PROTEIN KINASE C (PKC) SIGNALING PATHWAY (PW:0000840)
Description
The protein kinase C family (PKC) comprises ~2% of the human kinome and can be subdivided into three subclasses: conventional or classical (cPKC), novel (nPKC) and atypical (aPKC). All isoforms contain a C-terminal kinase domain and an N-terminal autoinhibitory pseudosubstrate but differ in their responsiveness to second messengers. A tandem DAG-sensitive C1 domain is present in cPKC and nPKC with the latter group displaying a higher sensitivity. The C2 domain is Ca2+ sensitive in cPKC only. The single C1domain in aPKC is DAG-insensitive; this group depends on other lipids or protein-protein interactions for functional regulation. Collectively, the pathway regulates cell proliferation, differentiation, polarity and death and plays a role in the cardiac, immune and nervous systems. PKC signaling is initiated downstream of ligand-activated G protein coupled receptors (GPCR) that trigger the signal transduction mediated by the Galphaq family of heterotrimeric G proteins. The Galphaq activates the beta subtype of phospholipase C (PLC; PLC-B). Other PLC subtypes can be activated downstream of receptor tyrosine kinases (RTK) with potential role in PKC activation. PLC catalyzes the hydrolysis of PIP2 to produce DAG and IP3; IP3 promotes calcium release from ER. Calcium permeates almost every aspect of cellular processes - its uptake, storage, release, buffering and sensing is mediated by a broad range of transporters and channels, calcium-binding and signaling molecules that together constitute the 'calcium signaling kit' within the two inextricably connected pathways of calcium transport and signaling. Newly synthesized PKCs need priming for maturation - a process that involves a series of tightly controlled phosphorylation events. The Hsp90 chaperone and Cdc37co-chaperone are required for the proper processing of cPKC and nPKCs. Pdpk1 phosphorylates the activation loop of PLC, an event that is constitutive for cPKC and nPKCs but agonist dependent for aPKCs. A second phosphorylation at the turn motif, completes the maturation of PKC and is dependent on mTORC2 complex. Whether the role of mTORC2 is direct or indirect, via activation of an upstream kinase, is currently unclear. Mature, fully phosphorylated PKCs are in the cytoplasm and bound to the autoinhibitory pseudosubstrate. Signals that release calcium facilitate recruitment to the plasma membrane followed by DAG binding or there is direct membrane recruitment via high DAG affinity. At the membrane, PKC is in an open conformation which promotes release of pseudosubstrate and binding of a variety of interactors - adaptors or scaffolds and other binding partners and substrates, in order to fulfill many cellular tasks. The open conformation can also promotes dephosphorylation by members of PPM phosphatase family. Dephosphorylated PKC is sequestered in insoluble fraction for further dephosphorylation and subsequent degradation. However, it can also be bound by HSP70 which promotes its re-phosphorylation and re-enter into the signaling cycle. Internalization of receptors and conversion of DAG to PA by DGKs terminates signaling (not shown). Deregulation of PKC signaling pathway has been implicated in tumorigenesis and neurodegeneration.
To see the Ontology Report, for annotations, GViewer and download, click here [click to see the ontology report for related GO term -
GO:0070528 ]
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Pathway Diagram:
Genes in Pathway:
G
Btk
Bruton tyrosine kinase
ISO
RGD
PMID:15380937
RGD:5131492
NCBI chr X:97,722,796...97,762,315
Ensembl chr X:97,722,802...97,761,853
G
Cdc37
cell division cycle 37, HSP90 cochaperone
