PDK3

Chr X

pyruvate dehydrogenase kinase 3

Also known as: CMTX6, GS1-358P8.4

The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle, and thus is one of the major enzymes responsible for the regulation of glucose metabolism. The enzymatic activity of PDH is regulated by a phosphorylation/dephosphorylation cycle, and phosphorylation results in inactivation of PDH. The protein encoded by this gene is one of the three pyruvate dehydrogenase kinases that inhibits the PDH complex by phosphorylation of the E1 alpha subunit. This gene is predominantly expressed in the heart and skeletal muscles. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCharcot-Marie-Tooth disease, X-linked dominant, 6

Clinical highlights

Gene-disease validity (ClinGen)
Charcot-Marie-Tooth disease X-linked dominant 6 · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
20
Pubs (1 yr)
P/LP submissions
P/LP missense
0.55
LOEUF
DN
Mechanism· predicted
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GeneReview available — PDK3
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.55LOEUF
pLI 0.445
Z-score 2.75
OE 0.21 (0.100.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.32Z-score
OE missense 0.46 (0.380.56)
67 obs / 145.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.21 (0.100.55)
00.351.4
Missense OE?0.46 (0.380.56)
00.61.4
Synonymous OE?0.87
01.21.6
LoF obs/exp: 3 / 14.2Missense obs/exp: 67 / 145.8Syn Z: 0.77

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PDK3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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