GLRA1 glycine receptor alpha 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GLRA1provided by HGNC
Official Full Name: glycine receptor alpha 1provided by HGNC
Primary source: HGNC:HGNC:4326
See related: Ensembl:ENSG00000145888 MIM:138491; AllianceGenome:HGNC:4326
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; HKPX1
Summary: The protein encoded by this gene is a subunit of a pentameric inhibitory glycine receptor, which 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. Multiple transcript variants encoding different isoforms have been found. [provided by RefSeq, Dec 2015]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 5q33.1

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (151822513..151924851, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (152361497..152463867, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (151202074..151304412, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Four Turkish families with hyperekplexia: A missense mutation and the exon 1-7 deletion in the GLRA1 gene.
Title: Four Turkish families with hyperekplexia: A missense mutation and the exon 1-7 deletion in the GLRA1 gene.
The startle disease mutation alpha1S270T predicts shortening of glycinergic synaptic currents.
Title: The startle disease mutation α1S270T predicts shortening of glycinergic synaptic currents.
A Novel Glycine Receptor Variant with Startle Disease Affects Syndapin I and Glycinergic Inhibition.
Title: A Novel Glycine Receptor Variant with Startle Disease Affects Syndapin I and Glycinergic Inhibition.
The synthetic cannabinoid dehydroxylcannabidiol restores the function of a major GABAA receptor isoform in a cell model of hyperekplexia.
Title: The synthetic cannabinoid dehydroxylcannabidiol restores the function of a major GABA(A) receptor isoform in a cell model of hyperekplexia.
data implicated that ubiquitin modification of GlyRs-alpha1 represented an important way for peripheral inflammation to reduce spinal glycinergic inhibition and that interference with HUWE1 activity generated analgesic action by resuming GlyRs-alpha1-mediated synaptic transmission.
Title: Ubiquitination and inhibition of glycine receptor by HUWE1 in spinal cord dorsal horn.
Study found significant associations between the minor alleles of three SNPs (rs2915885, rs11167557, and rs1428159) within the glycine receptor alpha 1 subunit (GLRA1) and dimensional schizotypy, specifically with the disorganized symptoms dimension. However, there were no significant associations between any of the SNPs and the categorical diagnosis of schizotypal personality disorder.
Title: Dimensional Traits of Schizotypy Associated With Glycine Receptor GLRA1 Polymorphism: An Exploratory Candidate-Gene Association Study.
Data show that the same mutation in GLRA1 could have different phenotypic expressions, suggesting an underling mechanism of variable expressivity, even in the same pedigree.
Title: Clinical features and genetic analysis of two siblings with startle disease in an Italian family: a case report.
Using quantitative photoactivated localisation microscopy the authors found that alpha-1 and alpha-3 containing glycine receptors display the same alpha3:beta2 stoichiometry and gephyrin binding.
Title: Alpha subunit-dependent glycine receptor clustering and regulation of synaptic receptor numbers.
The data of this study demonstrated increased pain sensitivity and impaired central pain modulation in hyperekplexia patients with GLRA1 mutation.
Title: Mutations affecting glycinergic neurotransmission in hyperekplexia increase pain sensitivity.
results suggest that many extracellular domains are important for GlyR function
Title: Multiple regions in the extracellular domain of the glycine receptor determine receptor activity.

Submit: New GeneRIF Correction See all GeneRIFs (98)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hyperekplexia 1 MedGen: C4551954 OMIM: 149400 GeneReviews: Hereditary Hyperekplexia Overview	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to chloride channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables excitatory extracellular ligand-gated monoatomic ion channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables extracellularly glycine-gated chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables extracellularly glycine-gated chloride channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables glycine binding	IDA Inferred from Direct Assay more info	PubMed
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IDA Inferred from Direct Assay more info	PubMed
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	NAS Non-traceable Author Statement more info	PubMed
enables neurotransmitter receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables taurine binding	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane signaling receptor activity	IEA Inferred from Electronic Annotation more info
enables transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in acrosome reaction	IEA Inferred from Electronic Annotation more info
involved_in adult walking behavior	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amino acid stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to ethanol	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to zinc ion	IDA Inferred from Direct Assay more info	PubMed
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in chloride transport	IDA Inferred from Direct Assay more info	PubMed
involved_in excitatory postsynaptic potential	IEA Inferred from Electronic Annotation more info
involved_in inhibitory postsynaptic potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in monoatomic ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transmission of nerve impulse	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuromuscular process controlling posture	IEA Inferred from Electronic Annotation more info
involved_in neuronal action potential	IEA Inferred from Electronic Annotation more info
involved_in neuropeptide signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of acrosome reaction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of membrane potential	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info
involved_in regulation of respiratory gaseous exchange by nervous system process	IEA Inferred from Electronic Annotation more info
involved_in response to alcohol	ISS Inferred from Sequence or Structural Similarity more info
involved_in righting reflex	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within startle response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in startle response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic transmission, glycinergic	ISS Inferred from Sequence or Structural Similarity more info
involved_in visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of chloride channel complex	IEA Inferred from Electronic Annotation more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in glycinergic synapse	IEA Inferred from Electronic Annotation more info
located_in inhibitory synapse	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
located_in neuron projection	ISS Inferred from Sequence or Structural Similarity more info
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in perikaryon	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info
is_active_in synapse	IBA Inferred from Biological aspect of Ancestor more info
located_in synapse	ISS Inferred from Sequence or Structural Similarity more info
part_of transmembrane transporter complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: glycine receptor subunit alpha-1

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

NCBI Reference Sequences (RefSeq)

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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

4986..107324

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000171.4 → NP_000162.2 glycine receptor subunit alpha-1 isoform 2 precursor

See identical proteins and their annotated locations for NP_000162.2

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)

AC010312, AK226046, AK312702, BC074980, X52009

Consensus CDS

CCDS4320.1

UniProtKB/Swiss-Prot

P23415

Related

ENSP00000274576.5, ENST00000274576.9

Conserved Domains (1) summary

TIGR00860
Location:7 → 438

LIC; Cation transporter family protein
NM_001146040.2 → NP_001139512.1 glycine receptor subunit alpha-1 isoform 1 precursor

See identical proteins and their annotated locations for NP_001139512.1

Status: REVIEWED

Description

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

Source sequence(s)

AC010312, AK226046, BC114947, X52009

Consensus CDS

CCDS54942.1

UniProtKB/Swiss-Prot

B2R6T3, P23415, Q14C77, Q6DJV9

Related

ENSP00000411593.2, ENST00000455880.2

Conserved Domains (1) summary

TIGR00860
Location:7 → 446

LIC; Cation transporter family protein
NM_001292000.2 → NP_001278929.1 glycine receptor subunit alpha-1 isoform 3

See identical proteins and their annotated locations for NP_001278929.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an internal exon in the 5' region, which results in translation initiation at a downstream AUG start codon, and contains an alternate splice site at the 5' end of the last exon, compared to variant 1. The resulting isoform (3) has a shorter N-terminus and lacks an internal segment in the C-terminal region, compared to isoform 1.

Source sequence(s)

AC010312, AK226046, AK308539, BC114967

UniProtKB/TrEMBL

Q14C71

Conserved Domains (1) summary

TIGR00860
Location:1 → 355

LIC; Cation transporter family protein