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 56 71
Hyperinsulinism-Hyperammonemia Syndrome 56 12 52 58 73 29 13 54 6 39
Familial Hyperinsulinemic Hypoglycemia 6 12 73 15
Hhf6 56 12 73
Hi/ha Syndrome 12 58
Hyperinsulinemic Hypoglycemia Familial 6 52
Hyperinsulinism Hyperammonemia Syndrome 52
Ha/hi Syndrome 52
Hhs 73

Characteristics:

Orphanet epidemiological data:

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

OMIM:

56
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


External Ids:

Disease Ontology 12 DOID:0070217
OMIM 56 606762
OMIM Phenotypic Series 56 PS256450
ICD10 via Orphanet 33 E72.8
Orphanet 58 ORPHA35878
MedGen 41 C1847555
UMLS 71 C1847555

Summaries for Hyperinsulinemic Hypoglycemia, Familial, 6

NIH Rare Diseases : 52 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. Visit the Orphanet disease page for more resources.

MalaCards based summary : Hyperinsulinemic Hypoglycemia, Familial, 6, also known as hyperinsulinism-hyperammonemia syndrome, is related to carbonic anhydrase va deficiency, hyperammonemia due to and acute insulin response. 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 testes, 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 209)
# Related Disease Score Top Affiliating Genes
1 carbonic anhydrase va deficiency, hyperammonemia due to 31.7 NAGS GLUD1
2 acute insulin response 30.2 UCP2 ABCC8
3 hyperinsulinism 29.2 UCP2 SLC16A1 HADH GLUD1 GCK ABCC8
4 hyperinsulinemic hypoglycemia 29.2 SLC16A1 HADH GLUD1 GCK ABCC8
5 hypoglycemia 27.6 SLC16A1 PC HADH GLUD1 GCK ABCC8
6 tumoral calcinosis, hyperphosphatemic, familial, 1 12.0
7 hypotrichosis 1 12.0
8 hemochromatosis, type 1 11.8
9 hypogonadotropic hypogonadism 7 with or without anosmia 11.8
10 dyskeratosis congenita, x-linked 11.8
11 heart-hand syndrome, slovenian type 11.7
12 hypogonadotropic hypogonadism 11.7
13 hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 11.5
14 hypogonadotropic hypogonadism 15 with or without anosmia 11.4
15 hypothalamic hamartomas 11.3
16 charge syndrome 11.3
17 dyskeratosis congenita, autosomal dominant 1 11.2
18 hypogonadotropic hypogonadism 2 with or without anosmia 11.2
19 dyskeratosis congenita, autosomal recessive 5 11.2
20 kallmann syndrome 11.2
21 hoyeraal hreidarsson syndrome 11.2
22 hypotrichosis simplex 11.2
23 hypogonadotropic hypogonadism 3 with or without anosmia 11.0
24 hypogonadotropic hypogonadism 4 with or without anosmia 11.0
25 hypogonadotropic hypogonadism 5 with or without anosmia 11.0
26 hypogonadotropic hypogonadism 6 with or without anosmia 11.0
27 hypogonadotropic hypogonadism 8 with or without anosmia 11.0
28 hypogonadotropic hypogonadism 9 with or without anosmia 11.0
29 hypogonadotropic hypogonadism 10 with or without anosmia 11.0
30 hypogonadotropic hypogonadism 11 with or without anosmia 11.0
31 hypogonadotropic hypogonadism 12 with or without anosmia 11.0
32 hypogonadotropic hypogonadism 13 with or without anosmia 11.0
33 hypogonadotropic hypogonadism 14 with or without anosmia 11.0
34 hypogonadotropic hypogonadism 16 with or without anosmia 11.0
35 hypogonadotropic hypogonadism 17 with or without anosmia 11.0
36 hypogonadotropic hypogonadism 18 with or without anosmia 11.0
37 hypogonadotropic hypogonadism 19 with or without anosmia 11.0
38 hypogonadotropic hypogonadism 20 with or without anosmia 11.0
39 hypogonadotropic hypogonadism 21 with or without anosmia 11.0
40 hypogonadotropic hypogonadism 22 with or without anosmia 11.0
41 bombay phenotype 11.0
42 tumoral calcinosis, hyperphosphatemic, familial, 2 11.0
43 tumoral calcinosis, hyperphosphatemic, familial, 3 11.0
44 hyperinsulinemic hypoglycemia, familial, 5 10.7
45 hyperinsulinemic hypoglycemia, familial, 4 10.7
46 human immunodeficiency virus type 1 10.5
47 fasting hypoglycemia 10.4
48 substance abuse 10.3
49 hyperinsulinemic hypoglycemia, familial, 2 10.3
50 fetal erythroblastosis 10.3 HADH 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:

56
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

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

45
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.56 EPM2AIP1 GCK GLUD1 HADH NAGS SLC16A1
2 homeostasis/metabolism MP:0005376 9.28 ABCC8 EPM2AIP1 GCK GLUD1 HADH NAGS

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, 54-28-4 14986
2
Vitamin E Approved, Nutraceutical, Vet_approved 59-02-9 14985
3 Tocotrienol Investigational 6829-55-6
4 Micronutrients
5 Trace Elements
6 Vitamins
7 Antioxidants
8 Nutrients
9 Protective Agents
10 Tocotrienols
11 Tocopherols

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Prevalence of Hypoglycemia and/or Hyperinsulinism/Hyperammonemia Syndrome in Patients With Idiopathic Seizures. Unknown status NCT00279851
2 Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome Active, not recruiting NCT03797222

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, Testes

Publications for Hyperinsulinemic Hypoglycemia, Familial, 6

Articles related to Hyperinsulinemic Hypoglycemia, Familial, 6:

(show top 50) (show all 55)
# 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. 6 54 56 61
11214910 2001
2
Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. 54 61 56 6
9571255 1998
3
Novel missense mutations in the glutamate dehydrogenase gene in the congenital hyperinsulinism-hyperammonemia syndrome. 61 6 56
10636977 2000
4
Clinical and molecular heterogeneity of familial hyperinsulinism. 6 56
9843361 1998
5
Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant. 56 6
9469993 1998
6
Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome. 61 56
11502802 2001
7
Hyperinsulinism/hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate-binding domain of glutamate dehydrogenase. 61 56
11297618 2001
8
Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome. 56 61
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. 56
16151898 2005
10
Familial Hyperinsulinism 6
20301549 2003
11
Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. 56
11518822 2001
12
A syndrome of congenital hyperinsulinism and hyperammonemia. 56
9108870 1997
13
Biochemical evaluation of a patient with a familial form of leucine-sensitive hypoglycemia and concomitant hyperammonemia. 56
8769351 1996
14
Regulation of glutamate metabolism and insulin secretion by glutamate dehydrogenase in hypoglycemic children. 54 61
19625687 2009
15
Effects of a GTP-insensitive mutation of glutamate dehydrogenase on insulin secretion in transgenic mice. 61 54
16574664 2006
16
Inhibitory effects of Cimicifuga heracleifolia extract on glutamate formation and glutamate dehydrogenase activity in cultured islets. 61 54
15232227 2004
17
Urinary alpha-ketoglutarate is elevated in patients with hyperinsulinism-hyperammonemia syndrome. 61 54
14967154 2004
18
Identification of the GTP binding site of human glutamate dehydrogenase by cassette mutagenesis and photoaffinity labeling. 54 61
11600502 2001
19
Allosteric discrimination at the NADH/ADP regulatory site of glutamate dehydrogenase. 61
31610054 2019
20
Glutamate dehydrogenase: Structure of a hyperinsulinism mutant, corrections to the atomic model, and insights into a regulatory site. 61
30367518 2019
21
Hyperinsulinism-hyperammonemia Syndrome in an Infant with Seizures. 61
30425915 2018
22
Ebselen Reversibly Inhibits Human Glutamate Dehydrogenase at the Catalytic Site. 61
29470101 2018
23
Ebselen: Mechanisms of Glutamate Dehydrogenase and Glutaminase Enzyme Inhibition. 61
29072450 2017
24
A severe case of hyperinsulinism due to hemizygous activating mutation of glutamate dehydrogenase. 61
28165182 2017
25
Robust regulation of hepatic pericentral amination by glutamate dehydrogenase kinetics. 61
27747338 2016
26
Identification of a Novel Activator of Mammalian Glutamate Dehydrogenase. 61
27808506 2016
27
Hyperinsulinism-hyperammonemia syndrome: a de novo mutation of the GLUD1 gene in twins and a review of the literature. 61
27383869 2016
28
Early Presentation of Hyperinsulinism/Hyperammonemia Syndrome in Three Serbian Patients. 61
26759084 2016
29
A novel mutation in GLUD1 causing hyperinsulinism-hyperammonemia in a patient with high density of homozygosity on microarray: a case report. 61
26839063 2016
30
Seizures and diagnostic difficulties in hyperinsulinism-hyperammonemia syndrome. 61
28621098 2016
31
Hyperinsulinism Hyperammonemia Syndrome, a Rare Clinical Constellation. 61
26962538 2016
32
Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene. 61
25781533 2015
33
Deregulation of glutamate dehydrogenase in human neurologic disorders. 61
23463419 2013
34
Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesis and management. 61
23384201 2013
35
Intractable absence seizures in hyperinsulinism-hyperammonemia syndrome. 61
22759688 2012
36
Green tea polyphenols control dysregulated glutamate dehydrogenase in transgenic mice by hijacking the ADP activation site. 61
21813650 2011
37
Two genetic forms of hyperinsulinemic hypoglycemia caused by dysregulation of glutamate dehydrogenase. 61
21130127 2011
38
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
39
The hyperinsulinism/hyperammonemia syndrome. 61
20936362 2010
40
Familial hyperinsulinism-hyperammonemia syndrome in a family with seizures: case report. 61
21073125 2010
41
Systemic activation of glutamate dehydrogenase increases renal ammoniagenesis: implications for the hyperinsulinism/hyperammonemia syndrome. 61
20332361 2010
42
On the reversibility of glutamate dehydrogenase and the source of hyperammonemia in the hyperinsulinism/hyperammonemia syndrome. 61
19895831 2010
43
Hyperammonemia and positive allopurinol test in hyperinsulinism-hyperammonemia syndrome: Taiwanese case report. 61
19379266 2009
44
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
45
Central nervous system hyperexcitability associated with glutamate dehydrogenase gain of function mutations. 61
15756227 2005
46
Hyperinsulinism/Hyperammonemia Syndrome: a synopsis. 61
15773041 2005
47
[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
48
Hyperinsulinism/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism. 61
15050973 2004
49
The structure of apo human glutamate dehydrogenase details subunit communication and allostery. 61
12054821 2002
50
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

