PDK2

pyruvate dehydrogenase kinase 2

Basic information

Region (hg38): 17:50094737-50112152

Links

ENSG00000005882

∙ NCBI:5164 ∙ OMIM:602525 ∙ HGNC:8810 ∙ Uniprot:Q15119 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDK2 gene.

not_specified (28 variants)
not_provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDK2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002611.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous					2 clinvar	2
missense			27 clinvar	1 clinvar		28
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	27	1	2

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDK2	protein_coding	protein_coding	ENST00000503176	11	17416

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000371	0.950	125719	1	28	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.05	155	245	0.632	0.0000142	2667
Missense in Polyphen		59	95.652	0.61682		1043
Synonymous	-0.958	116	104	1.12	0.00000691	773
Loss of Function	1.85	12	21.2	0.567	0.00000115	230

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000183	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000469	0.0000462
European (Non-Finnish)	0.000118	0.000114
Middle Eastern	0.000109	0.000109
South Asian	0.000200	0.000196
Other	0.000657	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis. {ECO:0000269|PubMed:17222789, ECO:0000269|PubMed:19833728, ECO:0000269|PubMed:21283817, ECO:0000269|PubMed:22123926, ECO:0000269|PubMed:7499431, ECO:0000269|PubMed:9787110}.;
Pathway: Signal Transduction;mtor signaling pathway;regulation of eif-4e and p70s6 kinase;pten dependent cell cycle arrest and apoptosis;skeletal muscle hypertrophy is regulated via akt-mtor pathway;Regulation of pyruvate dehydrogenase (PDH) complex;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Signaling by Retinoic Acid;Signaling by Nuclear Receptors (Consensus)

Recessive Scores

pRec: 0.172

Intolerance Scores

loftool: 0.575
rvis_EVS: -0.23
rvis_percentile_EVS: 37.11

Haploinsufficiency Scores

pHI: 0.0947
hipred: Y
hipred_score: 0.800
ghis: 0.536

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.978

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Pdk2
Phenotype: muscle phenotype;

Gene ontology

Biological process: glucose metabolic process;regulation of gluconeogenesis;protein phosphorylation;regulation of pH;insulin receptor signaling pathway;regulation of acetyl-CoA biosynthetic process from pyruvate;regulation of cellular ketone metabolic process;regulation of glucose metabolic process;cellular response to nutrient;cellular response to reactive oxygen species;glucose homeostasis;regulation of calcium-mediated signaling;intrinsic apoptotic signaling pathway by p53 class mediator
Cellular component: nucleoplasm;mitochondrion;mitochondrial matrix;cytosol;mitochondrial pyruvate dehydrogenase complex
Molecular function: protein kinase activity;pyruvate dehydrogenase (acetyl-transferring) kinase activity;ATP binding;protein homodimerization activity