Relevance to Autism

Genome-wide association analysis of 6222 ASD case-pseudocontrol pairs from the SPARK cohort in Matoba et al., 2020 identified a novel genome-wide significant locus (rs60527016 at chr8:38.19M-38.45M); subsequent massively parallel reporter assay (MPRA) identified a putative casual variant within this novel locus (rs7001340), and expression quantitative trait loci data demonstrated an association between the risk allele of rs7001340 and decreased expression of DDHD2 in both adult and prenatal brain tissue. DDHD2 had previously been shown in Parikshak et al., 2016 to be significantly downregulated in post-mortem cortex of individuals with autism compared to controls (logFC -0.28, P-value 5.67E-05, FDR 0.013), and Hall et al., 2020 demonstrated via transcriptome-wide association studies (TWAS) of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, bipolar disorder, major depressive disorder, and schizophrenia that genetic predictors of reduced expression of DDHD2 were significantly (P < 0.05) associated with all five tested neuropsychiatric conditions.

Molecular Function

This gene encodes a phospholipase enzyme containing sterile-alpha-motif (SAM), WWE, and DDHD domains. This protein participates in membrane trafficking between the endoplastic reticulum and the Golgi body. Mutations in this gene can cause autosomal recessive spastic paraplegia 54.

External Links

References