INSULIN SECRETION PATHWAY (PW:0000674)
Description
In
response to elevated blood glucose, the pancreatic beta cells of the islets of
Langerhans secrete insulin. Processed insulin is stored in secretory granules along
with other low molecular weight molecules and metals. Glucose levels couple to
changes in membrane potential to regulate secretion of insulin-granules. Beta
cells express a high capacity glucose transporter and the G6P insensitive
glucokinase. Fast uptake of glucose into the cell and rapid phosphorylation are
followed by its oxidative metabolism. The resulting Increase in ATP/ADP ratio
triggers closure of the ATP-sensitive potassium channel (K
ATP ) leading
to membrane depolarization and opening of voltage-gated calcium channels (VDCC).
Rise in calcium concentration induces fusion of insulin-granules with the
plasma membrane and SNARE-mediated exocytosis. Exocytosis of insulin-granules
is biphasic: an initial rapid release is followed by a slower but sustained
second release. The 'triggering' first phase involves granules at or near the
plasma membrane - the 'readily releasable pool' (RRP).The mobilization of
granules from a 'storage-granule pool' (SGP) along with those already docked
underlies the second 'amplifying' phase, largely independent of K
ATP
channels. The membrane depolarization that opens VDCC also activates the
voltage dependent potassium channels (Kcn) leading to re-polarization of the
membrane and closure of VDCC. The t-SNARE Snap25 and Stx1a co-localize and/or
interact with all channels to potentiate or modulate their activity. Shown is
Snap25 which has been reported to bind to and inhibit Kcn. During calcium
triggered membrane fusion, the minimal SNARE complex of Snap25, Stx1a and
v-SNARE Vamp2 changes from
trans to
cis configuration. Proposed calcium
sensors include members of the Syt family; Munc proteins regulate aspects of complex
assembly. Monomeric G protein Rho/Rac/Cdc42 and Rab mediated pathways regulate
cytoskeletal rearrangements, important for vesicular transport, and vesicular
trafficking, respectively. Cdc42 and Rac1, Rab27a and Rab3a are co-localized
with insulin-granules of one or both phases, their exact role under
investigation. The second phase of insulin secretion is less well understood; metabolic
coupling factors resulting from cycling of pyruvate in the course of glucose
metabolism have been suggested to play a role. NADPH, one such factor, can
inhibit Kcn activity. Identification of all components and regulators of the
pathway are subjects of intense research. The importance of delineating the
molecular details of insulin secretion pathway is heightened by the fact that
both release phases are impaired in type II diabetes.
To see the ontology report for annotations, GViewer and
download, click here [click to see the ontology
report for associated GO term - GO:0030073 and related entry at Reactome - REACT_18325.2 ]...(less)
Pathway Diagram:
Genes in Pathway:
G
Abcc8
ATP binding cassette subfamily C member 8
TAS
RGD
PMID:18940941 RGD:2311063
NCBI chr 1:105,734,992...105,816,272
G
Cacna1a
calcium voltage-gated channel subunit alpha1 A
TAS
RGD
PMID:16868246 RGD:2311105
NCBI chr19:40,425,560...40,724,810
G
Cacna1c
calcium voltage-gated channel subunit alpha1 C
TAS
RGD
PMID:16868246 RGD:2311105
NCBI chr 4:153,431,169...154,051,932
G
Cacna1d
calcium voltage-gated channel subunit alpha1 D
TAS
RGD
PMID:16868246 RGD:2311105
NCBI chr16:5,233,682...5,527,549
G
Cdc42
cell division cycle 42
ISO
RGD
PMID:19295123 RGD:2311087
NCBI chr 5:154,838,478...154,876,629
G
Gck
glucokinase
TAS
RGD
PMID:18774732 RGD:2311061
NCBI chr14:84,999,019...85,041,098
