PRKG1
protein kinase cGMP-dependent 1, the group of MicroRNA protein coding host genes|AGC family kinases
Basic information
Region (hg38): 10:50990888-52298423
Previous symbols: [ "PRKGR1B", "PRKG1B" ]
Links
Phenotypes
GenCC
Source:
- aortic aneurysm, familial thoracic 8 (Strong), mode of inheritance: AD
- aortic aneurysm, familial thoracic 8 (Moderate), mode of inheritance: AD
- familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
- familial thoracic aortic aneurysm and aortic dissection (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Aortic aneurysm, familial thoracic 8 | AD | Cardiovascular | Individuals have been described as suffering from sudden death secondary to aortic dissection/rupture, and surveillance and preventive measures, as well as early treatment of disease-related manifestations (including aortic aneurysms as well as other vascular anomalies), may help ameloriate morbidity and mortality | Cardiovascular | 16646045; 23910461 |
ClinVar
This is a list of variants' phenotypes submitted to
- Aortic_aneurysm,_familial_thoracic_8 (532 variants)
- Familial_thoracic_aortic_aneurysm_and_aortic_dissection (335 variants)
- not_provided (160 variants)
- not_specified (148 variants)
- PRKG1-related_disorder (23 variants)
- Connective_tissue_disorder (12 variants)
- Schizophrenia (1 variants)
- Gestational_diabetes_mellitus_uncontrolled (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKG1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006258.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 263 | 270 | ||||
| missense | 295 | 305 | ||||
| nonsense | 4 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 1 | 0 | 307 | 272 | 5 |
Highest pathogenic variant AF is 6.8496e-7
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKG1 | protein_coding | protein_coding | ENST00000373980 | 18 | 1307166 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000623 | 125722 | 0 | 7 | 125729 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.98 | 211 | 373 | 0.566 | 0.0000184 | 4538 |
| Missense in Polyphen | 58 | 130.27 | 0.44524 | 1703 | ||
| Synonymous | -0.931 | 150 | 136 | 1.10 | 0.00000713 | 1241 |
| Loss of Function | 5.19 | 4 | 38.9 | 0.103 | 0.00000190 | 490 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000291 | 0.0000291 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000945 | 0.0000924 |
| European (Non-Finnish) | 0.0000353 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine protein kinase that acts as key mediator of the nitric oxide (NO)/cGMP signaling pathway. GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates MRVI1/IRAG and inhibits IP3- induced Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling alters also gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle. {ECO:0000269|PubMed:10567269, ECO:0000269|PubMed:11162591, ECO:0000269|PubMed:11723116, ECO:0000269|PubMed:12082086, ECO:0000269|PubMed:14608379, ECO:0000269|PubMed:15194681, ECO:0000269|PubMed:16990611, ECO:0000269|PubMed:8182057}.;
- Disease
- DISEASE: Aortic aneurysm, familial thoracic 8 (AAT8) [MIM:615436]: A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. {ECO:0000269|PubMed:23910461}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Platelet activation - Homo sapiens (human);Regulation of lipolysis in adipocytes - Homo sapiens (human);Long-term depression - Homo sapiens (human);Gap junction - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Salivary secretion - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);MicroRNAs in cardiomyocyte hypertrophy;Cardiac Hypertrophic Response;VEGFA-VEGFR2 Signaling Pathway;Signaling by WNT;Signal Transduction;ion channels and their functional role in vascular endothelium;Immune System;Rap1 signalling;Adaptive Immune System;actions of nitric oxide in the heart;IL-7 signaling;Ca2+ pathway;Beta-catenin independent WNT signaling;Hemostasis;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;EPO signaling;cGMP effects;Nitric oxide stimulates guanylate cyclase;VEGF;Platelet homeostasis;Regulation of p38-alpha and p38-beta
(Consensus)
Recessive Scores
- pRec
- 0.707
Intolerance Scores
- loftool
- 0.0367
- rvis_EVS
- -0.8
- rvis_percentile_EVS
- 12.46
Haploinsufficiency Scores
- pHI
- 0.987
- hipred
- Y
- hipred_score
- 0.814
- ghis
- 0.594
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.985
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkg1
- Phenotype
- muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); digestive/alimentary phenotype; immune 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); hematopoietic 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);
Gene ontology
- Biological process
- neuron migration;protein phosphorylation;signal transduction;dendrite development;cGMP-mediated signaling;actin cytoskeleton organization;forebrain development;regulation of GTPase activity;relaxation of vascular smooth muscle;negative regulation of platelet aggregation;negative regulation of vascular smooth muscle cell proliferation;negative regulation of vascular associated smooth muscle cell migration
- Cellular component
- cytoplasm;Golgi apparatus;cytosol;plasma membrane
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;cGMP-dependent protein kinase activity;calcium channel regulator activity;protein binding;ATP binding;cGMP binding