ISO
RGD
PMID:19934406
RGD:5131489
NCBI chr 8:19,677,400...19,690,761
Ensembl chr 8:19,671,938...19,690,809
G
Copb1
COPI coat complex subunit beta 1
ISO
RGD
PMID:18491053
RGD:5131491
NCBI chr 1:168,404,334...168,438,589
Ensembl chr 1:168,404,335...168,438,416
G
Fscn1
fascin actin-bundling protein 1
ISO
RGD
PMID:15380937
RGD:5131492
NCBI chr12:11,597,042...11,610,183
Ensembl chr12:11,597,048...11,610,211
G
Fyn
FYN proto-oncogene, Src family tyrosine kinase
ISO
RGD
PMID:15380937
RGD:5131492
NCBI chr20:42,767,733...42,960,903
Ensembl chr20:42,766,369...42,959,911
G
Hsp90aa1
heat shock protein 90 alpha family class A member 1
ISO
RGD
PMID:19934406
RGD:5131489
NCBI chr 6:129,702,376...129,707,907
Ensembl chr 6:129,702,383...129,707,268
G
Lck
LCK proto-oncogene, Src family tyrosine kinase
ISO
RGD
PMID:15380937
RGD:5131492
NCBI chr 5:141,888,318...141,916,945
Ensembl chr 5:141,888,326...141,903,794
G
Ldb3
LIM domain binding 3
ISO
RGD
PMID:18491053 PMID:15380937
RGD:5131491 , RGD:5131492
NCBI chr16:9,855,768...9,920,108
Ensembl chr16:9,855,927...9,918,532
G
Pard3
par-3 family cell polarity regulator
ISO
RGD
PMID:16525119
RGD:5132275
NCBI chr19:55,080,282...55,630,111
Ensembl chr19:55,080,282...55,629,778
G
Pard6a
par-6 family cell polarity regulator alpha
ISO
RGD
PMID:16525119
RGD:5132275
NCBI chr19:33,589,531...33,591,900
Ensembl chr19:33,589,542...33,591,900
G
Pard6b
par-6 family cell polarity regulator beta
ISO
RGD
PMID:16525119
RGD:5132275
NCBI chr 3:156,790,540...156,811,620
Ensembl chr 3:156,790,540...156,811,622
G
Pard6g
par-6 family cell polarity regulator gamma
ISO
RGD
PMID:16525119
RGD:5132275
NCBI chr18:73,497,992...73,565,048
Ensembl chr18:73,498,021...73,565,029
G
Pcnt
pericentrin
ISO
RGD
PMID:15380937
RGD:5131492
NCBI chr20:12,190,597...12,278,723
Ensembl chr20:12,191,648...12,278,710
G
Pdpk1
3-phosphoinositide dependent protein kinase-1
ISO
RGD
PMID:19934406
RGD:5131489
NCBI chr10:13,105,435...13,182,664
Ensembl chr10:13,105,498...13,174,623
G
Phlpp1
PH domain and leucine rich repeat protein phosphatase 1
IMP ISO
RGD
PMID:20819118 PMID:18511290
RGD:8693633 , RGD:5131497
NCBI chr13:22,308,532...22,530,978
Ensembl chr13:22,308,548...22,530,977
G
Phlpp2
PH domain and leucine rich repeat protein phosphatase 2
ISO
RGD
PMID:18511290
RGD:5131497
NCBI chr19:37,835,125...37,901,804
Ensembl chr19:37,835,125...37,905,513
G
Pick1
protein interacting with PRKCA 1
ISO
RGD
PMID:18491053
RGD:5131491
NCBI chr 7:110,796,623...110,816,850
Ensembl chr 7:110,797,117...110,816,848
G
Plcb1
phospholipase C beta 1
ISO
RGD
PMID:17524618
RGD:5131502
NCBI chr 3:122,059,988...122,772,896
Ensembl chr 3:122,060,031...122,772,869
G
Plcb2
phospholipase C, beta 2
ISO
RGD
PMID:17524618
RGD:5131502
NCBI chr 3:105,683,676...105,704,384
Ensembl chr 3:105,684,815...105,704,302
G
Plcb3
phospholipase C beta 3
ISO
RGD
PMID:17524618
RGD:5131502
NCBI chr 1:204,143,257...204,160,384
Ensembl chr 1:204,144,956...204,160,228
G
Plcb4
phospholipase C, beta 4
ISO
RGD
PMID:17524618
RGD:5131502
NCBI chr 3:122,952,965...123,322,522
Ensembl chr 3:122,953,196...123,322,392
G
Prkca
protein kinase C, alpha
ISO
RGD
PMID:19934406
RGD:5131489
NCBI chr10:92,889,390...93,288,013
Ensembl chr10:92,894,012...93,288,012
G
Prkcb
protein kinase C, beta
ISO
RGD
PMID:19934406
RGD:5131489
NCBI chr 1:176,832,173...177,163,539
Ensembl chr 1:176,832,226...177,163,536
G
Prkcd
protein kinase C, delta
ISO
RGD
PMID:19934406
RGD:5131489
NCBI chr16:5,769,217...5,799,380
Ensembl chr16:5,769,215...5,799,352
G
Prkce
protein kinase C, epsilon
ISO
RGD
PMID:19934406
RGD:5131489
NCBI chr 6:7,965,048...8,451,966
Ensembl chr 6:7,965,048...8,451,719
G
Prkcg
protein kinase C, gamma
ISO
RGD
PMID:19934406
RGD:5131489
