PRKACB
protein kinase cAMP-activated catalytic subunit beta, the group of AGC family kinases|Protein kinase A subunits
Basic information
Region (hg38): 1:84078062-84238498
Links
Phenotypes
GenCC
Source:
- cardioacrofacial dysplasia 2 (Moderate), mode of inheritance: AD
- cardioacrofacial dysplasia 2 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cardioacrofacial dysplasia 2 | AD | Cardiovascular | Cardioacrofacial dysplasia 2 may include congenital cardiovascular anomalies (among other features), and awareness may allow prompt recognition and management of these issues | Cardiovascular; Craniofacial; Dental; Musculoskeletal; Neurologic | 33058759 |
| Mosaicism has been described in Cardioacrofacial dysplasia 2 |
ClinVar
This is a list of variants' phenotypes submitted to
- Cardioacrofacial dysplasia 2 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKACB 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 | 15 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 1 | |||||
| Total | 1 | 0 | 16 | 0 | 0 |
Variants in PRKACB
This is a list of pathogenic ClinVar variants found in the PRKACB region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-84144361-A-C | Uncertain significance (Dec 03, 2022) | |||
| 1-84144444-G-A | Inborn genetic diseases | Uncertain significance (Jul 25, 2023) | ||
| 1-84144479-G-A | Inborn genetic diseases | Uncertain significance (Dec 28, 2023) | ||
| 1-84144497-G-A | Inborn genetic diseases | Uncertain significance (Dec 12, 2023) | ||
| 1-84144525-A-G | Inborn genetic diseases | Uncertain significance (Sep 07, 2022) | ||
| 1-84144531-C-T | Inborn genetic diseases | Uncertain significance (Aug 15, 2023) | ||
| 1-84144541-C-A | PRKACB-related disorder | Uncertain significance (Dec 19, 2022) | ||
| 1-84164417-G-A | PRKACB-related disorder | Uncertain significance (Mar 25, 2024) | ||
| 1-84175057-G-A | PRKACB-related disorder | Uncertain significance (Jul 19, 2024) | ||
| 1-84179191-G-A | Uncertain significance (Mar 01, 2024) | |||
| 1-84179234-C-T | Uncertain significance (Sep 02, 2022) | |||
| 1-84182209-G-A | Inborn genetic diseases | Uncertain significance (Feb 22, 2023) | ||
| 1-84182237-C-A | Uncertain significance (Jan 09, 2024) | |||
| 1-84182252-C-T | Cardioacrofacial dysplasia 2 | Pathogenic (Dec 28, 2020) | ||
| 1-84182295-G-C | Inborn genetic diseases | Uncertain significance (Jan 12, 2024) | ||
| 1-84184051-G-C | Uncertain significance (Jan 05, 2024) | |||
| 1-84184061-C-A | Cardioacrofacial dysplasia 2 | Pathogenic (Dec 28, 2020) | ||
| 1-84184062-A-G | Cardioacrofacial dysplasia 2 | Pathogenic (Dec 28, 2020) | ||
| 1-84184062-A-T | Cardioacrofacial dysplasia 2 | Pathogenic (Feb 02, 2022) | ||
| 1-84185112-T-G | Inborn genetic diseases | Uncertain significance (Aug 22, 2023) | ||
| 1-84196695-G-C | Cardioacrofacial dysplasia 2 | Uncertain significance (May 22, 2022) | ||
| 1-84202743-G-C | Cardioacrofacial dysplasia 2 | Pathogenic (Dec 28, 2020) | ||
| 1-84214199-G-A | Inborn genetic diseases | Uncertain significance (May 24, 2024) | ||
| 1-84214262-T-C | Cardioacrofacial dysplasia 2 | Uncertain significance (Nov 09, 2023) | ||
| 1-84214303-A-G | Inborn genetic diseases | Uncertain significance (Jun 27, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKACB | protein_coding | protein_coding | ENST00000370685 | 10 | 160437 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.351 | 0.649 | 125598 | 0 | 8 | 125606 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.80 | 90 | 202 | 0.445 | 0.00000967 | 2614 |
| Missense in Polyphen | 16 | 65.811 | 0.24312 | 899 | ||
| Synonymous | 0.347 | 65 | 68.7 | 0.947 | 0.00000316 | 716 |
| Loss of Function | 3.35 | 5 | 22.0 | 0.228 | 0.00000107 | 285 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000161 | 0.000153 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000550 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000362 | 0.0000352 |
| Middle Eastern | 0.0000550 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which regulates its ability to bind RNA (PubMed:21880142). {ECO:0000269|PubMed:12420224, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21880142}.;
- Pathway
- Prion diseases - Homo sapiens (human);Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Platelet activation - Homo sapiens (human);Cortisol synthesis and secretion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Regulation of lipolysis in adipocytes - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Tight junction - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Bile secretion - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Vasopressin-regulated water reabsorption - Homo sapiens (human);Gap junction - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Renin secretion - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Taste transduction - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Excitatory Neural Signalling Through 5-HTR 4 and Serotonin;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Intracellular Signalling Through Prostacyclin Receptor and Prostacyclin;Corticotropin Activation of Cortisol Production;Excitatory Neural Signalling Through 5-HTR 7 and Serotonin ;Excitatory Neural Signalling Through 5-HTR 6 and Serotonin ;Vasopressin Regulation of Water Homeostasis;Intracellular Signalling Through PGD2 receptor and Prostaglandin D2;Intracellular Signalling Through LHCGR Receptor and Luteinizing Hormone/Choriogonadotropin;Intracellular Signalling Through FSH Receptor and Follicle Stimulating Hormone;Intracellular Signalling Through Histamine H2 Receptor and Histamine;Dopamine Activation of Neurological Reward System;AMP-activated Protein Kinase (AMPK) Signaling;miRs in Muscle Cell Differentiation;Dopamine metabolism;Common Pathways Underlying Drug Addiction;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;MAPK Signaling Pathway;Chemokine signaling pathway;Lipid Metabolism Pathway;Liver steatosis AOP;Ras Signaling;Hedgehog Signaling Pathway;Calcium Regulation in the Cardiac Cell;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Developmental Biology;Signaling by GPCR;Signal Transduction;mechanism of gene regulation by peroxisome proliferators via ppara;phospholipase c-epsilon pathway;GLI3 is processed to GLI3R by the proteasome;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;HDL assembly;nitric oxide signaling pathway;stathmin and breast cancer resistance to antimicrotubule agents;Plasma lipoprotein assembly;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;VEGFA-VEGFR2 Pathway;rho-selective guanine exchange factor akap13 mediates stress fiber formation;chrebp regulation by carbohydrates and camp;signaling pathway from g-protein families;how progesterone initiates the oocyte maturation;protein kinase a at the centrosome;attenuation of gpcr signaling;activation of camp-dependent protein kinase pka;Metabolism of carbohydrates;Metabolism of lipids;Glucagon signaling in metabolic regulation;PKA-mediated phosphorylation of key metabolic factors;GPCR Dopamine D1like receptor;MAPK6/MAPK4 signaling;Factors involved in megakaryocyte development and platelet production;GPCR Adenosine A2A receptor;GPCR signaling-cholera toxin;CD209 (DC-SIGN) signaling;C-type lectin receptors (CLRs);Hedgehog;Innate Immune System;Immune System;Metabolism;Rap1 signalling;Adaptive Immune System;PKA activation;PKA-mediated phosphorylation of CREB;p73 transcription factor network;Calmodulin induced events;CaM pathway;Transport of small molecules;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Regulation of insulin secretion;Neuronal System;actions of nitric oxide in the heart;akap95 role in mitosis and chromosome dynamics;Degradation of GLI2 by the proteasome;Degradation of GLI1 by the proteasome;Hedgehog ,off, state;DARPP-32 events;Glycolysis;IL-7 signaling;GPCR signaling-G alpha s PKA and ERK;Signaling by Hedgehog;Triglyceride catabolism;Triglyceride metabolism;ROBO receptors bind AKAP5;Glucocorticoid receptor regulatory network;Hemostasis;DAG and IP3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;EPO signaling;Plasma lipoprotein assembly, remodeling, and clearance;Signaling by ROBO receptors;Signaling by VEGF;Ca-dependent events;PLC beta mediated events;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;RET signaling;Axon guidance;CREB phosphorylation through the activation of Adenylate Cyclase;Glucose metabolism;PKA activation in glucagon signalling;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;Vasopressin regulates renal water homeostasis via Aquaporins;Aquaporin-mediated transport;Signaling by Receptor Tyrosine Kinases;Integration of energy metabolism;VEGF;GPCR downstream signalling;Intracellular signaling by second messengers;GMCSF-mediated signaling events;p75(NTR)-mediated signaling;Alpha4 beta1 integrin signaling events;IL3-mediated signaling events
(Consensus)
Recessive Scores
- pRec
- 0.341
Intolerance Scores
- loftool
- 0.434
- rvis_EVS
- -0.43
- rvis_percentile_EVS
- 25.15
Haploinsufficiency Scores
- pHI
- 0.923
- hipred
- Y
- hipred_score
- 0.775
- ghis
- 0.645
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkacb
- Phenotype
- embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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); skeleton phenotype;
Gene ontology
- Biological process
- neural tube closure;stimulatory C-type lectin receptor signaling pathway;renal water homeostasis;protein phosphorylation;signal transduction;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;blood coagulation;activation of protein kinase A activity;high-density lipoprotein particle assembly;negative regulation of meiotic cell cycle;regulation of protein processing;cellular response to glucagon stimulus;response to clozapine;negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning
- Cellular component
- nucleoplasm;centrosome;cytosol;plasma membrane;cAMP-dependent protein kinase complex;intercellular bridge;perinuclear region of cytoplasm;extracellular exosome;ciliary base
- Molecular function
- magnesium ion binding;protein serine/threonine kinase activity;cAMP-dependent protein kinase activity;protein binding;ATP binding;ubiquitin protein ligase binding;protein kinase A regulatory subunit binding