G
Kcnb1
potassium voltage-gated channel subfamily B member 1
TAS
RGD
PMID:12830383 RGD:2311121
NCBI chr 3:176,239,285...176,332,408
G
Kcnj11
potassium inwardly-rectifying channel, subfamily J, member 11
TAS
RGD
PMID:18940941 RGD:2311063
NCBI chr 1:105,727,473...105,731,167
G
Rab27a
RAB27A, member RAS oncogene family
ISO
RGD
PMID:19295123 RGD:2311087
NCBI chr 8:82,663,373...82,717,267
G
Rab3a
RAB3A, member RAS oncogene family
ISO
RGD
PMID:19295123 RGD:2311087
NCBI chr16:18,718,164...18,722,273
G
Slc2a2
solute carrier family 2 member 2
TAS
RGD
PMID:18774732 RGD:2311061
NCBI chr 2:113,537,884...113,568,422
G
Snap25
synaptosome associated protein 25
TAS
RGD
PMID:12830383 RGD:2311121
NCBI chr 3:124,041,898...124,123,761
G
Stx1a
syntaxin 1A
ISO
RGD
PMID:19295123 RGD:2311087
NCBI chr12:27,278,517...27,306,547
G
Stxbp1
syntaxin binding protein 1
ISO
RGD
PMID:19295123 RGD:2311087
NCBI chr 3:36,474,428...36,536,120
G
Syt7
synaptotagmin 7
TAS IMP
RGD
PMID:18713958 PMID:17709608 RGD:2311148 , RGD:2311143
NCBI chr 1:216,456,148...216,518,718
G
Syt7_v1
synaptotagmin 7, variant 1
IMP
RGD
PMID:17709608 RGD:2311143
G
Syt9
synaptotagmin 9
TAS IMP
RGD
PMID:18713958 PMID:16165130 RGD:2311148 , RGD:2311147
NCBI chr 1:161,275,882...161,456,384
G
Unc13a
unc-13 homolog A
ISO
RGD
PMID:19295123 RGD:2311087
NCBI chr16:18,333,910...18,381,813
G
Vamp2
vesicle-associated membrane protein 2
ISO
RGD
PMID:19295123 RGD:2311087
NCBI chr10:54,292,423...54,296,657
G
Abcc8
ATP binding cassette subfamily C member 8
ISO
DNA:missense mutation::A1369S (human)
RGD
PMID:17259403 RGD:2313628
NCBI chr 1:105,734,992...105,816,272
G
Kcnj11
potassium inwardly-rectifying channel, subfamily J, member 11
ISO
polymorphisms in the human gene are linked to altered insulin secretion; E23K polymorphism appears to confer susceptibility to diabetes type-2 in Caucasian population
RGD
PMID:15565284 PMID:17259403 RGD:2313610 , RGD:2313628
NCBI chr 1:105,727,473...105,731,167
Pathway Gene Annotations
Disease Annotations Associated with Genes in the insulin secretion pathway
Abcc8 atrial heart septal defect , brain edema , Brain Injuries , cardiac arrest , Colorectal Neoplasms , Congenital Hyperinsulinism , congestive heart failure , cryptorchidism , diabetes mellitus , Dwarfism , Endotoxemia , epilepsy , familial hyperinsulinemic hypoglycemia 1 , familial hyperinsulinemic hypoglycemia 2 , gastroesophageal reflux disease , genetic disease , Growth Disorders , hyperinsulinemic hypoglycemia , hyperinsulinism , Hyperplasia , hypertension , hypoglycemia , intellectual disability , leucine-sensitive hypoglycemia of infancy , Macrocephaly , maturity-onset diabetes of the young , maturity-onset diabetes of the young type 1 , maturity-onset diabetes of the young type 12 , maturity-onset diabetes of the young type 13 , middle cerebral artery infarction , Muscle Hypotonia , Myocardial Reperfusion Injury , Necrosis , neonatal diabetes mellitus , Neonatal Hypoglycemia, Simulating Foetopathia Diabetica , Neuraminidase Deficiency , newborn respiratory distress syndrome , Parkinsonism , permanent neonatal diabetes mellitus , Permanent Neonatal Diabetes Mellitus 3 , polyhydramnios , Pulmonary Arterial Hypertension , Retrognathia , sciatic neuropathy , Spinal Cord Injuries , status epilepticus , Stroke , Subarachnoid Hemorrhage , transient neonatal diabetes mellitus , Transient Neonatal Diabetes Mellitus, 2 , Transient Neonatal Diabetes Mellitus, 3 , Traumatic Subarachnoid Hemorrhage , type 1 diabetes mellitus , type 2 diabetes mellitus Cacna1a Aicardi-Goutieres Syndrome 4 , alpha-mannosidosis , Alternating Hemiplegia of Childhood 1 , amyotrophic lateral