HHF3
MCID: HYP601
MIFTS: 52

Hyperinsulinemic Hypoglycemia, Familial, 3 (HHF3)

Categories: Blood diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hyperinsulinemic Hypoglycemia, Familial, 3

MalaCards integrated aliases for Hyperinsulinemic Hypoglycemia, Familial, 3:

Name: Hyperinsulinemic Hypoglycemia, Familial, 3 56 13 71
Hyperinsulinism Due to Glucokinase Deficiency 12 52 58 29 6
Hhf3 56 12 52 73
Familial Hyperinsulinemic Hypoglycemia 3 12 73 15
Hyperinsulinemic Hypoglycemia Due to Glucokinase Deficiency 12 58
Congenital Hyperinsulinism 73 71
Persistent Hyperinsulinemic Hypoglycemia of Infancy 73
Hypoglycemia, Hyperinsulinemic, Familial, Type 3 39
Hyperinsulinemic Hypoglycemia Familial 3 52
Phhi 73

Characteristics:

Orphanet epidemiological data:

58
hyperinsulinism due to glucokinase deficiency
Inheritance: Autosomal dominant;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity (see hhf1 )


HPO:

31
hyperinsulinemic hypoglycemia, familial, 3:
Inheritance autosomal dominant inheritance heterogeneous


Classifications:

Orphanet: 58  
Inborn errors of metabolism
Rare endocrine diseases


External Ids:

Disease Ontology 12 DOID:0070216
OMIM 56 602485
OMIM Phenotypic Series 56 PS256450
ICD10 via Orphanet 33 E16.1
Orphanet 58 ORPHA79299
MedGen 41 C1865290
UMLS 71 C1865290 C3888018

Summaries for Hyperinsulinemic Hypoglycemia, Familial, 3

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 79299 Definition Hyperinsulism due to glucokinase deficiency (HIGCK) is a form of diazoxide-sensitive diffuse hyperinsulinism (see this term), caused by a lowered threshold for insulin release, characterized by an excessive/ uncontrolled insulin secretion (inappropriate for the level of glycemia) and recurrent episodes of profound hypoglycemia induced by fasting and protein rich meals, requiring rapid and intensive treatment to prevent neurological sequelae. Epidemiology Prevalence for congenital isolated hyperinsulinism (CHI, see this term) is estimated at 1/50,000 live births. GCK alterations are noted in 1.2% of patients with non-syndromic CHI. Clinical description Clinical picture is similar to that described in CHI with mild manifestations leading to a delay in diagnosis until adulthood. A notable clinical feature is the remarkable stability of their hypoglycemia consistent with a resetting of the threshold for insulin release. The clinical spectrum can range from mild and intermediate cases that respond well to dietary modifications and medical management with diazoxide to severe cases that are unresponsive to diazoxide necessitating near-total pancreatectomy. The potential development of type 2 diabetes with age is another notable feature Neurological sequelae due to rapidly falling glucose levels are rare. Etiology Activating mutations of GCK (7p15.3-p15.1) that encodes glucokinase have been identified to cause HIGCK. Glucokinase has been described as the glucose sensor of pancreatic beta-cells . These mutations localize to an allosteric activator site and increase the protein's affinity to glucose and its efficacy in ATP-dependent phosphorylation of glucose, causing resetting of the threshold for insulin release at a value lower than normal. Recently, a somatic activating mutation in GCK has been proposed as a cause of a novel form of diazoxide-responsive focal CHI. Inactivating mutations GCK have been identified in cases of maturity onset diabetes of the young 2 (MODY 2, see this term). Genetic counseling Most activating mutations of genes GCK identified to date are dominant. De novo mutations have also been reported. Visit the Orphanet disease page for more resources.

MalaCards based summary : Hyperinsulinemic Hypoglycemia, Familial, 3, also known as hyperinsulinism due to glucokinase deficiency, is related to hyperinsulinemic hypoglycemia, familial, 4 and hyperinsulinemic hypoglycemia, familial, 1. An important gene associated with Hyperinsulinemic Hypoglycemia, Familial, 3 is GCK (Glucokinase), and among its related pathways/superpathways are Metabolism of proteins and Developmental Biology. The drugs lanreotide and Angiopeptin have been mentioned in the context of this disorder. Affiliated tissues include brain, kidney and pancreas, and related phenotypes are recurrent hypoglycemia and hyperinsulinemic hypoglycemia

Disease Ontology : 12 A hyperinsulinemic hypoglycemia characterized by autosomal dominant inheritance of a reduced threshold for insulin release and hypoglycemia induced by fasting or protein rich meals that has material basis in activating mutations in the GCK gene on chromosome 7p13.