NCBI chr 1:65,832,851...65,860,676
Ensembl chr 1:65,832,855...65,859,384
G
Prkch
protein kinase C, eta
ISO IMP
RGD
PMID:19934406 PMID:9677361
RGD:5131489 , RGD:5131657
NCBI chr 6:92,292,000...92,490,663
Ensembl chr 6:92,292,000...92,490,654
G
Prkci
protein kinase C, iota
ISO
RGD
PMID:19934406 PMID:16525119
RGD:5131489 , RGD:5132275
NCBI chr 2:112,321,919...112,382,305
Ensembl chr 2:112,321,929...112,382,352
G
Prkcq
protein kinase C, theta
ISO
RGD
PMID:19934406
RGD:5131489
NCBI chr17:67,246,394...67,379,049
Ensembl chr17:67,246,394...67,378,704
G
Prkcz
protein kinase C, zeta
ISO IMP
RGD
PMID:19934406 PMID:20570724 PMID:16525119
RGD:5131489 , RGD:5131661 , RGD:5132275
NCBI chr 5:165,817,786...165,930,386
Ensembl chr 5:165,819,466...165,930,367
G
Rack1
receptor for activated C kinase 1
ISO
RGD
PMID:18491053
RGD:5131491
NCBI chr10:33,169,415...33,174,896
Ensembl chr10:33,169,169...33,174,975
G
Rasa1
RAS p21 protein activator 1
IMP
RGD
PMID:7588705
RGD:10002727
NCBI chr 2:15,857,704...15,940,757
Ensembl chr 2:15,857,980...15,940,854
Pathway Gene Annotations
Disease Annotations Associated with Genes in the protein kinase C (PKC) signaling pathway
Btk Adenoviridae Infections , agammaglobulinemia , agammaglobulinemia 1 , Anaphylaxis , arthus reaction , autistic disorder , B-Cell Chronic Lymphocytic Leukemia , B-cell lymphoma , Breast Neoplasms , Burkitt lymphoma , central nervous system lymphoma , colitis , colon adenocarcinoma , colorectal cancer , common variable immunodeficiency , COVID-19 , cryptococcosis , deafness-dystonia-optic neuronopathy syndrome , developmental and epileptic encephalopathy 9 , diffuse large B-cell lymphoma , endometriosis of uterus , Enterovirus Infections , Experimental Arthritis , Fabry disease , genetic disease , Hypothermia , influenza A , isolated growth hormone deficiency type III , leishmaniasis , listeriosis , lung adenocarcinoma , lung non-small cell carcinoma , Lymphatic Metastasis , mantle cell lymphoma , nasopharynx carcinoma , oral squamous cell carcinoma , Pneumococcal Pneumonia , primary immunodeficiency disease , ROLANDIC EPILEPSY, INTELLECTUAL DISABILITY, AND SPEECH DYSPRAXIA, X-LINKED , Streptococcus pneumonia , syndromic X-linked intellectual disability Lubs type , X-linked agammaglobulinemia , X-Linked Hypogammaglobulinemia Cdc37 genetic disease Copb1 Baralle-Macken Syndrome , cataract , genetic disease , intellectual disability , osteochondrodysplasia Fscn1 Bile Duct Neoplasms , cholangiocarcinoma , common bile duct neoplasm , Gallbladder Neoplasms , genetic disease , Neoplasm Metastasis , pancreatic cancer , pancreatic ductal carcinoma Fyn adult T-cell leukemia/lymphoma , Alzheimer's disease , Burns , Catalepsy , Experimental Liver Cirrhosis , genetic disease , peripheral T-cell lymphoma , primary ovarian insufficiency , pulmonary fibrosis , schizophrenia , Sepsis , Stomach Neoplasms , temporal lobe epilepsy Hsp90aa1 Alzheimer's disease , anaplastic large cell lymphoma , Breast Neoplasms , Charcot-Marie-Tooth disease axonal type 2O , Cognitive Dysfunction , colon cancer , contact dermatitis , Ductal Carcinoma , Experimental Diabetes Mellitus , Frontotemporal Lobar Degeneration , genetic disease , human immunodeficiency virus infectious disease , intrahepatic cholangiocarcinoma , Knee Osteoarthritis , Neoplasm Metastasis , Neurodevelopmental Disorders , portal hypertension , rheumatoid arthritis Lck allergic conjunctivitis , dilated cardiomyopathy , genetic disease , human immunodeficiency virus infectious disease , immunodeficiency 22 , retinal degeneration , RETINAL DYSTROPHY WITH INNER RETINAL DYSFUNCTION AND GANGLION CELL ABNORMALITIES , severe combined immunodeficiency Ldb3 arrhythmogenic right ventricular cardiomyopathy , cardiomyopathy , congenital myopathy , congenital structural myopathy , dilated cardiomyopathy , dilated cardiomyopathy 1A , dilated cardiomyopathy 1B , dilated cardiomyopathy 1BB , dilated cardiomyopathy 1C , dilated cardiomyopathy 1H , Dilated Cardiomyopathy with Left Ventricular Noncompaction , distal myopathy , familial hypertrophic cardiomyopathy , genetic disease , hypertrophic cardiomyopathy , hypertrophic cardiomyopathy 1 , hypertrophic cardiomyopathy 14 , Isolated Noncompaction of the Ventricular Myocardium , juvenile polyposis syndrome , Left Ventricular Noncompaction 1 , long QT syndrome , myofibrillar myopathy , myofibrillar myopathy 1 , myofibrillar myopathy 4 , Myofibrillar Myopathy, ZASP-Related , myotonic dystrophy type 1 , neuromuscular disease , PTEN hamartoma tumor syndrome , Ventricular Tachycardia Pard3 autism spectrum disorder , genetic disease , neural tube defect , primary ovarian insufficiency , prostate cancer , Prostatic Neoplasms Pard6a autosomal dominant dyskeratosis congenita 6 , chromosome 16q22 deletion syndrome , genetic disease Pard6b autism spectrum disorder , genetic disease Pard6g Burn-McKeown syndrome , chromosome 18q deletion syndrome , genetic disease , intestinal volvulus , Neurodevelopmental Disorders , Oculootofacial Dysplasia , pulmonary valve stenosis , Volvulus Of Midgut Pcnt autistic disorder , Axenfeld-Rieger syndrome type 3 , cataract 9 multiple types , developmental and epileptic encephalopathy 30 , Developmental Disabilities , Down syndrome , genetic disease , homocystinuria , intellectual disability , megacolon , Microcephalic Osteodysplastic Primordial Dwarfism , microcephalic osteodysplastic primordial dwarfism type II , microcephaly , primary ciliary dyskinesia , progressive myoclonus epilepsy , Seckel syndrome 1 , Seckel syndrome 2 , vascular dementia Pdpk1 Breast Neoplasms , congestive heart failure , diffuse large B-cell lymphoma , epilepsy , genetic disease , idiopathic generalized epilepsy , lung non-small cell carcinoma , Lymphatic Metastasis , prostate adenocarcinoma , prostate cancer , short-rib thoracic dysplasia 9 with or without polydactyly Phlpp1 chromosome 18q deletion syndrome , epilepsy , genetic disease , intellectual disability , multiple congenital anomalies-hypotonia-seizures syndrome 1 , Neoplastic Cell Transformation , prostate cancer Phlpp2 autosomal dominant dyskeratosis congenita 6 , genetic disease Pick1 adenylosuccinase lyase deficiency , amphetamine abuse , Emery-Dreifuss muscular dystrophy , genetic disease , myoclonic dystonia 26 , neurodegeneration with brain iron accumulation 2A , substance-induced psychosis Plcb1 acute myeloid leukemia , Alagille syndrome , ALAGILLE SYNDROME 1 , Alzheimer's disease , benign epilepsy with centrotemporal spikes , Colonic Neoplasms , congenital myasthenic syndrome 18 , developmental and epileptic encephalopathy 1 , developmental and epileptic encephalopathy 12 , epilepsy , genetic disease , myelodysplastic syndrome , myocardial infarction , Pain , schizophrenia , visual epilepsy , West syndrome Plcb2 Bloom syndrome , colorectal cancer , genetic disease , Moebius syndrome , thrombocytopenia Plcb3 chronic ulcer of skin , Experimental Diabetes Mellitus , genetic disease , high grade glioma , Huntington's disease , intellectual disability , leukocyte adhesion deficiency 3 , myocardial infarction , spondylometaphyseal dysplasia with corneal dystrophy Plcb4 Alagille syndrome , ALAGILLE SYNDROME 1 , Auriculocondylar Syndrome , Auriculocondylar Syndrome 1 , Auriculocondylar Syndrome 2 , congenital myasthenic syndrome 18 , developmental and epileptic encephalopathy 12 , genetic disease , long QT syndrome , melanoma , prostate cancer , uveal melanoma Prkca brain ischemia , Breast Neoplasms , Cardiomegaly , chordoid glioma , congestive heart failure , dilated cardiomyopathy , ductal carcinoma in situ , endometrial carcinoma , Experimental Diabetes Mellitus , genetic disease , high grade glioma , hypertension , Intestinal Neoplasms , ischemia , large cell carcinoma , Left Ventricular Hypertrophy , metabolic dysfunction-associated steatotic liver disease , nephrogenic diabetes insipidus , occupational asthma , ovarian cancer , ovarian carcinoma , Pituitary Neoplasms , Polyuria , prostate carcinoma , Reperfusion Injury , Right Ventricular Hypertrophy , urinary bladder cancer Prkcb adult T-cell leukemia/lymphoma , Alzheimer's disease , autistic disorder , Cardiomegaly , Colorectal Neoplasms , congestive heart failure , Diabetic Nephropathies , dilated cardiomyopathy , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Fetal Diseases , genetic disease , Hyperalgesia , hyperglycemia , hypertension , immune system disease , Insulin Resistance , Left Ventricular Hypertrophy , lung non-small cell carcinoma , Myocardial Reperfusion Injury , obesity , sensorineural hearing loss , silicosis , status epilepticus , Stomach Neoplasms , type 2 diabetes mellitus Prkcd autoimmune lymphoproliferative syndrome type 3 , brain ischemia , Burns , Cardiomegaly , Chemical and Drug Induced Liver Injury , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Fever , genetic disease , hyperinsulinism , hypertension , Hypothermia , Insulin Resistance , Intestinal Neoplasms , Left Ventricular Hypertrophy , metabolic dysfunction-associated steatotic liver disease , muscular disease , Myocardial Ischemia , Myocardial Reperfusion Injury , obesity , Parkinsonism , portal hypertension , restrictive cardiomyopathy , Right Ventricular Hypertrophy , steatotic liver disease , Stroke , toxic encephalopathy Prkce Cardiomegaly , cardiomyopathy , Colorectal Neoplasms , coronary stenosis , Diabetic Nephropathies , Experimental Diabetes Mellitus , genetic disease , Hyperalgesia , hypertension , Liver Neoplasms , Lynch syndrome , metabolic dysfunction-associated steatotic liver disease , myocardial infarction , Myocardial Ischemia , peripheral nervous system disease , substance-related disorder , type 2 diabetes mellitus Prkcg Animal Disease Models , autosomal dominant cerebellar ataxia , autosomal recessive spinocerebellar ataxia 14 , cerebellar ataxia , familial cold autoinflammatory syndrome 2 , genetic disease , hereditary ataxia , Hyperalgesia , intellectual disability , middle cerebral artery infarction , primary cerebellar degeneration , retinitis pigmentosa , Spinal Cord Injuries , spinocerebellar ataxia type 14 , Spinocerebellar Ataxias , trigeminal neuralgia Prkch cerebral infarction , genetic disease , obesity , substance-related disorder Prkci abdominal obesity-metabolic syndrome , autistic disorder , autosomal dominant dyskeratosis congenita 1 , Experimental Diabetes Mellitus , Fanconi syndrome , genetic disease , invasive ductal carcinoma , obesity , ovarian carcinoma , type 2 diabetes mellitus Prkcq Crohn's disease , genetic disease , Hyperammonemia , hyperinsulinism , hypoparathyroidism-deafness-renal disease syndrome , inflammatory bowel disease 1 , Insulin Resistance , primary cutaneous T-cell non-Hodgkin lymphoma , prostate adenocarcinoma , retinal detachment , rheumatoid arthritis , Sepsis , type 1 diabetes mellitus Prkcz autism spectrum disorder , Cardiomegaly , chromosome 1p36 deletion syndrome , congenital myasthenic syndrome 8 , dilated cardiomyopathy 1LL , Ehlers-Danlos syndrome spondylodysplastic type 2 , genetic disease , Goldberg-Shprintzen syndrome , Hyperalgesia , hyperglycemia , idiopathic generalized