GLRA1
glycine receptor alpha 1, the group of Glycine receptors
Basic information
Region (hg38): 5:151822513-151924851
Previous symbols: [ "STHE" ]
Links
Phenotypes
GenCC
Source:
- hereditary hyperekplexia (Supportive), mode of inheritance: AD
- hyperekplexia 1 (Definitive), mode of inheritance: AD
- hyperekplexia 1 (Definitive), mode of inheritance: AR
- hyperekplexia 1 (Strong), mode of inheritance: AR
- hyperekplexia 1 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hyperekplexia 1 | AD/AR | Neurologic | Neonates are at risk of sudden death from apnea/aspiration, and surveillance, as well as primary prevention with medical treatments (eg, clonazepam) may be beneficial | Neurologic | 1334371; 8298642; 7881416; 11104232; 8571969; 16832093; 20301437 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary hyperekplexia (24 variants)
- Hyperekplexia 1 (10 variants)
- not provided (4 variants)
- Sleep myoclonus (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLRA1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 91 | 95 | ||||
| missense | 16 | 169 | 11 | 206 | ||
| nonsense | 9 | |||||
| start loss | 3 | |||||
| frameshift | 11 | 15 | ||||
| inframe indel | 5 | |||||
| splice donor/acceptor (+/-2bp) | 12 | |||||
| splice region | 12 | 15 | 2 | 29 | ||
| non coding | 44 | 19 | 68 | |||
| Total | 29 | 29 | 184 | 146 | 25 |
Highest pathogenic variant AF is 0.0000263
Variants in GLRA1
This is a list of pathogenic ClinVar variants found in the GLRA1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-151822682-G-A | Hyperekplexia 1 • Hereditary hyperekplexia | Benign/Likely benign (Jul 05, 2022) | ||
| 5-151822682-G-T | Hereditary hyperekplexia | Uncertain significance (Nov 29, 2022) | ||
| 5-151822683-T-C | Inborn genetic diseases | Uncertain significance (Dec 14, 2023) | ||
| 5-151822684-G-T | Hereditary hyperekplexia • Seizure | Conflicting classifications of pathogenicity (May 22, 2024) | ||
| 5-151822686-A-G | Hereditary hyperekplexia | Uncertain significance (Jan 16, 2024) | ||
| 5-151822687-C-T | Hereditary hyperekplexia | Uncertain significance (Jul 27, 2022) | ||
| 5-151822688-G-A | Hereditary hyperekplexia | Likely benign (Aug 29, 2023) | ||
| 5-151822690-C-A | Hyperekplexia 1 | Uncertain significance (Jan 12, 2018) | ||
| 5-151822692-T-C | Hereditary hyperekplexia | Uncertain significance (Mar 20, 2023) | ||
| 5-151822697-A-G | Hereditary hyperekplexia | Likely benign (Jul 12, 2022) | ||
| 5-151822698-C-T | Hyperekplexia 1 • Hereditary hyperekplexia | Uncertain significance (Dec 18, 2023) | ||
| 5-151822699-G-A | Hereditary hyperekplexia | Uncertain significance (Nov 15, 2022) | ||
| 5-151822702-C-T | Hereditary hyperekplexia | Uncertain significance (Mar 24, 2023) | ||
| 5-151822704-A-G | Hereditary hyperekplexia | Uncertain significance (Dec 30, 2020) | ||
| 5-151822707-T-C | Hereditary hyperekplexia | Uncertain significance (Jan 07, 2024) | ||
| 5-151822708-T-G | Hereditary hyperekplexia | Uncertain significance (Oct 22, 2023) | ||
| 5-151822710-T-C | Hereditary hyperekplexia | Uncertain significance (Sep 01, 2022) | ||
| 5-151822727-C-A | Hyperekplexia 1 • Hereditary hyperekplexia • Inborn genetic diseases | Conflicting classifications of pathogenicity (Jan 22, 2024) | ||
| 5-151822728-A-G | Hereditary hyperekplexia • Hyperekplexia 1 • Inborn genetic diseases • not specified | Uncertain significance (Jun 11, 2024) | ||
| 5-151822730-G-A | Hereditary hyperekplexia | Likely benign (Jul 29, 2020) | ||
| 5-151822731-T-C | Hereditary hyperekplexia | Uncertain significance (Sep 02, 2021) | ||
| 5-151822737-A-G | Hereditary hyperekplexia | Uncertain significance (Oct 03, 2022) | ||
| 5-151822739-G-A | Hereditary hyperekplexia | Likely benign (Feb 11, 2022) | ||
| 5-151822749-A-G | Hereditary hyperekplexia | Uncertain significance (Nov 14, 2022) | ||
| 5-151822750-T-C | Hereditary hyperekplexia | Uncertain significance (Dec 28, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GLRA1 | protein_coding | protein_coding | ENST00000455880 | 9 | 102330 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000158 | 0.994 | 125702 | 0 | 46 | 125748 | 0.000183 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.42 | 195 | 259 | 0.752 | 0.0000151 | 3042 |
| Missense in Polyphen | 58 | 108.26 | 0.53574 | 1234 | ||
| Synonymous | 0.0198 | 97 | 97.2 | 0.997 | 0.00000541 | 869 |
| Loss of Function | 2.41 | 10 | 22.3 | 0.449 | 0.00000127 | 241 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000324 | 0.000322 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000924 | 0.000925 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.0000792 | 0.0000791 |
| Middle Eastern | 0.000924 | 0.000925 |
| South Asian | 0.000131 | 0.000131 |
| Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Glycine receptors are ligand-gated chloride channels (PubMed:23994010, PubMed:25730860). Channel opening is triggered by extracellular glycine (PubMed:2155780, PubMed:7920629, PubMed:14551753, PubMed:16144831, PubMed:22715885, PubMed:22973015, PubMed:25973519, PubMed:9009272). Channel opening is also triggered by taurine and beta-alanine (PubMed:16144831, PubMed:9009272). Channel characteristics depend on the subunit composition; heteropentameric channels are activated by lower glycine levels and display faster desensitization (PubMed:14551753). Plays an important role in the down-regulation of neuronal excitability (PubMed:8298642, PubMed:9009272). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Channel activity is potentiated by ethanol (PubMed:25973519). Potentiation of channel activity by intoxicating levels of ethanol contribute to the sedative effects of ethanol (By similarity). {ECO:0000250|UniProtKB:Q64018, ECO:0000269|PubMed:14551753, ECO:0000269|PubMed:16144831, ECO:0000269|PubMed:2155780, ECO:0000269|PubMed:22715885, ECO:0000269|PubMed:22973015, ECO:0000269|PubMed:23994010, ECO:0000269|PubMed:25445488, ECO:0000269|PubMed:25730860, ECO:0000269|PubMed:25973519, ECO:0000269|PubMed:7920629, ECO:0000269|PubMed:7925268, ECO:0000269|PubMed:9009272, ECO:0000305|PubMed:8298642}.;
- Disease
- DISEASE: Hyperekplexia 1 (HKPX1) [MIM:149400]: A neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli. {ECO:0000269|PubMed:10514101, ECO:0000269|PubMed:24108130, ECO:0000269|PubMed:25730860, ECO:0000269|PubMed:7611730, ECO:0000269|PubMed:7881416, ECO:0000269|PubMed:7925268, ECO:0000269|PubMed:7981700, ECO:0000269|PubMed:8298642, ECO:0000269|PubMed:8571969, ECO:0000269|PubMed:8733061, ECO:0000269|PubMed:9009272, ECO:0000269|PubMed:9067762, ECO:0000269|PubMed:9920650, ECO:0000269|Ref.18}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Neuroactive ligand-receptor interaction - Homo sapiens (human);Neuronal System;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses
(Consensus)
Recessive Scores
- pRec
- 0.201
Intolerance Scores
- loftool
- 0.0783
- rvis_EVS
- -0.51
- rvis_percentile_EVS
- 21.56
Haploinsufficiency Scores
- pHI
- 0.311
- hipred
- Y
- hipred_score
- 0.528
- ghis
- 0.439
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.645
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Glra1
- Phenotype
- immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- glra1
- Affected structure
- tonic skeletal muscle contraction
- Phenotype tag
- abnormal
- Phenotype quality
- process quality
Gene ontology
- Biological process
- action potential;startle response;regulation of respiratory gaseous exchange by neurological system process;ion transport;chloride transport;muscle contraction;signal transduction;neuropeptide signaling pathway;chemical synaptic transmission;acrosome reaction;visual perception;adult walking behavior;ion transmembrane transport;regulation of membrane potential;response to amino acid;nervous system process;neuromuscular process controlling posture;protein homooligomerization;protein heterooligomerization;negative regulation of transmission of nerve impulse;synaptic transmission, glycinergic;righting reflex;excitatory postsynaptic potential;inhibitory postsynaptic potential;cellular response to amino acid stimulus;cellular response to zinc ion;cellular response to ethanol;response to alcohol;chloride transmembrane transport;positive regulation of acrosome reaction
- Cellular component
- endoplasmic reticulum;plasma membrane;integral component of plasma membrane;external side of plasma membrane;integral component of membrane;cell junction;dendrite;chloride channel complex;neuron projection;neuronal cell body;perikaryon;intracellular membrane-bounded organelle;calyx of Held;synapse;postsynaptic membrane;inhibitory synapse;glycinergic synapse;integral component of presynaptic membrane;integral component of postsynaptic specialization membrane
- Molecular function
- transmembrane signaling receptor activity;extracellular ligand-gated ion channel activity;chloride channel activity;protein binding;zinc ion binding;glycine binding;extracellularly glycine-gated chloride channel activity;taurine binding;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential