KIAA0586

Cilia effects upon perturbation of KIAA0586

Cilia number / % ciliated:

Decreased cilia number

Ciliogenesis screen results (3 screens)

• Kim2016: No effect
• Breslow et al. 2018 (CRISPR) [CRISPR]: Increased Signaling (Negative Regulator) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: Joubert Candidate / Ciliogenesis Defect (robust z=-2.55, ciliated=18.1%) PMID:26595381

Phenotypes

Human ciliopathy phenotype:

Joubert syndrome 23; short-rib thoracic dysplasia 14 with polydactyly; Joubert syndrome; Joubert syndrome and related disorders

Ciliopathy associations

• Hydrolethalus Syndrome
• Joubert Syndrome
• Short-Rib Thoracic Dysplasia

References: PMID:26096313, PMID:26166481, PMID:39063141, PMID:36580738, PMID:36538006, PMID:29458881, PMID:32080096, PMID:41020477, PMID:42859478

Subcellular localization

basal body, centrosome

References: PMID:19144723, PMID:31816441, PMID:32080096, PMID:26166481

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Signaling (Hedgehog, GPCRs, ion channels)

Function

Required for ciliogenesis and sonic hedgehog/SHH signaling. Role in primary cilia formation and microtubule organisation (19144723). Component of a CP110-containing protein complex required for centrosome and cilia function, 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. Essential for centrosomal migration prior to ciliogenesis (24421332). Mutated in Joubert syndrome (26096313) and in skeletal ciliopathies (31816441, 32080096) KIAA0586 … is essential for primary ciliogenesis. In control cells … protrude from 60% of cells … only 20% of mutant cells bear a primary cilia. (26166481) Homozygous KIAA0586 c.1815G>A, a splice variant causing exon 14 skipping, is a founder allele for short-rib polydactyly syndrome type IV (Beemer-Langer syndrome) in Romani families (PMID 42859478).