS","run_date":"2026-06-10T02:59:50","timeline":{"discoveries":[{"year":2005,"finding":"MKKS/BBS6 is a Group II chaperonin-like protein that does not oligomerize (unlike canonical chaperonins) and localizes predominantly within the pericentriolar material (PCM). During interphase it is confined to lateral surfaces of the PCM; 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 of BBS6. siRNA-mediated silencing of BBS6 causes cytokinesis defects resulting in multinucleate and multicentrosomal cells.","method":"Live-cell imaging, immunofluorescence/fractionation for localization; domain-deletion constructs to map centrosomal targeting; patient mutation functional assays; RNAi knockdown with cytokinesis phenotype readout; phylogenomic analysis of chaperonin evolution","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (localization, domain mapping, patient mutations, RNAi phenotype) in a single focused study; findings replicated conceptually by subsequent work","pmids":["15731008"],"is_preprint":false},{"year":2007,"finding":"Disease-causing mutant forms of MKKS are rapidly degraded via the ubiquitin-proteasome pathway in a manner dependent on the E3 ubiquitin ligase CHIP (a chaperone-dependent ubiquitin ligase). Wild-type MKKS shuttles between the centrosome and cytosol; rapidly degraded mutants fail to localize to the centrosome. Proteasome inhibition causes MKKS mutants to form insoluble structures at the centrosome. CHIP and partner chaperones HSP70/HSC70 and HSP90 preferentially recognize MKKS mutants, indicating abnormal conformation of disease mutants.","method":"Pulse-chase/protein stability assays; proteasome inhibitor experiments; co-immunoprecipitation of CHIP/HSP70/HSP90 with MKKS; live-cell imaging of centrosomal shuttling; RNAi knockdown of CHIP; immunofluorescence after proteasome inhibition","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, live-cell imaging, RNAi, and proteasome inhibitor experiments in a single lab with multiple orthogonal methods","pmids":["18094050"],"is_preprint":false},{"year":2012,"finding":"The domain deleted in the Cep290rd16 allele directly interacts with MKKS. BBS patient-derived MKKS mutations disrupt this CEP290-MKKS interaction. Combined subminimal knockdown of mkks and cep290 in zebrafish produces synergistic sensory defects. Paradoxically, combining Cep290rd16 and Mkks knockout alleles in mice improves ciliogenesis and sensory function compared with either mutant alone, suggesting that altered CEP290-MKKS association affects integrity of multiprotein complexes at the cilia transition zone and basal body.","method":"Co-immunoprecipitation (direct protein-protein interaction); zebrafish morpholino epistasis; mouse double-mutant genetic epistasis with ciliogenesis and sensory functional readouts","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct Co-IP interaction, patient mutation validation, zebrafish epistasis, and mouse double-mutant rescue all in one study","pmids":["22446187"],"is_preprint":false},{"year":2017,"finding":"BBS6 undergoes active nuclear-cytoplasmic transport. The McKusick-Kaufman syndrome allele BBS6-H84Y;A242S is defective in nuclear-cytoplasmic transport but maintains cilia function. BBS6 interacts with the SWI/SNF chromatin remodeling protein SMARCC1 (smarcc1a in zebrafish), and through this interaction modulates SMARCC1 subcellular localization. Transcriptional profiling shows similar changes following smarcc1a and bbs6 manipulation, placing BBS6 upstream of SMARCC1-dependent transcriptional regulation.","method":"Nuclear-cytoplasmic fractionation and transport assays; transgenic zebrafish with inducible bbs6 for pulldown/mass spectrometry identification of binding partners; co-immunoprecipitation of BBS6-SMARCC1; immunofluorescence of SMARCC1 localization upon BBS6 manipulation; transcriptional profiling","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (fractionation, pulldown/MS, Co-IP, localization, transcriptomics) in a single focused study","pmids":["28753627"],"is_preprint":false},{"year":2005,"finding":"Mkks knockout mice develop retinal degeneration (via apoptosis), failure of spermatozoa flagella formation, elevated blood pressure, obesity (associated with hyperphagia and decreased activity), and olfactory/social dominance deficits, but not polydactyly or vaginal abnormalities, indicating that complete loss of MKKS function causes BBS-like phenotype whereas MKS-specific alleles produce distinct outcomes.","method":"Mkks(-/-) mouse knockout with histological, physiological, and behavioral phenotyping","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean knockout mouse with multiple defined