Variations for Hyperinsulinemic Hypoglycemia, Familial, 6

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

6 (show top 50) (show all 72) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GLUD1 NM_005271.5(GLUD1):c.1519C>T (p.His507Tyr)SNV Pathogenic 16121 rs121909730 10:88813137-88813137 10:87053380-87053380
2 GLUD1 NM_005271.5(GLUD1):c.1493C>T (p.Ser498Leu)SNV Pathogenic 16122 rs121909731 10:88817449-88817449 10:87057692-87057692
3 GLUD1 NM_005271.5(GLUD1):c.1501T>C (p.Ser501Pro)SNV Pathogenic 16123 rs121909732 10:88813155-88813155 10:87053398-87053398
4 GLUD1 NM_005271.5(GLUD1):c.1495G>A (p.Gly499Ser)SNV Pathogenic 16124 rs121909733 10:88813161-88813161 10:87053404-87053404
5 GLUD1 NM_005271.5(GLUD1):c.1496G>A (p.Gly499Asp)SNV Pathogenic 16125 rs121909734 10:88813160-88813160 10:87053403-87053403
6 GLUD1 NM_005271.5(GLUD1):c.1046A>C (p.Glu349Ala)SNV Pathogenic 16126 rs121909735 10:88820685-88820685 10:87060928-87060928
7 GLUD1 NM_005271.5(GLUD1):c.953G>A (p.Arg318Lys)SNV Pathogenic 16127 rs121909736 10:88820778-88820778 10:87061021-87061021
8 GLUD1 NM_005271.5(GLUD1):c.820C>T (p.Arg274Cys)SNV Pathogenic 16128 rs56275071 10:88822514-88822514 10:87062757-87062757
9 GLUD1 NM_005271.5(GLUD1):c.965G>A (p.Arg322His)SNV Pathogenic 16129 rs121909737 10:88820766-88820766 10:87061009-87061009
10 GLUD1 NM_005271.5(GLUD1):c.1496G>T (p.Gly499Val)SNV Pathogenic 226111 rs121909734 10:88813160-88813160 10:87053403-87053403
11 GLUD1 NM_005271.5(GLUD1):c.1498G>A (p.Ala500Thr)SNV Likely pathogenic 211086 rs797045597 10:88813158-88813158 10:87053401-87053401
12 GLUD1 NM_005271.5(GLUD1):c.-44C>TSNV Conflicting interpretations of pathogenicity 301401 rs886047379 10:88854570-88854570 10:87094813-87094813
13 GLUD1 NM_005271.5(GLUD1):c.1402+10G>ASNV Conflicting interpretations of pathogenicity 301393 rs202067232 10:88818897-88818897 10:87059140-87059140
14 GLUD1 NM_005271.5(GLUD1):c.677T>G (p.Met226Arg)SNV Uncertain significance 301396 rs886047377 10:88827884-88827884 10:87068127-87068127
15 GLUD1 NM_005271.5(GLUD1):c.546T>C (p.Ala182=)SNV Uncertain significance 301398 rs886047378 10:88835761-88835761 10:87076004-87076004
16 GLUD1 NM_005271.5(GLUD1):c.154C>A (p.His52Asn)SNV Uncertain significance 301399 rs750420022 10:88854373-88854373 10:87094616-87094616
17 GLUD1 NM_005271.5(GLUD1):c.919C>T (p.Gln307Ter)SNV Uncertain significance 301394 rs886047375 10:88822415-88822415 10:87062658-87062658
18 GLUD1 NM_005271.5(GLUD1):c.*1548C>TSNV Uncertain significance 301372 rs886047366 10:88809960-88809960 10:87050203-87050203
19 GLUD1 NM_005271.5(GLUD1):c.*1270C>TSNV Uncertain significance 301377 rs886047370 10:88810238-88810238 10:87050481-87050481
20 GLUD1 NM_005271.5(GLUD1):c.*496G>ASNV Uncertain significance 301384 rs886047372 10:88811012-88811012 10:87051255-87051255
21 GLUD1 NM_005271.5(GLUD1):c.*205A>GSNV Uncertain significance 301386 rs886047373 10:88811303-88811303 10:87051546-87051546
22 GLUD1 NM_005271.5(GLUD1):c.*1436G>ASNV Uncertain significance 301375 rs886047369 10:88810072-88810072 10:87050315-87050315
23 GLUD1 NM_005271.5(GLUD1):c.*64T>GSNV Uncertain significance 301387 rs760101776 10:88811444-88811444 10:87051687-87051687
24 GLUD1 NM_005271.5(GLUD1):c.1652A>G (p.Asn551Ser)SNV Uncertain significance 301389 rs373705613 10:88811533-88811533 10:87051776-87051776
25 GLUD1 NM_005271.5(GLUD1):c.*64T>CSNV Uncertain significance 301388 rs760101776 10:88811444-88811444 10:87051687-87051687
26 GLUD1 NM_005271.5(GLUD1):c.1557+12G>ASNV Uncertain significance 301390 rs201872390 10:88813087-88813087 10:87053330-87053330
27 GLUD1 NM_005271.5(GLUD1):c.1515C>T (p.Ile505=)SNV Uncertain significance 301391 rs774771496 10:88813141-88813141 10:87053384-87053384
28 GLUD1 NM_005271.5(GLUD1):c.1403-11T>CSNV Uncertain significance 301392 rs886047374 10:88817550-88817550 10:87057793-87057793
29 GLUD1 NM_005271.5(GLUD1):c.*1545C>TSNV Uncertain significance 301373 rs886047367 10:88809963-88809963 10:87050206-87050206
30 GLUD1 NM_005271.5(GLUD1):c.*1464C>TSNV Uncertain significance 301374 rs886047368 10:88810044-88810044 10:87050287-87050287
31 GLUD1 NM_005271.5(GLUD1):c.*1252T>CSNV Uncertain significance 301378 rs886047371 10:88810256-88810256 10:87050499-87050499
32 GLUD1 NM_005271.5(GLUD1):c.*970A>GSNV Uncertain significance 301381 rs760207211 10:88810538-88810538 10:87050781-87050781
33 GLUD1 NM_005271.5(GLUD1):c.446-7CCA[4]short repeat Uncertain significance 225380 rs753723749 10:88836414-88836415 10:87076657-87076658
34 GLUD1 NM_005271.5(GLUD1):c.1078_1079insAGTCCATTCTGG (p.Gly360_Phe361insGluSerIleLeu)insertion Uncertain significance 856464 10:88820563-88820564 10:87060806-87060807
35 GLUD1 NM_005271.5(GLUD1):c.635A>G (p.Lys212Arg)SNV Uncertain significance 848715 10:88834319-88834319 10:87074562-87074562
36 GLUD1 NM_005271.5(GLUD1):c.*1515A>GSNV Uncertain significance 877597 10:88809993-88809993 10:87050236-87050236
37 GLUD1 NM_005271.5(GLUD1):c.*1501G>CSNV Uncertain significance 877598 10:88810007-88810007 10:87050250-87050250
38 GLUD1 NM_005271.5(GLUD1):c.*1419T>GSNV Uncertain significance 877599 10:88810089-88810089 10:87050332-87050332
39 GLUD1 NM_005271.5(GLUD1):c.1442A>T (p.His481Leu)SNV Uncertain significance 533800 rs1169592069 10:88817500-88817500 10:87057743-87057743
40 GLUD1 NM_005271.5(GLUD1):c.1100A>G (p.Tyr367Cys)SNV Uncertain significance 548490 rs766896575 10:88820542-88820542 10:87060785-87060785
41 GLUD1 NM_005271.5(GLUD1):c.1181C>T (p.Pro394Leu)SNV Uncertain significance 650460 10:88820461-88820461 10:87060704-87060704
42 GLUD1 NM_005271.5(GLUD1):c.1132A>G (p.Ile378Val)SNV Uncertain significance 656107 10:88820510-88820510 10:87060753-87060753
43 GLUD1 NM_005271.5(GLUD1):c.*1211T>CSNV Uncertain significance 878613 10:88810297-88810297 10:87050540-87050540
44 GLUD1 NM_005271.5(GLUD1):c.*1181C>ASNV Uncertain significance 878614 10:88810327-88810327 10:87050570-87050570
45 GLUD1 NM_005271.5(GLUD1):c.*1139T>CSNV Uncertain significance 878615 10:88810369-88810369 10:87050612-87050612
46 GLUD1 NM_005271.5(GLUD1):c.*998C>TSNV Uncertain significance 878616 10:88810510-88810510 10:87050753-87050753
47 GLUD1 NM_005271.5(GLUD1):c.*868A>CSNV Uncertain significance 879213 10:88810640-88810640 10:87050883-87050883
48 GLUD1 NM_005271.5(GLUD1):c.*469C>ASNV Uncertain significance 879214 10:88811039-88811039 10:87051282-87051282
49 GLUD1 NM_005271.5(GLUD1):c.1500A>G (p.Ala500=)SNV Uncertain significance 880412 10:88813156-88813156 10:87053399-87053399
50 GLUD1 NM_005271.5(GLUD1):c.330G>A (p.Lys110=)SNV Uncertain significance 878672 10:88854197-88854197 10:87094440-87094440