epilepsy , immunodeficiency 16 , immunodeficiency 38 , Insulin Resistance , Joubert syndrome 25 , Left Ventricular Hypertrophy , leukemia , Neurodevelopmental Disorders , Peroxisome Biogenesis Disorder, Complementation Group 7 , Prostatic Neoplasms , Shprintzen-Goldberg Craniosynostosis , type 2 diabetes mellitus Rack1 morphine dependence , Mouth Neoplasms , squamous cell carcinoma , transient cerebral ischemia Rasa1 Animal Mammary Neoplasms , arteriovenous malformation , basal cell carcinoma , Capillary Malformation-Arteriovenous Malformation , Capillary Malformation-Arteriovenous Malformation 1 , carcinoma , Central Nervous System Venous Angioma , Chemical and Drug Induced Liver Injury , Experimental Mammary Neoplasms , familial adenomatous polyposis 1 , genetic disease , hereditary hemorrhagic telangiectasia , Hereditary Neoplastic Syndromes , Infantile Capillary Hemangioma , Klippel-Trenaunay syndrome , Left Ventricular Hypertrophy , lung adenocarcinoma , Multiple Basal Cell Carcinoma , Neurodevelopmental Disorders , Port-Wine Stain , squamous cell carcinoma , Sturge-Weber syndrome , Vascular Malformations
abdominal obesity-metabolic syndrome Prkci acute myeloid leukemia Plcb1 Adenoviridae Infections Btk adenylosuccinase lyase deficiency Pick1 adult T-cell leukemia/lymphoma Fyn , Prkcb agammaglobulinemia Btk agammaglobulinemia 1 Btk Alagille syndrome Plcb1 , Plcb4 ALAGILLE SYNDROME 1 Plcb1 , Plcb4 allergic conjunctivitis Lck Alzheimer's disease Fyn , Hsp90aa1 , Plcb1 , Prkcb amphetamine abuse Pick1 Anaphylaxis Btk anaplastic large cell lymphoma Hsp90aa1 Animal Disease Models Prkcg Animal Mammary Neoplasms Rasa1 arrhythmogenic right ventricular cardiomyopathy Ldb3 arteriovenous malformation Rasa1 arthus reaction Btk Auriculocondylar Syndrome Plcb4 Auriculocondylar Syndrome 1 Plcb4 Auriculocondylar Syndrome 2 Plcb4 autism spectrum disorder Pard3 , Pard6b , Prkcz autistic disorder Btk , Pcnt , Prkcb , Prkci autoimmune lymphoproliferative syndrome type 3 Prkcd autosomal dominant cerebellar ataxia Prkcg autosomal dominant dyskeratosis congenita 1 Prkci autosomal dominant dyskeratosis congenita 6 Pard6a , Phlpp2 autosomal recessive spinocerebellar ataxia 14 Prkcg Axenfeld-Rieger syndrome type 3 Pcnt B-Cell Chronic Lymphocytic Leukemia Btk B-cell lymphoma Btk Baralle-Macken Syndrome Copb1 basal cell carcinoma Rasa1 benign epilepsy with centrotemporal spikes Plcb1 Bile Duct Neoplasms Fscn1 Bloom syndrome Plcb2 brain ischemia Prkca , Prkcd Breast Neoplasms Btk , Hsp90aa1 , Pdpk1 , Prkca Burkitt lymphoma Btk Burn-McKeown syndrome Pard6g Burns Fyn , Prkcd Capillary Malformation-Arteriovenous Malformation Rasa1 Capillary Malformation-Arteriovenous Malformation 1 Rasa1 carcinoma Rasa1 Cardiomegaly Prkca , Prkcb , Prkcd , Prkce , Prkcz cardiomyopathy Ldb3 , Prkce Catalepsy Fyn cataract Copb1 cataract 9 multiple types Pcnt central nervous system lymphoma Btk Central Nervous System Venous Angioma Rasa1 cerebellar ataxia Prkcg cerebral infarction Prkch Charcot-Marie-Tooth disease axonal type 2O Hsp90aa1 Chemical and Drug Induced Liver Injury Prkcd , Rasa1 cholangiocarcinoma Fscn1 chordoid glioma Prkca chromosome 16q22 deletion syndrome Pard6a chromosome 18q deletion syndrome Pard6g , Phlpp1 chromosome 1p36 deletion syndrome Prkcz chronic ulcer of skin Plcb3 Cognitive Dysfunction Hsp90aa1 colitis Btk colon adenocarcinoma Btk colon cancer Hsp90aa1 Colonic Neoplasms Plcb1 colorectal cancer Btk , Plcb2 Colorectal Neoplasms Prkcb , Prkce common bile duct neoplasm Fscn1 common variable immunodeficiency Btk congenital myasthenic syndrome 18 Plcb1 , Plcb4 congenital myasthenic syndrome 8 Prkcz congenital myopathy Ldb3 congenital structural myopathy Ldb3 congestive heart