STHE
MCID: HYP097
MIFTS: 62

Hyperekplexia (STHE)

Categories: Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Hyperekplexia

MalaCards integrated aliases for Hyperekplexia:

Name: Hyperekplexia 12 73 43 58 36 29 54 6 15
Hereditary Hyperekplexia 12 25 20 43 58 6
Kok Disease 12 20 58
Congenital Stiff Man Syndrome 12 58
Familial Startle Disease 12 58
Hereditary Hyperexplexia 58 70
Stiff-Baby Syndrome 20 43
Sthe 20 43
Stiff-Person Syndrome, Congenital 20
Congenital Stiff-Person Syndrome 43
Stiff-Man Syndrome, Congenital 20
Startle Reaction, Exaggerated 20
Congenital Stiff-Man Syndrome 43
Exaggerated Startle Reaction 20
Startle Disease, Familial 20
Hyperekplexia, Hereditary 39
Hyperexplexia Hereditary 20
Hyperekplexia Hereditary 6
Familial Hyperekplexia 43
Stiff-Person Syndrome 70
Stiff Baby Syndrome 58
Startle Syndrome 43
Startle Disease 12

Characteristics:

Orphanet epidemiological data:

58
hereditary hyperekplexia
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Hyperekplexia

GARD : 20 Hereditary hyperekplexia is a nervous system disorder ( neurological disorder ), that is usually noticed shortly after birth. Symptoms in a newborn include generalized muscle stiffness while awake ( hypertonia ) and exaggerated startle reflex to unexpected loud noises, visual stimuli, or touch. Following the startle reaction, infants experience a brief period in which they are very rigid and are unable to move. During these rigid periods, some infants may stop breathing (apnea), which can be fatal and has been associated with sudden infant death syndrome (SIDS). Muscle stiffness usually fades completely during the first few years of life. However the exaggerated startle reflex and periods of rigidity may continue throughout a person's life. Depending on the severity of the continued symptoms, a child or adult with hereditary hyperekplexia may have an increased risk of falling or otherwise injuring themselves. In some cases, children with hereditary hyperekplexia may have mild developmental delays. Abdominal hernias and congenital dislocation of the hip have also been associated with hereditary hyperekplexia. Diagnosis of hereditary hyperekplexia requires the three main features: generalized stiffness immediately after birth, excessive startle reflex to unexpected stimuli, and a short period of generalized stiffness following the startle response. Of note, the results of routine blood tests, urinalysis, brain imaging studies, or EEG are usually normal. Hereditary hyperekplexia has different inheritance patterns and is associated with changes ( mutations ) in at least five genes. Genetic testing is available to detect the genetic changes. Clonazepam is the most commonly used treatment and successfully reduces symptoms in most people.

MalaCards based summary : Hyperekplexia, also known as hereditary hyperekplexia, is related to hyperekplexia 1 and hyperekplexia 3, and has symptoms including fever, myoclonus and opisthotonus. An important gene associated with Hyperekplexia is GLRA1 (Glycine Receptor Alpha 1), and among its related pathways/superpathways are Neuroactive ligand-receptor interaction and Synaptic vesicle cycle. The drugs Carmustine and Mechlorethamine have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and eye, and related phenotypes are spasticity and hyperreflexia

Disease Ontology : 12 A nervous system disease characterized by an exaggerated startle response to sudden, unexpected auditory or tactile stimuli and hypertonia.

MedlinePlus Genetics : 43 Hereditary hyperekplexia is a condition in which affected infants have increased muscle tone (hypertonia) and an exaggerated startle reaction to unexpected stimuli, especially loud noises. Following the startle reaction, infants experience a brief period in which they are very rigid and unable to move. During these rigid periods, some infants stop breathing, which, if prolonged, can be fatal. Infants with hereditary hyperekplexia have hypertonia at all times, except when they are sleeping.Other signs and symptoms of hereditary hyperekplexia can include muscle twitches when falling asleep (hypnagogic myoclonus) and movements of the arms or legs while asleep. Some infants, when tapped on the nose, extend their head forward and have spasms of the limb and neck muscles. Rarely, infants with hereditary hyperekplexia experience recurrent seizures (epilepsy).The signs and symptoms of hereditary hyperekplexia typically fade by age 1. However, older individuals with hereditary hyperekplexia may still startle easily and have periods of rigidity, which can cause them to fall down. They may also continue to have hypnagogic myoclonus or movements during sleep. As they get older, individuals with this condition may have a low tolerance for crowded places and loud noises. People with hereditary hyperekplexia who have epilepsy have the seizure disorder throughout their lives.Hereditary hyperekplexia may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of unexplained death in babies younger than 1 year.

KEGG : 36 Hyperekplexia, also known as startle disease, is a paroxysmal neurological disorder caused by defects in glycinergic neurotransmission. Hyperekplexia is characterized by neonatal hypertonia and an exaggerated startle reflex in response to acoustic or tactile stimuli. Genetic analysis has revealed mutations in genes for several postsynaptic proteins involved in orchestrating glycinergic neurotransmission, including the glycine receptor (GlyR) alpha1 and beta subunits.

Wikipedia : 73 Hyperekplexia /ˌhaɪ.pɚ.ɛkˈplɛk.si.ə/ ("exaggerated surprise") is a very rare neurologic disorder... more...

GeneReviews: NBK1260

Related Diseases for Hyperekplexia

Diseases in the Hyperekplexia family:

Hyperekplexia 1 Hyperekplexia 3
Hyperekplexia 2 Hyperekplexia 4
Sporadic Hyperekplexia

Diseases related to Hyperekplexia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 101)
# Related Disease Score Top Affiliating Genes
1 hyperekplexia 1 33.1 GPHN GLRA1
2 hyperekplexia 3 33.0 SLC6A9 SLC6A5 GLRA1
3 molybdenum cofactor deficiency 32.0 MOCS1 GPHN GLRA1
4 stiff-person syndrome 30.6 GPHN GLRB GLRA1 DPP6
5 autism spectrum disorder 30.0 SOD1 SLC6A2 GPHN GABRG2 DPP6 ARHGEF9
6 hyperekplexia 2 11.6
7 developmental and epileptic encephalopathy 8 11.5
8 hyperekplexia 4 11.5
9 sandhoff disease 11.2
10 gm2-gangliosidosis, ab variant 11.2
11 tay-sachs disease 11.2
12 gm1 gangliosidosis 11.2
13 spastic tetraplegia and axial hypotonia, progressive 11.0
14 sporadic hyperekplexia 11.0
15 asparagine synthetase deficiency 10.9
16 clpb deficiency 10.9
17 jumping frenchmen of maine 10.6
18 hypertonia 10.6
19 periodic limb movement disorder 10.4 SLC6A5 GLRB GLRA1
20 brittle cornea syndrome 2 10.4 SLC6A5 SLC6A2
21 brain stem infarction 10.4 SLC6A5 GLRA3 GARS1
22 molybdenum cofactor deficiency, complementation group c 10.4 MOCS1 GPHN
23 ritscher-schinzel syndrome 2 10.4 GPHN ARHGEF9
24 glycine encephalopathy 10.4 SLC6A9 SLC6A5 GPHN GLRA1 GARS1
25 charcot-marie-tooth disease, axonal, type 2l 10.4 GARS1 DCAF8
26 molybdenum cofactor deficiency, complementation group a 10.3 MOCS1 GPHN
27 kagami-ogata syndrome 10.3 SLC32A1 GPHN GLRA2
28 giant axonal neuropathy 2 10.3 SOD1 DCAF8
29 myoclonus 10.3
30 dravet syndrome 10.3 GPHN GABRG2 ARHGEF9
31 autism 10.2 SOD1 SLC6A2 GPHN GABRG2 DPP6 ARHGEF9
32 charcot-marie-tooth disease, axonal, type 2f 10.2 GARS1 DCAF8
33 encephalopathy 10.2
34 cyanosis, transient neonatal 10.1
35 seizure disorder 10.1
36 progressive muscular atrophy 10.1 SOD1 DPP6
37 sudden infant death syndrome 10.1
38 alacrima, achalasia, and mental retardation syndrome 10.1
39 aspiration pneumonia 10.1
40 inguinal hernia 10.1
41 spasticity 10.1
42 tremor 10.1
43 mutism 10.1
44 akinetic mutism 10.1
45 disease of mental health 10.1 SOD1 SLC6A5 SLC6A2 SLC32A1 GPHN GLRB
46 umbilical hernia 10.0
47 microcephaly 10.0
48 status epilepticus 10.0
49 spastic paraparesis 10.0
50 creutzfeldt-jakob disease 9.9

Graphical network of the top 20 diseases related to Hyperekplexia:



Diseases related to Hyperekplexia

Symptoms & Phenotypes for Hyperekplexia

Human phenotypes related to Hyperekplexia:

58 31 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
2 hyperreflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001347
3 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
4 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
5 gastroesophageal reflux 58 31 hallmark (90%) Very frequent (99-80%) HP:0002020
6 myoclonus 58 31 hallmark (90%) Very frequent (99-80%) HP:0001336
7 muscle stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003552
8 fasciculations 58 31 hallmark (90%) Very frequent (99-80%) HP:0002380
9 hiatus hernia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002036
10 rigidity 58 31 hallmark (90%) Very frequent (99-80%) HP:0002063
11 esophagitis 58 31 hallmark (90%) Very frequent (99-80%) HP:0100633
12 sleep disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0002360
13 gait disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0001288
14 umbilical hernia 58 31 frequent (33%) Frequent (79-30%) HP:0001537
15 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
16 hip dislocation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002827
17 seizure 31 occasional (7.5%) HP:0001250
18 seizures 58 Occasional (29-5%)
19 hypertonia 58 Very frequent (99-80%)
20 hernia 58 Frequent (79-30%)
21 abnormality of movement 58 Very frequent (99-80%)
22 joint dislocation 58 Occasional (29-5%)

UMLS symptoms related to Hyperekplexia:


fever; myoclonus; opisthotonus; increased sweating; muscle rigidity; hyperexplexia

MGI Mouse Phenotypes related to Hyperekplexia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.22 ARHGEF9 ATAD1 GABRG2 GARS1 GLRA1 GLRA2
2 growth/size/body region MP:0005378 10.1 ATAD1 DCAF8 GABRG2 GARS1 GLRA1 GLRA2
3 mortality/aging MP:0010768 10 ATAD1 GABRG2 GARS1 GLRA1 GLRA2 GLRB
4 muscle MP:0005369 9.61 GARS1 GLRA1 GLRB SLC32A1 SLC6A5 SLC6A9
5 nervous system MP:0003631 9.55 ARHGEF9 ATAD1 DPP6 GABRG2 GARS1 GLRA1

Drugs & Therapeutics for Hyperekplexia

Drugs for Hyperekplexia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 50)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Carmustine Approved, Investigational Phase 2 154-93-8 2578
2
Mechlorethamine Approved, Investigational Phase 2 51-75-2 4033
3
Cytarabine Approved, Investigational Phase 2 147-94-4 6253
4
Melphalan Approved Phase 2 148-82-3 4053 460612
5
Etoposide Approved Phase 2 33419-42-0 36462
6
Prednisone Approved, Vet_approved Phase 2 53-03-2 5865
7
Sargramostim Approved, Investigational Phase 1, Phase 2 123774-72-1, 83869-56-1
8
Mesna Approved, Investigational Phase 1, Phase 2 3375-50-6 598
9
Methylprednisolone hemisuccinate Approved Phase 1, Phase 2 2921-57-5
10
Methylprednisolone Approved, Vet_approved Phase 1, Phase 2 83-43-2 6741
11
Prednisolone Approved, Vet_approved Phase 1, Phase 2 50-24-8 5755
12
Prednisolone acetate Approved, Vet_approved Phase 1, Phase 2 52-21-1
13
Prednisolone phosphate Approved, Vet_approved Phase 1, Phase 2 302-25-0
14
rituximab Approved Phase 1, Phase 2 174722-31-7 10201696
15
Cyclophosphamide Approved, Investigational Phase 1, Phase 2 50-18-0, 6055-19-2 2907
16
Lenograstim Approved, Investigational Phase 1, Phase 2 135968-09-1
17
Phenylalanine Approved, Investigational, Nutraceutical Phase 2 63-91-2 6140
18
Cortisone Experimental Phase 2 53-06-5 222786
19
Prednisolone hemisuccinate Experimental Phase 1, Phase 2 2920-86-7
20 Anti-Infective Agents Phase 2
21 Tubulin Modulators Phase 2
22 Etoposide phosphate Phase 2
23 Antimitotic Agents Phase 2
24 Dermatologic Agents Phase 2
25 Antimetabolites Phase 2
26 Antiviral Agents Phase 2
27 Podophyllotoxin Phase 2 518-28-5
28 Nitrogen Mustard Compounds Phase 2
29 Keratolytic Agents Phase 2
30 Antirheumatic Agents Phase 1, Phase 2
31 Antineoplastic Agents, Immunological Phase 1, Phase 2
32 Hormones Phase 1, Phase 2
33 polysaccharide-K Phase 1, Phase 2
34 Gastrointestinal Agents Phase 1, Phase 2
35 Immunosuppressive Agents Phase 1, Phase 2
36 Antiemetics Phase 1, Phase 2
37 Methylprednisolone Acetate Phase 1, Phase 2
38 Neuroprotective Agents Phase 1, Phase 2
39 Hormone Antagonists Phase 1, Phase 2
40 Protective Agents Phase 1, Phase 2
41 glucocorticoids Phase 1, Phase 2
42 Alkylating Agents Phase 1, Phase 2
43 Antineoplastic Agents, Hormonal Phase 1, Phase 2
44 Antilymphocyte Serum Phase 1, Phase 2
45 Anti-Inflammatory Agents Phase 1, Phase 2
46 Antibodies, Monoclonal Phase 1, Phase 2
47 Thymoglobulin Phase 1, Phase 2
48
L-Alanine Nutraceutical Phase 2 56-41-7 5950
49
Glutamic acid Approved, Nutraceutical 56-86-0 33032
50 Autoantibodies

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 IVIg in Glycine Receptor Antibody Positive Stiff-person Syndrome (SPS) Spectrum Disorders. Withdrawn NCT03749096 Phase 3 Intravenous Immunoglobulins, Human;Placebos
2 Efficacy of Rituximab in Patients With Stiff Person Syndrome With Anti-GAD Antibodies: A Randomized Placebo-Controlled Trial Completed NCT00091897 Phase 2 Rituximab;rituximab or placebo
3 High-Dose Immunosuppressive Therapy Using Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) + Thymoglobulin Followed by Syngeneic or Autologous Hematopoietic Cell Transplantation for Patients With Autoimmune Neurologic Diseases Recruiting NCT00716066 Phase 2 Carmustine;Cytarabine;Etoposide;Melphalan;Prednisone
4 Non-myeloablative Hematopoietic Stem Cell Transplantation for Stiff Person Syndrome (SPS) and Anti-GAD Antibody Variants: Progressive Encephalomyelitis With Rigidity and Myoclonus (PERM), and Adult Onset Autoimmune Anti-GAD Positive Cerebellar Ataxia Terminated NCT02282514 Phase 1, Phase 2 Cyclophosphamide;Mesna;rATG;Methylprednisolone;G-CSF;Rituxan
5 The Efficacy of High-Dose Intravenous Immunoglobulin Therapy in Patients With Stiff-Man Syndrome: A Double-Blind, Placebo-Controlled Trial Completed NCT00001550 Phase 1 IVIg
6 Natural History and Immunopathogenesis of Stiff Person Syndrome (SPS) Completed NCT00030940
7 Efficacy and Mechanism of Action of SCIg in Patients With Stiff Person Syndrome Not yet recruiting NCT03829826
8 Immunogenetic Characteristics in Autoimmune Encephalitis and Related Disorders: HLA Analysis Not yet recruiting NCT04106596
9 Effects of Mutations of the Glycine Gene Associated With Hyperekplexia on Central Pain Processing Terminated NCT01476514

Search NIH Clinical Center for Hyperekplexia

Genetic Tests for Hyperekplexia

Genetic tests related to Hyperekplexia:

# Genetic test Affiliating Genes
1 Hyperekplexia 29

Anatomical Context for Hyperekplexia

MalaCards organs/tissues related to Hyperekplexia:

40
Brain, Spinal Cord, Eye, Cortex, Globus Pallidus, Hypothalamus

Publications for Hyperekplexia

Articles related to Hyperekplexia:

(show top 50) (show all 425)
# Title Authors PMID Year
1
Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. 61 54 25 6
16751771 2006
2
A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors. 25 54 6 61
8651283 1996
3
Familiar Hyperekplexia, a Potential Cause of Cautious Gait: A New Korean Case and a Systematic Review of Phenotypes. 25 6 61
28122427 2017
4
GLRB is the third major gene of effect in hyperekplexia. 25 6 61
23184146 2013
5
Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia. 6 25 61
20631190 2010
6
Two novel mutations of the glycine receptor gene in a Taiwanese hyperekplexia family. 61 6 25
15365143 2004
7
Clinical and genetic investigation of 17 Japanese patients with hyperekplexia. 20 61 25
25356525 2015
8
Recessive hyperekplexia mutations of the glycine receptor alpha1 subunit affect cell surface integration and stability. 54 6 61
19732286 2009
9
The novel hyperekplexia allele GLRA1(S267N) affects the ethanol site of the glycine receptor. 54 61 6
18043720 2008
10
Hyperekplexia in Kurdish families: a possible GLRA1 founder mutation. 61 54 6
16832093 2006
11
Novel missense mutation (Y279S) in the GLRA1 gene causing hyperekplexia. 6 61 54
16236274 2006
12
Recessive hyperekplexia due to a new mutation (R100H) in the GLRA1 gene. 6 61 54
16078201 2005
13
Hereditary hyperekplexia caused by novel mutations of GLRA1 in Turkish families. 54 6 61
15771552 2004
14
Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality. 54 61 6
14622583 2003
15
Functional characterization of compound heterozygosity for GlyRalpha1 mutations in the startle disease hyperekplexia. 61 54 6
12169101 2002
16
Hyperekplexia associated with compound heterozygote mutations in the beta-subunit of the human inhibitory glycine receptor (GLRB). 54 6 61
11929858 2002
17
A novel recessive hyperekplexia allele GLRA1 (S231R): genotyping by MALDI-TOF mass spectrometry and functional characterisation as a determinant of cellular glycine receptor trafficking. 61 54 6
11973623 2002
18
A mutation (V260M) in the middle of the M2 pore-lining domain of the glycine receptor causes hereditary hyperekplexia. 54 6 61
11781706 2001
19
Mutations in the glycine receptor alpha1 subunit (GLRA1) gene in hereditary hyperekplexia pedigrees: evidence for non-penetrance of mutation Y279C. 6 54 61
11389164 2001
20
Hyperekplexia phenotype due to compound heterozygosity for GLRA1 gene mutations. 54 6 61
10514101 1999
21
Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating. 61 54 6
9920650 1999
22
Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis. 6 61 54
8733061 1996
23
A novel mutation (Gln266-->His) in the alpha 1 subunit of the inhibitory glycine-receptor gene (GLRA1) in hereditary hyperekplexia. 54 6 61
8571969 1996
24
Mutational analysis of familial and sporadic hyperekplexia. 6 61 54
7611730 1995
25
Startle disease mutations reduce the agonist sensitivity of the human inhibitory glycine receptor. 6 61 54
7518444 1994
26
A novel compound mutation in GLRA1 cause hyperekplexia in a Chinese boy- a case report and review of the literature. 61 6
28985719 2017
27
Disturbed neuronal ER-Golgi sorting of unassembled glycine receptors suggests altered subcellular processing is a cause of human hyperekplexia. 6 61
25568133 2015
28
Disturbances of Ligand Potency and Enhanced Degradation of the Human Glycine Receptor at Affected Positions G160 and T162 Originally Identified in Patients Suffering from Hyperekplexia. 61 6
26733802 2015
29
Neonatal hyperekplexia with homozygous p.R392H mutation in GLRA1. 6 61
25036534 2014
30
New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms. 61 6
24108130 2013
31
Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease. 6 61
22700964 2012
32
Novel mutation in GLRB in a large family with hereditary hyperekplexia. 61 6
21391991 2012
33
Hyperekplexia caused by dominant-negative suppression of glyra1 function. 6 61
17536053 2007
34
Major and minor form of hereditary hyperekplexia. 54 61 25
12210885 2002
35
Compound heterozygosity and nonsense mutations in the alpha(1)-subunit of the inhibitory glycine receptor in hyperekplexia. 6 61
11702206 2001
36
Hyperekplexia-like syndromes without mutations in the GLRA1 gene. 54 61 25
9350397 1997
37
Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel. 61 6
9009272 1997
38
Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the alpha 1 subunit of the inhibitory glycine receptor. 61 6
7881416 1994
39
Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. 61 6
8298642 1993
40
Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q. 61 6
1334371 1992
41
Teaching Video NeuroImages: Cautious walking gait in siblings with hereditary hyperekplexia. 25 61
31010918 2019
42
Clinical features and genetic analysis of two siblings with startle disease in an Italian family: a case report. 25 61
30866851 2019
43
Movement disorders in early MS and related diseases: A prospective observational study. 25 61
30859004 2019
44
GLRA1 mutation and long-term follow-up of the first hyperekplexia family. 61 25
30109271 2018
45
Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. 61 25
29053777 2018
46
Utilization of genomic sequencing for population screening of immunodeficiencies in the newborn. 6
28617419 2017
47
Hyperekplexia: Report on phenotype and genotype of 16 Jordanian patients. 20 61
27843043 2017
48
Clinical Reasoning: A 35-year-old woman with hyperstartling, stiffness, and accidental falls: A startling diagnosis. 6
28138086 2017
49
A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report. 25 61
26968164 2016
50
Ethnicity can predict GLRA1 genotypes in hyperekplexia. 25 61
24970905 2015

Variations for Hyperekplexia

ClinVar genetic disease variations for Hyperekplexia:

6 (show top 50) (show all 426)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SLC6A5 NM_004211.5(SLC6A5):c.1131C>A (p.Tyr377Ter) SNV Pathogenic 5761 rs121908493 GRCh37: 11:20639301-20639301
GRCh38: 11:20617755-20617755
2 SLC6A5 NM_004211.5(SLC6A5):c.1294delinsTT (p.Val432fs) Indel Pathogenic 5762 rs281864924 GRCh37: 11:20648287-20648287
GRCh38: 11:20626741-20626741
3 SLC6A5 NM_004211.5(SLC6A5):c.1472A>G (p.Tyr491Cys) SNV Pathogenic 5763 rs121908494 GRCh37: 11:20649602-20649602
GRCh38: 11:20628056-20628056
4 SLC6A5 NM_004211.5(SLC6A5):c.1888C>T (p.Gln630Ter) SNV Pathogenic 5764 rs121908495 GRCh37: 11:20660023-20660023
GRCh38: 11:20638477-20638477
5 SLC6A5 NM_004211.5(SLC6A5):c.916C>G (p.Leu306Val) SNV Pathogenic 5765 rs121908496 GRCh37: 11:20629129-20629129
GRCh38: 11:20607583-20607583
6 SLC6A5 NM_004211.5(SLC6A5):c.1526A>G (p.Asn509Ser) SNV Pathogenic 5766 rs121908497 GRCh37: 11:20652263-20652263
GRCh38: 11:20630717-20630717
7 SLC6A5 NM_004211.5(SLC6A5):c.1274C>T (p.Thr425Met) SNV Pathogenic 5767 rs121908498 GRCh37: 11:20648267-20648267
GRCh38: 11:20626721-20626721
8 GLRA1 NM_000171.4(GLRA1):c.896G>A (p.Arg299Gln) SNV Pathogenic 16061 rs121918408 GRCh37: 5:151230967-151230967
GRCh38: 5:151851406-151851406
9 GLRA1 NM_000171.4(GLRA1):c.815T>A (p.Ile272Asn) SNV Pathogenic 16062 rs121918409 GRCh37: 5:151231048-151231048
GRCh38: 5:151851487-151851487
10 GLRA1 NM_000171.4(GLRA1):c.920A>G (p.Tyr307Cys) SNV Pathogenic 16063 rs121918410 GRCh37: 5:151208621-151208621
GRCh38: 5:151829060-151829060
11 GLRA1 NM_000171.4(GLRA1):c.882G>C (p.Gln294His) SNV Pathogenic 16064 rs121918411 GRCh37: 5:151230981-151230981
GRCh38: 5:151851420-151851420
12 GLRA1 NM_000171.4(GLRA1):c.910A>G (p.Lys304Glu) SNV Pathogenic 16065 rs121918412 GRCh37: 5:151230953-151230953
GRCh38: 5:151851392-151851392
13 GLRA1 NM_000171.4(GLRA1):c.832C>A (p.Pro278Thr) SNV Pathogenic 16066 rs121918413 GRCh37: 5:151231031-151231031
GRCh38: 5:151851470-151851470
14 GLRA1 NM_000171.4(GLRA1):c.690C>A (p.Tyr230Ter) SNV Pathogenic 16069 rs121918415 GRCh37: 5:151234608-151234608
GRCh38: 5:151855047-151855047
15 GLRA1 NM_000171.4(GLRA1):c.862G>A (p.Val288Met) SNV Pathogenic 16070 rs121918416 GRCh37: 5:151231001-151231001
GRCh38: 5:151851440-151851440
16 GLRA1 NM_000171.4(GLRA1):c.777C>G (p.Ser259Arg) SNV Pathogenic 16071 rs121918417 GRCh37: 5:151231086-151231086
GRCh38: 5:151851525-151851525
17 GLRA1 NM_001146040.1(GLRA1):c.(?_-287)_(912+?)del Deletion Pathogenic 16072 GRCh37:
GRCh38:
18 GLRA1 NM_000171.4(GLRA1):c.971C>A (p.Ser324Ter) SNV Pathogenic 16073 rs121918418 GRCh37: 5:151208570-151208570
GRCh38: 5:151829009-151829009
19 GLRA1 NM_000171.4(GLRA1):c.884G>A (p.Ser295Asn) SNV Pathogenic 16074 rs267606848 GRCh37: 5:151230979-151230979
GRCh38: 5:151851418-151851418
20 GLRB NM_000824.5(GLRB):c.596T>G (p.Met199Arg) SNV Pathogenic 31539 rs398122856 GRCh37: 4:158058024-158058024
GRCh38: 4:157136872-157136872
21 SLC6A5 NM_004211.5(SLC6A5):c.1530T>G (p.Ser510Arg) SNV Pathogenic 31540 rs281864926 GRCh37: 11:20652267-20652267
GRCh38: 11:20630721-20630721
22 GLRA1 NM_000171.4(GLRA1):c.737G>A (p.Arg246Gln) SNV Pathogenic 38329 rs281864916 GRCh37: 5:151231126-151231126
GRCh38: 5:151851565-151851565
23 GLRA1 NM_000171.4(GLRA1):c.801G>C (p.Trp267Cys) SNV Pathogenic 38330 rs281864917 GRCh37: 5:151231062-151231062
GRCh38: 5:151851501-151851501
24 GLRA1 NM_000171.4(GLRA1):c.892T>A (p.Ser298Thr) SNV Pathogenic 38333 rs281864920 GRCh37: 5:151230971-151230971
GRCh38: 5:151851410-151851410
25 GLRA1 NM_000171.4(GLRA1):c.920A>C (p.Tyr307Ser) SNV Pathogenic 38334 rs121918410 GRCh37: 5:151208621-151208621
GRCh38: 5:151829060-151829060
26 GLRA1 NM_000171.4(GLRA1):c.921del (p.Ser306_Tyr307insTer) Deletion Pathogenic 38335 rs281864921 GRCh37: 5:151208620-151208620
GRCh38: 5:151829059-151829059
27 SLC6A5 NM_004211.5(SLC6A5):c.1444T>C (p.Trp482Arg) SNV Pathogenic 38370 rs281864925 GRCh37: 11:20649574-20649574
GRCh38: 11:20628028-20628028
28 SLC6A5 NM_004211.5(SLC6A5):c.323del (p.Pro108fs) Deletion Pathogenic 38371 rs281864923 GRCh37: 11:20622990-20622990
GRCh38: 11:20601444-20601444
29 GPHN NM_020806.4(GPHN):c.28A>T (p.Asn10Tyr) SNV Pathogenic 5973 rs121908539 GRCh37: 14:66975273-66975273
GRCh38: 14:66508555-66508555
30 GLRA1 NM_000171.3(GLRA1):c.(?_-287)_697+?del Deletion Pathogenic 41004 GRCh37: 5:151234601-151304397
GRCh38: 5:151855040-151924836
31 GLRB NM_000824.5(GLRB):c.752G>A (p.Gly251Asp) SNV Pathogenic 16058 rs121909749 GRCh37: 4:158064959-158064959
GRCh38: 4:157143807-157143807
32 GLRA1 NM_000171.4(GLRA1):c.477-1G>A SNV Pathogenic 487340 rs762864856 GRCh37: 5:151235945-151235945
GRCh38: 5:151856384-151856384
33 GLRA1 NM_000171.4(GLRA1):c.252+2T>C SNV Pathogenic 522679 rs1554085893 GRCh37: 5:151266280-151266280
GRCh38: 5:151886719-151886719
34 GLRB NM_000824.5(GLRB):c.448dup (p.Ser150fs) Duplication Pathogenic 574411 rs1560962569 GRCh37: 4:158057765-158057766
GRCh38: 4:157136613-157136614
35 GLRB NM_000824.5(GLRB):c.123-2A>G SNV Pathogenic 574419 rs1415892964 GRCh37: 4:158041706-158041706
GRCh38: 4:157120554-157120554
36 SLC6A5 NM_004211.5(SLC6A5):c.571C>T (p.Arg191Ter) SNV Pathogenic 579017 rs376783257 GRCh37: 11:20625862-20625862
GRCh38: 11:20604316-20604316
37 GLRB NM_000824.5(GLRB):c.472del (p.Gln158fs) Deletion Pathogenic 582806 rs1560962636 GRCh37: 4:158057793-158057793
GRCh38: 4:157136641-157136641
38 GLRA1 NC_000005.10:g.(?_151924474)_(151924569_?)del Deletion Pathogenic 583758 GRCh37: 5:151304035-151304130
GRCh38: 5:151924474-151924569
39 GLRB NM_000824.5(GLRB):c.24del (p.Phe9_Leu10insTer) Deletion Pathogenic 653331 rs1380139789 GRCh37: 4:157999199-157999199
GRCh38: 4:157078047-157078047
40 SLC6A5 NM_004211.5(SLC6A5):c.808C>T (p.Gln270Ter) SNV Pathogenic 658045 rs778603956 GRCh37: 11:20628681-20628681
GRCh38: 11:20607135-20607135
41 GLRB NM_000824.5(GLRB):c.122+1G>A SNV Pathogenic 802099 rs1579175843 GRCh37: 4:157999299-157999299
GRCh38: 4:157078147-157078147
42 GLRA1 NM_000171.4(GLRA1):c.283C>T (p.Gln95Ter) SNV Pathogenic 1031444 GRCh37: 5:151239539-151239539
GRCh38: 5:151859978-151859978
43 SLC6A5 NM_004211.5(SLC6A5):c.187C>T (p.Gln63Ter) SNV Pathogenic 1034063 GRCh37: 11:20622858-20622858
GRCh38: 11:20601312-20601312
44 GLRA1 NM_000171.4(GLRA1):c.22C>T (p.Arg8Ter) SNV Pathogenic 956517 GRCh37: 5:151304089-151304089
GRCh38: 5:151924528-151924528
45 GLRA1 NM_000171.4(GLRA1):c.298del (p.Arg100fs) Deletion Pathogenic 16067 rs281864915 GRCh37: 5:151239524-151239524
GRCh38: 5:151859963-151859963
46 GLRA1 NM_000171.4(GLRA1):c.523A>G (p.Met175Val) SNV Pathogenic 16068 rs121918414 GRCh37: 5:151235898-151235898
GRCh38: 5:151856337-151856337
47 GLRA1 NM_000171.4(GLRA1):c.288G>T (p.Trp96Cys) SNV Pathogenic 242681 rs281864912 GRCh37: 5:151239534-151239534
GRCh38: 5:151859973-151859973
48 GLRA1 NM_000171.4(GLRA1):c.298del (p.Arg100fs) Deletion Pathogenic 16067 rs281864915 GRCh37: 5:151239524-151239524
GRCh38: 5:151859963-151859963
49 GLRA1 NM_000171.4(GLRA1):c.839G>A (p.Arg280His) SNV Pathogenic 242679 rs281864918 GRCh37: 5:151231024-151231024
GRCh38: 5:151851463-151851463
50 GLRA1 NM_000171.4(GLRA1):c.1030C>T (p.Arg344Ter) SNV Pathogenic 242682 rs281864913 GRCh37: 5:151208511-151208511
GRCh38: 5:151828950-151828950

Copy number variations for Hyperekplexia from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 194977 5 147200000 152100000 Deletion GLRA1 Hyperekplexia

Expression for Hyperekplexia

Search GEO for disease gene expression data for Hyperekplexia.

Pathways for Hyperekplexia

Pathways related to Hyperekplexia according to KEGG:

36
# Name Kegg Source Accession
1 Neuroactive ligand-receptor interaction hsa04080
2 Synaptic vesicle cycle hsa04721

Pathways related to Hyperekplexia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.86 SLC7A10 SLC6A9 SLC6A5 SLC6A2 SLC32A1 GLRB
2
Show member pathways
12.2 GLRB GLRA4 GLRA3 GLRA2 GLRA1 GABRG2
3 11.71 SLC6A9 SLC6A5 SLC6A2
4
Show member pathways
11.67 SLC6A9 SLC6A5 SLC6A2 SLC32A1
5
Show member pathways
10.79 GLRB GLRA4 GLRA3 GLRA2 GLRA1 GABRG2
6
Show member pathways
10.58 SLC32A1 GABRG2

GO Terms for Hyperekplexia

Cellular components related to Hyperekplexia according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 10.34 SOD1 SLC7A10 SLC6A9 SLC6A5 SLC6A2 SLC32A1
2 integral component of plasma membrane GO:0005887 10.11 SLC7A10 SLC6A9 SLC6A5 SLC6A2 GLRB GLRA3
3 cell projection GO:0042995 10.07 GPHN GLRB GLRA3 GLRA2 GLRA1 GARS1
4 cell junction GO:0030054 10.01 GPHN GLRB GLRA3 GLRA2 GLRA1 GABRG2
5 synapse GO:0045202 9.97 SLC32A1 GPHN GLRB GLRA3 GLRA2 GLRA1
6 dendrite GO:0030425 9.91 TRAK1 SLC32A1 GPHN GLRB GLRA3 GLRA1
7 neuron projection GO:0043005 9.86 SOD1 SLC6A2 SLC32A1 GLRB GLRA3 GLRA2
8 GABA-ergic synapse GO:0098982 9.71 SLC32A1 GLRB GABRG2
9 integral component of presynaptic membrane GO:0099056 9.69 SLC6A9 SLC6A5 GLRA1
10 dense core granule GO:0031045 9.61 SOD1 SLC6A9 SLC6A5
11 inhibitory synapse GO:0060077 9.55 SLC32A1 GLRA1
12 chloride channel complex GO:0034707 9.55 GLRB GLRA3 GLRA2 GLRA1 GABRG2
13 postsynaptic membrane GO:0045211 9.5 GPHN GLRB GLRA3 GLRA2 GLRA1 GABRG2
14 glycine-gated chloride channel complex GO:0016935 9.48 GLRB GLRA3
15 glycinergic synapse GO:0098690 8.92 SLC6A5 GLRB GLRA2 GLRA1

Biological processes related to Hyperekplexia according to GeneCards Suite gene sharing:

(show all 27)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 10.03 SLC32A1 GLRB GLRA3 GLRA2 GLRA1 GABRG2
2 ion transmembrane transport GO:0034220 9.92 GLRB GLRA3 GLRA2 GLRA1 GABRG2
3 neuropeptide signaling pathway GO:0007218 9.81 GLRB GLRA3 GLRA2 GLRA1
4 regulation of membrane potential GO:0042391 9.8 GLRB GLRA3 GLRA2 GLRA1 GABRG2
5 sodium ion transmembrane transport GO:0035725 9.78 SLC6A9 SLC6A5 SLC6A2
6 excitatory postsynaptic potential GO:0060079 9.78 GLRB GLRA3 GLRA2 GLRA1
7 regulation of postsynaptic membrane potential GO:0060078 9.74 GLRB GLRA2 GABRG2
8 neurotransmitter transport GO:0006836 9.73 SLC6A9 SLC6A5 SLC6A2 SLC32A1
9 chloride transmembrane transport GO:1902476 9.72 GLRB GLRA3 GLRA2 GLRA1 GABRG2
10 amino acid transmembrane transport GO:0003333 9.71 SLC7A10 SLC6A9 SLC32A1
11 chemical synaptic transmission GO:0007268 9.7 SLC6A5 SLC6A2 GLRB GLRA3 GLRA2 GLRA1
12 response to amino acid GO:0043200 9.67 GLRB GLRA3 GLRA2 GLRA1
13 chloride transport GO:0006821 9.65 GLRB GLRA3 GLRA2 GLRA1 GABRG2
14 adult walking behavior GO:0007628 9.63 GLRB GLRA1
15 neuromuscular process GO:0050905 9.63 GLRB GLRA1
16 glycine transport GO:0015816 9.63 SLC6A9 SLC6A5 SLC32A1
17 cellular response to zinc ion GO:0071294 9.62 GLRA2 GLRA1
18 acrosome reaction GO:0007340 9.62 GLRB GLRA1
19 cellular response to ethanol GO:0071361 9.61 GLRA2 GLRA1
20 startle response GO:0001964 9.6 GLRB GLRA1
21 righting reflex GO:0060013 9.59 GLRB GLRA1
22 molybdopterin cofactor biosynthetic process GO:0032324 9.58 MOCS1 GPHN
23 Mo-molybdopterin cofactor biosynthetic process GO:0006777 9.58 MOCS1 GPHN
24 gamma-aminobutyric acid receptor clustering GO:0097112 9.55 GPHN GLRB
25 glycine import across plasma membrane GO:1903804 9.49 SLC6A9 SLC6A5
26 nervous system process GO:0050877 9.35 GLRB GLRA3 GLRA2 GLRA1 GABRG2
27 synaptic transmission, glycinergic GO:0060012 9.02 SLC6A5 GLRB GLRA3 GLRA2 GLRA1

Molecular functions related to Hyperekplexia according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 transmembrane signaling receptor activity GO:0004888 9.92 GLRB GLRA3 GLRA2 GLRA1 GABRG2
2 ion channel activity GO:0005216 9.85 GLRB GLRA3 GLRA2 GLRA1 GABRG2
3 neurotransmitter receptor activity GO:0030594 9.77 GLRB GLRA3 GLRA2 GLRA1 GABRG2
4 chloride channel activity GO:0005254 9.72 GLRB GLRA3 GLRA2 GLRA1 GABRG2
5 symporter activity GO:0015293 9.71 SLC6A9 SLC6A5 SLC6A2
6 transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential GO:1904315 9.71 GLRB GLRA2 GLRA1 GABRG2
7 glycine transmembrane transporter activity GO:0015187 9.61 SLC6A9 SLC6A5 SLC32A1
8 glycine-gated chloride ion channel activity GO:0022852 9.51 GLRA3 GLRA2
9 extracellularly glycine-gated ion channel activity GO:0016933 9.49 GLRB GLRA1
10 glycine:sodium symporter activity GO:0015375 9.48 SLC6A9 SLC6A5
11 glycine binding GO:0016594 9.46 GLRB GLRA3 GLRA2 GLRA1
12 transmitter-gated ion channel activity GO:0022824 9.43 GLRA3 GLRA2 GLRA1
13 extracellular ligand-gated ion channel activity GO:0005230 9.35 GLRB GLRA3 GLRA2 GLRA1 GABRG2
14 extracellularly glycine-gated chloride channel activity GO:0016934 8.92 GLRB GLRA3 GLRA2 GLRA1

Sources for Hyperekplexia

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
Content
Loading form....