PRKAR1A
protein kinase cAMP-dependent type I regulatory subunit alpha, the group of Protein kinase A subunits
Basic information
Region (hg38): 17:68511779-68551319
Previous symbols: [ "PRKAR1", "TSE1" ]
Links
Phenotypes
GenCC
Source:
- Acrodysostosis 1 with or without hormone resistance (Definitive), mode of inheritance: AD
- pigmented nodular adrenocortical disease, primary, 1 (Strong), mode of inheritance: AD
- pigmented nodular adrenocortical disease, primary, 1 (Moderate), mode of inheritance: AD
- Carney complex, type 1 (Definitive), mode of inheritance: AD
- Acrodysostosis 1 with or without hormone resistance (Strong), mode of inheritance: AD
- acrodysostosis (Supportive), mode of inheritance: AD
- Carney complex (Supportive), mode of inheritance: AD
- familial atrial myxoma (Supportive), mode of inheritance: AD
- primary pigmented nodular adrenocortical disease (Supportive), mode of inheritance: AD
- acrodysostosis with multiple hormone resistance (Supportive), mode of inheritance: AD
- acrodysostosis with multiple hormone resistance (Definitive), mode of inheritance: AD
- Carney complex, type 1 (Definitive), mode of inheritance: AD
- Acrodysostosis 1 with or without hormone resistance (Strong), mode of inheritance: AD
- Carney complex, type 1 (Strong), mode of inheritance: AD
- Carney complex, type 1 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Pigmented nodular adrenocortical disease, primary, 1; Carney complex, type 1; Myxoma, intracardiac; Acrodysostosis 1, with or without hormone resistance | AD | Endocrine; Oncologic | Surveillance for neoplasms (eg, cardiac myxomas), as well as multiple endocrine-related manifestations can allow early detection and treatment, which can involve surgical excision of the neoplasm; Additional surveillance for endocrine abnormalities can allow early interventions | Cardiovascular; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Oncologic | 1263542; 579530; 6329005; 4010501; 3465316; 3365080; 2605794; 2586567; 1571257; 9415461; 9215269; 9805140; 10523219; 10974026; 10973256; 11549623; 12213893; 20507346; 21651393; 22464252; 22464250; 20301463 |
ClinVar
This is a list of variants' phenotypes submitted to
- Carney complex, type 1 (741 variants)
- Hereditary cancer-predisposing syndrome (368 variants)
- not provided (115 variants)
- Acrodysostosis 1 with or without hormone resistance (85 variants)
- not specified (58 variants)
- Carney complex (23 variants)
- Acrodysostosis (18 variants)
- Familial atrial myxoma (8 variants)
- PRKAR1A-related condition (4 variants)
- Familial atrial myxoma;Carney complex, type 1;Pigmented nodular adrenocortical disease, primary, 1;Acrodysostosis 1 with or without hormone resistance (3 variants)
- Pigmented nodular adrenocortical disease, primary, 1 (2 variants)
- Carney complex, type 1;Acrodysostosis 1 with or without hormone resistance;Pigmented nodular adrenocortical disease, primary, 1;Familial atrial myxoma (2 variants)
- Pigmented nodular adrenocortical disease, primary, 1;Acrodysostosis 1 with or without hormone resistance;Carney complex, type 1;Familial atrial myxoma (2 variants)
- Carney complex, type 1;Pigmented nodular adrenocortical disease, primary, 1;Acrodysostosis 1 with or without hormone resistance;Familial atrial myxoma (1 variants)
- Carney complex, type 1;Familial atrial myxoma;Pigmented nodular adrenocortical disease, primary, 1;Acrodysostosis 1 with or without hormone resistance (1 variants)
- Arrhythmogenic right ventricular dysplasia 10 (1 variants)
- Carney complex, type 1;Acrodysostosis 1 with or without hormone resistance;Familial atrial myxoma;Pigmented nodular adrenocortical disease, primary, 1 (1 variants)
- Pigmented nodular adrenocortical disease, primary, 1;Familial atrial myxoma;Carney complex, type 1;Acrodysostosis 1 with or without hormone resistance (1 variants)
- Acrodysostosis 1 with or without hormone resistance;Carney complex, type 1;Familial atrial myxoma;Pigmented nodular adrenocortical disease, primary, 1 (1 variants)
- Pigmented nodular adrenocortical disease, primary, 1;Carney complex, type 1;Familial atrial myxoma;Acrodysostosis 1 with or without hormone resistance (1 variants)
- Acrodysostosis 1 with or without hormone resistance;Pigmented nodular adrenocortical disease, primary, 1;Carney complex (1 variants)
- Familial atrial myxoma;Pigmented nodular adrenocortical disease, primary, 1;Acrodysostosis 1 with or without hormone resistance;Carney complex, type 1 (1 variants)
- Medulloblastoma (1 variants)
- Familial atrial myxoma;Acrodysostosis 1 with or without hormone resistance;Carney complex, type 1;Pigmented nodular adrenocortical disease, primary, 1 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKAR1A 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 | 229 | 231 | ||||