UniProtKB/Swiss-Prot : 73 Familial hyperinsulinemic hypoglycemia 3: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.

More information from OMIM: 602485 PS256450

Related Diseases for Hyperinsulinemic Hypoglycemia, Familial, 3

Diseases in the Hyperinsulinemic Hypoglycemia family:

Hyperinsulinemic Hypoglycemia, Familial, 1 Hyperinsulinemic Hypoglycemia, Familial, 2
Hyperinsulinemic Hypoglycemia, Familial, 3 Hyperinsulinemic Hypoglycemia, Familial, 6
Hyperinsulinemic Hypoglycemia, Familial, 5 Hyperinsulinemic Hypoglycemia, Familial, 4
Hyperinsulinemic Hypoglycemia, Familial, 7

Diseases related to Hyperinsulinemic Hypoglycemia, Familial, 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 126)
# Related Disease Score Top Affiliating Genes
1 hyperinsulinemic hypoglycemia, familial, 4 32.7 CEP55 AURKB
2 hyperinsulinemic hypoglycemia, familial, 1 32.3 H4C14 H4C13 H4C12 H2AC18
3 hyperinsulinemic hypoglycemia, familial, 2 32.0 H4C14 H4C13 H4C12 H2AC18
4 hyperinsulinemic hypoglycemia 32.0 H2AC18 GCK
5 hyperoxaluria, primary, type i 28.1 H4C14 H4C13 H4C12 H2AC18
6 primary hyperoxaluria 28.0 H4C14 H4C13 H4C12 H2AC18
7 hyperinsulinemic hypoglycemia, familial, 5 12.4
8 hyperinsulinemic hypoglycemia, familial, 6 11.5
9 hypoglycemia 11.1
10 hyperinsulinism 10.7
11 autosomal recessive disease 10.5
12 hyperglycemia 10.4
13 carbonic anhydrase va deficiency, hyperammonemia due to 10.4
14 insulinoma 10.3
15 maturity-onset diabetes of the young 10.3
16 diabetes mellitus, noninsulin-dependent 10.2
17 paternal uniparental disomy 10.2
18 overgrowth syndrome 10.2
19 beckwith-wiedemann syndrome 10.2
20 ocular motor apraxia 10.2
21 gallbladder disease 1 10.2
22 diabetes mellitus, insulin-dependent, 11 10.2
23 abdominal obesity-metabolic syndrome 1 10.2
24 cyanosis, transient neonatal 10.2
25 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 10.2
26 glucose intolerance 10.2
27 hypertrichosis 10.2
28 adenoma 10.2
29 neuroblastoma 10.2
30 kabuki syndrome 1 10.2
31 acute insulin response 10.2
32 monogenic diabetes 10.2
33 hypotonia 10.2
34 atrial standstill 1 10.1
35 hemihyperplasia, isolated 10.1
36 alacrima, achalasia, and mental retardation syndrome 10.1
37 neonatal diabetes mellitus 10.1
38 hypertrophic cardiomyopathy 10.1
39 cerebral palsy 10.1
40 enterocolitis 10.0
41 insulin-like growth factor i 10.0
42 fanconi renotubular syndrome 2 10.0
43 helix syndrome 10.0
44 pulmonary hypertension 10.0
45 fanconi syndrome 10.0
46 exocrine pancreatic insufficiency 10.0
47 gonadal dysgenesis 10.0
48 glycogen storage disease 10.0
49 turner syndrome 10.0
50 hepatoblastoma 10.0

Graphical network of the top 20 diseases related to Hyperinsulinemic Hypoglycemia, Familial, 3:



Diseases related to Hyperinsulinemic Hypoglycemia, Familial, 3

Symptoms & Phenotypes for Hyperinsulinemic Hypoglycemia, Familial, 3

Human phenotypes related to Hyperinsulinemic Hypoglycemia, Familial, 3:

58 31 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 recurrent hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001988
2 hyperinsulinemic hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000825
3 fasting hyperinsulinemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008283
4 hypoketotic hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001985
5 abnormal c-peptide level 58 31 hallmark (90%) Very frequent (99-80%) HP:0030794
6 muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0001324
7 fatigue 58 31 frequent (33%) Frequent (79-30%) HP:0012378
8 hand tremor 58 31 frequent (33%) Frequent (79-30%) HP:0002378
9 seizure 31 frequent (33%) HP:0001250
10 type ii diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0005978
11 coma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001259
12 abnormality of the autonomic nervous system 58 31 very rare (1%) Very rare (<4-1%) HP:0002270
13 intellectual disability 31 HP:0001249
14 seizures 58 Frequent (79-30%)
15 diabetes mellitus 31 HP:0000819
16 abnormality of nervous system physiology 58 Very rare (<4-1%)
17 hypoglycemic coma 31 HP:0001325
18 hypoglycemic seizures 31 HP:0002173

Symptoms via clinical synopsis from OMIM:

56
Laboratory Abnormalities:
hyperinsulinemia
hypoglycemia, nonketotic

Neurologic Central Nervous System:
seizures, hypoglycemic
loss of consciousness due to hypoglycemia
mental retardation due to repeated episodes of hypoglycemia
coma, hypoglycemic

Endocrine Features:
hyperinsulinemic hypoglycemia
diabetes mellitus, insulin-dependent, late onset (uncommon)

Clinical features from OMIM:

602485

GenomeRNAi Phenotypes related to Hyperinsulinemic Hypoglycemia, Familial, 3 according to GeneCards Suite gene sharing:

26 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 9.5 H2AC18 H4C13
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 9.5 H4C13
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.5 H2AC18 H4C13
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-165 9.5 H2AC18
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-168 9.5 H2AC18 H4C13
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 9.5 H4C14
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-198 9.5 H4C13
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.5 H2AC18
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 9.5 H2AC18
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-42 9.5 H4C14
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-43 9.5 H2AC18
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-73 9.5 H4C14
13 Decreased cell–culture–derived Hepatitis C virus (HCVcc; Luc–Jc1) infection GR00234-A-2 8.96 AURKB GCK

Drugs & Therapeutics for Hyperinsulinemic Hypoglycemia, Familial, 3

Drugs for Hyperinsulinemic Hypoglycemia, Familial, 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 46)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
lanreotide Approved Phase 4 108736-35-2
2 Angiopeptin Phase 4
3
Diazoxide Approved Phase 2 364-98-7 3019
4
Pancrelipase Approved, Investigational Phase 2 53608-75-6
5
Exenatide Approved, Investigational Phase 1, Phase 2 141758-74-9 15991534
6
Glucagon Approved Phase 1, Phase 2 16941-32-5
7
tannic acid Approved Phase 1, Phase 2 1401-55-4
8
Benzocaine Approved, Investigational Phase 1, Phase 2 94-09-7, 1994-09-7 2337
9 pancreatin Phase 2
10 Gastrointestinal Agents Phase 2
11 Anti-Obesity Agents Phase 1, Phase 2
12 Antineoplastic Agents, Hormonal Phase 2
13 Polygeline Phase 1, Phase 2
14 lysine Phase 1, Phase 2
15 Radiopharmaceuticals Phase 1, Phase 2
16 Plasma Substitutes Phase 1, Phase 2
17 Blood Substitutes Phase 1, Phase 2
18 Glucagon-Like Peptide 1 Phase 1, Phase 2
19
Acarbose Approved, Investigational Phase 1 56180-94-0 441184
20
Octreotide Approved, Investigational Phase 1 83150-76-9 383414 6400441
21
Somatostatin Approved, Investigational Phase 1 38916-34-6, 51110-01-1 53481605
22
Levodopa Approved Phase 1 59-92-7 6047
23
Lactitol Approved, Investigational Phase 1 585-88-6, 585-86-4 493591
24 Cardiac Glycosides Phase 1
25 Glycoside Hydrolase Inhibitors Phase 1
26 Insulin, Globin Zinc Phase 1
27 insulin Phase 1
28 Incretins Phase 1
29
Insulin aspart Approved 116094-23-6 16132418
30
Tocopherol Approved, Investigational 1406-66-2, 54-28-4 14986
31
Dopamine Approved 51-61-6, 62-31-7 681
32
Vitamin E Approved, Nutraceutical, Vet_approved 59-02-9 14985
33 Tocotrienol Investigational 6829-55-6
34 Micronutrients
35 Trace Elements
36 Vitamins
37 Antioxidants
38 Nutrients
39 Protective Agents
40 Tocotrienols
41 Tocopherols
42 Dihydroxyphenylalanine
43 Neurotransmitter Agents
44 Dopamine Agents
45 Fluorides
46 Hypoglycemic Agents

Interventional clinical trials:

(show all 35)
# Name Status NCT ID Phase Drugs
1 Treatment With Lanreotide Autogel (Somatostatin Analogue) in Patients With Congenital Hyperinsulinism of Infancy Already Treated With Somatostatin Analog by Pump Unknown status NCT01070758 Phase 4 Lanreotide autogel
2 A Two-Period, Open-label Trial Evaluating the Efficacy and Safety of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism Recruiting NCT03777176 Phase 3 dasiglucagon
3 A Randomized Trial in 2 Parts: Double-Blind, Placebo-Controlled, Crossover Part 1 and Open-label Part 2, Evaluating the Efficacy and Safety of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism Recruiting NCT04172441 Phase 2, Phase 3 dasiglucagon;Placebo
4 18F-DOPA PET Imaging: an Evaluation of Biodistribution and Safety Recruiting NCT03042416 Phase 3 18F-DOPA
5 An Extension Trial Evaluating the Long-term Safety and Efficacy of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism Enrolling by invitation NCT03941236 Phase 3 dasiglucagon
6 Localization of Focal Forms of Hyperinsulinism of Infancy With 18F-labeled L-fluoro-DOPA PET Scan Completed NCT00674440 Phase 2 F-DOPA
7 A Phase II Safety and Efficacy Study of 18F-L-Fluoro-DOPA PET/CT Scan Localization of Focal Pancreatic Lesions in Children With Hyperinsulinemic Hypoglycemia Completed NCT01468454 Phase 2 18 F-DOPA
8 A Single-Dose Open-Label Study of XOMA 358 in Subjects With Congenital Hyperinsulinism (HI) Completed NCT02604485 Phase 2 Cohort 1;Cohort 2;Cohort 3;Cohort 4
9 Role of GLP-1 in Congenital Hyperinsulinism:Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity Completed NCT00897676 Phase 1, Phase 2 Exendin-(9-39);placebo
10 An Open Label Pilot Study of the Effects of the Glucagon-like Peptide-1 Receptor Antagonist, Exendin-(9-39) on Glycemic Control in Subjects With Congenital Hyperinsulinism Completed NCT00571324 Phase 1, Phase 2 Exendin-(9-39)
11 A Phase 2 Proof-of-Concept Study of CSI-Glucagon™ (Continuous Subcutaneous Glucagon Infusion) to Prevent Hypoglycemia With Lower Intravenous Glucose Infusion Rates in Children up to One Year of Age With Congenital Hyperinsulinism Completed NCT02937558 Phase 2 Glucagon
12 Replace Sandostatine® in Three Daily Subcutaneous Injections by a Single Intramuscular Injection of Sandostatine® LP Per Month in Patients With a Diffuse Form of Hyperinsulinism Completed NCT00987168 Phase 2 Sandostatine LP
13 Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass Completed NCT03984370 Phase 2 ZP4207
14 A Phase 2, Interventional, Randomized, Double-Blind, Placebo-Controlled Pilot Study of Glucagon RTU in Subjects Who Experience Hyperinsulinemic Hypoglycemia After Bariatric Surgery Completed NCT03770637 Phase 2 Glucagon RTU
15 Effect of Gelofusine on 111In-DTPA-AHX-Lys40-Exendin 4 Uptake in the Kidney Completed NCT02541734 Phase 1, Phase 2 Gelofusine;Placebo
16 Role of Glucagon-Like Peptide-1 (GLP-1) in Congenital Hyperinsulinism: Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia Terminated NCT00835328 Phase 1, Phase 2 Exendin (9-39);Vehicle
17 Pasireotide for Prevention of Hypoglycemia in Patients With Hyperinsulinemic Hypoglycemia Withdrawn NCT03053284 Phase 2 Pasireotide 0.6Mg Solution for Injection;Saline Solution
18 Pilot Study of the Efficacy and Safety of Sirolimus in the Treatment of Congenital Hyperinsulinism. Withdrawn NCT02524639 Phase 1, Phase 2 Sirolimus
19 A Pilot Study Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia Post-RYGB Completed NCT02685852 Phase 1 Exenatide;Acarbose;Placebo
20 18F-Fluoro-L- DOPA PET Imaging for the Detection and Localization of Focal Congenital Hyperinsulinism Recruiting NCT04205604 Phase 1
21 The Use of Fluorodopa F 18 Positron Emission Tomography Combined With Computed Tomography in Congenital Hyperinsulinism and Insulinoma Recruiting NCT02021604 Phase 1 Fluorodopa F 18
22 Treatment Plan for an Individual Patient With Pasireotide for Hyperinsulinemic Hypoglycemia Recruiting NCT03103009 Phase 1 Pasireotide
23 Long Term Glucose Metabolism in Conservatively Treated Patients With Congenital Hyperinsulinism Unknown status NCT01819584
24 Towards Individualized Surgery in Non-focal Congenital Hyperinsulinism Completed NCT02108730
25 New Imaging Procedure for the Localisation of Insulinoma Completed NCT02127541
26 Bihormonal Bionic Pancreas for the Treatment of Diabetes Post-Pancreatectomy in Children With Congenital Hyperinsulinism - A Pilot Study Completed NCT03303196
27 Prevention of Hypoglycemia in Patients With Post-Gastric Bypass Hyperinsulinemic Hypoglycemia Completed NCT01933490
28 The Physiology of Glucagon-like-peptide-1 Espression in Patients With Endogenous Hyperinsulinism: Correlation With Histopathology Recruiting NCT03768518
29 Application of Raw Corn Starch on Patients With Unoperated Insulinoma is Helpful to Decrease Risk of Hypoglycemia Recruiting NCT03930368
30 Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome Active, not recruiting NCT03797222
31 Compassionate Use of SOM230 for Individual Patient (NS, 14-Jan-1986) With Hyperinsulinemic/Hypoglycemia Available NCT02835131 Pasireotide
32 Expanded Access Use of 18F-L-Fluoro-DOPA PET/CT Scan Localization of Focal Pancreatic Lesions in Subjects With Hyperinsulinemic Hypoglycemia Available NCT01916148 18F-DOPA
33 Phase II Study of the Use of [18F]-DOPA in Hyperinsulinemic Hypoglycemia Available NCT02533219 18 F-DOPA
34 Deciphering the Enigma of Postprandial Hyperinsulinaemic Hypoglycaemia After Bariatric Surgery, Part 1 C: Effect of Postprandial Hypoglycaemia on Driving Performance. Not yet recruiting NCT04330196
35 Deciphering the Enigma of Postprandial Hyperinsulinaemic Hypoglycaemia After Bariatric Surgery Part 1 B: Evaluation of the Neuro-endocrine Response to Hypoglycaemia. Not yet recruiting NCT04334161

