PRKAA2
protein kinase AMP-activated catalytic subunit alpha 2, the group of Protein kinase AMP-activated catalytic subunit alphas
Basic information
Region (hg38): 1:56645313-56715335
Previous symbols: [ "PRKAA" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (10 variants)
- not provided (5 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKAA2 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 | 10 | 10 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 2 | 2 | ||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 10 | 1 | 2 |
Variants in PRKAA2
This is a list of pathogenic ClinVar variants found in the PRKAA2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-56645402-G-C | not specified | Uncertain significance (Dec 17, 2023) | ||
| 1-56645406-C-A | not specified | Uncertain significance (May 18, 2023) | ||
| 1-56645430-C-T | not specified | Uncertain significance (Dec 18, 2023) | ||
| 1-56674374-T-C | Benign (Jul 06, 2018) | |||
| 1-56674397-A-G | PRKAA2-related disorder | Benign (Sep 13, 2019) | ||
| 1-56691485-C-T | not specified | Uncertain significance (Sep 29, 2023) | ||
| 1-56692379-C-T | High myopia | Uncertain significance (Dec 17, 2018) | ||
| 1-56695958-A-G | not specified | Uncertain significance (Feb 16, 2023) | ||
| 1-56696027-T-C | not specified | Uncertain significance (Aug 10, 2021) | ||
| 1-56696099-C-T | PRKAA2-related disorder | Likely benign (Jul 03, 2019) | ||
| 1-56696120-A-G | PRKAA2-related disorder | Likely benign (May 28, 2019) | ||
| 1-56703967-C-T | PRKAA2-related disorder | Benign/Likely benign (Nov 26, 2019) | ||
| 1-56703994-A-G | not specified | Uncertain significance (Oct 10, 2023) | ||
| 1-56704041-G-A | not specified | Uncertain significance (Jan 19, 2022) | ||
| 1-56704116-T-G | not specified | Uncertain significance (Oct 13, 2023) | ||
| 1-56704121-T-C | PRKAA2-related disorder | Benign (Jun 12, 2019) | ||
| 1-56704196-T-A | not specified | Uncertain significance (Jan 31, 2024) | ||
| 1-56704227-G-A | not specified | Uncertain significance (Feb 16, 2023) | ||
| 1-56704348-C-T | not specified | Uncertain significance (Mar 07, 2024) | ||
| 1-56704418-G-A | Likely benign (Aug 07, 2018) | |||
| 1-56704432-C-T | not specified | Uncertain significance (Feb 02, 2022) | ||
| 1-56706197-T-C | Benign (Jun 13, 2018) | |||
| 1-56707511-C-T | not specified | Uncertain significance (Oct 17, 2023) | ||
| 1-56707516-C-T | not specified | Uncertain significance (Apr 26, 2023) | ||
| 1-56707610-C-T | not specified | Uncertain significance (Mar 11, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKAA2 | protein_coding | protein_coding | ENST00000371244 | 9 | 70014 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.53e-8 | 0.936 | 125700 | 0 | 48 | 125748 | 0.000191 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.99 | 207 | 304 | 0.680 | 0.0000159 | 3637 |
| Missense in Polyphen | 60 | 132.12 | 0.45414 | 1545 | ||
| Synonymous | 0.587 | 97 | 105 | 0.927 | 0.00000543 | 1039 |
| Loss of Function | 1.88 | 16 | 26.4 | 0.606 | 0.00000163 | 306 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000494 | 0.000482 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000241 | 0.000237 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.000234 | 0.000229 |
| Other | 0.00 | 0.00 |
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. Involved in insulin receptor/INSR internalization (PubMed:25687571). 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. 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 phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation. Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity). {ECO:0000250|UniProtKB:Q8BRK8, 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:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:7959015}.;
- 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;Diuretics Pathway, Pharmacodynamics;AMP-activated Protein Kinase (AMPK) Signaling;Target Of Rapamycin (TOR) Signaling;Energy Metabolism;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Leptin signaling pathway;Corticotropin-releasing hormone signaling pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;JAK-STAT;fig-met-1-last-solution;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Lipid Metabolism Pathway;Liver steatosis AOP;PI3K-AKT-mTOR - VitD3 Signalling;PI3K-Akt Signaling Pathway;Insulin Signaling;Signal Transduction;Gene expression (Transcription);Vesicle-mediated transport;reversal of insulin resistance by leptin;chrebp regulation by carbohydrates and camp;Membrane Trafficking;Generic Transcription Pathway;Metabolism of lipids;AMPK inhibits chREBP transcriptional activation activity;Import of palmitoyl-CoA into the mitochondrial matrix;RNA Polymerase II Transcription;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;Metabolism;Ghrelin;Fatty acid metabolism;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;Activation of PPARGC1A (PGC-1alpha) by phosphorylation;Mitochondrial biogenesis;Translocation of GLUT4 to the plasma membrane;Integration of energy metabolism;VEGF;insulin;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.230
Intolerance Scores
- loftool
- 0.774
- rvis_EVS
- -0.67
- rvis_percentile_EVS
- 15.62
Haploinsufficiency Scores
- pHI
- 0.964
- hipred
- Y
- hipred_score
- 0.585
- ghis
- 0.628
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.984
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkaa2
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system 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); immune system phenotype; renal/urinary system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- protein phosphorylation;fatty acid biosynthetic process;cholesterol biosynthetic process;cell cycle arrest;signal transduction;lipid biosynthetic process;positive regulation of autophagy;negative regulation of gene expression;response to muscle activity;Wnt signaling pathway;macroautophagy;positive regulation of macroautophagy;regulation of macroautophagy;cellular response to nutrient levels;negative regulation of TOR signaling;cellular response to oxidative stress;histone-serine phosphorylation;intracellular signal transduction;cellular response to drug;cellular response to glucose starvation;regulation of fatty acid biosynthetic process;glucose homeostasis;regulation of circadian rhythm;negative regulation of apoptotic process;positive regulation of glycolytic process;rhythmic process;fatty acid homeostasis;regulation of stress granule assembly;regulation of microtubule cytoskeleton organization;cellular response to calcium ion;cellular response to glucose stimulus;cellular response to prostaglandin E stimulus;energy homeostasis;positive regulation of cellular protein localization;negative regulation of tubulin deacetylation;positive regulation of peptidyl-lysine acetylation
- Cellular component
- nucleus;nucleoplasm;cytoplasm;Golgi apparatus;cytosol;cytoplasmic stress granule;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;protein serine/threonine/tyrosine kinase activity;protein binding;ATP binding;histone serine kinase activity;metal ion binding;[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity;[acetyl-CoA carboxylase] kinase activity