{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMKKS, also known as BBS6, is a chaperonin‐like protein that plays a central role in the pathogenesis of Bardet–Biedl syndrome (BBS) and McKusick–Kaufman syndrome. Early genetic studies proposed that BBS might result from a triallelic model involving mutations in multiple BBS genes including MKKS, and subsequent analyses demonstrated that MKKS/BBS6 is a Group II chaperonin–like protein derived from the CCT/TRiC family. Notably, MKKS does not form the typical oligomeric complexes of other chaperonins; instead, it predominantly localizes to the pericentriolar material, shuttling dynamically between the centrosome and the cytosol to mediate centrosomal functions that are critical for ciliogenesis and proper cell division."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional analyses have shown that disease‐causing mutations in MKKS disrupt its normal centrosomal association. Under normal conditions, the substrate–binding apical domain of MKKS is sufficient for centrosomal targeting; however, patient–derived missense mutations result in mislocalization and enhanced degradation via the ubiquitin–proteasome pathway. Such defects in MKKS not only compromise cytokinesis by yielding multinucleate and multicentrosomal cells but are also linked to disturbances in actin cytoskeleton dynamics—evidenced by abnormal stress fiber and focal adhesion organization—likely through deregulation of RhoA activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its cellular functions, variation in the MKKS gene has been implicated in a spectrum of clinical phenotypes. Several genetic studies have reported MKKS variants in patients with classical BBS features such as retinal dystrophy, polydactyly, and renal anomalies, as well as an association with obesity and metabolic syndrome in diverse populations. Moreover, while genetic screening in various cohorts has underscored the heterogeneity and complex inheritance patterns of MKKS–related disorders—including isolated retinitis pigmentosa or limited BBS phenotypes—preliminary investigations also suggest that untranslated upstream open reading frames (uORFs) in MKKS might participate in post–transcriptional regulation, although their roles remain to be established."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "N Katsanis, S J Ansley, J L Badano, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddg188"}], "href": "https://doi.org/10.1093/hmg/ddg188"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12837689"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12837689"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jun Chul Kim, Young Y Ou, Jose L Badano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity disorder Bardet-Biedl syndrome, is a novel centrosomal component required for cytokinesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.01676"}], "href": "https://doi.org/10.1242/jcs.01676"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15731008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15731008"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Michael Benzinou, Andrew Walley, Stephan Lobbens, et al. 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