cellular and physiological phenotypes, replicated phenotype concept across BBS mouse models","pmids":["15772095"],"is_preprint":false},{"year":2003,"finding":"A BBS6 (putative chaperonin) missense mutation introduced in mammalian cells causes dramatic mislocalization of the BBS6 protein compared with wild-type, and heterozygous BBS6 mutations can act as epistatic modifiers potentiating a phenotype caused by two recessive mutations at an independent BBS locus (triallelic model).","method":"Transfection of wild-type vs. patient-derived missense mutant BBS6 in mammalian cells with immunofluorescence localization; genetic epistasis analysis in human pedigrees","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — cell-based mislocalization assay plus human pedigree genetic epistasis, single lab","pmids":["12837689"],"is_preprint":false},{"year":2016,"finding":"The MKKS/BBS6 H395R patient mutation decreases the interaction of MKKS/BBS6 with BBS12 in protein-protein interaction assays in HEK-293T and ARPE-19 cells, though to a lesser extent than other BBS6 mutations associated with syndromic retinitis pigmentosa, consistent with a milder phenotype.","method":"Co-immunoprecipitation / protein-protein interaction assays in two cell lines (HEK-293T and ARPE-19) comparing wild-type vs. H395R mutant MKKS/BBS6 interaction with BBS12","journal":"Molecular vision","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single-lab Co-IP in cell lines, single method, no in vitro reconstitution","pmids":["26900326"],"is_preprint":false},{"year":2022,"finding":"BBS6, together with TRiC/CCT chaperonins, forms a co-complex required for the localization of the adhesion GPCR ADGRV1 to primary cilia. Knockdown of BBS6 results in reduced ciliated cells and shorter primary cilia. In the absence of the TRiC/CCT-BBS chaperonin co-complex, ADGRV1 is depleted from the ciliary base and degraded via the proteasome.","method":"siRNA knockdown of BBS6 with ciliogenesis phenotype (reduced ciliated cells, shorter cilia); co-complex interaction identified by ciliary proteome interaction network; immunofluorescence of ADGRV1 localization upon BBS6 knockdown; proteasome inhibitor experiments","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — multiple methods (knockdown, localization, proteasome inhibitor) but preprint, single lab, not yet peer-reviewed","pmids":[],"is_preprint":true},{"year":2022,"finding":"Loss of Bbs6 in RPE-J cells showed no functionality phenotype for phagocytosis (negative finding: Bbs6 loss did not impair photoreceptor outer segment binding or phagocytosis in RPE cells, in contrast to loss of IFT20 or IFT88).","method":"Bbs6 depletion in RPE-J cells with phagocytosis assay (outer segment binding and internalization) and apical membrane morphology analysis","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single negative result in a preprint, single cell line, single lab","pmids":[],"is_preprint":true}],"current_model":"MKKS/BBS6 is a divergent Group II chaperonin-like protein that localizes to the pericentriolar material (PCM) via its apical domain, shuttles between the centrosome and cytosol, and is required for cytokinesis; disease-causing mutations misfold BBS6, leading to CHIP-mediated ubiquitin-proteasome degradation and failure of centrosomal localization; BBS6 also undergoes nuclear-cytoplasmic transport, interacts with the SWI/SNF subunit SMARCC1 to modulate its localization and transcriptional output (underlying congenital heart defects in McKusick-Kaufman syndrome), interacts with CEP290 at the ciliary transition zone/basal body to regulate ciliogenesis, and participates in a TRiC/CCT-BBS chaperonin co-complex required for ciliary targeting of client proteins such as ADGRV1."},"narrative":{"mechanistic_narrative":"MKKS/BBS6 is a divergent Group II chaperonin-like protein that operates at the centrosome and primary cilium to coordinate cell division and ciliogenesis [PMID:15731008]. Unlike canonical chaperonins it does not oligomerize; instead it localizes to the pericentriolar material via its predicted substrate-binding apical domain, shifting from the lateral PCM in interphase to the whole PCM and the intercellular bridge during mitosis, and its loss causes cytokinesis failure with multinucleate, multicentrosomal cells [PMID:15731008]. Wild-type BBS6 shuttles between the centrosome and cytosol, whereas disease-causing mutations misfold the protein so that it fails to reach the centrosome and is recognized by HSP70/HSC70 and HSP90 together with the chaperone-dependent E3 ligase CHIP, which targets the mutants for ubiquitin-proteasome degradation [PMID:18094050]. At the ciliary transition