CLTC was classified as an ASD candidate gene in males in Kim et al., 2024 following a combined TADA analysis consisting of a novel Korean ASD cohort in addition to the Simons Simplex Collection and the SPARK cohort. De novo ASD-associated variants in CLTC included three de novo loss-of-function variants (two in probands from the Autism Sequencing Consortium, one in a proband from the MSSNG cohort), a de novo missense variant predicted to be deleterious by REVEL and MPC in a SPARK proband, and a de novo missense variant with a CADD score > 20 in a Korean ASD proband (De Rubeis et al., 2012; Satterstrom et al., 2020; Zhou et al., 2022; Wang et al., 2023; Kim et al., 2024). Heterozygous mutations in this gene are also responsible for autosomal dominant intellectual developmental disorder-56 (MRD56; OMIM 617854); autism reported in 3/10 individuals with de novo CLTC variants in Nabais S et al., 2020.
Molecular Function
Clathrin is a major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits. These specialized organelles are involved in the intracellular trafficking of receptors and endocytosis of a variety of macromolecules. The basic subunit of the clathrin coat is composed of three heavy chains and three light chains.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Whole genome sequencing analysis identifies sex differences of familial pattern contributing to phenotypic diversity in autism
De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy
