Neurological ciliopathies

Gene: CBY1

This gene currently has no phenotype in OMIM. Checked that is the correct gene by looking in PubMed:33131181 to make sure the same gene name is listed. It is. Gene-checked tag added.

Created: 16 Oct 2023, 4:10 p.m. | Last Modified: 16 Oct 2023, 4:10 p.m.

Panel Version: 3.13

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 3:10 p.m. | Last Modified: 10 Oct 2023, 3:10 p.m.

Panel Version: 3.12

Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 33131181 reports two frame shifting CBY1 variants ( NM_015373.3:c.189_190del; p.(Val65*) & NM_015373.3:c.64_65dup; p.(Asn23Profs*24)), one in each of two consanguineous families, where the parents were heterozygous and the affected children were homozygous. Extensive functional studies have shown the role of CBY1 in cilial formation and function, and the disruptive effect of the variants (PMID: 33131181; 25103236; 25220153).

Created: 18 Apr 2023, 3:09 p.m. | Last Modified: 18 Apr 2023, 3:09 p.m.

Panel Version: 3.2

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 18 Apr 2023, 2:50 p.m. | Last Modified: 18 Apr 2023, 2:50 p.m.

Panel Version: 3.2

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Three cases in two unrelated consanguineous families with homozygous loss of function variants, with ID as a feature of the phenotype. Multiple null model organisms recapitulate the human phenotype: Null mouse model had cystic kidneys, a phenotype common to ciliopathies. Reducing Cby levels in Xenopus laevis model reduced the density of multiciliated cells, the number of basal bodies per multiciliated cell, and the numbers of neural tube primary cilia; it also led to abnormal development of the neural crest, central nervous system, and pronephros. Depletion of cby1 in zebrafish results in ciliopathy‐related phenotypes.
Sources: Literature

Created: 21 Jan 2021, 9:22 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
intellectual disability; cerebellar ataxia; molar tooth sign; polydactyly; Joubert syndrome

Publications

• 33131181
• 25103236
• 25220153

Variants in this GENE are reported as part of current diagnostic practice