PDK2pyruvate dehydrogenase kinase 2
Autism Reports / Total Reports
4 / 6Rare Variants / Common Variants
4 / 0Aliases
PDK2, PDHK2, PDKIIAssociated Syndromes
-Chromosome Band
17q21.33Associated Disorders
-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.
External Links
SFARI Genomic Platforms
Reports related to PDK2 (6 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Primary | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
2 | Support | Prevalence and architecture of de novo mutations in developmental disorders | et al. (2017) | No | - |
3 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
4 | Recent Recommendation | Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity | Coe BP , et al. (2018) | No | - |
5 | Support | - | Marcogliese PC et al. (2022) | Yes | - |
6 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
Rare Variants (4)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.1076A>C | p.Tyr359Ser | missense_variant | De novo | - | - | 28135719 | et al. (2017) | |
c.95C>A | p.Ser32Tyr | missense_variant | De novo | - | Multiplex | 28263302 | C Yuen RK et al. (2017) | |
c.359G>A | p.Arg120Gln | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.669+1G>A | - | splice_site_variant | Familial | Maternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate


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).
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
4/1/2022

Decreased from 3 to 2
Description
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).
10/1/2019

Decreased from 4 to 3
New Scoring Scheme
Description
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).
Reports Added
[New Scoring Scheme]1/1/2019

Increased from to 4
Description
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).
Krishnan Probability Score
Score 0.451610927332
Ranking 10633/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.16897552451649
Ranking 7238/18225 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.82799909465783
Ranking 2799/18665 scored genes
[Show Scoring Methodology]
Zhang D Score
Score -0.076305946710867
Ranking 11425/20870 scored genes
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