GLRA1 glycine receptor, alpha 1 [Homo sapiens] - Gene

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Summary

Official Symbol: GLRA1provided by HGNC
Official Full Name: glycine receptor, alpha 1provided by HGNC
Primary source: HGNC:4326
See related: Ensembl:ENSG00000145888; HPRD:00719; MIM:138491; Vega:OTTHUMG00000130121
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: STHE; MGC138878; MGC138879
Summary: The protein encoded by this gene is a subunit of a pentameric inhibitory glycine receptor. The receptor mediates postsynaptic inhibition in the central nervous system. Defects in this gene are a cause of startle disease (STHE), also known as hereditary hyperekplexia or congenital stiff-person syndrome. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]

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Genomic context

Location :: 5q32

Sequence :: Chromosome: 5; NC_000005.9 (151202074..151304397, complement)

See GLRA1 in Epigenomics, MapViewer

Chromosome 5 - NC_000005.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Mutations in the GlyR alpha-1 subunit, M287L and Q266I, resulted in a small but general impairment of glycine action, that is most evident in the glycine-induced maximal currents.
Title: Characterization of two mutations, M287L and Q266I, in the α1 glycine receptor subunit that modify sensitivity to alcohols.
Hereditary hyperekplexia-causing mutations that modify alpha1 beta GlyR channel function are almost exclusively located in the alpha1 to the exclusion of the beta subunit.
Title: β Subunit M2-M3 loop conformational changes are uncoupled from α1 β glycine receptor channel gating: implications for human hereditary hyperekplexia.
By slowing and impairing channel gating in GLRA1, the K276E mutation facilitates the detection of closed reaction intermediates in the activation pathway of glycine channels.
Title: The α1K276E startle disease mutation reveals multiple intermediate states in the gating of glycine receptors.
Activation and desensitization induce distinct conformational changes at the extracellular-transmembrane domain interface of the glycine receptor
Title: Activation and desensitization induce distinct conformational changes at the extracellular-transmembrane domain interface of the glycine receptor.
ethanol appears to stabilize the GlyR model built on a presumably open form of the ligand-gated channel.
Title: Microsecond simulations indicate that ethanol binds between subunits and could stabilize an open-state model of a glycine receptor.
Selective alterations in GlyRalpha1 subunit function contribute to inhibitory insufficiency in motoneurons early in the disease process of amyotrophic lateral sclerosis.
Title: Glycine receptor channels in spinal motoneurons are abnormal in a transgenic mouse model of amyotrophic lateral sclerosis.
Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin
Title: Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway.
the coordination environment of Cu(2)(+) in the human alpha1-glycine receptor
Title: Pulsed electron spin resonance resolves the coordination site of Cu²(+) ions in α1-glycine receptor.
sequencing of GLRA1 in 88 new unrelated hyperekplexia patients revealed 19 sequence variants in 30 index cases, of which 21 were inherited in recessive or compound heterozygote modes; investigated functional effects of 11 novel and 2 recurrent mutations
Title: Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia.
Presence of an impermeant Ca(2+) ion in the Glra1 channel pore region just external to the selectivity filter tends to electrostatically retard outward movement of Na(+) ions and to enhance movement of Cl(-) ions down their energy gradients.
Title: External divalent cations increase anion-cation permeability ratio in glycine receptor channels.

Submit: New GeneRIF Correction See all (67)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Hyperekplexia and spastic paraparesis

MIM: 138491

Hereditary hyperekplexia (HPX) is characterized by generalized stiffness immediately after birth that normalizes during the first years of life; excessive startle reflex (eye blinking and a flexor spasm of the trunk) to unexpected (particularly auditory) stimuli; and a short period of generalized stiffness following the startle response during which voluntary movements are impossible. Exaggerated head-retraction reflex (HRR) consisting of extension of the head followed by violent flexor spasms of limbs and neck muscles elicited by tapping the tip of the nose is observed in most children. Other findings include periodic limb movements in sleep (PLMS) and hypnagogic (occurring when falling asleep) myoclonus. Sudden infant death (SIDS) has been reported. Intellect is usually normal; mild intellectual disability may occur.

