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 70
Hyperinsulinism-Hyperammonemia Syndrome 57 12 20 58 72 29 13 54 6 39
Familial Hyperinsulinemic Hypoglycemia 6 12 72 15
Hhf6 57 12 72
Hi/ha Syndrome 12 58
Hyperinsulinemic Hypoglycemia Familial 6 20
Hyperinsulinism Hyperammonemia Syndrome 20
Ha/hi Syndrome 20
Hhs 72

Characteristics:

Orphanet epidemiological data:

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

OMIM®:

57 (Updated 20-May-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 70 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: 35878 Definition Hyperinsulinism-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. Epidemiology Prevalence is estimated at 1 in 200,000. Clinical description Clinical 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. Etiology Glutamate 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 counseling Most 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.

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 heart and 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 : 72 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 hyperinsulinism 29.6 UCP2 SLC16A1 KCNJ11 HADH GLUD1 GCK
5 hyperinsulinemic hypoglycemia 29.5 SLC16A1 KCNJ11 HADH GLUD1 GCK ABCC8
6 hyperglycemia 29.3 KCNJ11 GCK ABCC8
7 hypotrichosis 1 11.5
8 tumoral calcinosis, hyperphosphatemic, familial, 1 11.5
9 dyskeratosis congenita, x-linked 11.3
10 heart-hand syndrome, slovenian type 11.2
11 hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 11.2
12 charge syndrome 11.1
13 dyskeratosis congenita, autosomal dominant 1 11.0
14 dyskeratosis congenita, autosomal recessive 5 11.0
15 hoyeraal hreidarsson syndrome 11.0
16 hypotrichosis simplex 10.9
17 tumoral calcinosis, hyperphosphatemic, familial, 2 10.9
18 tumoral calcinosis, hyperphosphatemic, familial, 3 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 argininosuccinic aciduria 10.2 NAGS HADH
27 hyperinsulinemic hypoglycemia, familial, 2 10.2
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 biotinidase deficiency 10.1 PC HADH
32 neu-laxova syndrome 2 10.1 NAGS GLUD1 ABCC8
33 glutaric acidemia i 10.1 PC HADH
34 urea cycle disorder 10.1 PC NAGS
35 coronary heart disease 1 10.1
36 variola major 10.1
37 disease of mental health 10.1
38 smallpox 10.1
39 gastroesophageal reflux 10.0
40 gastroparesis 10.0
41 dystonia 10.0
42 learning disability 10.0
43 splenomegaly 10.0
44 maturity-onset diabetes of the young, type 11 10.0 KCNJ11 ABCC8
45 multiple carboxylase deficiency 10.0 PC HADH
46 cardiomyopathy, dilated, 1o 10.0 KCNJ11 ABCC8
47 coronary artery vasospasm 10.0 KCNJ11 ABCC8
48 cantu syndrome 10.0 KCNJ11 ABCC8
49 3-hydroxyacyl-coa dehydrogenase deficiency 10.0 HADH GLUD1 GCK
50 monocarboxylate transporter 1 deficiency 10.0 SLC16A1 PC 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 fasting hyperinsulinemia 58 31 frequent (33%) Frequent (79-30%) HP:0008283
8 hyperinsulinemic hypoglycemia 58 31 frequent (33%) Frequent (79-30%) HP:0000825
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 20-May-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 20-May-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 Micronutrients
5 Trace Elements
6 Nutrients
7 Antioxidants
8 Protective Agents
9 Vitamins
10 Tocotrienols
11 Tocopherols

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
Heart, Liver

Publications for Hyperinsulinemic Hypoglycemia, Familial, 6

Articles related to Hyperinsulinemic Hypoglycemia, Familial, 6:

