HHF6
MCID: HYP807
MIFTS: 52

Hyperinsulinemic Hypoglycemia, Familial, 6 (HHF6)

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

Aliases & Classifications for Hyperinsulinemic Hypoglycemia, Familial, 6

MalaCards integrated aliases for Hyperinsulinemic Hypoglycemia, Familial, 6:

Name: Hyperinsulinemic Hypoglycemia, Familial, 6 57 71
Hyperinsulinism-Hyperammonemia Syndrome 57 12 20 58 73 29 13 54 6 39
Familial Hyperinsulinemic Hypoglycemia 6 12 73 15
Hhf6 57 12 73
Hi/ha Syndrome 12 58
Hyperinsulinemic Hypoglycemia Familial 6 20
Hyperinsulinism Hyperammonemia Syndrome 20
Ha/hi Syndrome 20
Hhs 73

Characteristics:

Orphanet epidemiological data:

58
hyperinsulinism-hyperammonemia syndrome
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity (see hhf1 )
mean age at onset of hypoglycemia may be delayed (median, 9 months, diagnosis sometimes made in adulthood)


HPO:

31
hyperinsulinemic hypoglycemia, familial, 6:
Inheritance autosomal dominant inheritance heterogeneous


Classifications:

Orphanet: 58  
Inborn errors of metabolism
Rare endocrine diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0070217
OMIM® 57 606762
OMIM Phenotypic Series 57 PS256450
ICD10 via Orphanet 33 E72.8
Orphanet 58 ORPHA35878
MedGen 41 C1847555
UMLS 71 C1847555

Summaries for Hyperinsulinemic Hypoglycemia, Familial, 6

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 35878DefinitionHyperinsulinism-hyperammonemia syndrome (HIHA) is a frequent form of diazoxide-sensitive diffuse hyperinsulinism (see this term), characterized by an excessive/ uncontrolled insulin secretion (inappropriate for the level of glycemia), asymptomatic hyperammonemia and recurrent episodes of profound hypoglycemia induced by fasting and protein rich meals, requiring rapid and intensive treatment to prevent neurological sequelae. Epilepsy and cognitive deficit that are unrelated to hypoglycemia may also occur.EpidemiologyPrevalence is estimated at 1 in 200,000.Clinical descriptionClinical features are similar to those described in congenital isolated hyperinsulinism (see this term), but the manifestations are milder with diagnosis delayed until late infancy. Hypoglycemia is triggered by fasting or a protein-rich meal (leucine sensitive hypoglycemia) and is easily controlled by diazoxide. Asymptomatic and persistent hyperammonemia (about 3 to 5 times the normal range) is observed. Children with HIHA frequently present seizures (most commonly atypical or absence) and learning difficulties. Neurologic abnormalities appear to be unrelated to hypoglycemia.EtiologyGlutamate dehydrogenase (GDH) is a mitochondrial matrix enzyme that catalyzes the oxidative deamination of glutamate, yielding alpha-ketoglutarate and an ammonia by-product. Production of alpha-ketoglutarate leads to an increase in intracellular ATP causing the closure of ATP-sensitive potassium channels (SUR1/Kir6.2). This in turn leads to an influx of calcium ions and the ensuing cellular depolarization triggers the secretion of insulin from pancreatic beta-cells. GDH is under a complex regulatory control of allosterically activating leucine and inhibiting GTP. Dominantly expressed, missense mutations of GLUD1 (10q23.3) that encodes GDH, increase enzyme activity by reducing its sensitivity to allosteric inhibition by guanosine triphosphate (GTP). The role of hyperammonemia is not known; it may primarily be the result of the renal expression of altered forms of GDH.Genetic counselingMost activating mutations of the gene GLUD1 are de novo, but the familial forms that have been reported are dominant. Incomplete variance and clinical variability are noted within the same families.Visit the Orphanet disease page for more resources.

