KIAA0586

Highest pathogenic variant AF is 0.003834522

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000354386

Coding exons

34

Length

121114

Individuals with no LoFs

123905

Homozygous LoFs

1

Heterozygous LoFs

747

Defined

124653

p

0.00300

Function

FUNCTION: 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). {ECO:0000250|UniProtKB:E9PV87, ECO:0000250|UniProtKB:Q1G7G9, ECO:0000269|PubMed:24421332}.;

Disease

DISEASE: Joubert syndrome 23 (JBTS23) [MIM:616490]: A mild form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. {ECO:0000269|PubMed:26026149, ECO:0000269|PubMed:26096313, ECO:0000269|PubMed:26386044, ECO:0000269|PubMed:26386247, ECO:0000269|PubMed:26429889}. Note=The disease is caused by mutations affecting the gene represented in this entry. Some patients with biallelic KIAA0586 mutations manifest a disease phenotype with features of Joubert syndrome and additional findings of a small thorax and respiratory problems consistent with Jeune syndrome (Joubert-Jeune ciliopathy). {ECO:0000269|PubMed:26386044}.; DISEASE: Short-rib thoracic dysplasia 14 with polydactyly (SRTD14) [MIM:616546]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:26166481}. Note=The disease is caused by mutations affecting the gene represented in this entry.;