sclerosis , Ataxia , attention deficit hyperactivity disorder , Auditory Neuropathy , autism spectrum disorder , bone marrow disease , cerebellar ataxia , cerebral palsy , cerebral venous thrombosis , Charcot-Marie-Tooth disease dominant intermediate B , childhood absence epilepsy , childhood electroclinical syndrome , combined immunodeficiency , combined T cell and B cell immunodeficiency , developmental and epileptic encephalopathy 1 , developmental and epileptic encephalopathy 2 , developmental and epileptic encephalopathy 42 , developmental and epileptic encephalopathy 52 , Developmental Disabilities , disorder of sexual development , Dysarthria , epilepsy , episodic ataxia , episodic ataxia type 2 , exfoliation syndrome , familial hemiplegic migraine , familial hemiplegic migraine 1 , generalized dystonia , generalized epilepsy , genetic disease , glutaric acidemia I , intellectual disability , Lambert-Eaton myasthenic syndrome , learning disability , Marshall-Smith syndrome , migraine , migraine with aura , Muscle Spasticity , myelitis , myoclonic-atonic epilepsy , Nervous System Malformations , neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures , Neurodevelopmental Disorders , neurogenic bladder , Neurologic Gait Disorders , progressive bulbar palsy , spastic ataxia , Spastic Paraparesis , spinocerebellar ataxia type 6 , Spinocerebellar Ataxias , Sporadic Hemiplegic Migraine , subependymal giant cell astrocytoma , sudden infant death syndrome , temporal lobe epilepsy , Tremor , vascular dementia Cacna1c acute stress disorder , alcohol dependence , Alzheimer's disease , amyloidosis , anxiety disorder , arrhythmogenic right ventricular cardiomyopathy , autism spectrum disorder , autistic disorder , bipolar disorder , breast ductal carcinoma , Brugada syndrome , Brugada syndrome 3 , Cardiac Arrhythmias , cardiomyopathy , catecholaminergic polymorphic ventricular tachycardia , cerebral palsy , Cognitive Dysfunction , Congenital Limb Deformities , congestive heart failure , dilated cardiomyopathy , epilepsy , esophageal atresia , Familial Ventricular Tachycardia , Fetal Growth Retardation , genetic disease , Genetic Predisposition to Disease , Heart Block , Hyperphosphatemic Familial Tumoral Calcinosis 1 , hypertension , hypertrophic cardiomyopathy , hypertrophic cardiomyopathy 1 , hypoglycemia , intellectual disability , invasive ductal carcinoma , Joint Instability , Language Development Disorders , long QT syndrome , long QT syndrome 1 , long QT syndrome 8 , major depressive disorder , neurodevelopmental disorder with dysmorphic facies and distal limb anomalies , neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures , Neurodevelopmental Disorders , post-traumatic stress disorder , primary immunodeficiency disease , Psychomotor Agitation , restrictive cardiomyopathy , Romano-Ward Syndrome , schizophrenia , short QT syndrome , Sudden Cardiac Death , Sudden Death , Sudden Unexpected Nocturnal Death Syndrome , Timothy syndrome , Tremor , Ventricular Fibrillation, Paroxysmal Familial, 1 , Ventricular Tachycardia , Wolff-Parkinson-White syndrome Cacna1d adenoma , Alcohol Withdrawal Seizures , Animal Disease Models , autism spectrum disorder , autosomal recessive Alport syndrome , bipolar disorder , Bradycardia , colon adenocarcinoma , colon adenoma , congenital disorder of glycosylation Iw , Deafness , Drug-Induced Dyskinesia , epilepsy , Fetal Growth Retardation , genetic disease , Hearing Loss , Heart Block , intellectual disability , long QT syndrome , Memory Disorders , Meniere's disease , Presbycusis , Primary Aldosteronism, Seizures, and Neurologic Abnormalities , primary