MalaCards based summary : Hyperinsulinemic Hypoglycemia, Familial, 6, also known as hyperinsulinism-hyperammonemia syndrome, is related to hypoglycemia and diabetes mellitus, ketosis-prone. An important gene associated with Hyperinsulinemic Hypoglycemia, Familial, 6 is GLUD1 (Glutamate Dehydrogenase 1), and among its related pathways/superpathways are Metabolism and Carbon metabolism. The drugs Tocopherol and Vitamin E have been mentioned in the context of this disorder. Affiliated tissues include liver, and related phenotypes are reactive hypoglycemia and asymptomatic hyperammonemia

Disease Ontology : 12 A hyperinsulinemic hypoglycemia characterized by autosomal dominant inheritance of excessive insulin secretion, asymptomatic hyperammonemia and episodes of hypoglycemia induced by fasting or protein rich meals that has material basis in mutation in the GLUD1 gene on chromosome 10q23.3.

UniProtKB/Swiss-Prot : 73 Familial hyperinsulinemic hypoglycemia 6: Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. In HHF6 elevated oxidation rate of glutamate to alpha- ketoglutarate stimulates insulin secretion in the pancreatic beta cells, while they impair detoxification of ammonium in the liver.

More information from OMIM: 606762 PS256450

Related Diseases for Hyperinsulinemic Hypoglycemia, Familial, 6

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, 6 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 120)
# Related Disease Score Top Affiliating Genes
1 hypoglycemia 30.0 SLC16A1 KCNJ11 HADH GLUD1 GCK ABCC8
2 diabetes mellitus, ketosis-prone 29.9 KCNJ11 ABCC8
3 acute insulin response 29.7 UCP2 KCNJ11 ABCC8
4 hyperglycemia 29.6 KCNJ11 GCK ABCC8
5 hyperinsulinism 29.6 UCP2 SLC16A1 KCNJ11 HADH GLUD1 GCK
6 hyperinsulinemic hypoglycemia 29.5 SLC16A1 KCNJ11 HADH GLUD1 GCK ABCC8
7 hypotrichosis 1 11.5
8 tumoral calcinosis, hyperphosphatemic, familial, 1 11.5
9 dyskeratosis congenita, x-linked 11.3
10 hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 11.2
11 heart-hand syndrome, slovenian type 11.2
12 charge syndrome 11.1
13 dyskeratosis congenita, autosomal dominant 1 11.0
14 dyskeratosis congenita, autosomal recessive 5 11.0
15 hypotrichosis simplex 10.9
16 tumoral calcinosis, hyperphosphatemic, familial, 2 10.9
17 tumoral calcinosis, hyperphosphatemic, familial, 3 10.9
18 hoyeraal hreidarsson syndrome 10.9
19 carbonic anhydrase va deficiency, hyperammonemia due to 10.7
20 hyperinsulinemic hypoglycemia, familial, 5 10.5
21 hyperinsulinemic hypoglycemia, familial, 4 10.5
22 seizure disorder 10.3
23 fasting hypoglycemia 10.3
24 substance abuse 10.3
25 fetal erythroblastosis 10.2 HADH GLUD1
26 hyperinsulinemic hypoglycemia, familial, 2 10.2
27 argininosuccinic aciduria 10.2 NAGS HADH
28 global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies 10.1
29 dumping syndrome 10.1
30 maple syrup urine disease 10.1 NAGS HADH GLUD1
31 neu-laxova syndrome 2 10.1 NAGS GLUD1 ABCC8
32 biotinidase deficiency 10.1 PC HADH
33 urea cycle disorder 10.1 PC NAGS
34 coronary heart disease 1 10.1
35 variola major 10.1
36 smallpox 10.1
37 gastroesophageal reflux 10.0
38 gastroparesis 10.0
39 dystonia 10.0
40 learning disability 10.0
41 splenomegaly 10.0
42 maturity-onset diabetes of the young, type 11 10.0 KCNJ11 ABCC8
43 multiple carboxylase deficiency 10.0 PC HADH
44 cardiomyopathy, dilated, 1o 10.0 KCNJ11 ABCC8
45 coronary artery vasospasm 10.0 KCNJ11 ABCC8
46 epiphyseal dysplasia, multiple, with early-onset diabetes mellitus 10.0 KCNJ11 ABCC8
47 3-hydroxyacyl-coa dehydrogenase deficiency 10.0 HADH GLUD1 GCK
48 cantu syndrome 10.0 KCNJ11 ABCC8
49 monocarboxylate transporter 1 deficiency 10.0 SLC16A1 PC GLUD1
50 gordon holmes syndrome 10.0 GLUD2 GLUD1

