Diagnostic exome sequencing in 100 patients with severe intellectual disability (ID) and their parents in de Ligt et al., 2012 identified a maternally-inherited missense variant in the TRPC5 gene in a male ID proband who was also diagnosed with autism spectrum disorder (ASD) and Tourette syndrome. Analysis of 54 male patients presenting with intellectual disability (ID) and a family history suggesting X-linked inheritance or maternal skewed X-chromosome inactivation using an X-chromosome-specific microarray in Mignon-Ravix et al., 2014 identified a deletion of the first exon of the TRPC5 gene in a child presenting with ID and autism spectrum disorder (ASD). Leitao et al., 2022 presented four previously unreported individuals with TRPC5 variants: three brothers with ASD and intellectual disability with a maternally-inherited missense variant that was experimentally confirmed to result in a constitutively active current; and a male patient with high-functioning ASD with a maternally-inherited nonsense variant. De novo coding variants in TRPC5 have also been identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), in patients with DD/ID (Deciphering Developmental Disorders Study 2015; Lelieveld et al., 2016), and in a proband with congenital heart disease (Homsy et al., 2015).
Molecular Function
This gene belongs to the transient receptor family. It encodes one of the seven mammalian TRPC (transient receptor potential channel) proteins. The encoded protein is a multi-pass membrane protein and is thought to form a receptor-activated non-selective calcium permeant cation channel. The protein is active alone or as a heteromultimeric assembly with TRPC1, TRPC3, and TRPC4. It also interacts with multiple proteins including calmodulin, CABP1, enkurin, Na(+)-H+ exchange regulatory factor (NHERF ), interferon-induced GTP-binding protein (MX1), ring finger protein 24 (RNF24), and SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Diagnostic exome sequencing in persons with severe intellectual disability.
Intragenic rearrangements in X-linked intellectual deficiency: results of a-CGH in a series of 54 patients and identification of TRPC5 and KLHL15 as potential XLID genes
