GLRA1

glycine receptor alpha 1, the group of Glycine receptors

Basic information

Region (hg38): 5:151822513-151924851

Previous symbols: [ "STHE" ]

Links

ENSG00000145888

∙ NCBI:2741 ∙ OMIM:138491 ∙ HGNC:4326 ∙ Uniprot:P23415 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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: CGD

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 ClinVar and linked to the GLRA1 gene.

Hereditary_hyperekplexia (429 variants)
Hyperekplexia_1 (87 variants)
not_provided (78 variants)
Inborn_genetic_diseases (42 variants)
GLRA1-related_disorder (15 variants)
not_specified (14 variants)
Seizure (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. These statistics are base on transcript: NM_000000171.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	100 clinvar	4 clinvar	105
missense	18 clinvar	27 clinvar	203 clinvar	15 clinvar	2 clinvar	265
nonsense	9 clinvar	3 clinvar	1 clinvar			13
start loss			4			4
frameshift	11 clinvar	5 clinvar				16
splice donor/acceptor (+/-2bp)	3 clinvar	8 clinvar				11
Total	41	43	209	115	6

Highest pathogenic variant AF is 0.0003335524

Loading clinvar variants...

GnomAD

Source: gnomAD

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: dbNSFP

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