hyperaldosteronism , prostate cancer , sciatic neuropathy , sick sinus syndrome , Sinoatrial Node Dysfunction and Deafness , Supraventricular Tachycardia , type 2 diabetes mellitus Cdc42 3-hydroxy-3-methylglutaryl-CoA lyase deficiency , Adrenal Gland Neoplasms , Alzheimer's disease , Animal Mammary Neoplasms , bipolar disorder , carcinoma , cleft palate , congenital disorder of glycosylation Ir , Experimental Arthritis , Experimental Mammary Neoplasms , fibrosarcoma , genetic disease , human immunodeficiency virus infectious disease , hyperprolinemia type 2 , microvillus inclusion disease , Necrosis , Neurodevelopmental Disorders , Noonan Like Syndrome , pancreatic cancer , Parkinson's disease 6 , Reperfusion Injury , rhinitis , Spinal Cord Injuries , Takenouchi-Kosaki Syndrome , temporal lobe epilepsy Gck Bone Marrow Failure Syndrome 2 , Congenital Hyperinsulinism , coronary artery disease , diabetes mellitus , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , familial hyperinsulinemic hypoglycemia 3 , genetic disease , gestational diabetes , hyperglycemia , hyperinsulinemic hypoglycemia , hyperinsulinism , hypertension , hypoglycemia , Insulin Resistance , Liver Injury , maturity-onset diabetes of the young , maturity-onset diabetes of the young type 1 , maturity-onset diabetes of the young type 2 , maturity-onset diabetes of the young type 3 , Metabolic Syndrome , neonatal diabetes mellitus , Nijmegen breakage syndrome , obesity , permanent neonatal diabetes mellitus , Permanent Neonatal Diabetes Mellitus 1 , pleomorphic xanthoastrocytoma , steatotic liver disease , transient neonatal diabetes mellitus , type 2 diabetes mellitus Kcnb1 developmental and epileptic encephalopathy , developmental and epileptic encephalopathy 26 , Diaphragmatic Hernia , early infantile epileptic encephalopathy , epilepsy , generalized epilepsy , genetic disease , intellectual disability , Marfanoid Mental Retardation Syndrome, Autosomal , Mobility Limitation , Muscle Hypotonia , Myoclonic Epilepsies , Neurodevelopmental Disorders , Peripheral Nerve Injuries , schizophrenia , spinal muscular atrophy Kcnj11 atopic dermatitis , Congenital Hyperinsulinism , Developmental Delay, Epilepsy, and Neonatal Diabetes , diabetes mellitus , epilepsy , Experimental Diabetes Mellitus , familial hyperinsulinemic hypoglycemia 1 , familial hyperinsulinemic hypoglycemia 2 , genetic disease , hyperinsulinemic hypoglycemia , hyperinsulinism , hypertension , hypoglycemia , Insulin Resistance , intellectual disability , Kidney Reperfusion Injury , Left Ventricular Hypertrophy , leucine-sensitive hypoglycemia of infancy , maturity-onset diabetes of the young , maturity-onset diabetes of the young type 1 , maturity-onset diabetes of the young type 13 , Myocardial Ischemia , Myocardial Reperfusion Injury , neonatal diabetes mellitus , Neonatal Hypoglycemia, Simulating Foetopathia Diabetica , Parkinsonism , permanent neonatal diabetes mellitus , Permanent Neonatal Diabetes Mellitus 1 , Permanent Neonatal Diabetes Mellitus 2 , Permanent Neonatal Diabetes Mellitus 3 , prediabetes syndrome , sciatic neuropathy , status epilepticus , transient neonatal diabetes mellitus , Transient Neonatal Diabetes Mellitus, 2 , Transient Neonatal Diabetes Mellitus, 3 , type 1 diabetes mellitus , type 2 diabetes mellitus Rab27a Bloom syndrome , Chediak-Higashi syndrome , colorectal cancer , Congenital Abnormalities , Disease Progression , genetic disease , Griscelli syndrome , Griscelli syndrome type 2 , hemophagocytic lymphohistiocytosis , Hermansky-Pudlak syndrome 1 , Hypopigmentation , multisystem inflammatory syndrome in children , Neoplasm