(show top 50) (show all 58)
# 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. 57 54 61 6
11214910 2001
2
Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. 61 54 6 57
9571255 1998
3
Novel missense mutations in the glutamate dehydrogenase gene in the congenital hyperinsulinism-hyperammonemia syndrome. 61 6 57
10636977 2000
4
Clinical and molecular heterogeneity of familial hyperinsulinism. 6 57
9843361 1998
5
Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant. 6 57
9469993 1998
6
Hyperinsulinism-hyperammonemia Syndrome in an Infant with Seizures. 6 61
30425915 2018
7
A severe case of hyperinsulinism due to hemizygous activating mutation of glutamate dehydrogenase. 6 61
28165182 2017
8
Early Presentation of Hyperinsulinism/Hyperammonemia Syndrome in Three Serbian Patients. 61 6
26759084 2016
9
Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome. 61 57
11502802 2001
10
Hyperinsulinism/hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate-binding domain of glutamate dehydrogenase. 61 57
11297618 2001
11
Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome. 61 57
11241047 2001
12
Clinical and Molecular Spectrum of Glutamate Dehydrogenase Gene Defects in 26 Chinese Congenital Hyperinsulinemia Patients. 6
30306091 2018
13
Clinical and genetic characterization of congenital hyperinsulinism in Spain. 6
27188453 2016
14
Mutational analysis of ABCC8, KCNJ11, GLUD1, HNF4A and GCK genes in 30 Chinese patients with congenital hyperinsulinism. 6
25008049 2014
15
Whole genome SNP genotyping and exome sequencing reveal novel genetic variants and putative causative genes in congenital hyperinsulinism. 6
23869231 2013
16
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
17
Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. 57
11518822 2001
18
A syndrome of congenital hyperinsulinism and hyperammonemia. 57
9108870 1997
19
Biochemical evaluation of a patient with a familial form of leucine-sensitive hypoglycemia and concomitant hyperammonemia. 57
8769351 1996
20
Regulation of glutamate metabolism and insulin secretion by glutamate dehydrogenase in hypoglycemic children. 61 54
19625687 2009
21
Effects of a GTP-insensitive mutation of glutamate dehydrogenase on insulin secretion in transgenic mice. 61 54
16574664 2006
22
Inhibitory effects of Cimicifuga heracleifolia extract on glutamate formation and glutamate dehydrogenase activity in cultured islets. 54 61
15232227 2004
23
Urinary alpha-ketoglutarate is elevated in patients with hyperinsulinism-hyperammonemia syndrome. 61 54
14967154 2004
24
Identification of the GTP binding site of human glutamate dehydrogenase by cassette mutagenesis and photoaffinity labeling. 54 61
11600502 2001
25
Allosteric discrimination at the NADH/ADP regulatory site of glutamate dehydrogenase. 61
31610054 2019
26
Glutamate dehydrogenase: Structure of a hyperinsulinism mutant, corrections to the atomic model, and insights into a regulatory site. 61
30367518 2019
27
Ebselen Reversibly Inhibits Human Glutamate Dehydrogenase at the Catalytic Site. 61
29470101 2018
28
Ebselen: Mechanisms of Glutamate Dehydrogenase and Glutaminase Enzyme Inhibition. 61
29072450 2017
29
Robust regulation of hepatic pericentral amination by glutamate dehydrogenase kinetics. 61
27747338 2016
30
Identification of a Novel Activator of Mammalian Glutamate Dehydrogenase. 61
27808506 2016
31
Hyperinsulinism-hyperammonemia syndrome: a de novo mutation of the GLUD1 gene in twins and a review of the literature. 61
27383869 2016
32
A novel mutation in GLUD1 causing hyperinsulinism-hyperammonemia in a patient with high density of homozygosity on microarray: a case report. 61
26839063 2016
33
Seizures and diagnostic difficulties in hyperinsulinism-hyperammonemia syndrome. 61
28621098 2016
34
Hyperinsulinism Hyperammonemia Syndrome, a Rare Clinical Constellation. 61
26962538 2016
35
Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene. 61
25781533 2015
36
Deregulation of glutamate dehydrogenase in human neurologic disorders. 61
23463419 2013
37
Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesis and management. 61
23384201 2013
38
Intractable absence seizures in hyperinsulinism-hyperammonemia syndrome. 61
22759688 2012
39
Two genetic forms of hyperinsulinemic hypoglycemia caused by dysregulation of glutamate dehydrogenase. 61
21130127 2011
40
Green tea polyphenols control dysregulated glutamate dehydrogenase in transgenic mice by hijacking the ADP activation site. 61
21813650 2011
41
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
42
The hyperinsulinism/hyperammonemia syndrome. 61
20936362 2010
43
Familial hyperinsulinism-hyperammonemia syndrome in a family with seizures: case report. 61
21073125 2010
44
Systemic activation of glutamate dehydrogenase increases renal ammoniagenesis: implications for the hyperinsulinism/hyperammonemia syndrome. 61
20332361 2010
45
On the reversibility of glutamate dehydrogenase and the source of hyperammonemia in the hyperinsulinism/hyperammonemia syndrome. 61
19895831 2010
46
Hyperammonemia and positive allopurinol test in hyperinsulinism-hyperammonemia syndrome: Taiwanese case report. 61
19379266 2009
47
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
48
Central nervous system hyperexcitability associated with glutamate dehydrogenase gain of function mutations. 61
15756227 2005
49
Hyperinsulinism/Hyperammonemia Syndrome: a synopsis. 61
15773041 2005
50
[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

