GLRA3 glycine receptor alpha 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GLRA3provided by HGNC
Official Full Name: glycine receptor alpha 3provided by HGNC
Primary source: HGNC:HGNC:4328
See related: Ensembl:ENSG00000145451 MIM:600421; AllianceGenome:HGNC:4328
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
Summary: This gene encodes a member of the ligand-gated ion channel protein family. The encoded protein is a member of the glycine receptor subfamily. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]
Expression: Biased expression in brain (RPKM 2.6), adrenal (RPKM 0.4) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 4q34.1

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (174636920..174829247, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (177976596..178167115, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (175558071..175750398, complement)

Chromosome 4 - NC_000004.12 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?

In this study, the association between the common rs10011025 variant in the GLRA3 locus, and albuminuria, was confirmed in 1259 independent Finnish individuals with type 1 diabetes (p = 0.0013), and meta-analysis of all Finnish individuals yielded a genome-wide significant association.
Title: Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes.
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.
This study explores the roles of Tyr and Trp residues in the extracellular domains of the glycine receptor alpha 3 and shows that four such residues that have not been previously studied (Y24, Y58, W170, and Y197) contribute significantly to the function of the protein.
Title: Identification of Novel Functionally Important Aromatic Residue Interactions in the Extracellular Domain of the Glycine Receptor.
X-ray crystal structure of human homopentameric GlyRalpha3 in complex with AM-3607, a potentiator of the same class with increased potency, and the agonist glycine, at 2.6-A resolution.
Title: Crystal structures of human glycine receptor α3 bound to a novel class of analgesic potentiators.
data show that the current-voltage relationships of homomeric channels formed by the alpha2 or alpha3 subunits change upon receptor desensitization from a linear to an inwardly rectifying shape, in contrast to their heteromeric counterparts.
Title: Electrophysiological Signature of Homomeric and Heteromeric Glycine Receptor Channels.
3.0 A X-ray structure of the human glycine receptor-alpha3 homopentamer in complex with a high affinity, high-specificity antagonist, strychnine
Title: Crystal structure of human glycine receptor-α3 bound to antagonist strychnine.
Protein kinase (PK)A-dependent phosphorylation of alpha3 GlyRs produces a conformational change that propagates to the glycine-binding site.
Title: Phosphorylation of α3 glycine receptors induces a conformational change in the glycine-binding site.
Determines location of mouse glycine alpha 3.
Title: Genetic mapping of the glycine receptor alpha 3 subunit on mouse chromosome 8.
Results indicate that the multifunctional basic motif of the TM3-4 loop is capable of mediating a karyopherin-dependent intracellular sorting of full-length GlyRs.
Title: Multifunctional basic motif in the glycine receptor intracellular domain induces subunit-specific sorting.
the spliced insert within the large TM 3-4 loop of alpha3 Gly receptors serves to stabilize the overall spatial structure of the domain, and present a control unit that regulates gating of the receptor ion channel
Title: Novel regulatory site within the TM3-4 loop of human recombinant alpha3 glycine receptors determines channel gating and domain structure.

Submit: New GeneRIF Correction See all GeneRIFs (11)

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

EBI GWAS Catalog

Description
Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

SHGC-13973 (e-PCR)
- UniSTS:3074

G31579 (e-PCR)
- UniSTS:57880

D4S1539 (e-PCR), detects polymorphism
- UniSTS:42543

D4S3331 (e-PCR), detects polymorphism
- UniSTS:74633

RH123181 (e-PCR)
- UniSTS:135562

D4S1539 (e-PCR), detects polymorphism
- UniSTS:63415

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 glycine binding	IEA Inferred from Electronic Annotation more info
enables glycine-gated chloride ion channel activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables neurotransmitter receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane signaling receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
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 excitatory postsynaptic potential	IEA Inferred from Electronic Annotation more info
involved_in protein homooligomerization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of membrane potential	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in dendrite	IEA Inferred from Electronic Annotation more info
part_of glycine-gated chloride channel complex	IDA Inferred from Direct Assay more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor 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
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-3

Names: glycine receptor, alpha-3 polypeptide; ligand gated ion channel

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.

mRNA and Protein(s)

NM_001042543.3 → NP_001036008.1 glycine receptor subunit alpha-3 isoform b precursor

See identical proteins and their annotated locations for NP_001036008.1

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as alpha3K) lacks an in-frame exon in the 3' coding region, compared to variant 1. The encoded isoform (b) is shorter, compared to isoform a.

Source sequence(s)

AC107216, BC036086, U93917

Consensus CDS

CCDS43283.1

UniProtKB/Swiss-Prot

O75311

Related

ENSP00000345284.5, ENST00000340217.5

Conserved Domains (1) summary

TIGR00860
Location:12 → 436

LIC; Cation transporter family protein
NM_006529.4 → NP_006520.2 glycine receptor subunit alpha-3 isoform a precursor

See identical proteins and their annotated locations for NP_006520.2

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as alpha3L) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

AC107216, AF018157, BC036086

Consensus CDS

CCDS3822.1

UniProtKB/Swiss-Prot

D3DP44, O75311, O75816, Q5D0E3

Related

ENSP00000274093.3, ENST00000274093.8

Conserved Domains (1) summary

TIGR00860
Location:12 → 451

LIC; Cation transporter family protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

174636920..174829247 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047416196.1 → XP_047272152.1 glycine receptor subunit alpha-3 isoform X2
XM_047416195.1 → XP_047272151.1 glycine receptor subunit alpha-3 isoform X1
XM_017008630.2 → XP_016864119.1 glycine receptor subunit alpha-3 isoform X5

Conserved Domains (1) summary

TIGR00860
Location:5 → 411

LIC; Cation transporter family protein
XM_047416197.1 → XP_047272153.1 glycine receptor subunit alpha-3 isoform X3
XM_011532268.3 → XP_011530570.1 glycine receptor subunit alpha-3 isoform X6

UniProtKB/TrEMBL

Q9UPF3

Conserved Domains (2) summary

pfam02931
Location:1 → 58

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:65 → 253

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
XM_011532267.3 → XP_011530569.1 glycine receptor subunit alpha-3 isoform X4

Conserved Domains (2) summary

pfam02931
Location:47 → 253

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:260 → 309

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region