zone and basal body BBS6 directly binds CEP290, an interaction disrupted by BBS patient mutations and required for the integrity of multiprotein complexes that govern ciliogenesis and sensory function [PMID:22446187]. BBS6 also undergoes active nuclear-cytoplasmic transport and interacts with the SWI/SNF chromatin-remodeling subunit SMARCC1, controlling SMARCC1 localization and acting upstream of its transcriptional output; the McKusick-Kaufman syndrome allele BBS6-H84Y;A242S is selectively defective in this nuclear transport while retaining cilia function [PMID:28753627]. Consistent with these cellular roles, Mkks-null mice display a Bardet-Biedl-like phenotype including retinal degeneration, sperm flagellar failure, obesity, and sensory deficits [PMID:15772095]. BBS6 additionally engages other BBS chaperonin-family proteins, with patient mutations weakening its interaction with BBS12 [PMID:26900326].","teleology":[{"year":2003,"claim":"Established the first cellular consequence of disease-associated BBS6 mutations and a genetic role as an epistatic modifier, framing BBS6 as a misfolding-prone protein within an oligogenic disease architecture.","evidence":"Transfection of wild-type vs. patient missense BBS6 with immunofluorescence localization; epistasis analysis in human pedigrees","pmids":["12837689"],"confidence":"Medium","gaps":["Did not define the normal subcellular compartment of BBS6","No biochemical mechanism for mislocalization","Triallelic modifier effect from pedigrees only"]},{"year":2005,"claim":"Defined where BBS6 acts and what it does in the cell cycle, showing it is a non-oligomerizing chaperonin-like protein that targets the PCM via its apical domain and is required for cytokinesis.","evidence":"Live-cell imaging, fractionation, domain-deletion mapping, patient mutation assays, and RNAi cytokinesis readout","pmids":["15731008"],"confidence":"High","gaps":["No substrate of the apical domain identified","Mechanism linking centrosomal loss to cytokinesis failure unresolved","Whether chaperonin folding activity is exerted at all"]},{"year":2005,"claim":"Connected the molecular role to organismal physiology, showing complete loss of MKKS produces a BBS-like multisystem phenotype distinct from MKS-specific alleles.","evidence":"Mkks(-/-) knockout mouse with histological, physiological, and behavioral phenotyping","pmids":["15772095"],"confidence":"High","gaps":["Cellular mechanism behind each phenotype not dissected","Does not explain why MKS-specific alleles differ","No tissue-specific causal pathway"]},{"year":2007,"claim":"Explained why disease mutants fail functionally, showing they adopt abnormal conformations recognized by HSP70/HSP90-CHIP and are cleared by the proteasome before reaching the centrosome.","evidence":"Protein stability assays, proteasome inhibition, reciprocal Co-IP of CHIP/HSP70/HSP90, live-cell imaging, and CHIP RNAi","pmids":["18094050"],"confidence":"High","gaps":["Native folded structure of wild-type BBS6 not solved","Whether CHIP regulates wild-type turnover normally unclear","Centrosomal shuttling mechanism undefined"]},{"year":2012,"claim":"Placed BBS6 in a direct interaction with CEP290 at the transition zone, revealing that altered BBS6-CEP290 association reshapes the integrity of ciliary basal body complexes.","evidence":"Direct Co-IP, patient mutation validation, zebrafish morpholino epistasis, and mouse double-mutant genetic epistasis with ciliary readouts","pmids":["22446187"],"confidence":"High","gaps":["Mechanism of the paradoxical double-mutant rescue unexplained","Stoichiometry and architecture of the transition-zone complex unknown","How BBS6 stabilizes the complex not defined"]},{"year":2016,"claim":"Extended the misfolding model to BBS-complex assembly, showing a patient mutation weakens the BBS6-BBS12 interaction in proportion to phenotypic severity.","evidence":"Co-IP/protein interaction assays in HEK-293T and ARPE-19 cells comparing wild-type and H395R mutant","pmids":["26900326"],"confidence":"Medium","gaps":["No in vitro reconstitution of the interaction","Functional consequence of reduced BBS12 binding untested","Single method"]},{"year":2017,"claim":"Revealed a non-ciliary, nuclear role: BBS6 shuttles into the nucleus and partners with the SWI/SNF subunit SMARCC1 to control its localization and transcription, separating the transcriptional function (McKusick-Kaufman allele) from ciliary function.","evidence":"Nuclear-cytoplasmic fractionation/transport assays, inducible-bbs6 pulldown/MS, Co-IP, SMARCC1 localization imaging, and transcriptional profiling in zebrafish","pmids":["28753627"],"confidence":"High","gaps":["Direct chromatin