Relevance to Autism

Gillentine et al., 2021 reported 13 previously unpublished individuals with variants in the HNRNPK gene, including an ASD proband from the SPARK cohort; a total of five individuals from this cohort presented with autism spectrum disorder, including two individuals with de novo likely gene-disruptive (LGD) variants and two individuals with de novo missense variants with CADD scores greater than 20 in HNRNPK. A proband with a de novo HNRNPK missense variant from the Deciphering Developmental Disorders study that was originally described in Kaplanis et al., 2020 was subsequently reported in Gillentine et al., 2021 to also present with autism spectrum disorder.

Molecular Function

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA 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 is located in the nucleoplasm and has three repeats of KH domains that binds to RNAs. It is distinct among other hnRNP proteins in its binding preference; it binds tenaciously to poly(C). This protein is also thought to have a role during cell cycle progession. Heterozygous mutations in the HNRNPK gene are responsible for Au-Kline syndrome (OMIM 616580), a neurodevelopmental disorder characterized by developmental delay and

External Links

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