Submission Details

The HNRNPK gene is located on chromosome 9 at 9q21.32 and encodes the heterogeneous nuclear ribonucleoprotein K protein, which is one of the major pre-mRNA-binding proteins. HNRNPK was first reported in association with Au Kline syndrome in 2015 (26173930: Au et al. 2015). Evidence supporting this gene-disease relationship includes case-level data and experimental data. At least eight de novo heterozygous variants have been reported in the literature, including fives loss-of-function variants, two missense variants, and one intron variant predicted to result in an inframe insertion, in six publications (26173930: Au et al. 2015; 26954065: Lange et al. 2016; 28771707: Miyake et al. 2017; 28374925: Dentici et al. 2017; 29904177: Au et al. 2018; 32588992: Yamada et al. 2020). The mechanism for disease is loss-of-function. The hnRNP K protein was shown to be expressed in rat hippocampal neuron and colocalized with VGLUT1 (a presynaptic protein) and PSD-95 (a postsynaptic scaffolding protein), and in mouse leukemic monocyte macrophage RAW264.7 cells, a significant increase in GSK3β-hnRNPK interaction was observed (24990929: Folci et al. 2014; 26638989: Fan et al. 2015). In summary, there is strong evidence to support the relationship between HNRNPK and Au Kline syndrome (autosomal dominant).

PubMed IDs:

26173930 26954065 28771707 28374925 29904177 32588992 26638989 24990929

Assertion Criteria:

Click here to view assertion criteria

https://www.clinicalgenome.org/site/assets/files/3975/gene-disease_validity_standard_operating_procedures_version_7-1.pdf

Submitter Submitted Date:

10/15/2020

The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).

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