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

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 9.35 PC NAGS HADH GLUD2 GLUD1
2 mitochondrion GO:0005739 9.23 UCP2 PC NAGS HADH GLUD2 GLUD1

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 glucose metabolic process GO:0006006 9.52 WDTC1 GCK
2 positive regulation of insulin secretion GO:0032024 9.51 GLUD1 GCK
3 cellular response to insulin stimulus GO:0032869 9.5 WDTC1 UCP2 GCK
4 cellular amino acid metabolic process GO:0006520 9.49 GLUD2 GLUD1
5 negative regulation of insulin secretion GO:0046676 9.48 HADH ABCC8
6 cellular glucose homeostasis GO:0001678 9.46 GCK ABCC8
7 pyruvate metabolic process GO:0006090 9.43 SLC16A1 PC
8 response to insulin GO:0032868 9.43 HADH EPM2AIP1 ABCC8
9 positive regulation of glycogen biosynthetic process GO:0045725 9.4 GCK EPM2AIP1
10 glutamate metabolic process GO:0006536 9.37 NAGS GLUD2
11 regulation of insulin secretion GO:0050796 9.33 SLC16A1 GCK ABCC8
12 glutamate biosynthetic process GO:0006537 8.96 GLUD2 GLUD1
13 glutamate catabolic process GO:0006538 8.62 GLUD2 GLUD1

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 9.37 GLUD2 GLUD1
2 NAD+ binding GO:0070403 9.32 HADH GLUD1
3 leucine binding GO:0070728 9.26 GLUD2 GLUD1
4 oxidoreductase activity, acting on the CH-NH2 group of donors, NAD or NADP as acceptor GO:0016639 9.16 GLUD2 GLUD1
5 glutamate dehydrogenase [NAD(P)+] activity GO:0004353 8.96 GLUD2 GLUD1
6 glutamate dehydrogenase (NAD+) activity GO:0004352 8.62 GLUD2 GLUD1

Sources for Hyperinsulinemic Hypoglycemia, Familial, 6

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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