Invasiveness , non-Langerhans-cell histiocytosis , platelet storage pool deficiency , urinary bladder cancer Rab3a Ependymomas , Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 Slc2a2 Breast Neoplasms , diabetes mellitus , Experimental Diabetes Mellitus , Fanconi syndrome , Fanconi-Bickel syndrome , Fetal Growth Retardation , gastrinoma , genetic disease , Glucagonoma , glycogen storage disease , hepatocellular carcinoma , insulinoma , long QT syndrome , maturity-onset diabetes of the young type 1 , neural tube defect , pancreatic ductal carcinoma , steatotic liver disease , type 2 diabetes mellitus Snap25 ALAGILLE SYNDROME 1 , attention deficit hyperactivity disorder , Bardet-Biedl syndrome , bipolar disorder , congenital myasthenic syndrome , congenital myasthenic syndrome 18 , depressive disorder , developmental and epileptic encephalopathy , developmental and epileptic encephalopathy 12 , developmental and epileptic encephalopathy 2 , Developmental Disabilities , Down syndrome , early infantile epileptic encephalopathy , epilepsy , epilepsy with generalized tonic-clonic seizures , Experimental Diabetes Mellitus , focal epilepsy , genetic disease , intellectual disability , microcephaly , Muscle Hypotonia , Neurodevelopmental Disorders , Neuromuscular Manifestations , obesity , optic atrophy , psychotic disorder , schizophrenia , stereotypic movement disorder , Tics , type 2 diabetes mellitus Stx1a autism spectrum disorder , autistic disorder , Creutzfeldt-Jakob disease , disease of mental health , epilepsy , genetic disease , Hirschsprung's disease , intestinal volvulus , Neurodevelopmental Disorders , pleomorphic xanthoastrocytoma , schizophrenia , Volvulus Of Midgut , Williams-Beuren syndrome Stxbp1 autism spectrum disorder , autistic disorder , Bardet-Biedl syndrome 1 , Bardet-Biedl syndrome 17 , cerebellar ataxia , cerebellar hypoplasia , congenital disorder of glycosylation Iu , developmental and epileptic encephalopathy , developmental and epileptic encephalopathy 31A , developmental and epileptic encephalopathy 4 , Developmental Disabilities , Developmental Disease , Duchenne muscular dystrophy , dystonia , early infantile epileptic encephalopathy , epilepsy , generalized epilepsy , genetic disease , intellectual disability , microcephaly , Muscle Hypotonia , Muscle Spasticity , Myoclonic Epilepsies , myoclonic-atonic epilepsy , neurodegenerative disease , Neurodevelopmental Disorders , non-syndromic intellectual disability , pathologic nystagmus , primary coenzyme Q10 deficiency 7 , prostate cancer , salt and pepper syndrome , spastic ataxia , strabismus , Tremor , West syndrome Syt7 Hereditary Paraganglioma-Pheochromocytoma Syndromes , intellectual disability , leukocyte adhesion deficiency 3 , myoepithelioma , paraganglioma Unc13a amyotrophic lateral sclerosis , amyotrophic lateral sclerosis type 1 , autistic disorder , cerebellar ataxia , Febrile Seizures , Fetal Growth Retardation , Neurodevelopmental Disorders , Tremor Vamp2 common variable immunodeficiency , Diamond-Blackfan anemia , dyskeratosis congenita , genetic disease , Li-Fraumeni syndrome , NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA AND AUTISTIC FEATURES WITH OR WITHOUT HYPERKINETIC MOVEMENTS , Neurodevelopmental Disorders , very long chain acyl-CoA dehydrogenase deficiency
