PRKAG1
protein kinase AMP-activated non-catalytic subunit gamma 1
Basic information
Region (hg38): 12:49002273-49018807
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 PRKAG1 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 | 13 | 13 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 13 | 0 | 0 |
Variants in PRKAG1
This is a list of pathogenic ClinVar variants found in the PRKAG1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-49002905-C-A | EBV-positive nodal T- and NK-cell lymphoma | Likely benign (-) | ||
| 12-49003186-A-T | not specified | Uncertain significance (Dec 16, 2023) | ||
| 12-49003203-G-C | not specified | Uncertain significance (Aug 26, 2022) | ||
| 12-49003817-C-T | not specified | Uncertain significance (Apr 09, 2024) | ||
| 12-49003819-T-C | not specified | Uncertain significance (May 26, 2023) | ||
| 12-49003834-G-A | not specified | Uncertain significance (May 08, 2024) | ||
| 12-49003837-C-T | not specified | Uncertain significance (Oct 29, 2021) | ||
| 12-49004572-G-T | not specified | Uncertain significance (Aug 08, 2023) | ||
| 12-49004581-C-T | not specified | Uncertain significance (Jul 06, 2021) | ||
| 12-49005325-C-T | not specified | Uncertain significance (Nov 18, 2022) | ||
| 12-49005789-A-G | not specified | Uncertain significance (Nov 03, 2023) | ||
| 12-49005805-G-A | not specified | Uncertain significance (Aug 16, 2021) | ||
| 12-49005826-A-G | not specified | Uncertain significance (Nov 08, 2021) | ||
| 12-49005837-T-C | not specified | Uncertain significance (Jan 09, 2024) | ||
| 12-49013080-C-T | not specified | Uncertain significance (Oct 06, 2021) | ||
| 12-49013100-G-A | not specified | Uncertain significance (Jul 26, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKAG1 | protein_coding | protein_coding | ENST00000316299 | 12 | 16924 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0000362 | 0.990 | 125717 | 0 | 31 | 125748 | 0.000123 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.85 | 113 | 183 | 0.616 | 0.00000969 | 2204 |
| Missense in Polyphen | 24 | 59.378 | 0.40419 | 763 | ||
| Synonymous | 0.353 | 66 | 69.8 | 0.946 | 0.00000352 | 675 |
| Loss of Function | 2.28 | 11 | 22.7 | 0.484 | 0.00000139 | 245 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000210 | 0.000210 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000132 | 0.000132 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.000168 | 0.000163 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: AMP/ATP-binding 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. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive. {ECO:0000269|PubMed:21680840}.;
- Pathway
- 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);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);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;Angiopoietin Like Protein 8 Regulatory Pathway;Leptin and adiponectin;Lipid Metabolism Pathway;Liver steatosis AOP;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Signal Transduction;Gene expression (Transcription);Vesicle-mediated transport;reversal of insulin resistance by leptin;rho-selective guanine exchange factor akap13 mediates stress fiber formation;chrebp regulation by carbohydrates and camp;protein kinase a at the centrosome;Membrane Trafficking;Generic Transcription Pathway;RNA Polymerase II Transcription;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;insulin Mam;TP53 Regulates Metabolic Genes;akap95 role in mitosis and chromosome dynamics;Macroautophagy;Cellular responses to external stimuli;IL-7 signaling;JAK STAT pathway and regulation;EPO signaling;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Activation of PPARGC1A (PGC-1alpha) by phosphorylation;Mitochondrial biogenesis;Translocation of GLUT4 to the plasma membrane;VEGF;insulin;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.157
Intolerance Scores
- loftool
- 0.337
- rvis_EVS
- 0.19
- rvis_percentile_EVS
- 66.82
Haploinsufficiency Scores
- pHI
- 0.622
- hipred
- Y
- hipred_score
- 0.694
- ghis
- 0.475
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkag1
- Phenotype
- liver/biliary system phenotype; 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; immune system phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- regulation of glycolytic process;protein phosphorylation;fatty acid biosynthetic process;cell cycle arrest;signal transduction;spermatogenesis;positive regulation of gene expression;macroautophagy;positive regulation of protein kinase activity;import into nucleus;regulation of protein serine/threonine kinase activity
- Cellular component
- nucleoplasm;cytosol;membrane;nucleotide-activated protein kinase complex
- Molecular function
- protein kinase activity;AMP-activated protein kinase activity;cAMP-dependent protein kinase activity;protein binding;ATP binding;cAMP-dependent protein kinase regulator activity;AMP binding;protein kinase binding;ADP binding