Aliases: PDHK2, PDKII
Chromosome No: 17
Chromosome Band: 17q21.33
Genetic Category: Rare single gene variant--Rare single gene variant/Functional
ASD Reports: 6
Recent Reports: 1
Annotated variants: 4
Associated CNVs: 4
Evidence score: 2
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Relevance to Autism
De novo missense variants in the PDK2 gene have been identified in two probands with ASD (Iossifov et al., 2014; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified PDK2 as a gene with an excess of missense variants with CADD scores > 30 (false discovery rata < 5%, count >1) (Coe et al., 2018). Functional analysis of the ASD-associated p.Arg120Gln missense variant, which was originally identified in an SSC proband, in Drosophila in Marcogliese et al., 2022 demonstrated a loss-of-function effect (failure to reduce expected viability to the extent of corresponding reference allele upon ubiquitous overexpression).
Molecular Function
This gene encodes a member of the pyruvate dehydrogenase kinase family. The encoded protein phosphorylates pyruvate dehydrogenase, down-regulating the activity of the mitochondrial pyruvate dehydrogenase complex.
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