PDP1

Chr 8

pyruvate dehydrogenase phosphatase catalytic subunit 1

Also known as: PDH, PDP, PDPC, PDPC 1, PPM2A, PPM2C

NCBI Gene: 54704 ENSG00000164951 UniProt: Q8IY26

The pyruvate dehydrogenase phosphatase catalytic subunit dephosphorylates and activates the E1 component of the pyruvate dehydrogenase complex, which is essential for converting pyruvate to acetyl-CoA in mitochondrial energy metabolism. Mutations cause pyruvate dehydrogenase phosphatase deficiency with autosomal recessive inheritance. This disorder affects cellular energy production and typically involves neurological manifestations due to impaired mitochondrial function.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Pyruvate dehydrogenase (E1) is one of the three components (E1, E2, and E3) of the large pyruvate dehydrogenase complex. Pyruvate dehydrogenase kinases catalyze phosphorylation of serine residues of E1 to inactivate the E1 component and inhibit the complex. Pyruvate dehydrogenase phosphatases catalyze the dephosphorylation and activation of the E1 component to reverse the effects of pyruvate dehydrogenase kinases. Pyruvate dehydrogenase phosphatase is a heterodimer consisting of catalytic and regulatory subunits. Two catalytic subunits have been reported; one is predominantly expressed in skeletal muscle and another one is is much more abundant in the liver. The catalytic subunit, encoded by this gene, is the former, and belongs to the protein phosphatase 2C (PP2C) superfamily. Along with the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinases, this enzyme is located in the mitochondrial matrix. Mutation in this gene causes pyruvate dehydrogenase phosphatase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]

GeneReviews ResearchGenerating clinical summary…

LOEUF 0.49

Clinical Summary— PDP1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 104 VUS of 207 total submissions

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GeneReview available — PDP1

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

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.451

Z-score 3.15

OE 0.21 (0.10–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.62Z-score

OE missense 0.74 (0.66–0.82)

220 obs / 298.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.10–0.49)

0≤0.351.4

Missense OE?0.74 (0.66–0.82)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 4 / 18.7Missense obs/exp: 220 / 298.7Syn Z: -0.77

ClinVar Variant Classifications

207 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic4

VUS104

Likely Benign83

Benign4

Conflicting5

Pathogenic

Likely Pathogenic

104

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	1	0	3
Likely Pathogenic	4	0	0	0	4
VUS	5	96	3	0	104
Likely Benign	0	0	7	76	83
Benign	0	0	4	0	4
Conflicting	—				5
Total	10	97	15	76	203

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

38 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap PDP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →