PDK4

pyruvate dehydrogenase kinase 4

Basic information

Region (hg38): 7:95583499-95596516

Links

ENSG00000004799 ∙ NCBI:5166 ∙ OMIM:602527 ∙ HGNC:8812 ∙ Uniprot:Q16654 ∙ 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 PDK4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDK4 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			18		1	19
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	19	1	1

Variants in PDK4

This is a list of pathogenic ClinVar variants found in the PDK4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-95585665-G-T		not specified	Uncertain significance (Jul 13, 2022)
7-95585748-C-T		not specified	Uncertain significance (Feb 05, 2024)
7-95587041-C-G		not specified	Uncertain significance (Jun 04, 2024)
7-95587429-T-G		not specified	Uncertain significance (Sep 21, 2023)
7-95587431-C-T		not specified	Uncertain significance (Jun 07, 2023)
7-95587500-A-G		not specified	Uncertain significance (May 17, 2023)
7-95587513-C-T		not specified	Uncertain significance (Apr 04, 2024)
7-95587717-G-C			Likely benign (Jul 18, 2018)
7-95587738-G-T		not specified	Uncertain significance (Dec 07, 2022)
7-95587745-T-G		not specified	Uncertain significance (Feb 23, 2023)
7-95587774-G-A		not specified	Uncertain significance (Apr 17, 2024)
7-95589711-A-C		not specified	Uncertain significance (Apr 20, 2024)
7-95591994-C-T		not specified	Uncertain significance (Feb 10, 2022)
7-95592050-G-A		not specified	Uncertain significance (Apr 08, 2022)
7-95592595-G-T		not specified	Uncertain significance (Dec 22, 2023)
7-95592767-G-T		not specified	Uncertain significance (Feb 15, 2023)
7-95592881-T-A		not specified	Uncertain significance (Dec 15, 2023)
7-95592889-T-C			Benign (Apr 02, 2018)
7-95592926-G-C		not specified	Uncertain significance (Dec 27, 2023)
7-95595065-G-A		not specified	Uncertain significance (Jul 19, 2022)
7-95595117-C-G		not specified	Uncertain significance (Oct 05, 2023)
7-95595123-G-A			Uncertain significance (Apr 01, 2019)
7-95596203-T-G		not specified	Uncertain significance (Jun 07, 2023)
7-95596220-T-G		not specified	Uncertain significance (Apr 09, 2024)
7-95596235-A-C		Malignant tumor of prostate	Uncertain significance (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDK4	protein_coding	protein_coding	ENST00000005178	11	12993

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.14e-12	0.149	125666	0	82	125748	0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.351	208	223	0.934	0.0000112	2677
Missense in Polyphen		97	102.38	0.94747		1176
Synonymous	-1.27	92	77.8	1.18	0.00000367	781
Loss of Function	0.677	19	22.5	0.846	0.00000117	273

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000711	0.000703
Ashkenazi Jewish	0.00	0.00
East Asian	0.000441	0.000381
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000390	0.000387
Middle Eastern	0.000441	0.000381
South Asian	0.000329	0.000327
Other	0.000498	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Kinase that plays a key role in 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 in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. 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. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism. {ECO:0000269|PubMed:15955060, ECO:0000269|PubMed:18658136, ECO:0000269|PubMed:21816445, ECO:0000269|PubMed:21852536}.
• Pathway: Estrogen Receptor Pathway;Nuclear Receptors Meta-Pathway;Amino Acid metabolism;Signal Transduction;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: 0.354

Intolerance Scores

• loftool: 0.801
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Haploinsufficiency Scores

• pHI: 0.215
• hipred: N
• hipred_score: 0.443
• ghis: 0.486

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.961

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pdk4
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; skeleton phenotype; hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: glucose metabolic process;protein phosphorylation;regulation of pH;insulin receptor signaling pathway;cellular response to starvation;regulation of acetyl-CoA biosynthetic process from pyruvate;regulation of cellular ketone metabolic process;regulation of glucose metabolic process;regulation of fatty acid biosynthetic process;glucose homeostasis;response to starvation;regulation of bone resorption;regulation of fatty acid oxidation;cellular response to fatty acid;reactive oxygen species metabolic process;negative regulation of anoikis
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: protein kinase activity;pyruvate dehydrogenase (acetyl-transferring) kinase activity;ATP binding