Relevance to Autism

A LoF variant in the PCDH11X gene was identified in a male ASD proband, but not in male or female controls, in Lim et al., 2013. A second LoF variant in this gene was identifed in a male ASD proband by whole genome sequencing as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple LoF variants and a probability of LoF intolerance rate (pLI) > 0.65, PCDH11X was determined to be an ASD candidate gene in Yuen et al., 2017. An X-chromosome-wide association study of 6,873 individuals with autism from MSSNG, SSC, and SPARK (5,639 males and 1,234 females) and 8,981 controls (3,911 males and 5,070 females) in Mendes et al., 2025 identified an intergenic SNP adjacent to the PCDH11X gene that reached the significance threshold for association in male-XWAS, meta-XWAS, and both-XWAS analyses, as well as an intronic SNP in PCDH11X that reached the significance threshold for association in a meta-XWAS analysis.

Molecular Function

This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog, despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell-cell recognition essential for the segmental development and function of the central nervous system. Disruption of this gene may be associated with developmental dyslexia.

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