targets downstream of BBS6-SMARCC1 not defined","Whether BBS6 acts as a chaperone for SMARCC1 unknown","Link to congenital heart defects mechanistic detail limited"]},{"year":2022,"claim":"Proposed a chaperonin co-complex mechanism, with BBS6 acting alongside TRiC/CCT to deliver client GPCR ADGRV1 to the cilium and protect it from proteasomal degradation.","evidence":"siRNA knockdown with ciliogenesis phenotype, ciliary proteome interaction network, ADGRV1 localization imaging, and proteasome inhibition (preprint)","pmids":[],"confidence":"Medium","gaps":["Preprint, single lab, not peer-reviewed","Direct chaperone activity on ADGRV1 not reconstituted","Generality of clients beyond ADGRV1 untested"]},{"year":null,"claim":"It remains unknown what endogenous substrates BBS6 folds and how its chaperonin-like apical domain, centrosomal, ciliary, and nuclear activities are mechanistically integrated within a single protein.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structure of wild-type BBS6 or defined folding cycle","No validated direct folding substrate","Coordination of centrosomal, transition-zone, and nuclear pools unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[0,7]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,3]}],"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":[2,7]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[3]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[2,7]},{"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":[1,7]}],"complexes":["TRiC/CCT-BBS chaperonin co-complex","BBSome-related BBS chaperonin module (BBS6-BBS12)"],"partners":["CEP290","SMARCC1","BBS12","STUB1","HSPA8","HSP90"],"other_free_text":[]}},"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 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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":"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":"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":"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":"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":8,"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":"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":16877,"output_tokens":2778,"usd":0.04615,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10084,"output_tokens":3492,"usd":0.06886,"stage2_stop_reason":"end_turn"},"total_usd":0.11501,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"MKKS/BBS6 is a Group II chaperonin-like protein that does not oligomerize (unlike canonical chaperonins) and localizes predominantly within the pericentriolar material (PCM). During interphase it is confined to lateral surfaces of the PCM; 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 of BBS6. siRNA-mediated silencing of BBS6 causes cytokinesis defects resulting in multinucleate and multicentrosomal cells.\",\n      \"method\": \"Live-cell imaging, immunofluorescence/fractionation for localization; domain-deletion constructs to map centrosomal targeting; patient mutation functional assays; RNAi knockdown with cytokinesis phenotype readout; phylogenomic analysis of chaperonin evolution\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (localization, domain mapping, patient mutations, RNAi phenotype) in a single focused study; findings replicated conceptually by subsequent work\",\n      \"pmids\": [\"15731008\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Disease-causing mutant forms of MKKS are rapidly degraded via the ubiquitin-proteasome pathway in a manner dependent on the E3 ubiquitin ligase CHIP (a chaperone-dependent ubiquitin ligase). Wild-type MKKS shuttles between the centrosome and cytosol; rapidly degraded mutants fail to localize to the centrosome. Proteasome inhibition causes MKKS mutants to form insoluble structures at the centrosome. CHIP and partner chaperones HSP70/HSC70 and HSP90 preferentially recognize MKKS mutants, indicating abnormal conformation of disease mutants.\",\n      \"method\": \"Pulse-chase/protein stability assays; proteasome inhibitor experiments; co-immunoprecipitation of CHIP/HSP70/HSP90 with MKKS; live-cell imaging of centrosomal shuttling; RNAi knockdown of CHIP; immunofluorescence after proteasome inhibition\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, live-cell imaging, RNAi, and proteasome inhibitor experiments in a single lab with multiple orthogonal methods\",\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. BBS patient-derived MKKS mutations disrupt this CEP290-MKKS interaction. Combined subminimal knockdown of mkks and cep290 in zebrafish produces synergistic sensory defects. Paradoxically, combining Cep290rd16 and Mkks knockout alleles in mice improves ciliogenesis and sensory function compared with either mutant alone, suggesting that altered CEP290-MKKS association affects integrity of multiprotein complexes at the cilia transition zone and basal body.\",\n      \"method\": \"Co-immunoprecipitation (direct protein-protein interaction); zebrafish morpholino epistasis; mouse double-mutant genetic epistasis with ciliogenesis and sensory functional readouts\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct Co-IP interaction, patient mutation validation, zebrafish epistasis, and mouse double-mutant rescue all in one study\",\n      \"pmids\": [\"22446187\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"BBS6 undergoes active nuclear-cytoplasmic transport. The McKusick-Kaufman syndrome allele BBS6-H84Y;A242S is defective in nuclear-cytoplasmic transport but maintains cilia function. BBS6 interacts with the SWI/SNF chromatin remodeling protein SMARCC1 (smarcc1a in zebrafish), and through this interaction modulates SMARCC1 subcellular localization. Transcriptional profiling shows similar changes following smarcc1a and bbs6 manipulation, placing BBS6 upstream of SMARCC1-dependent transcriptional regulation.\",\n      \"method\": \"Nuclear-cytoplasmic fractionation and transport assays; transgenic zebrafish with inducible bbs6 for pulldown/mass spectrometry identification of binding partners; co-immunoprecipitation of BBS6-SMARCC1; immunofluorescence of SMARCC1 localization upon BBS6 manipulation; transcriptional profiling\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (fractionation, pulldown/MS, Co-IP, localization, transcriptomics) in a single focused study\",\n      \"pmids\": [\"28753627\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Mkks knockout mice develop retinal degeneration (via apoptosis), failure of spermatozoa flagella formation, elevated blood pressure, obesity (associated with hyperphagia and decreased activity), and olfactory/social dominance deficits, but not polydactyly or vaginal abnormalities, indicating that complete loss of MKKS function causes BBS-like phenotype whereas MKS-specific alleles produce distinct outcomes.\",\n      \"method\": \"Mkks(-/-) mouse knockout with histological, physiological, and behavioral phenotyping\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean knockout mouse with multiple defined cellular and physiological phenotypes, replicated phenotype concept across BBS mouse models\",\n      \"pmids\": [\"15772095\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"A BBS6 (putative chaperonin) missense mutation introduced in mammalian cells causes dramatic mislocalization of the BBS6 protein compared with wild-type, and heterozygous BBS6 mutations can act as epistatic modifiers potentiating a phenotype caused by two recessive mutations at an independent BBS locus (triallelic model).\",\n      \"method\": \"Transfection of wild-type vs. patient-derived missense mutant BBS6 in mammalian cells with immunofluorescence localization; genetic epistasis analysis in human pedigrees\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — cell-based mislocalization assay plus human pedigree genetic epistasis, single lab\",\n      \"pmids\": [\"12837689\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The MKKS/BBS6 H395R patient mutation decreases the interaction of MKKS/BBS6 with BBS12 in protein-protein interaction assays in HEK-293T and ARPE-19 cells, though to a lesser extent than other BBS6 mutations associated with syndromic retinitis pigmentosa, consistent with a milder phenotype.\",\n      \"method\": \"Co-immunoprecipitation / protein-protein interaction assays in two cell lines (HEK-293T and ARPE-19) comparing wild-type vs. H395R mutant MKKS/BBS6 interaction with BBS12\",\n      \"journal\": \"Molecular vision\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single-lab Co-IP in cell lines, single method, no in vitro reconstitution\",\n      \"pmids\": [\"26900326\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"BBS6, together with TRiC/CCT chaperonins, forms a co-complex required for the localization of the adhesion GPCR ADGRV1 to primary cilia. Knockdown of BBS6 results in reduced ciliated cells and shorter primary cilia. In the absence of the TRiC/CCT-BBS chaperonin co-complex, ADGRV1 is depleted from the ciliary base and degraded via the proteasome.