Characterizing two novel variants of the KDM5C gene causing X-linked intellectual disability

Takeaway

  • Two novel variants in KDM5C lead to reduced protein expression, stability and activity.

Why this matters

  • X-linked gene defects are common causes of intellectual disability.

  • KDM5C is one of the most commonly mutated genes in X-linked intellectual disability (XLID), which codes for a demethylase protein. Trimethylated histone H3 lysine 4 (H3K4me3) is a substrate of KDM5C and plays an important role in regulating gene transcription.

  • KDM5C is thought to play a central transcriptional repressive role in chromatin dynamics and epigenetic regulation during cell growth, differentiation and development. Alterations in the chromatin landscape may lead to disease.