Relevance to Autism

Chen et al., 2025 integrated cortex cell-specific cis-regulatory element annotations, a deep learning-based variant prediction model, and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 non-coding de novo mutations (ncDNMs) in ASD probands from Simons Simplex Collection (SSC) and Autism Speaks MSSNG resource (MSSNG) cohorts and identified a ncDNM that down-regulated expression of the DNAJC5 gene in a MSSNG proband. A de novo loss-of-function variant and a de novo missense variant in DNAJC5 have also been identified in ASD probands (Yuen et al., 2017; Zhou et al., 2022). An epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates, which has been associated with adverse health and neurodevelopmental outcomes, and DNA methylation in 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study in England-Mason et al., 2022 identified a Cytosine-phosphate-Guanine (Cpg) site (cg17343385) in DNAJC5 that associated with both high and low molecular weight phthalates in a venous buffy coat blood sample subset.

Molecular Function

This gene is a member of the J protein family. J proteins function in many cellular processes by regulating the ATPase activity of 70 kDa heat shock proteins. The encoded protein plays a role in membrane trafficking and protein folding, and has been shown to have anti-neurodegenerative properties. The encoded protein is known to play a role in cystic fibrosis and Huntington's disease. Heterozygous mutations in DNAJC5 are responsible for autosomal dominant Kufs-type neuronal ceroid lipofuscinosis 4 (CLN4; OMIM 162350), an autosomal dominant neurodegenerative disorder characterized by onset of symptoms in adulthood, including seizures, dementia, and behavioral and psychiatric manifestations (Velinov et al., 2012 and others).

External Links

References