Search NIH Clinical Center for Hyperinsulinemic Hypoglycemia, Familial, 3

Genetic Tests for Hyperinsulinemic Hypoglycemia, Familial, 3

Genetic tests related to Hyperinsulinemic Hypoglycemia, Familial, 3:

# Genetic test Affiliating Genes
1 Hyperinsulinism Due to Glucokinase Deficiency 29 GCK

Anatomical Context for Hyperinsulinemic Hypoglycemia, Familial, 3

MalaCards organs/tissues related to Hyperinsulinemic Hypoglycemia, Familial, 3:

40
Brain, Kidney, Pancreas

Publications for Hyperinsulinemic Hypoglycemia, Familial, 3

Articles related to Hyperinsulinemic Hypoglycemia, Familial, 3:

# Title Authors PMID Year
1
Large islets, beta-cell proliferation, and a glucokinase mutation. 6 56
20375417 2010
2
Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation. 6 56
15277402 2004
3
The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapy. 6 56
11916951 2002
4
Familial hyperinsulinism caused by an activating glucokinase mutation. 6 56
9435328 1998
5
Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant. 56 6
9469993 1998
6
Familial Hyperinsulinism 6
20301549 2003
7
Association of neuroimmune guidance cue netrin-1 and its chemorepulsive receptor UNC5B with atherosclerotic plaque expression signatures and stability in human(s): Tampere Vascular Study (TVS). 61
24122613 2013
8
Differential regulation of repeated histone genes during the fission yeast cell cycle. 61
17452352 2007

Variations for Hyperinsulinemic Hypoglycemia, Familial, 3

ClinVar genetic disease variations for Hyperinsulinemic Hypoglycemia, Familial, 3:

