Shangguan et al., 2025 assembled genotype and phenotype data for 9 affected individuals from 9 unrelated families with predicted deleterious KMT2D variants through literature (Parisi et al., 2015; Sertelik et al., 2016; Luo et al., 2021) and two web-based databases (ClinVar and DECIPHER); all 9 probands were diagnosed with autism and presented with intellectual disability and dysmorphic facial features. In the same report, the authors observed that selective knockdown of Kmt2d in the mouse hippocampus resulted in defects in social behaviors and increased repetitive behavior, as well as decreased excitatory and increased inhibitory synaptic transmission. De novo variants in the KMT2D gene, including a loss-of-function variant and several potentially deleterious missense variants, have also been identified in ASD probands from the Simons Simplex Collection, the SPARK cohort, the Autism Sequencing Consortium, the MSSNG cohort, and a Korean ASD cohort (Iossifov et al., 2014; Yuen et al., 2017; Krupp et al., 2017; Satterstrom et al., 2020; Zhou et al., 2022; Kim et al., 2024; Tan et al., 2024).
Molecular Function
The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Deficiency of KMT2D causes autistic-like behavior in mice and zebrafish
Multilayered genetic dissection of autism: insights from whole-exome sequencing, molecular karyotyping, and cytogenetic analyses in a small Turkish cohort