Diagnosis Testing

The diagnosis of HPX is based on clinical findings. Five genes are known to be associated with HPX. GLRA1, encoding glycine receptor subunit 1, accounts for about 80% of HPX. The other genes in which mutation is causative are: SLC6A5, encoding the presynaptic sodium- and chloride-dependent glycine transporter 2 (GlyT2); GLRB, encoding glycine receptor subunit beta; GPHN, encoding the glycinergic clustering molecule, gephyrin; and ARHGEF9, encoding collybistin.

Genetic Counseling

HPX is inherited in an autosomal dominant or autosomal recessive manner. Most individuals diagnosed with autosomal dominant HPX have an affected parent; de novo mutations are rare. Each child of an individual with autosomal dominant HPX has a 50% chance of inheriting the mutation. The parents of a child with autosomal recessive HPX are obligate heterozygotes and therefore carry one mutant allele. At conception, each sib of an individual with autosomal recessive HPX has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. No laboratories offering molecular genetic testing for prenatal diagnosis for HPX are listed in the GeneTests Laboratory Directory; however, prenatal testing may be available for families in which the disease-causing mutation(s) has/have been identified through laboratories offering custom prenatal testing.

References

PMID: 20301437

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General gene information

Markers

D5S2588 (e-PCR)
- UniSTS:19212

RH71281 (e-PCR)
- UniSTS:18463

NoName (e-PCR)
- UniSTS:482145

bac5555T (e-PCR)
- UniSTS:181642

NoName (e-PCR)
- UniSTS:486606

NoName (e-PCR)
- UniSTS:481233

Genotypes

See GLRA1 SNP Geneview Report
See GLRA1 SNP Genotype Report
See GLRA1 SNP Variation Viewer Report

Homology

Homologs of the GLRA1 gene: The GLRA1 gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and C.elegans.
Map Viewer (Mouse, Rat)

Pathways from BioSystems

Ion channel transport, organism-specific biosystem (from REACTOME)
Ion channel transport, organism-specific biosystemIon channels mediate the flow of ions across the plasma membrane of cells. They are integral membrane proteins, typically a multimer of proteins, which, when arranged in the membrane, create a pore f...
Ligand-gated ion channel transport, organism-specific biosystem (from REACTOME)
Ligand-gated ion channel transport, organism-specific biosystemLigand-gated ion channels (LGICs) are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger (Purves, 2001).
Neuroactive ligand-receptor interaction, organism-specific biosystem (from KEGG)
Neuroactive ligand-receptor interaction, organism-specific biosystem
Neuroactive ligand-receptor interaction
Neuroactive ligand-receptor interaction, conserved biosystem (from KEGG)
Neuroactive ligand-receptor interaction, conserved biosystem
Neuroactive ligand-receptor interaction
Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
Transmembrane transport of small molecules, organism-specific biosystem
Transmembrane transport of small molecules

