PDK1

pyruvate dehydrogenase kinase 1

Basic information

Region (hg38): 2:172555372-172608669

Links

ENSG00000152256 ∙ NCBI:5163 ∙ OMIM:602524 ∙ HGNC:8809 ∙ Uniprot:Q15118 ∙ 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 PDK1 gene.

• Inborn genetic diseases (16 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDK1 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				1		1
missense			16	1		17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	2	0

Variants in PDK1

This is a list of pathogenic ClinVar variants found in the PDK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-172556194-C-T		not specified	Uncertain significance (May 09, 2022)
2-172556200-C-A		not specified	Uncertain significance (Feb 26, 2024)
2-172556233-T-G		not specified	Uncertain significance (Dec 19, 2023)
2-172556316-C-T		not specified	Uncertain significance (Oct 26, 2023)
2-172558729-A-C		not specified	Uncertain significance (Jun 29, 2022)
2-172558844-A-C		not specified	Uncertain significance (Feb 22, 2023)
2-172562273-A-T		not specified	Uncertain significance (Nov 23, 2022)
2-172562284-A-C		not specified	Uncertain significance (Dec 06, 2021)
2-172562287-T-C			Uncertain significance (Feb 08, 2023)
2-172564503-C-A			Likely benign (Apr 04, 2018)
2-172564513-A-C		not specified	Uncertain significance (Feb 08, 2023)
2-172564518-G-A			Likely benign (Jul 10, 2018)
2-172564559-T-C		not specified	Uncertain significance (Dec 19, 2023)
2-172564574-T-C		not specified	Uncertain significance (Jan 02, 2024)
2-172564658-T-C		not specified	Uncertain significance (Sep 25, 2023)
2-172564679-A-G		not specified	Uncertain significance (May 31, 2023)
2-172564681-C-G			not provided (-)
2-172564998-G-A		not specified	Uncertain significance (Feb 08, 2023)
2-172565038-T-G		not specified	Uncertain significance (Aug 17, 2022)
2-172566909-G-A		not specified	Uncertain significance (May 31, 2023)
2-172566915-G-C		not specified	Uncertain significance (Dec 21, 2022)
2-172568792-A-G		not specified	Uncertain significance (Mar 14, 2023)
2-172570777-C-G		not specified	Uncertain significance (Apr 28, 2022)
2-172570796-C-T		not specified	Uncertain significance (Sep 12, 2023)
2-172586288-G-A		not specified	Uncertain significance (Jun 23, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDK1	protein_coding	protein_coding	ENST00000282077	11	69723

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000110	0.988	125671	0	77	125748	0.000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.15	185	234	0.789	0.0000126	2833
Missense in Polyphen		69	92.034	0.74972		1102
Synonymous	0.473	78	83.5	0.934	0.00000458	838
Loss of Function	2.26	12	24.0	0.501	0.00000132	279

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000211	0.000211
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00163	0.00163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000282	0.000281
Middle Eastern	0.00163	0.00163
South Asian	0.000232	0.000229
Other	0.000164	0.000163

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. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress. {ECO:0000269|PubMed:17683942, ECO:0000269|PubMed:18541534, ECO:0000269|PubMed:22195962, ECO:0000269|PubMed:7499431}.
• Pathway: Central carbon metabolism in cancer - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Axon guidance - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Fc Epsilon Receptor I Signaling in Mast Cells;Integrated Lung Cancer Pathway;T-Cell Receptor and Co-stimulatory Signaling;JAK-STAT;TGF-beta Signaling Pathway;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;fig-met-1-last-solution;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;EPO Receptor Signaling;ErbB Signaling Pathway;DNA Damage Response (only ATM dependent);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;TGF_beta_Receptor;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;TNFalpha (Consensus)

Recessive Scores

• pRec: 0.0828

Intolerance Scores

• loftool: 0.798
• rvis_EVS: -0.31
• rvis_percentile_EVS: 31.93

Haploinsufficiency Scores

• pHI: 0.282
• hipred: Y
• hipred_score: 0.708
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.120

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pdk1
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: glucose metabolic process;protein phosphorylation;cell population proliferation;intrinsic apoptotic signaling pathway in response to oxidative stress;regulation of acetyl-CoA biosynthetic process from pyruvate;regulation of glucose metabolic process;hypoxia-inducible factor-1alpha signaling pathway
• Cellular component: nucleus;nucleolus;mitochondrion;mitochondrial matrix;mitochondrial pyruvate dehydrogenase complex
• Molecular function: protein kinase activity;pyruvate dehydrogenase (acetyl-transferring) kinase activity;protein binding;ATP binding