Aliases: MRX104, PDZD10, PDZK10
Chromosome No: X
Chromosome Band: Xp22.2
Genetic Category: Rare Single Gene variant-Syndromic-Syndromic/Functional
ASD Reports: 6
Recent Reports: 2
Annotated variants: 7
Associated CNVs: 13
Evidence score: 2
Relevance to Autism
Rare mutations in the FRMPD4 gene have been identified with autism and schizophrenia (Piton et al., 2011). X-exome sequencing of 405 unresolved families with X-linked intellectual disability (XLID) in Hu et al., 2016 identified a maternally-transmitted frameshift variant in the FRMPD4 gene that segregated with XLID in a family in which affected males presented with variable seizures, poor or absent speech, and behavioral problems; a de novo missense variant in FRMPD4 was also identified in an unrelated male proband presenting with ASD, developmental delay, and absent speech in this study. Piard et al., 2017 presented two novel families with four affected males carrying FRMPD4 mutations; three of these affected males presented with ASD in addition to intellectual disability, gross motor delay, and speech delay. Frmpd4-knockout mice were also shown to display hippocampal-dependent spatial learning and memory deficits in Piard et al., 2017.
This gene encodes a multi-domain (WW, PDZ, FERM) containing protein. Through its interaction with other proteins (such as PSD-95), it functions as a positive regulator of dendritic spine morphogenesis and density, and is required for the maintenance of excitatory synaptic transmission.