Variations for Hyperinsulinemic Hypoglycemia, Familial, 6

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

6 (show top 50) (show all 80)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GLUD1 NM_005271.5(GLUD1):c.1519C>T (p.His507Tyr) SNV Pathogenic 16121 rs121909730 GRCh37: 10:88813137-88813137
GRCh38: 10:87053380-87053380
2 GLUD1 NM_005271.5(GLUD1):c.1493C>T (p.Ser498Leu) SNV Pathogenic 16122 rs121909731 GRCh37: 10:88817449-88817449
GRCh38: 10:87057692-87057692
3 GLUD1 NM_005271.5(GLUD1):c.1501T>C (p.Ser501Pro) SNV Pathogenic 16123 rs121909732 GRCh37: 10:88813155-88813155
GRCh38: 10:87053398-87053398
4 GLUD1 NM_005271.5(GLUD1):c.1496G>A (p.Gly499Asp) SNV Pathogenic 16125 rs121909734 GRCh37: 10:88813160-88813160
GRCh38: 10:87053403-87053403
5 GLUD1 NM_005271.5(GLUD1):c.1046A>C (p.Glu349Ala) SNV Pathogenic 16126 rs121909735 GRCh37: 10:88820685-88820685
GRCh38: 10:87060928-87060928
6 GLUD1 NM_005271.5(GLUD1):c.953G>A (p.Arg318Lys) SNV Pathogenic 16127 rs121909736 GRCh37: 10:88820778-88820778
GRCh38: 10:87061021-87061021
7 GLUD1 NM_005271.5(GLUD1):c.820C>T (p.Arg274Cys) SNV Pathogenic 16128 rs56275071 GRCh37: 10:88822514-88822514
GRCh38: 10:87062757-87062757
8 GLUD1 NM_005271.5(GLUD1):c.965G>A (p.Arg322His) SNV Pathogenic 16129 rs121909737 GRCh37: 10:88820766-88820766
GRCh38: 10:87061009-87061009
9 GLUD1 NM_005271.5(GLUD1):c.1496G>T (p.Gly499Val) SNV Pathogenic 226111 rs121909734 GRCh37: 10:88813160-88813160
GRCh38: 10:87053403-87053403
10 GLUD1 NM_005271.5(GLUD1):c.1498G>A (p.Ala500Thr) SNV Likely pathogenic 211086 rs797045597 GRCh37: 10:88813158-88813158
GRCh38: 10:87053401-87053401
11 GLUD1 NM_005271.5(GLUD1):c.1402+10G>A SNV Conflicting interpretations of pathogenicity 301393 rs202067232 GRCh37: 10:88818897-88818897
GRCh38: 10:87059140-87059140
12 GLUD1 NM_005271.5(GLUD1):c.1100A>G (p.Tyr367Cys) SNV Uncertain significance 548490 rs766896575 GRCh37: 10:88820542-88820542
GRCh38: 10:87060785-87060785
13 GLUD1 NM_005271.5(GLUD1):c.1181C>T (p.Pro394Leu) SNV Uncertain significance 650460 rs777564388 GRCh37: 10:88820461-88820461
GRCh38: 10:87060704-87060704
14 GLUD1 NM_005271.5(GLUD1):c.1132A>G (p.Ile378Val) SNV Uncertain significance 656107 rs1589358775 GRCh37: 10:88820510-88820510
GRCh38: 10:87060753-87060753
15 GLUD1 NM_005271.5(GLUD1):c.635A>G (p.Lys212Arg) SNV Uncertain significance 848715 GRCh37: 10:88834319-88834319
GRCh38: 10:87074562-87074562
16 GLUD1 NM_005271.5(GLUD1):c.1078_1079insAGTCCATTCTGG (p.Gly360_Phe361insGluSerIleLeu) Insertion Uncertain significance 856464 GRCh37: 10:88820563-88820564
GRCh38: 10:87060806-87060807
17 GLUD1 NM_005271.5(GLUD1):c.*1515A>G SNV Uncertain significance 877597 GRCh37: 10:88809993-88809993
GRCh38: 10:87050236-87050236
18 GLUD1 NM_005271.5(GLUD1):c.*1501G>C SNV Uncertain significance 877598 GRCh37: 10:88810007-88810007
GRCh38: 10:87050250-87050250
19 GLUD1 NM_005271.5(GLUD1):c.*1419T>G SNV Uncertain significance 877599 GRCh37: 10:88810089-88810089
GRCh38: 10:87050332-87050332
20 GLUD1 NM_005271.5(GLUD1):c.1279-6G>A SNV Uncertain significance 877652 GRCh37: 10:88819036-88819036
GRCh38: 10:87059279-87059279
21 GLUD1 NM_005271.5(GLUD1):c.*1211T>C SNV Uncertain significance 878613 GRCh37: 10:88810297-88810297
GRCh38: 10:87050540-87050540
22 GLUD1 NM_005271.5(GLUD1):c.*1181C>A SNV Uncertain significance 878614 GRCh37: 10:88810327-88810327
GRCh38: 10:87050570-87050570
23 GLUD1 NM_005271.5(GLUD1):c.*1139T>C SNV Uncertain significance 878615 GRCh37: 10:88810369-88810369
GRCh38: 10:87050612-87050612
24 GLUD1 NM_005271.5(GLUD1):c.*998C>T SNV Uncertain significance 878616 GRCh37: 10:88810510-88810510
GRCh38: 10:87050753-87050753
25 GLUD1 NM_005271.5(GLUD1):c.330G>A (p.Lys110=) SNV Uncertain significance 878672 GRCh37: 10:88854197-88854197
GRCh38: 10:87094440-87094440
26 GLUD1 , SHLD2 NM_005271.5(GLUD1):c.55C>T (p.Leu19=) SNV Uncertain significance 878673 GRCh37: 10:88854472-88854472
GRCh38: 10:87094715-87094715
27 GLUD1 NM_005271.5(GLUD1):c.*868A>C SNV Uncertain significance 879213 GRCh37: 10:88810640-88810640
GRCh38: 10:87050883-87050883
28 GLUD1 NM_005271.5(GLUD1):c.*469C>A SNV Uncertain significance 879214 GRCh37: 10:88811039-88811039
GRCh38: 10:87051282-87051282
29 GLUD1 NM_005271.5(GLUD1):c.1500A>G (p.Ala500=) SNV Uncertain significance 880412 GRCh37: 10:88813156-88813156
GRCh38: 10:87053399-87053399
30 GLUD1 NM_005271.5(GLUD1):c.1279-3T>C SNV Uncertain significance 880413 GRCh37: 10:88819033-88819033
GRCh38: 10:87059276-87059276
31 GLUD1 , SHLD2 NM_005271.5(GLUD1):c.226C>T (p.Arg76Cys) SNV Uncertain significance 930939 GRCh37: 10:88854301-88854301
GRCh38: 10:87094544-87094544
32 GLUD1 NM_005271.5(GLUD1):c.1568G>A (p.Arg523His) SNV Uncertain significance 968471 GRCh37: 10:88811617-88811617
GRCh38: 10:87051860-87051860
33 GLUD1 , SHLD2 NM_005271.5(GLUD1):c.136G>A (p.Ala46Thr) SNV Uncertain significance 970685 GRCh37: 10:88854391-88854391
GRCh38: 10:87094634-87094634
34 GLUD1 NM_005271.5(GLUD1):c.1494G>A (p.Ser498=) SNV Uncertain significance 982988 GRCh37: 10:88817448-88817448
GRCh38: 10:87057691-87057691
35 GLUD1 NM_005271.5(GLUD1):c.1198-11CT[2] Microsatellite Uncertain significance 1007983 GRCh37: 10:88820004-88820005