\",\n      \"method\": \"siRNA knockdown of BBS6 with ciliogenesis phenotype (reduced ciliated cells, shorter cilia); co-complex interaction identified by ciliary proteome interaction network; immunofluorescence of ADGRV1 localization upon BBS6 knockdown; proteasome inhibitor experiments\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — multiple methods (knockdown, localization, proteasome inhibitor) but preprint, single lab, not yet peer-reviewed\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Loss of Bbs6 in RPE-J cells showed no functionality phenotype for phagocytosis (negative finding: Bbs6 loss did not impair photoreceptor outer segment binding or phagocytosis in RPE cells, in contrast to loss of IFT20 or IFT88).\",\n      \"method\": \"Bbs6 depletion in RPE-J cells with phagocytosis assay (outer segment binding and internalization) and apical membrane morphology analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single negative result in a preprint, single cell line, single lab\",\n      \"pmids\": [],\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 (PCM) via its apical domain, shuttles between the centrosome and cytosol, and is required for cytokinesis; disease-causing mutations misfold BBS6, leading to CHIP-mediated ubiquitin-proteasome degradation and failure of centrosomal localization; BBS6 also undergoes nuclear-cytoplasmic transport, interacts with the SWI/SNF subunit SMARCC1 to modulate its localization and transcriptional output (underlying congenital heart defects in McKusick-Kaufman syndrome), interacts with CEP290 at the ciliary transition zone/basal body to regulate ciliogenesis, and participates in a TRiC/CCT-BBS chaperonin co-complex required for ciliary targeting of client proteins such as ADGRV1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MKKS/BBS6 is a divergent Group II chaperonin-like protein that operates at the centrosome and primary cilium to coordinate cell division and ciliogenesis [#0]. Unlike canonical chaperonins it does not oligomerize; instead it localizes to the pericentriolar material via its predicted substrate-binding apical domain, shifting from the lateral PCM in interphase to the whole PCM and the intercellular bridge during mitosis, and its loss causes cytokinesis failure with multinucleate, multicentrosomal cells [#0]. Wild-type BBS6 shuttles between the centrosome and cytosol, whereas disease-causing mutations misfold the protein so that it fails to reach the centrosome and is recognized by HSP70/HSC70 and HSP90 together with the chaperone-dependent E3 ligase CHIP, which targets the mutants for ubiquitin-proteasome degradation [#1]. At the ciliary transition zone and basal body BBS6 directly binds CEP290, an interaction disrupted by BBS patient mutations and required for the integrity of multiprotein complexes that govern ciliogenesis and sensory function [#2]. BBS6 also undergoes active nuclear-cytoplasmic transport and interacts with the SWI/SNF chromatin-remodeling subunit SMARCC1, controlling SMARCC1 localization and acting upstream of its transcriptional output; the McKusick-Kaufman syndrome allele BBS6-H84Y;A242S is selectively defective in this nuclear transport while retaining cilia function [#3]. Consistent with these cellular roles, Mkks-null mice display a Bardet-Biedl-like phenotype including retinal degeneration, sperm flagellar failure, obesity, and sensory deficits [#4]. BBS6 additionally engages other BBS chaperonin-family proteins, with patient mutations weakening its interaction with BBS12 [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Established the first cellular consequence of disease-associated BBS6 mutations and a genetic role as an epistatic modifier, framing BBS6 as a misfolding-prone protein within an oligogenic disease architecture.\",\n      \"evidence\": \"Transfection of wild-type vs. patient missense BBS6 with immunofluorescence localization; epistasis analysis in human pedigrees\",\n      \"pmids\": [\"12837689\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Did not define the normal subcellular compartment of BBS6\", \"No biochemical mechanism for mislocalization\", \"Triallelic modifier effect from pedigrees only\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Defined where BBS6 acts and what it does in the cell cycle, showing it is a non-oligomerizing chaperonin-like protein that targets the PCM via its apical domain and is required for cytokinesis.\",\n      \"evidence\": \"Live-cell imaging, fractionation, domain-deletion mapping, patient mutation assays, and RNAi cytokinesis readout\",\n      \"pmids\": [\"15731008\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No substrate of the apical domain identified\", \"Mechanism linking centrosomal loss to cytokinesis failure unresolved\", \"Whether chaperonin folding activity is exerted at all\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Connected the molecular role to organismal physiology, showing complete loss of MKKS produces a BBS-like multisystem phenotype distinct from MKS-specific alleles.