PDPK1
3-phosphoinositide dependent protein kinase 1, the group of AGC family kinases
Basic information
Region (hg38): 16:2537979-2603190
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDPK1 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 | 3 | |||||
| missense | 15 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 15 | 3 | 0 |
Variants in PDPK1
This is a list of pathogenic ClinVar variants found in the PDPK1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 16-2538131-C-A | not specified | Uncertain significance (Dec 15, 2022) | ||
| 16-2557811-A-G | not specified | Uncertain significance (Jul 11, 2023) | ||
| 16-2557829-A-G | not specified | Uncertain significance (Jul 14, 2021) | ||
| 16-2557854-G-A | not specified | Uncertain significance (May 13, 2024) | ||
| 16-2557865-G-A | not specified | Uncertain significance (Apr 13, 2022) | ||
| 16-2557872-T-A | not specified | Uncertain significance (Aug 14, 2023) | ||
| 16-2557893-C-T | not specified | Uncertain significance (Oct 29, 2021) | ||
| 16-2557895-C-A | not specified | Uncertain significance (Oct 10, 2023) | ||
| 16-2561869-G-A | not specified | Uncertain significance (Aug 10, 2021) | ||
| 16-2577488-C-T | not specified | Uncertain significance (Oct 05, 2021) | ||
| 16-2586755-C-T | not specified | Uncertain significance (Aug 08, 2022) | ||
| 16-2586812-C-T | not specified | Uncertain significance (Sep 20, 2023) | ||
| 16-2586829-G-C | not specified | Uncertain significance (Nov 13, 2023) | ||
| 16-2597124-G-A | not specified | Uncertain significance (Jun 23, 2023) | ||
| 16-2597216-C-A | not specified | Uncertain significance (Aug 09, 2021) | ||
| 16-2597689-C-T | PDPK1-related disorder | Likely benign (Jun 18, 2019) | ||
| 16-2597733-G-A | not specified | Uncertain significance (Jul 27, 2022) | ||
| 16-2597749-G-A | PDPK1-related disorder | Likely benign (Mar 13, 2019) | ||
| 16-2597752-C-T | PDPK1-related disorder | Likely benign (Feb 27, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PDPK1 | protein_coding | protein_coding | ENST00000342085 | 14 | 65225 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.980 | 0.0199 | 125737 | 0 | 11 | 125748 | 0.0000437 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.01 | 95 | 168 | 0.564 | 0.0000100 | 3596 |
| Missense in Polyphen | 9 | 32.665 | 0.27552 | 1013 | ||
| Synonymous | -0.300 | 76 | 72.7 | 1.04 | 0.00000499 | 1042 |
| Loss of Function | 3.52 | 1 | 16.4 | 0.0610 | 9.63e-7 | 388 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000971 | 0.0000967 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF- kappa-B activation in macrophages. Isoform 3 is catalytically inactive. {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10480933, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:12167717, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:17371830, ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9094314, ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9707564, ECO:0000269|PubMed:9768361}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Non-small cell lung cancer - Homo sapiens (human);Focal adhesion - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Aldosterone-regulated sodium reabsorption - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Apoptosis - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Insulin Signalling;IGF-Core;MicroRNAs in cardiomyocyte hypertrophy;Angiogenesis overview;Integrin-mediated Cell Adhesion;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Signaling Pathways in Glioblastoma;B Cell Receptor Signaling Pathway;Interleukin-11 Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Cardiac Hypertrophic Response;Focal Adhesion;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Leptin Insulin Overlap;PPAR signaling pathway;Endometrial cancer;PI3K-Akt Signaling Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;T-Cell antigen Receptor (TCR) Signaling Pathway;Serotonin HTR1 Group and FOS Pathway;Signaling by GPCR;Disease;Signal Transduction;Gene expression (Transcription);mtor signaling pathway;role of erk5 in neuronal survival pathway;human cytomegalovirus and map kinase pathways;influence of ras and rho proteins on g1 to s transition;trefoil factors initiate mucosal healing;transcription factor creb and its extracellular signals;regulation of eif-4e and p70s6 kinase;il-2 receptor beta chain in t cell activation;akt signaling pathway;phospholipase c signaling pathway;ras signaling pathway;corticosteroids and cardioprotection;phospholipids as signalling intermediaries;regulation of bad phosphorylation;vegf hypoxia and angiogenesis;b cell survival pathway;VEGFA-VEGFR2 Pathway;nfat and hypertrophy of the heart ;phosphoinositides and their downstream targets;skeletal muscle hypertrophy is regulated via akt-mtor pathway;trka receptor signaling pathway;role of erbb2 in signal transduction and oncology;Generic