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
extracellular ligand-gated ion channel activity	IEA Inferred from Electronic Annotation more info
extracellular-glycine-gated chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to extracellular-glycine-gated chloride channel activity	IGI Inferred from Genetic Interaction more info	PubMed
extracellular-glycine-gated chloride channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
glycine binding	IDA Inferred from Direct Assay more info	PubMed
glycine binding	IEA Inferred from Electronic Annotation more info
ion channel activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
receptor activity	IEA Inferred from Electronic Annotation more info
taurine binding	IDA Inferred from Direct Assay more info	PubMed
transmitter-gated ion channel activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
adult walking behavior	IEA Inferred from Electronic Annotation more info
chloride transport	IDA Inferred from Direct Assay more info	PubMed
ion transmembrane transport	TAS Traceable Author Statement more info
ion transport	IDA Inferred from Direct Assay more info	PubMed
ion transport	IEA Inferred from Electronic Annotation more info
muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transmission of nerve impulse	IMP Inferred from Mutant Phenotype more info	PubMed
neuromuscular process controlling posture	IEA Inferred from Electronic Annotation more info
neuropeptide signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of acrosome reaction	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of action potential	IEA Inferred from Electronic Annotation more info
regulation of inhibitory postsynaptic membrane potential	IEA Inferred from Electronic Annotation more info
regulation of membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of respiratory gaseous exchange	IEA Inferred from Electronic Annotation more info
regulation of respiratory gaseous exchange by neurological system process	IEA Inferred from Electronic Annotation more info
righting reflex	IEA Inferred from Electronic Annotation more info
startle response	IMP Inferred from Mutant Phenotype more info	PubMed
synaptic transmission	IEA Inferred from Electronic Annotation more info
synaptic transmission, glycinergic	IEA Inferred from Electronic Annotation more info
transmembrane transport	TAS Traceable Author Statement more info
visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cell junction	IEA Inferred from Electronic Annotation more info
chloride channel complex	IEA Inferred from Electronic Annotation more info
external side of plasma membrane	IEA Inferred from Electronic Annotation more info
integral to membrane	NAS Non-traceable Author Statement more info	PubMed
integral to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
integral to plasma membrane	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
integral to plasma membrane	NAS Non-traceable Author Statement more info	PubMed
intracellular	IEA Inferred from Electronic Annotation more info
intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info	PubMed
membrane fraction	IEA Inferred from Electronic Annotation more info
plasma membrane	IEA Inferred from Electronic Annotation more info
plasma membrane	TAS Traceable Author Statement more info
postsynaptic membrane	IEA Inferred from Electronic Annotation more info
synapse	IEA Inferred from Electronic Annotation more info

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General protein information

Preferred Names: glycine receptor subunit alpha-1

Names: glycine receptor subunit alpha-1; glycine receptor 48 kDa subunit; glycine receptor strychnine-binding subunit

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011764.1 RefSeqGene

Range

5001..107324

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000171.3 → NP_000162.2 glycine receptor subunit alpha-1 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site at the 5' end of the last exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AK226046, AK312702, BC074980, X52009

Consensus CDS

CCDS4320.1

UniProtKB/Swiss-Prot

P23415

Related

ENSP00000274576, OTTHUMP00000160616, ENST00000274576, OTTHUMT00000252429

Conserved Domains (3) summary

TIGR00860
Location:7 – 438
Blast Score: 1348

LIC; Cation transporter family protein

pfam02931
Location:42 – 248
Blast Score: 523

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:255 – 334
Blast Score: 348

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
NM_001146040.1 → NP_001139512.1 glycine receptor subunit alpha-1 isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AK226046, BC114947, X52009

Consensus CDS

CCDS54942.1

UniProtKB/Swiss-Prot

P23415

Related

ENSP00000411593, OTTHUMP00000224176, ENST00000455880, OTTHUMT00000373959

Conserved Domains (3) summary

TIGR00860
Location:7 – 446
Blast Score: 1351

LIC; Cation transporter family protein

pfam02931
Location:42 – 248
Blast Score: 523

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:255 – 334
Blast Score: 348

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000005.9 Reference GRCh37.p5 Primary Assembly

Range

151202074..151304397, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000137.1 Alternate HuRef

Range

146347483..146449349, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC010312.5 (32910..53676)	None
genomic	AC091982.3	None
genomic	CH471062.2	EAW61656.1
		EAW61657.1
genomic	U77732.1	AAB38405.1
mRNA	AK226046.1	None
mRNA	AK308539.1	None
mRNA	AK312702.1	BAG35580.1
mRNA	BC074980.2	AAH74980.1
mRNA	BC114947.1	AAI14948.1
mRNA	BC114967.1	AAI14968.1
mRNA	DA749850.1	None
mRNA	X52009.1	CAA36258.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P23415.2	GenPept	UniProtKB/Swiss-Prot:P23415
Q14C71	GenPept	UniProtKB/TrEMBL:Q14C71
Q6LC95	GenPept	UniProtKB/TrEMBL:Q6LC95