Relevance to Autism

A de novo splice-site variant in the HNRNPD gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A de novo frameshift variant in this gene was subsequently identified in a proband from the 2017 Deciphering Developmental Disorders study; while the original report did not describe the clinical presentation of this proband, Gillentine et al., 2021 subsequently reported that he presented with autism spectrum disorder. Gillentine et al., 2021 reported ten previously unreported individuals with likely gene-disruptive (LGD) variants in HNRNPD, including an ASD proband from the SPARK cohort; in total, four of the novel patients in this report presented with autism spectrum disorder and had de novo LGD variants in HNRNPD.

Molecular Function

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are nucleic acid binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two repeats of quasi-RRM domains that bind to RNAs. It localizes to both the nucleus and the cytoplasm. This protein is implicated in the regulation of mRNA stability.

External Links

References