failure Pdpk1 , Prkca , Prkcb contact dermatitis Hsp90aa1 coronary stenosis Prkce COVID-19 Btk Crohn's disease Prkcq cryptococcosis Btk deafness-dystonia-optic neuronopathy syndrome Btk developmental and epileptic encephalopathy 1 Plcb1 developmental and epileptic encephalopathy 12 Plcb1 , Plcb4 developmental and epileptic encephalopathy 30 Pcnt developmental and epileptic encephalopathy 9 Btk Developmental Disabilities Pcnt Diabetic Nephropathies Prkcb , Prkce diffuse large B-cell lymphoma Btk , Pdpk1 dilated cardiomyopathy Lck , Ldb3 , Prkca , Prkcb dilated cardiomyopathy 1A Ldb3 dilated cardiomyopathy 1B Ldb3 dilated cardiomyopathy 1BB Ldb3 dilated cardiomyopathy 1C Ldb3 dilated cardiomyopathy 1H Ldb3 dilated cardiomyopathy 1LL Prkcz Dilated Cardiomyopathy with Left Ventricular Noncompaction Ldb3 distal myopathy Ldb3 Down syndrome Pcnt Ductal Carcinoma Hsp90aa1 ductal carcinoma in situ Prkca Ehlers-Danlos syndrome spondylodysplastic type 2 Prkcz Emery-Dreifuss muscular dystrophy Pick1 endometrial carcinoma Prkca endometriosis of uterus Btk Enterovirus Infections Btk epilepsy Pdpk1 , Phlpp1 , Plcb1 Experimental Arthritis Btk Experimental Diabetes Mellitus Hsp90aa1 , Plcb3 , Prkca , Prkcb , Prkcd , Prkce , Prkci Experimental Liver Cirrhosis Fyn , Prkcb , Prkcd Experimental Mammary Neoplasms Rasa1 Fabry disease Btk familial adenomatous polyposis 1 Rasa1 familial cold autoinflammatory syndrome 2 Prkcg familial hypertrophic cardiomyopathy Ldb3 Fanconi syndrome Prkci Fetal Diseases Prkcb Fever Prkcd Frontotemporal Lobar Degeneration Hsp90aa1 Gallbladder Neoplasms Fscn1 genetic disease Btk , Cdc37 , Copb1 , Fscn1 , Fyn , Hsp90aa1 , Lck , Ldb3 , Pard3 , Pard6a , Pard6b , Pard6g , Pcnt , Pdpk1 , Phlpp1 , Phlpp2 , Pick1 , Plcb1 , Plcb2 , Plcb3 , Plcb4 , Prkca , Prkcb , Prkcd , Prkce , Prkcg , Prkch , Prkci , Prkcq , Prkcz , Rasa1 Goldberg-Shprintzen syndrome Prkcz hereditary ataxia Prkcg hereditary hemorrhagic telangiectasia Rasa1 Hereditary Neoplastic Syndromes Rasa1 high grade glioma Plcb3 , Prkca homocystinuria Pcnt human immunodeficiency virus infectious disease Hsp90aa1 , Lck Huntington's disease Plcb3 Hyperalgesia Prkcb , Prkce , Prkcg , Prkcz Hyperammonemia Prkcq hyperglycemia Prkcb , Prkcz hyperinsulinism Prkcd , Prkcq hypertension Prkca , Prkcb , Prkcd , Prkce hypertrophic cardiomyopathy Ldb3 hypertrophic cardiomyopathy 1 Ldb3 hypertrophic cardiomyopathy 14 Ldb3 hypoparathyroidism-deafness-renal disease syndrome Prkcq Hypothermia Btk , Prkcd idiopathic generalized epilepsy Pdpk1 , Prkcz immune system disease Prkcb immunodeficiency 16 Prkcz immunodeficiency 22 Lck immunodeficiency 38 Prkcz Infantile Capillary Hemangioma Rasa1 inflammatory bowel disease 1 Prkcq influenza A Btk Insulin Resistance Prkcb , Prkcd , Prkcq , Prkcz intellectual disability Copb1 , Pcnt , Phlpp1 , Plcb3 , Prkcg Intestinal Neoplasms Prkca , Prkcd intestinal volvulus Pard6g intrahepatic cholangiocarcinoma Hsp90aa1 invasive ductal carcinoma Prkci ischemia Prkca isolated growth hormone deficiency type III Btk Isolated Noncompaction of the Ventricular Myocardium Ldb3 Joubert syndrome 25 Prkcz juvenile polyposis syndrome Ldb3 Klippel-Trenaunay syndrome Rasa1 Knee Osteoarthritis Hsp90aa1 large cell carcinoma Prkca Left Ventricular Hypertrophy Prkca , Prkcb , Prkcd , Prkcz , Rasa1 Left Ventricular Noncompaction 1 Ldb3 leishmaniasis Btk leukemia Prkcz leukocyte adhesion deficiency 3 Plcb3 listeriosis Btk Liver Neoplasms Prkce long QT syndrome Ldb3 , Plcb4 lung adenocarcinoma Btk , Rasa1 lung non-small cell carcinoma Btk , Pdpk1 , Prkcb Lymphatic Metastasis Btk , Pdpk1 Lynch syndrome Prkce mantle cell lymphoma Btk megacolon Pcnt melanoma Plcb4 metabolic dysfunction-associated steatotic