Aliases: GPRK2L, GPRK4a, IT11,GRK4
Chromosome No: 4
Chromosome Band: 4p16.3
Genetic Category: Rare single gene variant-Functional-Rare single gene variant/Functional
Associated Syndrome(s): Fragile X syndrome
ASD Reports: 6
Recent Reports: 1
Annotated variants: 5
Associated CNVs: 11
Evidence score: 3
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Relevance to Autism
Rare de novo variants in the GRK4 gene have been identified in ASD probands, including a de novo missense variant (p.Pro385Ala) in a proband from the Simons Simplex Collection (Iossifov et al., 2014; Yuen et al., 2017; Turner et al., 2017). Functional assessment of the ASD-associated p.Pro385Ala missense variant in Drosophila using an overexpression-based strategy in Macrogliese et al., 2022 demonstrated that flies overexpressing GRK4-p.Pro385Ala failed to reduce the expected viability to the extent of the corresponding reference allele upon overexpression, indicating a loss-of-function effect.
Molecular Function
This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating its deactivation. This gene has been linked to both genetic and acquired hypertension. Maurin et al. 2015 found evidence that FMRP negatively regulated the expression of GRK4 at the translational level in the cerebellum.
External Links
