PRKAA1
protein kinase AMP-activated catalytic subunit alpha 1, the group of Protein kinase AMP-activated catalytic subunit alphas
Basic information
Region (hg38): 5:40759388-40798374
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (8 variants)
- not provided (4 variants)
- Primary amenorrhea (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKAA1 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 | 2 | |||||
| missense | 10 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 1 | |||||
| Total | 0 | 0 | 9 | 2 | 2 |
Variants in PRKAA1
This is a list of pathogenic ClinVar variants found in the PRKAA1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKAA1 | protein_coding | protein_coding | ENST00000354209 | 10 | 38996 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.137 | 0.863 | 125000 | 0 | 15 | 125015 | 0.0000600 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.49 | 189 | 313 | 0.604 | 0.0000152 | 3792 |
| Missense in Polyphen | 71 | 150.02 | 0.47328 | 1791 | ||
| Synonymous | 0.322 | 101 | 105 | 0.960 | 0.00000481 | 1075 |
| Loss of Function | 3.62 | 7 | 27.5 | 0.255 | 0.00000145 | 348 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000290 | 0.0000290 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.0000624 | 0.0000617 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000101 | 0.0000980 |
| Other | 0.000165 | 0.000164 |
dbNSFP
Source:
- Function
- FUNCTION: Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. {ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);Circadian rhythm - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Tight junction - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Metformin Pathway, Pharmacodynamic;AMP-activated Protein Kinase (AMPK) Signaling;Target Of Rapamycin (TOR) Signaling;Energy Metabolism;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;SREBF and miR33 in cholesterol and lipid homeostasis;Leptin signaling pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;JAK-STAT;mir-124 predicted interactions with cell cycle and differentiation;ATM Signaling Network in Development and Disease;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Leptin and adiponectin;Lipid Metabolism Pathway;Liver steatosis AOP;PI3K-Akt Signaling Pathway;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Insulin Signaling;Signal Transduction;Gene expression (Transcription);reversal of insulin resistance by leptin;chrebp regulation by carbohydrates and camp;Generic Transcription Pathway;RNA Polymerase II Transcription;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;insulin Mam;TP53 Regulates Metabolic Genes;Macroautophagy;Cellular responses to external stimuli;IL-7 signaling;EGFR1;JAK STAT pathway and regulation;EPO signaling;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Leptin;VEGF;insulin
(Consensus)
Recessive Scores
- pRec
- 0.131
Intolerance Scores
- loftool
- 0.575
- rvis_EVS
- -0.49
- rvis_percentile_EVS
- 22.09
Haploinsufficiency Scores
- pHI
- 0.909
- hipred
- Y
- hipred_score
- 0.704
- ghis
- 0.680
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkaa1
- Phenotype
- growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; immune system phenotype;
Gene ontology
- Biological process
- activation of MAPK activity;response to hypoxia;glucose metabolic process;protein phosphorylation;fatty acid biosynthetic process;cholesterol biosynthetic process;cell cycle arrest;signal transduction;positive regulation of cell population proliferation;lipid biosynthetic process;response to UV;cold acclimation;response to gamma radiation;positive regulation of autophagy;positive regulation of gene expression;negative regulation of gene expression;response to activity;Wnt signaling pathway;macroautophagy;fatty acid oxidation;response to caffeine;cellular response to nutrient levels;negative regulation of TOR signaling;regulation of peptidyl-serine phosphorylation;cellular response to oxidative stress;histone-serine phosphorylation;intracellular signal transduction;cellular response to glucose starvation;glucose homeostasis;regulation of circadian rhythm;negative regulation of apoptotic process;positive regulation of cholesterol biosynthetic process;positive regulation of glycolytic process;negative regulation of glucosylceramide biosynthetic process;negative regulation of insulin receptor signaling pathway;rhythmic process;positive regulation of skeletal muscle tissue development;negative regulation of lipid catabolic process;protein heterooligomerization;fatty acid homeostasis;regulation of vesicle-mediated transport;motor behavior;CAMKK-AMPK signaling cascade;regulation of stress granule assembly;neuron cellular homeostasis;cellular response to hydrogen peroxide;regulation of microtubule cytoskeleton organization;cellular response to calcium ion;cellular response to glucose stimulus;cellular response to ethanol;cellular response to prostaglandin E stimulus;cellular response to organonitrogen compound;cellular response to hypoxia;energy homeostasis;response to camptothecin;positive regulation of mitochondrial transcription;positive regulation of cellular protein localization;positive regulation of protein targeting to mitochondrion;negative regulation of tubulin deacetylation;positive regulation of peptidyl-lysine acetylation
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol;apical plasma membrane;nuclear speck;axon;dendrite;nucleotide-activated protein kinase complex;neuronal cell body
- Molecular function
- chromatin binding;protein kinase activity;protein serine/threonine kinase activity;AMP-activated protein kinase activity;cAMP-dependent protein kinase activity;protein binding;ATP binding;protein C-terminus binding;histone serine kinase activity;metal ion binding;[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity;tau protein binding;tau-protein kinase activity;[acetyl-CoA carboxylase] kinase activity