3-hydroxy-3-methylglutaryl-CoA lyase deficiency Cdc42 acute stress disorder Cacna1c adenoma Cacna1d Adrenal Gland Neoplasms Cdc42 Aicardi-Goutieres Syndrome 4 Cacna1a ALAGILLE SYNDROME 1 Snap25 alcohol dependence Cacna1c Alcohol Withdrawal Seizures Cacna1d alpha-mannosidosis Cacna1a Alternating Hemiplegia of Childhood 1 Cacna1a Alzheimer's disease Cacna1c , Cdc42 amyloidosis Cacna1c amyotrophic lateral sclerosis Cacna1a , Unc13a amyotrophic lateral sclerosis type 1 Unc13a Animal Disease Models Cacna1d Animal Mammary Neoplasms Cdc42 anxiety disorder Cacna1c arrhythmogenic right ventricular cardiomyopathy Cacna1c Ataxia Cacna1a atopic dermatitis Kcnj11 atrial heart septal defect Abcc8 attention deficit hyperactivity disorder Cacna1a , Snap25 Auditory Neuropathy Cacna1a autism spectrum disorder Cacna1a , Cacna1c , Cacna1d , Stx1a , Stxbp1 autistic disorder Cacna1c , Stx1a , Stxbp1 , Unc13a autosomal recessive Alport syndrome Cacna1d Bardet-Biedl syndrome Snap25 Bardet-Biedl syndrome 1 Stxbp1 Bardet-Biedl syndrome 17 Stxbp1 bipolar disorder Cacna1c , Cacna1d , Cdc42 , Snap25 Bloom syndrome Rab27a bone marrow disease Cacna1a Bone Marrow Failure Syndrome 2 Gck Bradycardia Cacna1d brain edema Abcc8 Brain Injuries Abcc8 breast ductal carcinoma Cacna1c Breast Neoplasms Slc2a2 Brugada syndrome Cacna1c Brugada syndrome 3 Cacna1c carcinoma Cdc42 cardiac arrest Abcc8 Cardiac Arrhythmias Cacna1c cardiomyopathy Cacna1c catecholaminergic polymorphic ventricular tachycardia Cacna1c cerebellar ataxia Cacna1a , Stxbp1 , Unc13a cerebellar hypoplasia Stxbp1 cerebral palsy Cacna1a , Cacna1c cerebral venous thrombosis Cacna1a Charcot-Marie-Tooth disease dominant intermediate B Cacna1a Chediak-Higashi syndrome Rab27a childhood absence epilepsy Cacna1a childhood electroclinical syndrome Cacna1a cleft palate Cdc42 Cognitive Dysfunction Cacna1c colon adenocarcinoma Cacna1d colon adenoma Cacna1d colorectal cancer Rab27a Colorectal Neoplasms Abcc8 combined immunodeficiency Cacna1a combined T cell and B cell immunodeficiency Cacna1a common variable immunodeficiency Vamp2 Congenital Abnormalities Rab27a congenital disorder of glycosylation Ir Cdc42 congenital disorder of glycosylation Iu Stxbp1 congenital disorder of glycosylation Iw Cacna1d Congenital Hyperinsulinism Abcc8 , Gck , Kcnj11 Congenital Limb Deformities Cacna1c congenital myasthenic syndrome Snap25 congenital myasthenic syndrome 18 Snap25 congestive heart failure Abcc8 , Cacna1c coronary artery disease Gck Creutzfeldt-Jakob disease Stx1a cryptorchidism Abcc8 Deafness Cacna1d depressive disorder Snap25 developmental and epileptic encephalopathy Kcnb1 , Snap25 , Stxbp1 developmental and epileptic encephalopathy 1 Cacna1a developmental and epileptic encephalopathy 12 Snap25 developmental and epileptic encephalopathy 2 Cacna1a , Snap25 developmental and epileptic encephalopathy 26 Kcnb1 developmental and epileptic encephalopathy 31A Stxbp1 developmental and epileptic encephalopathy 4 Stxbp1 developmental and epileptic encephalopathy 42 Cacna1a developmental and epileptic encephalopathy 52 Cacna1a Developmental Delay, Epilepsy, and Neonatal Diabetes Kcnj11 Developmental Disabilities Cacna1a , Snap25 , Stxbp1 Developmental Disease Stxbp1 diabetes mellitus Abcc8 , Gck , Kcnj11 , Slc2a2 Diamond-Blackfan anemia Vamp2 Diaphragmatic Hernia Kcnb1 dilated cardiomyopathy Cacna1c disease of mental health Stx1a Disease Progression Rab27a disorder of sexual development Cacna1a Down syndrome Snap25 Drug-Induced Dyskinesia Cacna1d Duchenne muscular dystrophy Stxbp1 Dwarfism Abcc8 Dysarthria Cacna1a dyskeratosis congenita Vamp2 dystonia Stxbp1 early infantile epileptic encephalopathy Kcnb1 , Snap25 , Stxbp1 Endotoxemia Abcc8 Ependymomas Rab3a epilepsy Abcc8 , Cacna1a , Cacna1c , Cacna1d , Kcnb1 , Kcnj11 , Snap25 , Stx1a , Stxbp1 epilepsy with generalized tonic-clonic seizures Snap25 episodic ataxia Cacna1a episodic ataxia type 2 Cacna1a esophageal atresia Cacna1c exfoliation syndrome Cacna1a Experimental Arthritis Cdc42 Experimental Diabetes Mellitus Gck , Kcnj11 , Slc2a2 , Snap25 Experimental Liver Cirrhosis Gck Experimental Mammary Neoplasms Cdc42 familial hemiplegic migraine Cacna1a familial hemiplegic migraine 1 Cacna1a familial hyperinsulinemic hypoglycemia 1 Abcc8 , Kcnj11 familial hyperinsulinemic hypoglycemia 2 Abcc8 , Kcnj11 familial hyperinsulinemic hypoglycemia 3 Gck Familial Ventricular Tachycardia Cacna1c Fanconi syndrome Slc2a2 Fanconi-Bickel syndrome Slc2a2 Febrile Seizures Unc13a Fetal Growth Retardation Cacna1c , Cacna1d , Slc2a2 , Unc13a fibrosarcoma Cdc42 focal epilepsy Snap25 gastrinoma Slc2a2 gastroesophageal reflux disease Abcc8 generalized dystonia Cacna1a generalized epilepsy Cacna1a , Kcnb1 , Stxbp1 genetic disease Abcc8 , Cacna1a , Cacna1c , Cacna1d , Cdc42 , Gck , Kcnb1 , Kcnj11 , Rab27a , Slc2a2 , Snap25 , Stx1a , Stxbp1 , Vamp2 Genetic Predisposition to Disease Cacna1c gestational diabetes Gck Glucagonoma Slc2a2 glutaric acidemia I Cacna1a glycogen storage disease Slc2a2 Griscelli syndrome Rab27a Griscelli syndrome type 2 Rab27a Growth Disorders Abcc8 Hearing Loss Cacna1d Heart Block Cacna1c , Cacna1d hemophagocytic lymphohistiocytosis Rab27a hepatocellular carcinoma Slc2a2 Hereditary Paraganglioma-Pheochromocytoma Syndromes Syt7 Hermansky-Pudlak syndrome 1 Rab27a Hirschsprung's disease Stx1a human immunodeficiency virus infectious disease Cdc42 hyperglycemia Gck hyperinsulinemic hypoglycemia Abcc8 , Gck , Kcnj11 hyperinsulinism Abcc8 , Gck , Kcnj11 Hyperphosphatemic Familial Tumoral Calcinosis 1 Cacna1c Hyperplasia Abcc8 hyperprolinemia type 2 Cdc42 hypertension Abcc8 , Cacna1c , Gck , Kcnj11 hypertrophic cardiomyopathy Cacna1c hypertrophic cardiomyopathy 1 Cacna1c hypoglycemia Abcc8 , Cacna1c , Gck , Kcnj11 Hypopigmentation Rab27a Insulin Resistance Gck , Kcnj11 insulinoma Slc2a2 intellectual disability Abcc8 , Cacna1a , Cacna1c , Cacna1d , Kcnb1 , Kcnj11 , Snap25 , Stxbp1 , Syt7 intestinal volvulus Stx1a invasive ductal carcinoma Cacna1c Joint Instability Cacna1c Kidney Reperfusion Injury Kcnj11 Lambert-Eaton myasthenic syndrome Cacna1a Language Development Disorders Cacna1c learning disability Cacna1a Left Ventricular Hypertrophy Kcnj11 leucine-sensitive hypoglycemia of infancy Abcc8 , Kcnj11 leukocyte adhesion deficiency 3 Syt7 Li-Fraumeni syndrome Vamp2 Liver Injury Gck long QT syndrome Cacna1c , Cacna1d , Slc2a2 long QT syndrome 1 Cacna1c long QT syndrome 8 Cacna1c Macrocephaly Abcc8 major depressive disorder Cacna1c Marfanoid Mental Retardation Syndrome, Autosomal Kcnb1 Marshall-Smith syndrome Cacna1a maturity-onset diabetes of the young Abcc8 , Gck , Kcnj11 maturity-onset diabetes of the young type 1 Abcc8 , Gck , Kcnj11 , Slc2a2 maturity-onset diabetes of the young type 12 Abcc8 maturity-onset diabetes of the young type 13 Abcc8 , Kcnj11 maturity-onset diabetes of the young type 2 Gck maturity-onset diabetes of the young type 3 Gck Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 Rab3a Memory Disorders Cacna1d Meniere's disease Cacna1d Metabolic Syndrome Gck microcephaly Snap25 , Stxbp1 microvillus inclusion disease Cdc42 middle cerebral artery infarction Abcc8 migraine Cacna1a migraine with aura Cacna1a Mobility Limitation Kcnb1 multisystem inflammatory syndrome in children Rab27a Muscle Hypotonia Abcc8 , Kcnb1 , Snap25 , Stxbp1 Muscle Spasticity Cacna1a , Stxbp1 myelitis Cacna1a Myocardial Ischemia Kcnj11 Myocardial Reperfusion Injury Abcc8 , Kcnj11 Myoclonic Epilepsies Kcnb1 , Stxbp1 myoclonic-atonic epilepsy Cacna1a , Stxbp1 myoepithelioma Syt7 Necrosis Abcc8 , Cdc42 neonatal diabetes mellitus Abcc8 , Gck , Kcnj11 Neonatal Hypoglycemia, Simulating Foetopathia Diabetica Abcc8 , Kcnj11 Neoplasm Invasiveness Rab27a Nervous System Malformations Cacna1a neural tube defect Slc2a2 Neuraminidase Deficiency Abcc8 neurodegenerative disease Stxbp1 neurodevelopmental disorder with dysmorphic facies and distal limb anomalies Cacna1c NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA AND AUTISTIC FEATURES WITH OR WITHOUT HYPERKINETIC MOVEMENTS Vamp2 neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures Cacna1a , Cacna1c Neurodevelopmental Disorders Cacna1a , Cacna1c , Cdc42 , Kcnb1 , Snap25 , Stx1a , Stxbp1 , Unc13a , Vamp2 neurogenic bladder Cacna1a Neurologic Gait Disorders Cacna1a Neuromuscular Manifestations Snap25 newborn respiratory distress syndrome Abcc8 Nijmegen breakage syndrome Gck non-Langerhans-cell histiocytosis Rab27a non-syndromic intellectual disability Stxbp1 Noonan Like Syndrome Cdc42 obesity Gck , Snap25 optic atrophy Snap25 pancreatic cancer Cdc42 pancreatic ductal carcinoma Slc2a2 paraganglioma Syt7 Parkinson's disease 6 Cdc42 Parkinsonism Abcc8 , Kcnj11 pathologic nystagmus Stxbp1 Peripheral Nerve Injuries Kcnb1 permanent neonatal diabetes mellitus Abcc8 , Gck , Kcnj11 Permanent Neonatal Diabetes Mellitus 1 Gck , Kcnj11 Permanent Neonatal Diabetes Mellitus 2 Kcnj11 Permanent Neonatal Diabetes Mellitus 3 Abcc8 , Kcnj11 platelet storage pool deficiency Rab27a pleomorphic xanthoastrocytoma Gck , Stx1a polyhydramnios Abcc8 post-traumatic stress disorder Cacna1c prediabetes syndrome Kcnj11 Presbycusis Cacna1d Primary Aldosteronism, Seizures, and Neurologic Abnormalities Cacna1d primary coenzyme Q10 deficiency 7 Stxbp1 primary hyperaldosteronism Cacna1d primary immunodeficiency disease Cacna1c progressive bulbar palsy Cacna1a prostate cancer Cacna1d , Stxbp1 Psychomotor Agitation Cacna1c psychotic disorder Snap25 Pulmonary Arterial Hypertension Abcc8 Reperfusion Injury Cdc42 restrictive cardiomyopathy Cacna1c Retrognathia Abcc8 rhinitis Cdc42 Romano-Ward Syndrome Cacna1c salt and pepper syndrome Stxbp1 schizophrenia Cacna1c , Kcnb1 , Snap25 , Stx1a sciatic neuropathy Abcc8 , Cacna1d , Kcnj11 short QT syndrome Cacna1c sick sinus syndrome Cacna1d Sinoatrial Node Dysfunction and Deafness Cacna1d spastic ataxia Cacna1a , Stxbp1 Spastic Paraparesis Cacna1a Spinal Cord Injuries Abcc8 , Cdc42 spinal muscular atrophy Kcnb1 spinocerebellar ataxia type 6 Cacna1a Spinocerebellar Ataxias Cacna1a Sporadic Hemiplegic Migraine Cacna1a status epilepticus Abcc8 , Kcnj11 steatotic liver disease Gck , Slc2a2 stereotypic movement disorder Snap25 strabismus Stxbp1 Stroke Abcc8 Subarachnoid Hemorrhage Abcc8 subependymal giant cell astrocytoma Cacna1a Sudden Cardiac Death Cacna1c Sudden Death Cacna1c sudden infant death syndrome Cacna1a Sudden Unexpected Nocturnal Death Syndrome Cacna1c Supraventricular Tachycardia Cacna1d Takenouchi-Kosaki Syndrome Cdc42 temporal lobe epilepsy Cacna1a , Cdc42 Tics Snap25 Timothy syndrome Cacna1c transient neonatal diabetes mellitus Abcc8 , Gck , Kcnj11 Transient Neonatal Diabetes Mellitus, 2 Abcc8 , Kcnj11 Transient Neonatal Diabetes Mellitus, 3 Abcc8 , Kcnj11 Traumatic Subarachnoid Hemorrhage Abcc8 Tremor Cacna1a , Cacna1c , Stxbp1 , Unc13a type 1 diabetes mellitus Abcc8 , Kcnj11 type 2 diabetes mellitus Abcc8 , Cacna1d , Gck , Kcnj11 , Slc2a2 , Snap25 urinary bladder cancer Rab27a vascular dementia Cacna1a Ventricular Fibrillation, Paroxysmal Familial, 1 Cacna1c Ventricular Tachycardia Cacna1c very long chain acyl-CoA dehydrogenase deficiency Vamp2 Volvulus Of Midgut Stx1a West syndrome Stxbp1 Williams-Beuren syndrome Stx1a Wolff-Parkinson-White syndrome Cacna1c