6 (show top 50) (show all 70) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GCK NM_000162.5(GCK):c.1358_1360CGG[3] (p.Ala454dup)short repeat Pathogenic 435297 rs1554334433 7:44184769-44184770 7:44145170-44145171
2 GCK NM_000162.5(GCK):c.1165G>C (p.Val389Leu)SNV Pathogenic 435300 rs1350717554 7:44185184-44185184 7:44145585-44145585
3 GCK NM_000162.5(GCK):c.667G>A (p.Gly223Ser)SNV Pathogenic 435306 rs1360415315 7:44189371-44189371 7:44149772-44149772
4 GCK NM_000162.5(GCK):c.1363G>A (p.Val455Met)SNV Pathogenic 16140 rs104894012 7:44184770-44184770 7:44145171-44145171
5 GCK NM_000162.5(GCK):c.1367C>T (p.Ala456Val)SNV Pathogenic 16143 rs104894014 7:44184766-44184766 7:44145167-44145167
6 GCK NM_000162.5(GCK):c.641A>G (p.Tyr214Cys)SNV Pathogenic 16144 rs104894015 7:44189397-44189397 7:44149798-44149798
7 GCK GCK, VAL91LEUundetermined variant Pathogenic 16146
8 GCK NM_000162.5(GCK):c.544G>A (p.Val182Met)SNV Pathogenic 129144 rs587780345 7:44189603-44189603 7:44150004-44150004
9 GCK NM_000162.5(GCK):c.766G>A (p.Glu256Lys)SNV Pathogenic 265175 rs769268803 7:44187346-44187346 7:44147747-44147747
10 GCK NM_000162.5(GCK):c.676G>A (p.Val226Met)SNV Pathogenic/Likely pathogenic 36243 rs148311934 7:44189362-44189362 7:44149763-44149763
11 GCK NM_000162.5(GCK):c.1358C>T (p.Ser453Leu)SNV Likely pathogenic 36200 rs193922283 7:44184775-44184775 7:44145176-44145176
12 GCK NM_000162.5(GCK):c.435C>G (p.Pro145=)SNV Conflicting interpretations of pathogenicity 909540 7:44190603-44190603 7:44151004-44151004
13 GCK NM_000162.5(GCK):c.208+11G>ASNV Conflicting interpretations of pathogenicity 36206 rs77440690 7:44192889-44192889 7:44153290-44153290
14 GCK NM_000162.5(GCK):c.1253+12C>TSNV Conflicting interpretations of pathogenicity 911565 7:44185084-44185084 7:44145485-44145485
15 GCK NM_000162.5(GCK):c.-452G>ASNV Conflicting interpretations of pathogenicity 435293 rs187173652 7:44229004-44229004 7:44189405-44189405
16 GCK NM_000162.5(GCK):c.213C>T (p.Val71=)SNV Conflicting interpretations of pathogenicity 447393 rs143128547 7:44192020-44192020 7:44152421-44152421
17 GCK NM_000162.5(GCK):c.363+9C>TSNV Conflicting interpretations of pathogenicity 748518 7:44191861-44191861 7:44152262-44152262
18 GCK NM_000162.5(GCK):c.666C>T (p.Val222=)SNV Conflicting interpretations of pathogenicity 36242 rs193922318 7:44189372-44189372 7:44149773-44149773
19 GCK NM_000162.5(GCK):c.46-12C>TSNV Conflicting interpretations of pathogenicity 36222 rs142829768 7:44193074-44193074 7:44153475-44153475
20 GCK NM_000162.5(GCK):c.*11C>TSNV Conflicting interpretations of pathogenicity 255399 rs200698755 7:44184724-44184724 7:44145125-44145125
21 GCK NM_000162.5(GCK):c.363+10G>ASNV Conflicting interpretations of pathogenicity 360301 rs758495950 7:44191860-44191860 7:44152261-44152261
22 GCK NM_000162.5(GCK):c.*678G>TSNV Conflicting interpretations of pathogenicity 360290 rs555058443 7:44184057-44184057 7:44144458-44144458
23 GCK NM_000162.5(GCK):c.*270C>TSNV Uncertain significance 360297 rs886062348 7:44184465-44184465 7:44144866-44144866
