YIF1B

Cilia effects upon perturbation of YIF1B

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia in patient and Yif1b-KO fibroblasts; longer cilia in Yif1b-KO Purkinje cells

Phenotypes

Human ciliopathy phenotype:

Kaya-Barakat-Masson syndrome (KABAMAS; OMIM 619125): severe autosomal recessive neurodevelopmental disorder — profound global developmental delay, axial hypotonia, dystonia/dyskinesia, absent speech, feeding difficulties, microcephaly, and cerebral/cerebellar/pontine atrophy. Patient fibroblasts show reduced and shortened primary cilia (ciliary anchoring defects).

Ciliopathy associations

• Kaya-Barakat-Masson Syndrome

References: PMID:33103737, PMID:32006098

Subcellular localization

Not detected in cilia (Golgi/ER anterograde trafficking protein); included on functional grounds

References: doi:10.1093/brain/awaa235, PMID:33103737

Function

YIF1B encodes a ubiquitous ER-to-membrane anterograde trafficking protein involved in Golgi apparatus morphology. Biallelic mutations cause a post-natal neurodevelopmental syndrome (developmental and motor delay, visual deficits, ventricle enlargement, myelination defects, cerebellar atrophy). Although YIF1B is not detected within the primary cilium, its loss causes primary-cilium abnormalities in patient and Yif1b-KO mouse fibroblasts and altered ciliary architectural components in the KO brain, identifying YIF1B as the first gene linking Golgipathies and ciliopathies (Diaz et al., 2020, Brain). In fibroblasts from patients with YIF1B truncating or hypomorphic variants, fewer cells are ciliated, cilia are about one-third shorter and rootletin volume is increased, while the basal body proteins CEP83 and CEP164 are unchanged; Yif1b-KO mouse fibroblasts also have shorter cilia. In the Yif1b-KO brain, Purkinje cell cilia are about 11% longer, and CA1 pyramidal neurons show thicker striated rootlets, greater distance between centrioles and shorter basal bodies. Yif1b-KO males are infertile, with almost no spermatozoa; the few remaining sperm have disorganized axonemal microtubule doublets or supernumerary flagella (Diaz et al., 2020, Brain, PMID 33103737).