| missense | 284 | 291 | ||||
| nonsense | 16 | 18 | ||||
| start loss | 1 | |||||
| frameshift | 34 | 40 | ||||
| inframe indel | 8 | |||||
| splice donor/acceptor (+/-2bp) | 15 | |||||
| splice region ? | 1 | 34 | 39 | 3 | 77 | |
| non coding ? | 59 | 133 | 40 | 232 | ||
| Total | 60 | 13 | 359 | 363 | 41 |
Highest pathogenic variant AF is 0.00000657
Variants in PRKAR1A
This is a list of pathogenic ClinVar variants found in the PRKAR1A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-68512102-C-A | Benign (May 14, 2021) | |||
| 17-68512233-G-T | Likely benign (May 14, 2021) | |||
| 17-68512311-G-T | Benign (Jun 23, 2018) | |||
| 17-68512386-T-A | Carney complex, type 1 • Acrodysostosis 1 with or without hormone resistance | Uncertain significance (Jan 12, 2018) | ||
| 17-68512467-G-A | PRKAR1A-related disorder | Likely benign (Jul 01, 2022) | ||
| 17-68512468-G-A | PRKAR1A-related disorder | Likely benign (Feb 03, 2022) | ||
| 17-68512480-G-T | Carney complex, type 1 • Acrodysostosis 1 with or without hormone resistance | Benign (Jan 13, 2018) | ||
| 17-68512486-A-G | Benign (Mar 03, 2015) | |||
| 17-68512502-C-T | Carney complex • Acrodysostosis | Uncertain significance (Jun 14, 2016) | ||
| 17-68512506-G-T | not specified | Likely benign (May 26, 2017) | ||
| 17-68512519-A-AGCCTCGCGCCCGCCGCC | Carney complex, type 1 | Uncertain significance (Jan 26, 2022) | ||
| 17-68512530-C-T | Carney complex, type 1 • Acrodysostosis 1 with or without hormone resistance | Uncertain significance (Jan 13, 2018) | ||
| 17-68512539-C-A | Carney complex, type 1 • Acrodysostosis 1 with or without hormone resistance • PRKAR1A-related disorder | Conflicting classifications of pathogenicity (Sep 23, 2019) | ||
| 17-68512540-C-A | Carney complex, type 1 | Uncertain significance (Sep 21, 2023) | ||
| 17-68512540-C-T | Carney complex, type 1 | Uncertain significance (Jan 30, 2023) | ||
| 17-68512541-G-T | Carney complex, type 1 | Uncertain significance (Dec 13, 2021) | ||
| 17-68512542-TC-T | Carney complex, type 1 | Likely benign (May 02, 2023) | ||
| 17-68512543-C-A | Carney complex, type 1 | Uncertain significance (Dec 08, 2023) | ||
| 17-68512543-C-T | Carney complex, type 1 | Uncertain significance (Nov 08, 2022) | ||
| 17-68512544-C-G | Carney complex, type 1 | Uncertain significance (Jul 31, 2022) | ||
| 17-68512544-C-T | Carney complex, type 1 • Acrodysostosis 1 with or without hormone resistance • PRKAR1A-related disorder | Conflicting classifications of pathogenicity (Jan 28, 2024) | ||
| 17-68512545-C-G | Carney complex, type 1 | Uncertain significance (Jan 25, 2024) | ||
| 17-68512546-C-G | Carney complex, type 1 | Uncertain significance (Jan 22, 2024) | ||
| 17-68512548-G-T | Carney complex, type 1 | Uncertain significance (Dec 24, 2021) | ||
| 17-68512549-G-A | Pigmented nodular adrenocortical disease, primary, 1 • Carney complex, type 1 | Uncertain significance (Mar 18, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKAR1A | protein_coding | protein_coding | ENST00000589228 | 10 | 39540 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000148 | 125732 | 0 | 9 | 125741 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.12 | 89 | 219 | 0.406 | 0.0000132 | 2478 |
| Missense in Polyphen | 7 | 53.097 | 0.13184 | 613 | ||
| Synonymous | -2.11 | 103 | 79.1 | 1.30 | 0.00000466 | 744 |
| Loss of Function | 4.64 | 0 | 25.1 | 0.00 | 0.00000164 | 261 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000579 | 0.0000579 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000441 | 0.0000440 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. {ECO:0000269|PubMed:16491121, ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:26405036}.;
- Disease
- DISEASE: Carney complex 1 (CNC1) [MIM:160980]: CNC is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas. {ECO:0000269|PubMed:15371594, ECO:0000269|PubMed:18241045, ECO:0000269|PubMed:22785148, ECO:0000269|PubMed:23323113, ECO:0000269|PubMed:26405036}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Intracardiac myxoma (INTMYX) [MIM:255960]: Inheritance is autosomal recessive. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Primary pigmented nodular adrenocortical disease 1 (PPNAD1) [MIM:610489]: A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. PPNAD1 is most often diagnosed in patients with Carney complex, a multiple neoplasia syndrome. However it can also be observed in patients without other manifestations. {ECO:0000269|PubMed:12213893}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Acrodysostosis 1, with or without hormone resistance (ACRDYS1) [MIM:101800]: A form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone, and gonadotropin. However, not all patients show endocrine abnormalities. {ECO:0000269|PubMed:21651393, ECO:0000269|PubMed:22464250, ECO:0000269|PubMed:22464252, ECO:0000269|PubMed:22723333, ECO:0000269|PubMed:23043190, ECO:0000269|PubMed:23425300, ECO:0000269|PubMed:26405036}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Insulin signaling pathway - Homo sapiens (human);Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;miRs in Muscle Cell Differentiation;Mesodermal Commitment Pathway;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;Lipid Metabolism Pathway;Liver steatosis AOP;Calcium Regulation in the Cardiac Cell;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signaling by GPCR;Signal Transduction;mechanism of gene regulation by peroxisome proliferators via ppara;phospholipase c-epsilon pathway;gata3 participate in activating the th2 cytokine genes expression;repression of pain sensation by the transcriptional regulator dream;transcription factor creb and its extracellular signals;regulation of ck1/cdk5 by type 1 glutamate receptors;nitric oxide signaling pathway;stathmin and breast cancer resistance to antimicrotubule agents;cystic fibrosis transmembrane conductance regulator (cftr) and beta 2 adrenergic receptor (b2ar) pathway;regulation of bad phosphorylation;transcription regulation by methyltransferase of carm1;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;mcalpain and friends in cell motility;chrebp regulation by carbohydrates and camp;signaling pathway from g-protein families;how progesterone initiates the oocyte maturation;attenuation of gpcr signaling;activation of camp-dependent protein kinase pka;Glucagon signaling in metabolic regulation;GPCR Dopamine D1like receptor;Factors involved in megakaryocyte development and platelet production;GPCR Adenosine A2A receptor;GPCR signaling-cholera toxin;Hedgehog;Metabolism;PKA activation;PKA-mediated phosphorylation of CREB;Calmodulin induced events;CaM pathway;Transport of small molecules;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Regulation of insulin secretion;actions of nitric oxide in the heart;Hedgehog ,off, state;DARPP-32 events;IL-7 signaling;GPCR signaling-G alpha s PKA and ERK;Signaling by Hedgehog;EGFR1;Hemostasis;DAG and IP3 signaling;JAK STAT pathway and regulation;EPO signaling;Ca-dependent events;PLC beta mediated events;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;PKA activation in glucagon signalling;Vasopressin regulates renal water homeostasis via Aquaporins;Aquaporin-mediated transport;Integration of energy metabolism;VEGF;GPCR downstream signalling;Intracellular signaling by second messengers;Alpha4 beta1 integrin signaling events
(Consensus)
Recessive Scores
- pRec
- 0.727
Intolerance Scores
- loftool
- 0.0537
- rvis_EVS
- -0.34
- rvis_percentile_EVS
- 30.07
Haploinsufficiency Scores
- pHI
- 0.934
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.656
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- 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
- Prkar1a
- Phenotype
- vision/eye phenotype; digestive/alimentary phenotype; skeleton phenotype; immune system phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; neoplasm; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype; reproductive system 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); 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); normal phenotype; craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- prkar1aa
- Affected structure
- protein kinase activity
- Phenotype tag
- abnormal
- Phenotype quality
- increased occurrence
Gene ontology
- Biological process
- mesoderm formation;renal water homeostasis;regulation of transcription by RNA polymerase II;female meiotic nuclear division;blood coagulation;cGMP-mediated signaling;activation of protein kinase A activity;intracellular signal transduction;sarcomere organization;negative regulation of meiotic nuclear division;negative regulation of activated T cell proliferation;cardiac muscle cell proliferation;cellular response to glucagon stimulus;negative regulation of cAMP-dependent protein kinase activity
- Cellular component
- immunological synapse;cytoplasm;cytosol;axoneme;cAMP-dependent protein kinase complex;membrane;nucleotide-activated protein kinase complex;neuromuscular junction;protein-containing complex;plasma membrane raft;ciliary base;glutamatergic synapse
- Molecular function
- cAMP-dependent protein kinase inhibitor activity;protein binding;cAMP-dependent protein kinase regulator activity;protein domain specific binding;cAMP binding;ubiquitin protein ligase binding;protein kinase A catalytic subunit binding;3',5'-cyclic-GMP phosphodiesterase activity