GRCh38: 10:87060247-87060248
36 GLUD1 , SHLD2 NM_005271.5(GLUD1):c.3G>A (p.Met1Ile) SNV Uncertain significance 1010602 GRCh37: 10:88854524-88854524
GRCh38: 10:87094767-87094767
37 GLUD1 NM_005271.5(GLUD1):c.452G>C (p.Arg151Pro) SNV Uncertain significance 1019363 GRCh37: 10:88836407-88836407
GRCh38: 10:87076650-87076650
38 GLUD1 NM_005271.5(GLUD1):c.839T>C (p.Ile280Thr) SNV Uncertain significance 1030901 GRCh37: 10:88822495-88822495
GRCh38: 10:87062738-87062738
39 GLUD1 NM_005271.5(GLUD1):c.1495G>A (p.Gly499Ser) SNV Uncertain significance 16124 rs121909733 GRCh37: 10:88813161-88813161
GRCh38: 10:87053404-87053404
40 GLUD1 NM_005271.5(GLUD1):c.677T>G (p.Met226Arg) SNV Uncertain significance 301396 rs886047377 GRCh37: 10:88827884-88827884
GRCh38: 10:87068127-87068127
41 GLUD1 NM_005271.5(GLUD1):c.1652A>G (p.Asn551Ser) SNV Uncertain significance 301389 rs373705613 GRCh37: 10:88811533-88811533
GRCh38: 10:87051776-87051776
42 GLUD1 NM_005271.5(GLUD1):c.*205A>G SNV Uncertain significance 301386 rs886047373 GRCh37: 10:88811303-88811303
GRCh38: 10:87051546-87051546
43 GLUD1 NM_005271.5(GLUD1):c.*1548C>T SNV Uncertain significance 301372 rs886047366 GRCh37: 10:88809960-88809960
GRCh38: 10:87050203-87050203
44 GLUD1 NM_005271.5(GLUD1):c.*1436G>A SNV Uncertain significance 301375 rs886047369 GRCh37: 10:88810072-88810072
GRCh38: 10:87050315-87050315
45 GLUD1 NM_005271.5(GLUD1):c.*1252T>C SNV Uncertain significance 301378 rs886047371 GRCh37: 10:88810256-88810256
GRCh38: 10:87050499-87050499
46 GLUD1 NM_005271.5(GLUD1):c.919C>T (p.Gln307Ter) SNV Uncertain significance 301394 rs886047375 GRCh37: 10:88822415-88822415
GRCh38: 10:87062658-87062658
47 GLUD1 , SHLD2 NM_005271.5(GLUD1):c.-44C>T SNV Uncertain significance 301401 rs886047379 GRCh37: 10:88854570-88854570
GRCh38: 10:87094813-87094813
48 GLUD1 NM_005271.5(GLUD1):c.*970A>G SNV Uncertain significance 301381 rs760207211 GRCh37: 10:88810538-88810538
GRCh38: 10:87050781-87050781
49 GLUD1 NM_005271.5(GLUD1):c.*496G>A SNV Uncertain significance 301384 rs886047372 GRCh37: 10:88811012-88811012
GRCh38: 10:87051255-87051255
50 GLUD1 NM_005271.5(GLUD1):c.*64T>G SNV Uncertain significance 301387 rs760101776 GRCh37: 10:88811444-88811444
GRCh38: 10:87051687-87051687

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

72 (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
11.14 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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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