\",\n      \"evidence\": \"Mkks(-/-) knockout mouse with histological, physiological, and behavioral phenotyping\",\n      \"pmids\": [\"15772095\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Cellular mechanism behind each phenotype not dissected\", \"Does not explain why MKS-specific alleles differ\", \"No tissue-specific causal pathway\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Explained why disease mutants fail functionally, showing they adopt abnormal conformations recognized by HSP70/HSP90-CHIP and are cleared by the proteasome before reaching the centrosome.\",\n      \"evidence\": \"Protein stability assays, proteasome inhibition, reciprocal Co-IP of CHIP/HSP70/HSP90, live-cell imaging, and CHIP RNAi\",\n      \"pmids\": [\"18094050\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Native folded structure of wild-type BBS6 not solved\", \"Whether CHIP regulates wild-type turnover normally unclear\", \"Centrosomal shuttling mechanism undefined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Placed BBS6 in a direct interaction with CEP290 at the transition zone, revealing that altered BBS6-CEP290 association reshapes the integrity of ciliary basal body complexes.\",\n      \"evidence\": \"Direct Co-IP, patient mutation validation, zebrafish morpholino epistasis, and mouse double-mutant genetic epistasis with ciliary readouts\",\n      \"pmids\": [\"22446187\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mechanism of the paradoxical double-mutant rescue unexplained\", \"Stoichiometry and architecture of the transition-zone complex unknown\", \"How BBS6 stabilizes the complex not defined\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Extended the misfolding model to BBS-complex assembly, showing a patient mutation weakens the BBS6-BBS12 interaction in proportion to phenotypic severity.\",\n      \"evidence\": \"Co-IP/protein interaction assays in HEK-293T and ARPE-19 cells comparing wild-type and H395R mutant\",\n      \"pmids\": [\"26900326\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No in vitro reconstitution of the interaction\", \"Functional consequence of reduced BBS12 binding untested\", \"Single method\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Revealed a non-ciliary, nuclear role: BBS6 shuttles into the nucleus and partners with the SWI/SNF subunit SMARCC1 to control its localization and transcription, separating the transcriptional function (McKusick-Kaufman allele) from ciliary function.\",\n      \"evidence\": \"Nuclear-cytoplasmic fractionation/transport assays, inducible-bbs6 pulldown/MS, Co-IP, SMARCC1 localization imaging, and transcriptional profiling in zebrafish\",\n      \"pmids\": [\"28753627\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct chromatin targets downstream of BBS6-SMARCC1 not defined\", \"Whether BBS6 acts as a chaperone for SMARCC1 unknown\", \"Link to congenital heart defects mechanistic detail limited\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Proposed a chaperonin co-complex mechanism, with BBS6 acting alongside TRiC/CCT to deliver client GPCR ADGRV1 to the cilium and protect it from proteasomal degradation.\",\n      \"evidence\": \"siRNA knockdown with ciliogenesis phenotype, ciliary proteome interaction network, ADGRV1 localization imaging, and proteasome inhibition (preprint)\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Preprint, single lab, not peer-reviewed\", \"Direct chaperone activity on ADGRV1 not reconstituted\", \"Generality of clients beyond ADGRV1 untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what endogenous substrates BBS6 folds and how its chaperonin-like apical domain, centrosomal, ciliary, and nuclear activities are mechanistically integrated within a single protein.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No structure of wild-type BBS6 or defined folding cycle\", \"No validated direct folding substrate\", \"Coordination of centrosomal, transition-zone, and nuclear pools unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [0, 7]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [2, 7]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [2, 7]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1, 7]}\n    ],\n    \"complexes\": [\n      \"TRiC/CCT-BBS chaperonin co-complex\",\n      \"BBSome-related BBS chaperonin module (BBS6-BBS12)\"\n    ],\n    \"partners\": [\n      \"CEP290\",\n      \"SMARCC1\",\n      \"BBS12\",\n      \"STUB1\",\n      \"HSPA8\",\n      \"HSP90\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}