liver disease Prkca , Prkcd , Prkce Microcephalic Osteodysplastic Primordial Dwarfism Pcnt microcephalic osteodysplastic primordial dwarfism type II Pcnt microcephaly Pcnt middle cerebral artery infarction Prkcg Moebius syndrome Plcb2 morphine dependence Rack1 Mouth Neoplasms Rack1 Multiple Basal Cell Carcinoma Rasa1 multiple congenital anomalies-hypotonia-seizures syndrome 1 Phlpp1 muscular disease Prkcd myelodysplastic syndrome Plcb1 myocardial infarction Plcb1 , Plcb3 , Prkce Myocardial Ischemia Prkcd , Prkce Myocardial Reperfusion Injury Prkcb , Prkcd myoclonic dystonia 26 Pick1 myofibrillar myopathy Ldb3 myofibrillar myopathy 1 Ldb3 myofibrillar myopathy 4 Ldb3 Myofibrillar Myopathy, ZASP-Related Ldb3 myotonic dystrophy type 1 Ldb3 nasopharynx carcinoma Btk Neoplasm Metastasis Fscn1 , Hsp90aa1 Neoplastic Cell Transformation Phlpp1 nephrogenic diabetes insipidus Prkca neural tube defect Pard3 neurodegeneration with brain iron accumulation 2A Pick1 Neurodevelopmental Disorders Hsp90aa1 , Pard6g , Prkcz , Rasa1 neuromuscular disease Ldb3 obesity Prkcb , Prkcd , Prkch , Prkci occupational asthma Prkca Oculootofacial Dysplasia Pard6g oral squamous cell carcinoma Btk osteochondrodysplasia Copb1 ovarian cancer Prkca ovarian carcinoma Prkca , Prkci Pain Plcb1 pancreatic cancer Fscn1 pancreatic ductal carcinoma Fscn1 Parkinsonism Prkcd peripheral nervous system disease Prkce peripheral T-cell lymphoma Fyn Peroxisome Biogenesis Disorder, Complementation Group 7 Prkcz Pituitary Neoplasms Prkca Pneumococcal Pneumonia Btk Polyuria Prkca Port-Wine Stain Rasa1 portal hypertension Hsp90aa1 , Prkcd primary cerebellar degeneration Prkcg primary ciliary dyskinesia Pcnt primary cutaneous T-cell non-Hodgkin lymphoma Prkcq primary immunodeficiency disease Btk primary ovarian insufficiency Fyn , Pard3 progressive myoclonus epilepsy Pcnt prostate adenocarcinoma Pdpk1 , Prkcq prostate cancer Pard3 , Pdpk1 , Phlpp1 , Plcb4 prostate carcinoma Prkca Prostatic Neoplasms Pard3 , Prkcz PTEN hamartoma tumor syndrome Ldb3 pulmonary fibrosis Fyn pulmonary valve stenosis Pard6g Reperfusion Injury Prkca restrictive cardiomyopathy Prkcd retinal degeneration Lck retinal detachment Prkcq RETINAL DYSTROPHY WITH INNER RETINAL DYSFUNCTION AND GANGLION CELL ABNORMALITIES Lck retinitis pigmentosa Prkcg rheumatoid arthritis Hsp90aa1 , Prkcq Right Ventricular Hypertrophy Prkca , Prkcd ROLANDIC EPILEPSY, INTELLECTUAL DISABILITY, AND SPEECH DYSPRAXIA, X-LINKED Btk schizophrenia Fyn , Plcb1 Seckel syndrome 1 Pcnt Seckel syndrome 2 Pcnt sensorineural hearing loss Prkcb Sepsis Fyn , Prkcq severe combined immunodeficiency Lck short-rib thoracic dysplasia 9 with or without polydactyly Pdpk1 Shprintzen-Goldberg Craniosynostosis Prkcz silicosis Prkcb Spinal Cord Injuries Prkcg spinocerebellar ataxia type 14 Prkcg Spinocerebellar Ataxias Prkcg spondylometaphyseal dysplasia with corneal dystrophy Plcb3 squamous cell carcinoma Rack1 , Rasa1 status epilepticus Prkcb steatotic liver disease Prkcd Stomach Neoplasms Fyn , Prkcb Streptococcus pneumonia Btk Stroke Prkcd Sturge-Weber syndrome Rasa1 substance-induced psychosis Pick1 substance-related disorder Prkce , Prkch syndromic X-linked intellectual disability Lubs type Btk temporal lobe epilepsy Fyn thrombocytopenia Plcb2 toxic encephalopathy Prkcd transient cerebral ischemia Rack1 trigeminal neuralgia Prkcg type 1 diabetes mellitus Prkcq type 2 diabetes mellitus Prkcb , Prkce , Prkci , Prkcz urinary bladder cancer Prkca uveal melanoma Plcb4 vascular dementia Pcnt Vascular Malformations Rasa1 Ventricular Tachycardia Ldb3 visual epilepsy Plcb1 Volvulus Of Midgut Pard6g West syndrome Plcb1 X-linked agammaglobulinemia Btk X-Linked Hypogammaglobulinemia Btk