Transcription Pathway;Downstream TCR signaling;TCR signaling;Activation of AKT2;CD28 dependent PI3K/Akt signaling;CD28 co-stimulation;PI3K Cascade;Costimulation by the CD28 family;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;RNA Polymerase II Transcription;Integrin alphaIIb beta3 signaling;Fc epsilon receptor (FCERI) signaling;IGF signaling;Innate Immune System;Immune System;Ghrelin;Adaptive Immune System;insulin Mam;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Neuronal System;BCR;actions of nitric oxide in the heart;GPVI-mediated activation cascade;RHO GTPases activate PKNs;Platelet Aggregation (Plug Formation);Platelet activation, signaling and aggregation;IL-7 signaling;RHO GTPase Effectors;Signaling by Rho GTPases;TGF_beta_Receptor;role of nicotinic acetylcholine receptors in the regulation of apoptosis;control of skeletal myogenesis by hdac and calcium/calmodulin-dependent kinase (camk);EGFR1;Integrin signaling;CXCR4-mediated signaling events;ErbB1 downstream signaling;Hemostasis;the igf-1 receptor and longevity;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;BCR signaling pathway;PIP3 activates AKT signaling;JAK STAT pathway and regulation;PDGF;EPO signaling;Regulation of TP53 Activity;Class I PI3K signaling events;Transcriptional Regulation by TP53;Signaling by VEGF;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;RSK activation;CREB phosphorylation through the activation of Ras;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by Receptor Tyrosine Kinases;VEGF;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;Intracellular signaling by second messengers;mTOR signaling pathway;Insulin Pathway;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);IL8- and CXCR1-mediated signaling events;TCR signaling in naïve CD8+ T cells;CXCR3-mediated signaling events;IGF1 pathway;Signaling events mediated by Stem cell factor receptor (c-Kit);FAS (CD95) signaling pathway;Class I PI3K signaling events mediated by Akt;Trk receptor signaling mediated by PI3K and PLC-gamma;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);IL8- and CXCR2-mediated signaling events;FGF signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;TCR signaling in naïve CD4+ T cells;TGF-beta receptor signaling;VEGFR1 specific signals;CD4 T cell receptor signaling-NFkB cascade;Role of LAT2/NTAL/LAB on calcium mobilization;VEGFR2 mediated vascular permeability;insulin;VEGFR2 mediated cell proliferation;CD4 T cell receptor signaling
(Consensus)
Recessive Scores
- pRec
- 0.256
Haploinsufficiency Scores
- pHI
- 0.490
- hipred
- Y
- hipred_score
- 0.748
- ghis
- 0.648
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pdpk1
- Phenotype
- limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; endocrine/exocrine gland phenotype; neoplasm; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);
Gene ontology
- Biological process
- stimulatory C-type lectin receptor signaling pathway;type B pancreatic cell development;protein phosphorylation;negative regulation of protein kinase activity;hyperosmotic response;epidermal growth factor receptor signaling pathway;positive regulation of phospholipase activity;negative regulation of cardiac muscle cell apoptotic process;cell migration;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;calcium-mediated signaling;actin cytoskeleton organization;platelet activation;negative regulation of transforming growth factor beta receptor signaling pathway;T cell costimulation;activation of protein kinase B activity;cellular response to insulin stimulus;negative regulation of toll-like receptor signaling pathway;intracellular signal transduction;Fc-epsilon receptor signaling pathway;regulation of I-kappaB kinase/NF-kappaB signaling;regulation of mast cell degranulation;negative regulation of neuron apoptotic process;positive regulation of blood vessel endothelial cell migration;positive regulation of angiogenesis;protein autophosphorylation;focal adhesion assembly;T cell receptor signaling pathway;positive regulation of release of sequestered calcium ion into cytosol;cellular response to epidermal growth factor stimulus;extrinsic apoptotic signaling pathway;positive regulation of protein localization to plasma membrane;positive regulation of sprouting angiogenesis;positive regulation of vascular endothelial cell proliferation;cellular response to brain-derived neurotrophic factor stimulus;negative regulation of endothelial cell apoptotic process
- Cellular component
- nucleoplasm;cytoplasm;cytosol;plasma membrane;focal adhesion;postsynaptic density;cytoplasmic vesicle;cell projection;perikaryon
- Molecular function
- protein serine/threonine kinase activity;3-phosphoinositide-dependent protein kinase activity;insulin receptor binding;protein binding;ATP binding;phospholipase activator activity;kinase activity;protein kinase binding;phospholipase binding