Graphical network of the top 20 diseases related to Hyperinsulinemic Hypoglycemia, Familial, 6:



Diseases related to Hyperinsulinemic Hypoglycemia, Familial, 6

Symptoms & Phenotypes for Hyperinsulinemic Hypoglycemia, Familial, 6

Human phenotypes related to Hyperinsulinemic Hypoglycemia, Familial, 6:

58 31 (show all 16)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 reactive hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0012051
2 asymptomatic hyperammonemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008162
3 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
4 attention deficit hyperactivity disorder 58 31 frequent (33%) Frequent (79-30%) HP:0007018
5 specific learning disability 58 31 frequent (33%) Frequent (79-30%) HP:0001328
6 intellectual disability, moderate 58 31 frequent (33%) Frequent (79-30%) HP:0002342
7 hyperinsulinemic hypoglycemia 58 31 frequent (33%) Frequent (79-30%) HP:0000825
8 fasting hyperinsulinemia 58 31 frequent (33%) Frequent (79-30%) HP:0008283
9 increased urine alpha-ketoglutarate concentration 58 31 frequent (33%) Frequent (79-30%) HP:0012402
10 eeg with generalized epileptiform discharges 58 31 frequent (33%) Frequent (79-30%) HP:0011198
11 generalized non-motor (absence) seizure 31 frequent (33%) HP:0002121
12 intellectual disability 31 HP:0001249
13 generalized-onset seizure 58 Frequent (79-30%)
14 absence seizure 58 Frequent (79-30%)
15 hypoglycemic coma 31 HP:0001325
16 hypoglycemic seizures 31 HP:0002173

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Laboratory Abnormalities:
hypoglycemia
hyperinsulinemia
hyperammonemia, asymptomatic (2-5 times normal)

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

Endocrine Features:
hyperinsulinemic hypoglycemia

Clinical features from OMIM®:

606762 (Updated 05-Mar-2021)

MGI Mouse Phenotypes related to Hyperinsulinemic Hypoglycemia, Familial, 6:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.61 ABCC8 EPM2AIP1 GCK GLUD1 HADH KCNJ11
2 homeostasis/metabolism MP:0005376 9.32 ABCC8 EPM2AIP1 GCK GLUD1 HADH KCNJ11

Drugs & Therapeutics for Hyperinsulinemic Hypoglycemia, Familial, 6

Drugs for Hyperinsulinemic Hypoglycemia, Familial, 6 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 11)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Tocopherol Approved, Investigational 1406-66-2
2
Vitamin E Approved, Nutraceutical, Vet_approved 59-02-9 14985
3 Tocotrienol Investigational 6829-55-6
4 Protective Agents
5 Micronutrients
6 Antioxidants
7 Vitamins
8 Trace Elements
9 Tocotrienols
10 Tocopherols
11 Nutrients

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome Completed NCT03797222
2 Prevalence of Hypoglycemia and/or Hyperinsulinism/Hyperammonemia Syndrome in Patients With Idiopathic Seizures. Withdrawn NCT00279851

Search NIH Clinical Center for Hyperinsulinemic Hypoglycemia, Familial, 6

Genetic Tests for Hyperinsulinemic Hypoglycemia, Familial, 6

Genetic tests related to Hyperinsulinemic Hypoglycemia, Familial, 6:

# Genetic test Affiliating Genes
1 Hyperinsulinism-Hyperammonemia Syndrome 29 GLUD1

Anatomical Context for Hyperinsulinemic Hypoglycemia, Familial, 6

MalaCards organs/tissues related to Hyperinsulinemic Hypoglycemia, Familial, 6:

40
Liver

Publications for Hyperinsulinemic Hypoglycemia, Familial, 6

Articles related to Hyperinsulinemic Hypoglycemia, Familial, 6:

(show top 50) (show all 54)
# Title Authors PMID Year
1
Novel missense mutations outside the allosteric domain of glutamate dehydrogenase are prevalent in European patients with the congenital hyperinsulinism-hyperammonemia syndrome. 54 61 6 57
11214910 2001
2
Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. 6 57 54 61
9571255 1998
3
Novel missense mutations in the glutamate dehydrogenase gene in the congenital hyperinsulinism-hyperammonemia syndrome. 6 57 61
10636977 2000
4
Clinical and molecular heterogeneity of familial hyperinsulinism. 57 6
9843361 1998
5
Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant. 6 57
9469993 1998
6
Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome. 57 61
11502802 2001
7
Hyperinsulinism/hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate-binding domain of glutamate dehydrogenase. 61 57
11297618 2001
8
Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome. 61 57
11241047 2001
9
A case of hyperinsulinism/hyperammonaemia syndrome with reduced carbamoyl-phosphate synthetase-1 activity in liver: a pitfall in enzymatic diagnosis for hyperammonaemia. 57
16151898 2005
10
Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. 57
11518822 2001
11
A syndrome of congenital hyperinsulinism and hyperammonemia. 57
9108870 1997
12
Biochemical evaluation of a patient with a familial form of leucine-sensitive hypoglycemia and concomitant hyperammonemia. 57
8769351 1996
13
Regulation of glutamate metabolism and insulin secretion by glutamate dehydrogenase in hypoglycemic children. 61 54
19625687 2009
14
Effects of a GTP-insensitive mutation of glutamate dehydrogenase on insulin secretion in transgenic mice. 61 54
16574664 2006
15
Inhibitory effects of Cimicifuga heracleifolia extract on glutamate formation and glutamate dehydrogenase activity in cultured islets. 54 61
15232227 2004
16
Urinary alpha-ketoglutarate is elevated in patients with hyperinsulinism-hyperammonemia syndrome. 61 54
14967154 2004
17
Identification of the GTP binding site of human glutamate dehydrogenase by cassette mutagenesis and photoaffinity labeling. 54 61
11600502 2001
18
Allosteric discrimination at the NADH/ADP regulatory site of glutamate dehydrogenase. 61
31610054 2019
19
Glutamate dehydrogenase: Structure of a hyperinsulinism mutant, corrections to the atomic model, and insights into a regulatory site. 61
30367518 2019
20
Hyperinsulinism-hyperammonemia Syndrome in an Infant with Seizures. 61
30425915 2018
21
Ebselen Reversibly Inhibits Human Glutamate Dehydrogenase at the Catalytic Site. 61
29470101 2018
22
A severe case of hyperinsulinism due to hemizygous activating mutation of glutamate dehydrogenase. 61
28165182 2017
23
Ebselen: Mechanisms of Glutamate Dehydrogenase and Glutaminase Enzyme Inhibition. 61
29072450 2017
24
Robust regulation of hepatic pericentral amination by glutamate dehydrogenase kinetics. 61
27747338 2016
25
Identification of a Novel Activator of Mammalian Glutamate Dehydrogenase. 61
27808506 2016
26
Hyperinsulinism-hyperammonemia syndrome: a de novo mutation of the GLUD1 gene in twins and a review of the literature. 61
27383869 2016
27
Early Presentation of Hyperinsulinism/Hyperammonemia Syndrome in Three Serbian Patients. 61
26759084 2016
28
A novel mutation in GLUD1 causing hyperinsulinism-hyperammonemia in a patient with high density of homozygosity on microarray: a case report. 61
26839063 2016
29
Seizures and diagnostic difficulties in hyperinsulinism-hyperammonemia syndrome. 61
28621098 2016
30
Hyperinsulinism Hyperammonemia Syndrome, a Rare Clinical Constellation. 61
26962538 2016
31
Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene. 61
25781533 2015
32
Deregulation of glutamate dehydrogenase in human neurologic disorders. 61
23463419 2013
33
Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesis and management. 61
23384201 2013
34
Intractable absence seizures in hyperinsulinism-hyperammonemia syndrome. 61
22759688 2012
35
Green tea polyphenols control dysregulated glutamate dehydrogenase in transgenic mice by hijacking the ADP activation site. 61
21813650 2011
36
Two genetic forms of hyperinsulinemic hypoglycemia caused by dysregulation of glutamate dehydrogenase. 61
21130127 2011
37
Biochemical evaluation of an infant with hypoglycemia resulting from a novel de novo mutation of the GLUD1 gene and hyperinsulinism-hyperammonemia syndrome. 61
21932603 2011
38
The hyperinsulinism/hyperammonemia syndrome. 61
20936362 2010
39
Familial hyperinsulinism-hyperammonemia syndrome in a family with seizures: case report. 61
21073125 2010
40
Systemic activation of glutamate dehydrogenase increases renal ammoniagenesis: implications for the hyperinsulinism/hyperammonemia syndrome. 61
20332361 2010
41
On the reversibility of glutamate dehydrogenase and the source of hyperammonemia in the hyperinsulinism/hyperammonemia syndrome. 61
19895831 2010
42
Hyperammonemia and positive allopurinol test in hyperinsulinism-hyperammonemia syndrome: Taiwanese case report. 61
19379266 2009
43
Unregulated insulin secretion by pancreatic beta cells in hyperinsulinism/hyperammonemia syndrome: role of glutamate dehydrogenase, ATP-sensitive potassium channel, and nonselective cation channel. 61
16492972 2006
44
Central nervous system hyperexcitability associated with glutamate dehydrogenase gain of function mutations. 61
15756227 2005
45
Hyperinsulinism/Hyperammonemia Syndrome: a synopsis. 61
15773041 2005
46
[Hyperinsulinism-hyperammonemia syndrome due to a de novo mutation in exon 7 (G979A) of the glutamate dehydrogenase gene with excellent response to diazoxide]. 61
15530324 2004
47
Hyperinsulinism/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism. 61
15050973 2004
48
The structure of apo human glutamate dehydrogenase details subunit communication and allostery. 61
12054821 2002
49
Unregulated elevation of glutamate dehydrogenase activity induces glutamine-stimulated insulin secretion: identification and characterization of a GLUD1 gene mutation and insulin secretion studies with MIN6 cells overexpressing the mutant glutamate dehydrogenase. 61
11872671 2002
50
Persistent hyperinsulinaemic hypoglycaemia. 61
12069542 2002

Variations for Hyperinsulinemic Hypoglycemia, Familial, 6

ClinVar genetic disease variations for Hyperinsulinemic Hypoglycemia, Familial, 6:

6 (show top 50) (show all 76)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GLUD1 NM_005271.5(GLUD1):c.1496G>T (p.Gly499Val) SNV Pathogenic 226111 rs121909734 10:88813160-88813160 10:87053403-87053403
2 GLUD1 NM_005271.5(GLUD1):c.965G>A (p.Arg322His) SNV Pathogenic 16129 rs121909737 10:88820766-88820766 10:87061009-87061009
3 GLUD1 NM_005271.5(GLUD1):c.820C>T (p.Arg274Cys) SNV Pathogenic 16128 rs56275071 10:88822514-88822514 10:87062757-87062757
4 GLUD1 NM_005271.5(GLUD1):c.953G>A (p.Arg318Lys) SNV Pathogenic 16127 rs121909736 10:88820778-88820778 10:87061021-87061021
5 GLUD1 NM_005271.5(GLUD1):c.1046A>C (p.Glu349Ala) SNV Pathogenic 16126 rs121909735 10:88820685-88820685 10:87060928-87060928
6 GLUD1 NM_005271.5(GLUD1):c.1496G>A (p.Gly499Asp) SNV Pathogenic 16125 rs121909734 10:88813160-88813160 10:87053403-87053403
7 GLUD1 NM_005271.5(GLUD1):c.1501T>C (p.Ser501Pro) SNV Pathogenic 16123 rs121909732 10:88813155-88813155 10:87053398-87053398
8 GLUD1 NM_005271.5(GLUD1):c.1493C>T (p.Ser498Leu) SNV Pathogenic 16122 rs121909731 10:88817449-88817449 10:87057692-87057692
9 GLUD1 NM_005271.5(GLUD1):c.1519C>T (p.His507Tyr) SNV Pathogenic 16121 rs121909730 10:88813137-88813137 10:87053380-87053380
10 GLUD1 NM_005271.5(GLUD1):c.1498G>A (p.Ala500Thr) SNV Likely pathogenic 211086 rs797045597 10:88813158-88813158 10:87053401-87053401
11 GLUD1 NM_005271.5(GLUD1):c.1402+10G>A SNV Conflicting interpretations of pathogenicity 301393 rs202067232 10:88818897-88818897 10:87059140-87059140
12 GLUD1 NM_005271.5(GLUD1):c.635A>G (p.Lys212Arg) SNV Uncertain significance 848715 10:88834319-88834319 10:87074562-87074562
13 GLUD1 NM_005271.5(GLUD1):c.1078_1079insAGTCCATTCTGG (p.Gly360_Phe361insGluSerIleLeu) Insertion Uncertain significance 856464 10:88820563-88820564 10:87060806-87060807
14 GLUD1 NM_005271.5(GLUD1):c.*1515A>G SNV Uncertain significance 877597 10:88809993-88809993 10:87050236-87050236
15 GLUD1 NM_005271.5(GLUD1):c.*1501G>C SNV Uncertain significance 877598 10:88810007-88810007 10:87050250-87050250
16 GLUD1 NM_005271.5(GLUD1):c.*1419T>G SNV Uncertain significance 877599 10:88810089-88810089 10:87050332-87050332
17 GLUD1 NM_005271.5(GLUD1):c.1279-6G>A SNV Uncertain significance 877652 10:88819036-88819036 10:87059279-87059279
18 GLUD1 NM_005271.5(GLUD1):c.*1211T>C SNV Uncertain significance 878613 10:88810297-88810297 10:87050540-87050540
19 GLUD1 NM_005271.5(GLUD1):c.*1181C>A SNV Uncertain significance 878614 10:88810327-88810327 10:87050570-87050570
20 GLUD1 NM_005271.5(GLUD1):c.*1139T>C SNV Uncertain significance 878615 10:88810369-88810369 10:87050612-87050612
21 GLUD1 NM_005271.5(GLUD1):c.*998C>T SNV Uncertain significance 878616 10:88810510-88810510 10:87050753-87050753
22 GLUD1 NM_005271.5(GLUD1):c.330G>A (p.Lys110=) SNV Uncertain significance 878672 10:88854197-88854197 10:87094440-87094440
23 GLUD1 NM_005271.5(GLUD1):c.55C>T (p.Leu19=) SNV Uncertain significance 878673 10:88854472-88854472 10:87094715-87094715
24 GLUD1 NM_005271.5(GLUD1):c.*868A>C SNV Uncertain significance 879213 10:88810640-88810640 10:87050883-87050883
25 GLUD1 NM_005271.5(GLUD1):c.*469C>A SNV Uncertain significance 879214 10:88811039-88811039 10:87051282-87051282
26 GLUD1 NM_005271.5(GLUD1):c.1500A>G (p.Ala500=) SNV Uncertain significance 880412 10:88813156-88813156 10:87053399-87053399
27 GLUD1 NM_005271.5(GLUD1):c.1279-3T>C SNV Uncertain significance 880413 10:88819033-88819033 10:87059276-87059276
28 GLUD1 NM_005271.5(GLUD1):c.226C>T (p.Arg76Cys) SNV Uncertain significance 930939 10:88854301-88854301 10:87094544-87094544
29 GLUD1 NM_005271.5(GLUD1):c.1568G>A (p.Arg523His) SNV Uncertain significance 968471 10:88811617-88811617 10:87051860-87051860
30 GLUD1 NM_005271.5(GLUD1):c.136G>A (p.Ala46Thr) SNV Uncertain significance 970685 10:88854391-88854391 10:87094634-87094634
31 GLUD1 NM_005271.5(GLUD1):c.1494G>A (p.Ser498=) SNV Uncertain significance 982988 10:88817448-88817448 10:87057691-87057691
32 GLUD1 NM_005271.5(GLUD1):c.546T>C (p.Ala182=) SNV Uncertain significance 301398 rs886047378 10:88835761-88835761 10:87076004-87076004
33 GLUD1 NM_005271.5(GLUD1):c.154C>A (p.His52Asn) SNV Uncertain significance 301399 rs750420022 10:88854373-88854373 10:87094616-87094616
34 GLUD1 NM_005271.5(GLUD1):c.1442A>T (p.His481Leu) SNV Uncertain significance 533800 rs1169592069 10:88817500-88817500 10:87057743-87057743
35 GLUD1 NM_005271.5(GLUD1):c.1495G>A (p.Gly499Ser) SNV Uncertain significance 16124 rs121909733 10:88813161-88813161 10:87053404-87053404
36 GLUD1 NM_005271.5(GLUD1):c.1100A>G (p.Tyr367Cys) SNV Uncertain significance 548490 rs766896575 10:88820542-88820542 10:87060785-87060785
37 GLUD1 NM_005271.5(GLUD1):c.1181C>T (p.Pro394Leu) SNV Uncertain significance 650460 rs777564388 10:88820461-88820461 10:87060704-87060704
38 GLUD1 NM_005271.5(GLUD1):c.1132A>G (p.Ile378Val) SNV Uncertain significance 656107 rs1589358775 10:88820510-88820510 10:87060753-87060753
39 GLUD1 NM_005271.5(GLUD1):c.*205A>G SNV Uncertain significance 301386 rs886047373 10:88811303-88811303 10:87051546-87051546
40 GLUD1 NM_005271.5(GLUD1):c.677T>G (p.Met226Arg) SNV Uncertain significance 301396 rs886047377 10:88827884-88827884 10:87068127-87068127
41 GLUD1 NM_005271.5(GLUD1):c.1652A>G (p.Asn551Ser) SNV Uncertain significance 301389 rs373705613 10:88811533-88811533 10:87051776-87051776
42 GLUD1 NM_005271.5(GLUD1):c.*1548C>T SNV Uncertain significance 301372 rs886047366 10:88809960-88809960 10:87050203-87050203
43 GLUD1 NM_005271.5(GLUD1):c.*1436G>A SNV Uncertain significance 301375 rs886047369 10:88810072-88810072 10:87050315-87050315
44 GLUD1 NM_005271.5(GLUD1):c.*1252T>C SNV Uncertain significance 301378 rs886047371 10:88810256-88810256 10:87050499-87050499
45 GLUD1 NM_005271.5(GLUD1):c.919C>T (p.Gln307Ter) SNV Uncertain significance 301394 rs886047375 10:88822415-88822415 10:87062658-87062658
46 GLUD1 NM_005271.5(GLUD1):c.-44C>T SNV Uncertain significance 301401 rs886047379 10:88854570-88854570 10:87094813-87094813
47 GLUD1 NM_005271.5(GLUD1):c.*970A>G SNV Uncertain significance 301381 rs760207211 10:88810538-88810538 10:87050781-87050781
48 GLUD1 NM_005271.5(GLUD1):c.*496G>A SNV Uncertain significance 301384 rs886047372 10:88811012-88811012 10:87051255-87051255
49 GLUD1 NM_005271.5(GLUD1):c.*64T>G SNV Uncertain significance 301387 rs760101776 10:88811444-88811444 10:87051687-87051687
50 GLUD1 NM_005271.5(GLUD1):c.1557+12G>A SNV Uncertain significance 301390 rs201872390 10:88813087-88813087 10:87053330-87053330

UniProtKB/Swiss-Prot genetic disease variations for Hyperinsulinemic Hypoglycemia, Familial, 6:

73 (show all 13)
# Symbol AA change Variation ID SNP ID
1 GLUD1 p.Ser498Leu VAR_008666 rs121909731
2 GLUD1 p.Gly499Asp VAR_008667 rs121909734
3 GLUD1 p.Gly499Ser VAR_008668 rs121909733
4 GLUD1 p.Ser501Pro VAR_008669 rs121909732
5 GLUD1 p.His507Tyr VAR_008670 rs121909730
6 GLUD1 p.Arg318Lys VAR_009270 rs121909736
7 GLUD1 p.Glu349Ala VAR_009271 rs121909735
8 GLUD1 p.Ser270Cys VAR_016760
9 GLUD1 p.Arg274Cys VAR_016761 rs56275071
10 GLUD1 p.Arg318Thr VAR_016762
11 GLUD1 p.Tyr319Cys VAR_016763 rs155490613
12 GLUD1 p.Arg322Cys VAR_016764
13 GLUD1 p.Arg322His VAR_016765 rs121909737

Expression for Hyperinsulinemic Hypoglycemia, Familial, 6

Search GEO for disease gene expression data for Hyperinsulinemic Hypoglycemia, Familial, 6.

Pathways for Hyperinsulinemic Hypoglycemia, Familial, 6

Pathways related to Hyperinsulinemic Hypoglycemia, Familial, 6 according to GeneCards Suite gene sharing:

(show all 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.55 UCP2 SLC16A1 SIRT4 PC NAGS KCNJ11
2
Show member pathways
11.68 PC NAGS GLUD2 GLUD1 GCK
3
Show member pathways
11.56 KCNJ11 GCK ABCC8
4 11.5 PC HADH GLUD1
5 11.25 KCNJ11 ABCC8
6
Show member pathways
11.15 GLUD2 GLUD1
7 11.08 GLUD2 GLUD1
8
Show member pathways
10.96 GLUD2 GLUD1
9
Show member pathways
10.86 NAGS GLUD1
10
Show member pathways
10.86 NAGS GLUD2 GLUD1
11 10.82 GLUD2 GLUD1
12 10.78 PC HADH
13 10.66 UCP2 KCNJ11 HADH GCK ABCC8
14
Show member pathways
10.17 GLUD2 GLUD1

GO Terms for Hyperinsulinemic Hypoglycemia, Familial, 6

Cellular components related to Hyperinsulinemic Hypoglycemia, Familial, 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.43 SIRT4 PC NAGS HADH GLUD2 GLUD1
2 mitochondrion GO:0005739 9.32 UCP2 SIRT4 PC NAGS KCNJ11 HADH
3 inward rectifying potassium channel GO:0008282 9.16 KCNJ11 ABCC8

Biological processes related to Hyperinsulinemic Hypoglycemia, Familial, 6 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of insulin secretion GO:0032024 9.54 GLUD1 GCK
2 response to insulin GO:0032868 9.54 HADH EPM2AIP1 ABCC8
3 cellular amino acid metabolic process GO:0006520 9.52 GLUD2 GLUD1
4 cellular glucose homeostasis GO:0001678 9.51 GCK ABCC8
5 pyruvate metabolic process GO:0006090 9.49 SLC16A1 PC
6 glutamine metabolic process GO:0006541 9.48 SIRT4 GLUD1
7 inorganic cation transmembrane transport GO:0098662 9.46 KCNJ11 ABCC8
8 positive regulation of glycogen biosynthetic process GO:0045725 9.43 GCK EPM2AIP1
9 glutamate metabolic process GO:0006536 9.4 NAGS GLUD2
10 glutamate biosynthetic process GO:0006537 9.32 GLUD2 GLUD1
11 glutamate catabolic process GO:0006538 9.26 GLUD2 GLUD1
12 negative regulation of insulin secretion GO:0046676 9.26 SIRT4 KCNJ11 HADH ABCC8
13 tricarboxylic acid metabolic process GO:0072350 9.16 SIRT4 GLUD1
14 regulation of insulin secretion GO:0050796 9.02 SLC16A1 KCNJ11 HADH GCK ABCC8

Molecular functions related to Hyperinsulinemic Hypoglycemia, Familial, 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ADP binding GO:0043531 9.43 GLUD2 GLUD1
2 cation-transporting ATPase activity GO:0019829 9.4 KCNJ11 ABCC8
3 leucine binding GO:0070728 9.37 GLUD2 GLUD1
4 ATP-activated inward rectifier potassium channel activity GO:0015272 9.32 KCNJ11 ABCC8
5 oxidoreductase activity, acting on the CH-NH2 group of donors, NAD or NADP as acceptor GO:0016639 9.26 GLUD2 GLUD1
6 glutamate dehydrogenase [NAD(P)+] activity GO:0004353 9.16 GLUD2 GLUD1
7 glutamate dehydrogenase (NAD+) activity GO:0004352 8.96 GLUD2 GLUD1
8 NAD+ binding GO:0070403 8.8 SIRT4 HADH GLUD1

Sources for Hyperinsulinemic Hypoglycemia, Familial, 6

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....