KIAA0586

Last update 08 May 2025

Basic Info

Synonyms

JBTS23, KIAA0586, Protein TALPID3

+ [1]

Introduction

Required for ciliogenesis and sonic hedgehog/SHH signaling. Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1. May play a role in early ciliogenesis in the disappearance of centriolar satellites that preceeds ciliary vesicle formation (PubMed:24421332). Involved in regulation of cell intracellular organization. Involved in regulation of cell polarity (By similarity). Required for asymmetrical localization of CEP120 to daughter centrioles (By similarity).

100 Clinical Results associated with KIAA0586

100 Translational Medicine associated with KIAA0586

0 Patents (Medical) associated with KIAA0586

Literatures (Medical) associated with KIAA0586

01 Feb 2025·iScience

Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia

Article

Author: Olbrich, Heike ; Gatsogiannis, Christos ; Blanque, Anja ; Lindberg, Ulrika ; George, Sebastian ; Korenke, G Christoph ; Valente, Enza Maria ; Wohlgemuth, Kai ; Wallmeier, Julia ; Omran, Heymut ; Möller, Maike ; Teig, Norbert ; Van der Zwaag, Bert ; Swirski, Sebastian ; Neidhardt, John ; Bracht, Diana ; Lücke, Thomas ; Taudien, Jacqueline E ; Kroes, Hester Y ; D'Abrusco, Fulvio ; Jüschke, Christoph ; Veer, Dorothee ; Owczarek-Lipska, Marta

Pathogenic variants in KIAA0586/TALPID3 are associated with the ciliopathy Joubert syndrome (JS). We report individuals with KIAA0586/TALPID3 variants affected by primary and motile cilia defects leading to JS and chronic destructive airway disease. DNA variants were detected in three families by sequencing. In two unrelated families, a deep-intronic variant (KIAA0586/TALPID3:c.3990 + 3186G>A) activated a cryptic exon. We performed histological and functional analyses in native and air-liquid interface (ALI) cultured respiratory cells. Primary cilia lengths were measured in patient-derived fibroblasts. Our data associate KIAA0586/TALPID3 variants with a syndrome combining JS and chronic destructive airway disease, reduced number of motile cilia, disorganized basal body location, and ciliary clearance malfunction. Additionally, patient-derived cell lines showed primary cilia defects. Disease causing KIAA0586/TALPID3 variants, including a deep-intronic sequence variant, were associated with primary and motile cilia defects in JS patients. The combination of JS and respiratory symptoms should be considered indicative for KIAA0586/TALPID3 sequence alterations.

01 Jan 2025·European Journal of Human Genetics

Pathogenic cryptic variants detectable through exome data reanalysis significantly increase the diagnostic yield in Joubert syndrome

Article

Author: Battini, Roberta ; Leuzzi, Vincenzo ; Sirchia, Fabio ; Garau, Jessica ; Serpieri, Valentina ; D'Arrigo, Stefano ; Manti, Filippo ; Signorini, Sabrina ; Boltshauser, Eugen ; Boggioni, Monica ; Cattaneo, Luca ; Caputi, Caterina ; Borgatti, Renato ; Zanni, Ginevra ; Romaniello, Romina ; Valente, Enza Maria ; D'Abrusco, Fulvio ; Morelli, Federica ; Bertini, Enrico ; Giorgio, Elisa ; Taccagni, Cecilia Maria ; Gana, Simone ; Lemke, Johannes R ; Graziano, Claudio ; De Laurentiis, Arianna ; Petković Ramadža, Danijela

AbstractJoubert syndrome (JS) is a genetically heterogeneous neurodevelopmental ciliopathy. Despite exome sequencing (ES), several patients remain undiagnosed. This study aims to increase the diagnostic yield by uncovering cryptic variants through targeted ES reanalysis. We first focused on 26 patients in whom ES only disclosed heterozygous pathogenic coding variants in a JS gene. We reanalyzed raw ES data searching for copy number variants (CNVs) and intronic variants affecting splicing. We validated CNVs through real-time PCR or chromosomal microarray, and splicing variants through RT-PCR or minigenes. Cryptic variants were then searched in additional 44 ES-negative JS individuals. We identified cryptic “second hits” in 14 of 26 children (54%) and biallelic cryptic variants in 3 of 44 (7%), reaching a definite diagnosis in 17 of 70 (overall diagnostic gain 24%). We show that CNVs and intronic splicing variants are a common mutational mechanism in JS; more importantly, we demonstrate that a significant proportion of such variants can be disclosed simply through a focused reanalysis of available ES data, with a significantly increase of the diagnostic yield especially among patients previously found to carry heterozygous coding variants in the KIAA0586, CC2D2A and CPLANE1 genes.

01 Oct 2024·European Journal of Human Genetics

Molecular investigation in individuals with orofacial clefts and microphthalmia-anophthalmia-coloboma spectrum

Article

Author: Gil-da-Silva-Lopes, Vera Lúcia ; Helaers, Raphaël ; Vikkula, Miikka ; Pairet, Eleonore ; Lustosa Mendes, Elaine ; Monlleó, Isabella Lopes ; Vieira, Tarsis Paiva ; Atique Tacla, Milena ; Ribeiro, Erlane Marques ; de Mello Copelli, Matheus

This study describes genomic findings among individuals with both orofacial clefts (OC) and microphthalmia/anophthalmia/coloboma (MAC) recorded in the Brazilian Database on Craniofacial Anomalies (BDCA). Chromosomal microarray analysis (CMA) and Whole Exome Sequencing (WES) were performed in 17 individuals with OC-MAC. Clinical interpretation of molecular findings was based on data available at the BDCA and on re-examination. No copy number variants (CNVs) classified as likely pathogenic or pathogenic were detected by CMA. WES allowed a conclusive diagnosis in six individuals (35.29%), two of them with variants in the CHD7 gene, and the others with variants in the TFAP2A, POMT1, PTPN11, and TP63 genes with the following syndromes: CHARGE, CHD7-spectrum, Branchiooculofacial, POMT1-spectrum, LEOPARD, and ADULT. Variants of uncertain significance (VUS) possibly associated to the phenotypes were found in six other individuals. Among the individuals with VUSes, three individuals presented variants in genes associated to defects of cilia structure and/or function, including DYNC2H1, KIAA0586, WDR34, INTU, RPGRIP1L, KIF7, and LMNA. These results show that WES was the most effective molecular approach for OC-MAC in this cohort. This study also reinforces the genetic heterogeneity of OC-MAC, and the importance of genes related to ciliopathies in this phenotype.

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KIAA0586

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