24 GCK NM_000162.5(GCK):c.363+10G>CSNV Uncertain significance 360300 rs758495950 7:44191860-44191860 7:44152261-44152261
25 GCK NM_000162.5(GCK):c.*723A>GSNV Uncertain significance 360288 rs886062345 7:44184012-44184012 7:44144413-44144413
26 GCK NM_000162.5(GCK):c.*721C>TSNV Uncertain significance 360289 rs886062346 7:44184014-44184014 7:44144415-44144415
27 GCK NM_000162.5(GCK):c.*844A>CSNV Uncertain significance 360283 rs886062344 7:44183891-44183891 7:44144292-44144292
28 GCK NM_000162.5(GCK):c.*548G>ASNV Uncertain significance 360291 rs886062347 7:44184187-44184187 7:44144588-44144588
29 GCK NM_000162.5(GCK):c.393C>T (p.Ser131=)SNV Uncertain significance 360299 rs139139350 7:44190645-44190645 7:44151046-44151046
30 GCK NM_000162.5(GCK):c.*764C>TSNV Uncertain significance 360285 rs185418856 7:44183971-44183971 7:44144372-44144372
31 GCK NM_000162.5(GCK):c.1262A>G (p.Glu421Gly)SNV Uncertain significance 910353 7:44184871-44184871 7:44145272-44145272
32 GCK NM_000162.5(GCK):c.1120G>T (p.Val374Leu)SNV Uncertain significance 908614 7:44185229-44185229 7:44145630-44145630
33 GCK NM_000162.5(GCK):c.1024A>C (p.Thr342Pro)SNV Uncertain significance 908615 7:44185325-44185325 7:44145726-44145726
34 GCK NM_000162.5(GCK):c.792C>A (p.Gly264=)SNV Uncertain significance 909471 7:44187320-44187320 7:44147721-44147721
35 GCK NM_000162.5(GCK):c.675C>T (p.Ile225=)SNV Uncertain significance 910410 7:44189363-44189363 7:44149764-44149764
36 GCK NM_000162.5(GCK):c.649G>A (p.Asp217Asn)SNV Uncertain significance 911631 7:44189389-44189389 7:44149790-44149790
37 GCK NM_000162.5(GCK):c.-102G>CSNV Uncertain significance 908804 7:44228654-44228654 7:44189055-44189055
38 GCK NM_000162.5(GCK):c.-137C>GSNV Uncertain significance 909651 7:44228689-44228689 7:44189090-44189090
39 GCK NM_000162.5(GCK):c.1310C>T (p.Thr437Ile)SNV Uncertain significance 585914 rs1185622190 7:44184823-44184823 7:44145224-44145224
40 GCK NM_000162.5(GCK):c.-453C>TSNV Uncertain significance 435294 rs191795044 7:44229005-44229005 7:44189406-44189406
41 GCK NM_000162.5(GCK):c.-102G>ASNV Uncertain significance 435292 rs781377703 7:44228654-44228654 7:44189055-44189055
42 GCK NM_000162.5(GCK):c.680-14G>CSNV Uncertain significance 909472 7:44187446-44187446 7:44147847-44147847
43 GCK NM_000162.5(GCK):c.580-11C>TSNV Uncertain significance 908684 7:44189469-44189469 7:44149870-44149870
44 GCK NM_000162.5(GCK):c.483+3G>ASNV Uncertain significance 909539 7:44190552-44190552 7:44150953-44150953
45 GCK NM_000162.5(GCK):c.-279C>TSNV Uncertain significance 911818 7:44228831-44228831 7:44189232-44189232
46 GCK NM_000162.5(GCK):c.-396C>GSNV Uncertain significance 908862 7:44228948-44228948 7:44189349-44189349
47 GCK NM_000162.5(GCK):c.-449G>ASNV Uncertain significance 908863 7:44229001-44229001 7:44189402-44189402
48 GCK NM_000162.5(GCK):c.-455A>GSNV Uncertain significance 909717 7:44229007-44229007 7:44189408-44189408
49 GCK NM_000162.5(GCK):c.-456G>ASNV Uncertain significance 910637 7:44229008-44229008 7:44189409-44189409
50 GCK NM_000162.5(GCK):c.10G>A (p.Asp4Asn)SNV Uncertain significance 911766 7:44228543-44228543 7:44188944-44188944

UniProtKB/Swiss-Prot genetic disease variations for Hyperinsulinemic Hypoglycemia, Familial, 3:

73
# Symbol AA change Variation ID SNP ID
1 GCK p.Val455Met VAR_003715 rs104894012
2 GCK p.Thr65Ile VAR_078243
3 GCK p.Val91Leu VAR_078244
4 GCK p.Trp99Cys VAR_078245
5 GCK p.Glu442Lys VAR_078257 rs758737171
6 GCK p.Tyr214Cys VAR_079456 rs104894015
7 GCK p.Ala456Val VAR_079477 rs104894014

Expression for Hyperinsulinemic Hypoglycemia, Familial, 3

Search GEO for disease gene expression data for Hyperinsulinemic Hypoglycemia, Familial, 3.

Pathways for Hyperinsulinemic Hypoglycemia, Familial, 3

Pathways related to Hyperinsulinemic Hypoglycemia, Familial, 3 according to GeneCards Suite gene sharing:

(show all 17)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.34 RAB6B PMPCA H4C14 H4C13 H4C12 H2AC18
2
Show member pathways
13.16 H4C14 H4C13 H4C12 H2AC18 GCK
3
Show member pathways
13.09 H4C14 H4C13 H4C12 H2AC18 AURKB
4
Show member pathways
12.81 H4C14 H4C13 H4C12 H2AC18
5
Show member pathways
12.67 H4C14 H4C13 H4C12 H2AC18
6
Show member pathways
12.54 H4C14 H4C13 H4C12 H2AC18
7
Show member pathways
12.51 H4C14 H4C13 H4C12 H2AC18 AURKB
8
Show member pathways
12.33 H4C14 H4C13 H4C12 H2AC18
9
Show member pathways
12.31 H4C14 H4C13 H4C12
10
Show member pathways
12.15 H4C14 H4C13 H4C12 H2AC18
11
Show member pathways
12.05 H4C14 H4C13 H4C12
12 11.98 H4C14 H4C13 H4C12
13
Show member pathways
11.92 H4C14 H4C13 H4C12 H2AC18
14
Show member pathways
11.86 H4C14 H4C13 H4C12
15
Show member pathways
11.76 H4C14 H4C13 H4C12
16
Show member pathways
11.61 H4C14 H4C13 H4C12 H2AC18
17 10.39 H4C14 H4C13 H4C12

GO Terms for Hyperinsulinemic Hypoglycemia, Familial, 3

Cellular components related to Hyperinsulinemic Hypoglycemia, Familial, 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromosome GO:0005694 9.55 H4C14 H4C13 H4C12 H2AC18 AURKB
2 host cell nucleus GO:0042025 9.54 H4C14 H4C13 H4C12
3 nuclear chromosome, telomeric region GO:0000784 9.5 H4C14 H4C13 H4C12
4 nuclear chromosome GO:0000228 9.43 H4C14 H4C13 H4C12
5 nuclear nucleosome GO:0000788 9.13 H4C14 H4C13 H4C12
6 nucleosome GO:0000786 8.92 H4C14 H4C13 H4C12 H2AC18

Biological processes related to Hyperinsulinemic Hypoglycemia, Familial, 3 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 cellular protein metabolic process GO:0044267 9.71 H4C14 H4C13 H4C12
2 nucleosome assembly GO:0006334 9.7 H4C14 H4C13 H4C12
3 regulation of gene silencing by miRNA GO:0060964 9.69 H4C14 H4C13 H4C12
4 regulation of megakaryocyte differentiation GO:0045652 9.67 H4C14 H4C13 H4C12
5 double-strand break repair via nonhomologous end joining GO:0006303 9.65 H4C14 H4C13 H4C12
6 negative regulation of gene expression, epigenetic GO:0045814 9.63 H4C14 H4C13 H4C12
7 CENP-A containing nucleosome assembly GO:0034080 9.61 H4C14 H4C13 H4C12
8 DNA-templated transcription, initiation GO:0006352 9.58 H4C14 H4C13 H4C12
9 chromatin silencing at rDNA GO:0000183 9.54 H4C14 H4C13 H4C12
10 DNA replication-dependent nucleosome assembly GO:0006335 9.5 H4C14 H4C13 H4C12
11 telomere organization GO:0032200 9.43 H4C14 H4C13 H4C12
12 telomere capping GO:0016233 9.33 H4C14 H4C13 H4C12
13 DNA replication-independent nucleosome assembly GO:0006336 9.13 H4C14 H4C13 H4C12
14 negative regulation of megakaryocyte differentiation GO:0045653 8.8 H4C14 H4C13 H4C12

Molecular functions related to Hyperinsulinemic Hypoglycemia, Familial, 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein domain specific binding GO:0019904 9.13 H4C14 H4C13 H4C12
2 protein heterodimerization activity GO:0046982 8.92 H4C14 H4C13 H4C12 H2AC18

Sources for Hyperinsulinemic Hypoglycemia, Familial, 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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