PDK2

Chr 17

pyruvate dehydrogenase kinase 2

Also known as: PDHK2, PDKII

NCBI Gene: 5164UniProt: Q15119

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. Overexpression of this gene may play a role in both cancer and diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

0
Active trials
53
ClinVar variants
14
Pathogenic / LP
2.0
Missense Z
0.92
LOEUF
10
Pubs (2 yr)
Clinical Summary— PDK2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 35 VUS of 53 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.92LOEUF
pLI 0.000
Z-score 1.85
OE 0.57 (0.36–0.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.05Z-score
OE missense 0.63 (0.55–0.72)
155 obs / 245.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.57 (0.36–0.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.63 (0.55–0.72)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 12 / 21.2Missense obs/exp: 155 / 245.2Syn Z: -0.96

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic1
VUS35
Likely Benign1
Benign3
13
Pathogenic
1
Likely Pathogenic
35
VUS
1
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
1
0
1
VUS
0
33
2
0
35
Likely Benign
0
1
0
0
1
Benign
0
0
1
2
3
Total03417253

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

View in ClinVar →

Protein Context — Lollipop Plot

PDK2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PI3K/Akt signalling pathway and cancer.
Fresno Vara JA et al.·Cancer Treat Rev
2004Review
The OGT-c-Myc-PDK2 axis rewires the TCA cycle and promotes colorectal tumor growth.
Wang H et al.·Cell Death Differ
2024
Identification of programmed cell death-related genes and diagnostic biomarkers in endometriosis using a machine learning and Mendelian randomization approach.
Xie ZW et al.·Front Endocrinol (Lausanne)
2024
PDK2-enhanced glycolysis aggravates fibrosis via IL11 signaling pathway in Graves' orbitopathy.
Peng Z et al.·Front Immunol
2025
Depression, anxiety, and stress impair sperm quality via dysregulation of the mitochondrial PDK-PDC axis.
Wang W et al.·Reprod Biol Endocrinol
2025
PDK2 and ABCG2 genes polymorphisms are correlated with blood glucose levels and uric acid in Tibetan gout patients.
Ren YC et al.·Genet Mol Res
2016Cohort
Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia.
Cui L et al.·Cancer Gene Ther
2020
The chemical and biological properties of natural resorcylic acid lactones.
Gao Y et al.·Nat Prod Rep
2025Review
Reversing tozasertib resistance in glioma through inhibition of pyruvate dehydrogenase kinases.
Jane EP et al.·Mol Oncol
2022
Mechanism of Circ_HECW2 regulating osteoblast apoptosis in osteoporosis by attenuating the maturation of miR-1224-5p.
Zhang C et al.·J Orthop Surg Res
2024Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Identifying potential drug targets for sepsis-related adult respiratory distress syndrome through comprehensive genetic analysis and druggability assessment
Weng J et al.·J Glob Health
2025
Scutellarin Rescued Mitochondrial Damage through Ameliorating Mitochondrial Glucose Oxidation via the Pdk-Pdc Axis
Sheng N et al.·Adv Sci (Weinh)
2023
PDK1- and PDK2-mediated metabolic reprogramming contributes to the TGFbeta1-promoted stem-like properties in head and neck cancer
Sun WH et al.·Cancer Metab
2022
Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1alpha axis and insulin sensitivity
Luo Y et al.·Anim Nutr
2022
Targeting PDK2 rescues stress-induced impaired brain energy metabolism.
Wang C et al.·Mol Psychiatry
2023
The novel circular RNA HIPK3 accelerates the proliferation and invasion of hepatocellular carcinoma cells by sponging the micro RNA-124 or micro RNA-506/pyruvate dehydrogenase kinase 2 axis
Yu Q et al.·Bioengineered
2022
circPTP4A2-miR-330-5p-PDK2 Signaling Facilitates In Vivo Survival of HuMSCs on SF-SIS Scaffolds and Improves the Repair of Damaged Endometrium
Zheng Y et al.·Oxid Med Cell Longev
2022
Circ_0091579 enhances the malignancy of hepatocellular carcinoma via miR-1287/PDK2 axis
Shu J et al.·Open Life Sci
2021
Top 8 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients