PROTEIN KINASE A (PKA) SIGNALING PATHWAY (PW:0000543)
Description
Protein
kinase A (PKA) signaling is a widely used intracellular pathway and the major route for channeling the second messenger cAMP signal.
Ligand activated G-protein coupled receptors that transduce the signal via the
Gs alpha subunit of the heterotrimeric G protein lead to activation of the adenylyl
cyclase enzymes (AC) that catalyze the formation of cAMP from ATP. GTP-bound Gs
binds to AC and increases the affinity between the C1 and C2 cytoplasmic
domains whose interface constitutes the ATP binding site. Nine membrane-bound
and one soluble adenylyl cyclase have been so far identified. Most tissues
express more than one AC and almost every AC is expressed in the brain. cAMP
binding to the PKA complex leads to dissociation of the catalytic subunits from
the holoenzyme. In the inactive state, the holoenzyme consists of two catalytic
subunits (C) bound noncovalently to a regulatory dimer (RI or RII). There are two
type I and two type II regulatory subunits and three catalytic subunits in
humans; rodents express only two catalytic subunits. Each regulatory subunit
has two cAMP binding sites; type I has a higher affinity for cAMP than type II.
Binding of four molecules of cAMP to the regulatory dimer induces a
conformational change that leads to dissociation of the holoenzyme and release
of the catalytic monomers. cAMP is hydrolyzed by phosphodiesterases (PDE), the
only enzymes degrading cycling nucleotides. The 21 mammalian genes are
subdivided in 11 families based on kinetic and pharmacological properties. Of these,
3 families are specific for cAMP, 3 other for cGMP and 5 hydrolyze both. PDEs not
only contribute to the regulation of cAMP concentration but also modulate the
duration and extent of cAMP signaling, and thus of PKA. The compartmentalization
of PKA is mediated by the AKAP family of scaffold proteins (
A K inase
A nchoring
P rotein). AKAPs bring together PKA (and other kinases)
along with phosphatases and phosphodiesterases, in some cases AC and target
proteins to fine tune the many outcomes of PKA signaling. 14 Akap genes in
mammals give rise to more than 50 proteins. Primarily they target the regulatory
type II subunits; a few possess dual specificity and bind both subunits types.
The various combinations of AKAP-PKA allow for the diversity of cellular and
tissue distribution of the serine/threonine PKA complexes and the modulation of
their function and underlie the extensive use of this intracellular pathway.
PKA cross-talks or integrates with other signaling pathways. The PKA signaling
pathway has been implicated in many cellular and physiological processes, from
metabolism and reproduction, to cardiac function, memory and learning.
To see the ontology report for annotations,
GViewer and download click here [click to see the ontology report for related GO
term GO:0010737 and entry at Reactome - REACT_15530.1 ]...(less)
Pathway Diagram:
Genes in Pathway:
G
Adcy1 adenylate cyclase 1
ISO RGD
PMID:18948702 RGD:2312469
NCBI chr14:81,911,240...82,020,594
G
Adcy10 adenylate cyclase 10
ISO RGD
PMID:18948702 RGD:2312469
NCBI chr13:77,747,752...77,833,952
G
Adcy2 adenylate cyclase 2
ISO RGD
PMID:18948702 RGD:2312469
NCBI chr 1:34,375,639...34,822,237
G
Adcy3 adenylate cyclase 3
ISO RGD
PMID:18948702 RGD:2312469
NCBI chr 6:27,100,089...27,203,686
G
Adcy4 adenylate cyclase 4
ISO RGD
PMID:18948702 RGD:2312469
NCBI chr15:29,266,280...29,282,153
G
Adcy5 adenylate cyclase 5
ISO RGD
PMID:18948702 RGD:2312469
NCBI chr11:65,471,612...65,618,877
G
Adcy6 adenylate cyclase 6
ISO IDA RGD
PMID:18948702 PMID:15579502 RGD:2312469 , RGD:2313211
NCBI chr 7:129,742,827...129,763,922
G
Adcy7 adenylate cyclase 7
ISO RGD
PMID:18948702 RGD:2312469
NCBI chr19:18,740,875...18,798,924
G
Adcy8 adenylate cyclase 8
ISO RGD
PMID:18948702 RGD:2312469
NCBI chr 7:96,417,310...96,665,911
G
Adcy9 adenylate cyclase 9
ISO RGD
PMID:18948702 RGD:2312469
NCBI chr10:11,138,966...11,262,067
G
Akap1 A-kinase anchoring protein 1
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr10:73,621,021...73,654,123
G
Akap10 A-kinase anchoring protein 10
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr10:46,545,464...46,608,768
G
Akap11 A-kinase anchoring protein 11
ISO IMP RGD
PMID:14715913 PMID:19319965 PMID:18385542 RGD:2312475 , RGD:2312477 , RGD:2312637
NCBI chr15:53,911,635...53,956,138
G
Akap12 A-kinase anchoring protein 12
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr 1:40,730,123...40,819,863
G
Akap13 A-kinase anchoring protein 13
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr 1:129,313,183...129,619,647
G
Akap14 A-kinase anchoring protein 14
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr X:116,395,512...116,410,697
G
Akap2 A-kinase anchoring protein 2
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr 5:72,536,986...72,648,524
G
Akap3 A-kinase anchoring protein 3
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr 4:159,688,049...159,714,067
G
Akap4 A-kinase anchoring protein 4
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr X:15,435,391...15,445,684
G
Akap5 A-kinase anchoring protein 5
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr 6:95,051,527...95,061,075
G
Akap6 A-kinase anchoring protein 6
ISO IMP RGD
PMID:14715913 PMID:19319965 PMID:11296225 RGD:2312475 , RGD:2312477 , RGD:68716
NCBI chr 6:70,184,101...70,624,369
G
Akap7 A-kinase anchoring protein 7
ISO IMP RGD
PMID:14715913 PMID:19319965 PMID:17901878 RGD:2312475 , RGD:2312477 , RGD:2312630
NCBI chr 1:20,087,190...20,217,799
G
Akap8 A-kinase anchoring protein 8
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr 7:11,316,224...11,332,523
G
Akap9 A-kinase anchoring protein 9
ISO RGD
PMID:14715913 PMID:19319965 RGD:2312475 , RGD:2312477
NCBI chr 4:30,056,738...30,192,716
G
Crhr2 corticotropin releasing hormone receptor 2
IMP RGD
PMID:15911134 RGD:5131271
NCBI chr 4:84,222,897...84,265,924
G
Ezr ezrin
ISO RGD
PMID:14715913 RGD:2312475
NCBI chr 1:46,967,961...47,011,505
G
Pde10a phosphodiesterase 10A
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 1:51,765,743...52,218,086
G
Pde11a phosphodiesterase 11A
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 3:60,913,562...61,297,154
G
Pde1a phosphodiesterase 1A
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 3:64,745,140...65,025,178
G
Pde1b phosphodiesterase 1B
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 7:134,627,378...134,654,581
G
Pde1c phosphodiesterase 1C
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 4:85,300,858...85,777,948
G
Pde2a phosphodiesterase 2A
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 1:155,823,590...155,915,434
G
Pde3a phosphodiesterase 3A
ISO RGD
PMID:17376027 PMID:17376027 RGD:2312479 , RGD:2312479
NCBI chr 4:174,172,804...174,443,944
G
Pde3b phosphodiesterase 3B
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 1:168,606,762...168,770,078
G
Pde4a phosphodiesterase 4A
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 8:19,706,649...19,751,937
G
Pde4b phosphodiesterase 4B
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 5:116,799,827...117,367,707
G
Pde4c phosphodiesterase 4C
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr16:18,690,727...18,711,555
G
Pde4d phosphodiesterase 4D
ISO IMP RGD
PMID:17376027 PMID:11296225 RGD:2312479 , RGD:68716
NCBI chr 2:40,014,933...41,529,190
G
Pde7a phosphodiesterase 7A
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 2:101,714,767...101,806,853
G
Pde7b phosphodiesterase 7B
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 1:15,174,001...15,493,267
G
Pde8a phosphodiesterase 8A
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 1:135,166,143...135,288,986
G
Pde8b phosphodiesterase 8B
ISO RGD
PMID:17376027 RGD:2312479
NCBI chr 2:26,275,117...26,479,725
G
Prkaca protein kinase cAMP-activated catalytic subunit alpha
ISO RGD
PMID:14715913 RGD:2312475
NCBI chr19:24,155,081...24,178,430
G
Prkacb protein kinase cAMP-activated catalytic subunit beta
ISO RGD
PMID:14715913 RGD:2312475
NCBI chr 2:235,636,878...235,726,928
G
Prkar1a protein kinase cAMP-dependent type I regulatory subunit alpha
ISO RGD
PMID:14715913 RGD:2312475
NCBI chr10:94,621,042...94,639,534
G
Prkar1b protein kinase cAMP-dependent type I regulatory subunit beta
ISO RGD
PMID:14715913 RGD:2312475
NCBI chr12:15,492,233...15,624,942
G
Prkar2a protein kinase cAMP-dependent type II regulatory subunit alpha
ISO RGD
PMID:14715913 RGD:2312475
NCBI chr 8:109,393,189...109,458,832
G
Prkar2b protein kinase cAMP-dependent type II regulatory subunit beta
ISO RGD
PMID:14715913 RGD:2312475
NCBI chr 6:48,563,659...48,653,933
Pathway Gene Annotations
Disease Annotations Associated with Genes in the protein kinase A (PKA) signaling pathway
Adcy1 autosomal recessive nonsyndromic deafness 44 , genetic disease , Hyperkinesis , lung small cell carcinoma , pleomorphic xanthoastrocytoma , withdrawal disorder Adcy10 Cardiomegaly , gastrointestinal stromal tumor , genetic disease , Hypercalciuria, Absorptive, 2 , immunodeficiency 25 , male infertility , Optic Nerve Injuries , parathyroid carcinoma Adcy2 asthma , bipolar disorder , genetic disease Adcy3 diabetic angiopathy , genetic disease , major depressive disorder , morbid obesity , obesity , Tatton-Brown-Rahman syndrome Adcy4 Brain-Lung-Thyroid Syndrome , genetic disease , lysinuric protein intolerance , Specific Granule Deficiency Adcy5 alkaptonuria , Animal Mammary Neoplasms , Birth Weight , carcinoma , cardiomyopathy , distal muscular dystrophy 4 , Dyskinesia with Orofacial Involvement , Dyskinesia with Orofacial Involvement, Autosomal Dominant , Dyskinesia with Orofacial Involvement, Autosomal Recessive , Experimental Mammary Neoplasms , familial hypocalciuric hypercalcemia , Familial Thoracic Aortic Aneurysm 7 , Fibrosis , genetic disease , hypertension , language disorder , NEURODEVELOPMENTAL DISORDER WITH HYPERKINETIC MOVEMENTS AND DYSKINESIA , Neurodevelopmental Disorders , osteoporosis , Parkinson's disease , Primary Lymphedema with Myelodysplasia , type 2 diabetes mellitus , Ventricular Dysfunction, Left Adcy6 genetic disease , Lethal Congenital Contracture Syndrome 8 , ureteral obstruction Adcy7 acute myeloid leukemia , genetic disease , juvenile rheumatoid arthritis , nephronophthisis 14 , schizophrenia , ulcerative colitis Adcy8 diabetic angiopathy , genetic disease , Hyperkinesis , mood disorder , withdrawal disorder Adcy9 congenital heart disease , epilepsy , genetic disease , Greig cephalopolysyndactyly syndrome , idiopathic generalized epilepsy , Kohlschutter-Tonz syndrome , mood disorder , Neurodevelopmental Disorders , Rubinstein-Taybi syndrome , short-rib thoracic dysplasia 9 with or without polydactyly Akap1 brain ischemia , genetic disease , Joubert syndrome , obesity , prostate cancer Akap10 autistic disorder , genetic disease , Meckel Syndrome 9 , Potocki-Lupski syndrome , sudden infant death syndrome Akap11 bipolar disorder , genetic disease , Mouth Neoplasms , schizophrenia Akap12 Acute Lung Injury , brain ischemia , Breast Neoplasms , chronic kidney disease , colorectal carcinoma , COVID-19 , Experimental Autoimmune Encephalomyelitis , genetic disease , juvenile myelomonocytic leukemia , liver cirrhosis , osteosarcoma , sciatic neuropathy Akap13 Bloom syndrome , colorectal cancer , Esophageal Neoplasms , genetic disease , Prostatic Neoplasms , renal cell carcinoma Akap14 autistic disorder , Danon disease , genetic disease , syndromic X-linked intellectual disability 14 , syndromic X-linked intellectual disability Cabezas type , syndromic X-linked intellectual disability Lubs type Akap2 genetic disease , prostate cancer , Weight Gain Akap3 episodic ataxia type 1 , genetic disease , Hyperphosphatemic Familial Tumoral Calcinosis 1 , lymphoproliferative syndrome 2 , Spermatogenic Failure 82 Akap4 autistic disorder , congenital disorder of glycosylation type IIm , genetic disease , immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome , male infertility , neurodegeneration with brain iron accumulation 5 , Stocco Dos Santos type X-linked intellectual disability , syndromic X-linked intellectual disability Lubs type , X-linked epilepsy with variable learning disabilities and behavior disorders , X-linked severe congenital neutropenia Akap5 Alzheimer's disease , Cardiomegaly , COVID-19 , developmental coordination disorder , genetic disease , Memory Disorders , Tetany Akap6 anorexia nervosa , atrial fibrillation , Brain-Lung-Thyroid Syndrome , congestive heart failure , Duchenne muscular dystrophy , genetic disease , hypertrophic cardiomyopathy , intellectual disability , ovary epithelial cancer Akap7 genetic disease , substance-related disorder Akap8 genetic disease , long QT syndrome Akap9 amyloidosis , arrhythmogenic right ventricular cardiomyopathy , Arsenic Poisoning , atrial fibrillation , Brugada syndrome 1 , cardiac arrest , Cardiac Arrhythmias , cardiomyopathy , catecholaminergic polymorphic ventricular tachycardia , cerebral cavernous malformation , colorectal cancer , congestive heart failure , dilated cardiomyopathy , Familial Ventricular Tachycardia , genetic disease , hypertrophic cardiomyopathy , long QT syndrome , long QT syndrome 1 , long QT syndrome 11 , long QT syndrome 2 , pleomorphic xanthoastrocytoma , restrictive cardiomyopathy , Romano-Ward Syndrome , skin disease , Sudden Cardiac Death , Ventricular Fibrillation , Ventricular Tachycardia , Wolff-Parkinson-White syndrome Crhr2 Anorexia , anxiety disorder , asthma , Charcot-Marie-Tooth disease type 2 , Cocaine-Related Disorders , colitis , depressive disorder , Ehlers-Danlos syndrome kyphoscoliotic type 2 , Fetal Hypoxia , functional colonic disease , genetic disease , hypertension , Hypotension , Inflammation , irritable bowel syndrome , ischemia , Left Ventricular Hypertrophy , lung disease , muscular atrophy , pleomorphic xanthoastrocytoma , Pneumococcal Pneumonia , pneumonia , rhinitis Ezr 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome , Animal Mammary Neoplasms , carcinoma , Experimental Liver Cirrhosis , Experimental Mammary Neoplasms , genetic disease , Neoplasm Metastasis , osteoarthritis , primary ciliary dyskinesia 32 , Prostatic Neoplasms Pde10a Developmental Disabilities , genetic disease , Infantile-Onset Limb and Orofacial Dyskinesia , Muscle Hypotonia , Striatal Degeneration, Autosomal Dominant 2 , traumatic brain injury Pde11a Bardet-Biedl syndrome 16 , genetic disease , Primary Pigmented Nodular Adrenocortical Disease, 2 , schizophrenia , split hand-foot malformation 5 Pde1a genetic disease , Left Ventricular Hypertrophy Pde1b genetic disease , learning disability , Parkinsonism Pde1c autosomal dominant nonsyndromic deafness , autosomal dominant nonsyndromic deafness 74 , genetic disease , pleomorphic xanthoastrocytoma , prostate cancer , substance-related disorder Pde2a 3-methylglutaconic aciduria type 7b , Alzheimer's disease , Breast Neoplasms , cardiomyopathy , choreatic disease , dystonia , genetic disease , INTELLECTUAL DEVELOPMENTAL DISORDER WITH PAROXYSMAL DYSKINESIA OR SEIZURES , intellectual disability , Left Ventricular Hypertrophy , Muscle Hypotonia Pde3a Experimental Diabetes Mellitus , genetic disease , hypertension and brachydactyly syndrome , Left Ventricular Hypertrophy , myocardial infarction , obesity , prostate cancer , pulmonary hypertension , Stroke , thrombosis Pde3b genetic disease , intellectual disability , polycystic ovary syndrome Pde4a autistic disorder , brucellosis , genetic disease , visual epilepsy Pde4b acute myeloid leukemia , alcohol use disorder , amphetamine abuse , Arsenic Poisoning , asthma , autistic disorder , bipolar disorder , Burns , genetic disease , intellectual disability , Myocardial Ischemia , schizophrenia , skin disease Pde4c genetic disease , Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 Pde4d acrodysostosis , Acrodysostosis 2, with or without Hormone Resistance , amphetamine abuse , asthma , Brain Injuries , Coffin-Siris syndrome 6 , depressive disorder , esophageal atresia , genetic disease , intellectual disability , Neurodevelopmental Disorders , Prostatic Neoplasms , Stroke , transient cerebral ischemia Pde7a genetic disease Pde7b familial Behcet-like autoinflammatory syndrome , genetic disease , immunodeficiency 27A , prostate cancer Pde8a Bloom syndrome , colorectal cancer , genetic disease Pde8b basal ganglia disease , congenital adrenal hyperplasia , Dysarthria , genetic disease , Hermansky-Pudlak syndrome 2 , Muscle Rigidity , Nerve Degeneration , neurodegenerative disease , Neurodevelopmental Disorders , Primary Pigmented Nodular Adrenocortical Disease, 3 , Striatal Degeneration, Autosomal Dominant , Striatal Degeneration, Autosomal Dominant 1 Prkaca ACTH-independent macronodular adrenal hyperplasia 1 , adrenal cortical adenoma , Adrenal Gland Neoplasms , brain ischemia , Cardioacrofacial Dysplasia 1 , cholangiocarcinoma , congestive heart failure , fibrolamellar carcinoma , genetic disease , Hypoglossal Nerve Injuries , mixed fibrolamellar hepatocellular carcinoma , Neurodevelopmental Disorders , non-alcoholic fatty liver disease , Primary Pigmented Nodular Adrenocortical Disease, 4 Prkacb adrenal cortical adenoma , biliary tract benign neoplasm , brain ischemia , Cardioacrofacial Dysplasia 2 , cholangiocarcinoma , Cushing Syndrome , genetic disease , Hypoglossal Nerve Injuries , Prostatic Neoplasms Prkar1a acrodysostosis , Acrodysostosis 1, with or without Hormone Resistance , acute promyelocytic leukemia , Adrenal Cortex Neoplasms , alopecia , amelogenesis imperfecta type 1G , apparent mineralocorticoid excess syndrome , arrhythmogenic right ventricular dysplasia 10 , Carney complex , congenital adrenal hyperplasia , Cushing Syndrome , Familial Atrial Myxoma , genetic disease , Hereditary Neoplastic Syndromes , hyperglycemia , Insulin Resistance , medulloblastoma , muscular atrophy , Myxoma , neural tube defect , obesity , primary pigmented nodular adrenocortical disease , Primary Pigmented Nodular Adrenocortical Disease, 1 , thyroid gland follicular carcinoma , Usher Syndrome Type 4 Prkar1b genetic disease , hypertension , MARBACH-SCHAAF NEURODEVELOPMENTAL SYNDROME , Neurodevelopmental Disorders , primary ciliary dyskinesia , primary ciliary dyskinesia 18 , Tremor Prkar2a Aicardi-Goutieres Syndrome 1 , congestive heart failure , genetic disease , Progressive Microcephaly with Seizures and Cerebral and Cerebellar Atrophy Prkar2b congestive heart failure , genetic disease , granulosa cell tumor , obesity , pleomorphic xanthoastrocytoma
3-methylglutaconic aciduria type 7b Pde2a 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome Ezr acrodysostosis Pde4d , Prkar1a Acrodysostosis 1, with or without Hormone Resistance Prkar1a Acrodysostosis 2, with or without Hormone Resistance Pde4d ACTH-independent macronodular adrenal hyperplasia 1 Prkaca Acute Lung Injury Akap12 acute myeloid leukemia Adcy7 , Pde4b acute promyelocytic leukemia Prkar1a Adrenal Cortex Neoplasms Prkar1a adrenal cortical adenoma Prkaca , Prkacb Adrenal Gland Neoplasms Prkaca Aicardi-Goutieres Syndrome 1 Prkar2a alcohol use disorder Pde4b alkaptonuria Adcy5 alopecia Prkar1a Alzheimer's disease Akap5 , Pde2a amelogenesis imperfecta type 1G Prkar1a amphetamine abuse Pde4b , Pde4d amyloidosis Akap9 Animal Mammary Neoplasms Adcy5 , Ezr Anorexia Crhr2 anorexia nervosa Akap6 anxiety disorder Crhr2 apparent mineralocorticoid excess syndrome Prkar1a arrhythmogenic right ventricular cardiomyopathy Akap9 arrhythmogenic right ventricular dysplasia 10 Prkar1a Arsenic Poisoning Akap9 , Pde4b asthma Adcy2 , Crhr2 , Pde4b , Pde4d atrial fibrillation Akap6 , Akap9 autistic disorder Akap10 , Akap14 , Akap4 , Pde4a , Pde4b autosomal dominant nonsyndromic deafness Pde1c autosomal dominant nonsyndromic deafness 74 Pde1c autosomal recessive nonsyndromic deafness 44 Adcy1 Bardet-Biedl syndrome 16 Pde11a basal ganglia disease Pde8b biliary tract benign neoplasm Prkacb bipolar disorder Adcy2 , Akap11 , Pde4b Birth Weight Adcy5 Bloom syndrome Akap13 , Pde8a Brain Injuries Pde4d brain ischemia Akap1 , Akap12 , Prkaca , Prkacb Brain-Lung-Thyroid Syndrome Adcy4 , Akap6 Breast Neoplasms Akap12 , Pde2a brucellosis Pde4a Brugada syndrome 1 Akap9 Burns Pde4b carcinoma Adcy5 , Ezr cardiac arrest Akap9 Cardiac Arrhythmias Akap9 Cardioacrofacial Dysplasia 1 Prkaca Cardioacrofacial Dysplasia 2 Prkacb Cardiomegaly Adcy10 , Akap5 cardiomyopathy Adcy5 , Akap9 , Pde2a Carney complex Prkar1a catecholaminergic polymorphic ventricular tachycardia Akap9 cerebral cavernous malformation Akap9 Charcot-Marie-Tooth disease type 2 Crhr2 cholangiocarcinoma Prkaca , Prkacb choreatic disease Pde2a chronic kidney disease Akap12 Cocaine-Related Disorders Crhr2 Coffin-Siris syndrome 6 Pde4d colitis Crhr2 colorectal cancer Akap13 , Akap9 , Pde8a colorectal carcinoma Akap12 congenital adrenal hyperplasia Pde8b , Prkar1a congenital disorder of glycosylation type IIm Akap4 congenital heart disease Adcy9 congestive heart failure Akap6 , Akap9 , Prkaca , Prkar2a , Prkar2b COVID-19 Akap12 , Akap5 Cushing Syndrome Prkacb , Prkar1a Danon disease Akap14 depressive disorder Crhr2 , Pde4d developmental coordination disorder Akap5 Developmental Disabilities Pde10a diabetic angiopathy Adcy3 , Adcy8 dilated cardiomyopathy Akap9 distal muscular dystrophy 4 Adcy5 Duchenne muscular dystrophy Akap6 Dysarthria Pde8b Dyskinesia with Orofacial Involvement Adcy5 Dyskinesia with Orofacial Involvement, Autosomal Dominant Adcy5 Dyskinesia with Orofacial Involvement, Autosomal Recessive Adcy5 dystonia Pde2a Ehlers-Danlos syndrome kyphoscoliotic type 2 Crhr2 epilepsy Adcy9 episodic ataxia type 1 Akap3 esophageal atresia Pde4d Esophageal Neoplasms Akap13 Experimental Autoimmune Encephalomyelitis Akap12 Experimental Diabetes Mellitus Pde3a Experimental Liver Cirrhosis Ezr Experimental Mammary Neoplasms Adcy5 , Ezr Familial Atrial Myxoma Prkar1a familial Behcet-like autoinflammatory syndrome Pde7b familial hypocalciuric hypercalcemia Adcy5 Familial Thoracic Aortic Aneurysm 7 Adcy5 Familial Ventricular Tachycardia Akap9 Fetal Hypoxia Crhr2 fibrolamellar carcinoma Prkaca Fibrosis Adcy5 functional colonic disease Crhr2 gastrointestinal stromal tumor Adcy10 genetic disease Adcy1 , Adcy10 , Adcy2 , Adcy3 , Adcy4 , Adcy5 , Adcy6 , Adcy7 , Adcy8 , Adcy9 , Akap1 , Akap10 , Akap11 , Akap12 , Akap13 , Akap14 , Akap2 , Akap3 , Akap4 , Akap5 , Akap6 , Akap7 , Akap8 , Akap9 , Crhr2 , Ezr , Pde10a , Pde11a , Pde1a , Pde1b , Pde1c , Pde2a , Pde3a , Pde3b , Pde4a , Pde4b , Pde4c , Pde4d , Pde7a , Pde7b , Pde8a , Pde8b , Prkaca , Prkacb , Prkar1a , Prkar1b , Prkar2a , Prkar2b granulosa cell tumor Prkar2b Greig cephalopolysyndactyly syndrome Adcy9 Hereditary Neoplastic Syndromes Prkar1a Hermansky-Pudlak syndrome 2 Pde8b Hypercalciuria, Absorptive, 2 Adcy10 hyperglycemia Prkar1a Hyperkinesis Adcy1 , Adcy8 Hyperphosphatemic Familial Tumoral Calcinosis 1 Akap3 hypertension Adcy5 , Crhr2 , Prkar1b hypertension and brachydactyly syndrome Pde3a hypertrophic cardiomyopathy Akap6 , Akap9 Hypoglossal Nerve Injuries Prkaca , Prkacb Hypotension Crhr2 idiopathic generalized epilepsy Adcy9 immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome Akap4 immunodeficiency 25 Adcy10 immunodeficiency 27A Pde7b Infantile-Onset Limb and Orofacial Dyskinesia Pde10a Inflammation Crhr2 Insulin Resistance Prkar1a INTELLECTUAL DEVELOPMENTAL DISORDER WITH PAROXYSMAL DYSKINESIA OR SEIZURES Pde2a intellectual disability Akap6 , Pde2a , Pde3b , Pde4b , Pde4d irritable bowel syndrome Crhr2 ischemia Crhr2 Joubert syndrome Akap1 juvenile myelomonocytic leukemia Akap12 juvenile rheumatoid arthritis Adcy7 Kohlschutter-Tonz syndrome Adcy9 language disorder Adcy5 learning disability Pde1b Left Ventricular Hypertrophy Crhr2 , Pde1a , Pde2a , Pde3a Lethal Congenital Contracture Syndrome 8 Adcy6 liver cirrhosis Akap12 long QT syndrome Akap8 , Akap9 long QT syndrome 1 Akap9 long QT syndrome 11 Akap9 long QT syndrome 2 Akap9 lung disease Crhr2 lung small cell carcinoma Adcy1 lymphoproliferative syndrome 2 Akap3 lysinuric protein intolerance Adcy4 major depressive disorder Adcy3 male infertility Adcy10 , Akap4 MARBACH-SCHAAF NEURODEVELOPMENTAL SYNDROME Prkar1b Meckel Syndrome 9 Akap10 medulloblastoma Prkar1a Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 Pde4c Memory Disorders Akap5 mixed fibrolamellar hepatocellular carcinoma Prkaca mood disorder Adcy8 , Adcy9 morbid obesity Adcy3 Mouth Neoplasms Akap11 Muscle Hypotonia Pde10a , Pde2a Muscle Rigidity Pde8b muscular atrophy Crhr2 , Prkar1a myocardial infarction Pde3a Myocardial Ischemia Pde4b Myxoma Prkar1a Neoplasm Metastasis Ezr nephronophthisis 14 Adcy7 Nerve Degeneration Pde8b neural tube defect Prkar1a neurodegeneration with brain iron accumulation 5 Akap4 neurodegenerative disease Pde8b NEURODEVELOPMENTAL DISORDER WITH HYPERKINETIC MOVEMENTS AND DYSKINESIA Adcy5 Neurodevelopmental Disorders Adcy5 , Adcy9 , Pde4d , Pde8b , Prkaca , Prkar1b non-alcoholic fatty liver disease Prkaca obesity Adcy3 , Akap1 , Pde3a , Prkar1a , Prkar2b Optic Nerve Injuries Adcy10 osteoarthritis Ezr osteoporosis Adcy5 osteosarcoma Akap12 ovary epithelial cancer Akap6 parathyroid carcinoma Adcy10 Parkinson's disease Adcy5 Parkinsonism Pde1b pleomorphic xanthoastrocytoma Adcy1 , Akap9 , Crhr2 , Pde1c , Prkar2b Pneumococcal Pneumonia Crhr2 pneumonia Crhr2 polycystic ovary syndrome Pde3b Potocki-Lupski syndrome Akap10 primary ciliary dyskinesia Prkar1b primary ciliary dyskinesia 18 Prkar1b primary ciliary dyskinesia 32 Ezr Primary Lymphedema with Myelodysplasia Adcy5 primary pigmented nodular adrenocortical disease Prkar1a Primary Pigmented Nodular Adrenocortical Disease, 1 Prkar1a Primary Pigmented Nodular Adrenocortical Disease, 2 Pde11a Primary Pigmented Nodular Adrenocortical Disease, 3 Pde8b Primary Pigmented Nodular Adrenocortical Disease, 4 Prkaca Progressive Microcephaly with Seizures and Cerebral and Cerebellar Atrophy Prkar2a prostate cancer Akap1 , Akap2 , Pde1c , Pde3a , Pde7b Prostatic Neoplasms Akap13 , Ezr , Pde4d , Prkacb pulmonary hypertension Pde3a renal cell carcinoma Akap13 restrictive cardiomyopathy Akap9 rhinitis Crhr2 Romano-Ward Syndrome Akap9 Rubinstein-Taybi syndrome Adcy9 schizophrenia Adcy7 , Akap11 , Pde11a , Pde4b sciatic neuropathy Akap12 short-rib thoracic dysplasia 9 with or without polydactyly Adcy9 skin disease Akap9 , Pde4b Specific Granule Deficiency Adcy4 Spermatogenic Failure 82 Akap3 split hand-foot malformation 5 Pde11a Stocco Dos Santos type X-linked intellectual disability Akap4 Striatal Degeneration, Autosomal Dominant Pde8b Striatal Degeneration, Autosomal Dominant 1 Pde8b Striatal Degeneration, Autosomal Dominant 2 Pde10a Stroke Pde3a , Pde4d substance-related disorder Akap7 , Pde1c Sudden Cardiac Death Akap9 sudden infant death syndrome Akap10 syndromic X-linked intellectual disability 14 Akap14 syndromic X-linked intellectual disability Cabezas type Akap14 syndromic X-linked intellectual disability Lubs type Akap14 , Akap4 Tatton-Brown-Rahman syndrome Adcy3 Tetany Akap5 thrombosis Pde3a thyroid gland follicular carcinoma Prkar1a transient cerebral ischemia Pde4d traumatic brain injury Pde10a Tremor Prkar1b type 2 diabetes mellitus Adcy5 ulcerative colitis Adcy7 ureteral obstruction Adcy6 Usher Syndrome Type 4 Prkar1a Ventricular Dysfunction, Left Adcy5 Ventricular Fibrillation Akap9 Ventricular Tachycardia Akap9 visual epilepsy Pde4a Weight Gain Akap2 withdrawal disorder Adcy1 , Adcy8 Wolff-Parkinson-White syndrome Akap9 X-linked epilepsy with variable learning disabilities and behavior disorders Akap4 X-linked severe congenital neutropenia Akap4
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