GeneBe

GLRA2

protein-coding

glycine receptor alpha 2, the group of Glycine receptors

Gene summary

The glycine receptor consists of two subunits, alpha and beta, and acts as a pentamer. The protein encoded by this gene is an alpha subunit and can bind strychnine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

Previous symbols:
  • GLR

MANE transcript

NM_002063.4

Inheritance

XL

ClinVar variants

P:11U:93B:13

Top phenotype

Intellectual developmental disorder, X-linked, syndromic, Pilorge type

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chrX:14,529,298-14,731,812

External References & Databases

Ensembl (ENSG00000101958)NCBI Gene (2742)OMIM (305990)HGNC:4327GenCCUniProt (P23416)AlphaFoldClinVar (GLRA2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~202.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, X-linked, syndromic, Pilorge typeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0024772

Submitter: PanelApp Australia

intellectual developmental disorder, X-linked, syndromic, Pilorge typeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0024772

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Intellectual developmental disorder, X-linked, syndromic, Pilorge typeXL

Manifestation: Craniofacial; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 20479760; 26370147; 35294868Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GLRA2 variants in ClinVar

8 Conditions Cataloged
not providedTotal: 41
Inborn genetic diseasesTotal: 26
Intellectual developmental disorder, X-linked, syndromic, Pilorge typeTotal: 22
GLRA2-related disorderTotal: 12
See casesTotal: 8
not specifiedTotal: 6
GLRA2-related disordersTotal: 1
MyopiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002063.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
6
clinvar
1
clinvar
 14
missense
4
clinvar
6
clinvar
72
clinvar
6
clinvar
 88
nonsense
6
clinvar
 6
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
8
clinvar
 8
Total4793121117

Highest pathogenic variant AF is 0.000024001993

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002063.4RefSeqNP_002054.19MANE Select
ENST00000218075.9EnsemblENSP00000218075.49MANE Select
NM_001118885.2RefSeqNP_001112357.19Standard
NM_001118886.2RefSeqNP_001112358.19Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Neuroactive ligand-receptor interaction - Homo sapiens (human)
  • Neuronal System
  • Neurotransmitter receptors and postsynaptic signal transmission
  • Transmission across Chemical Synapses

Biological Process

  • signal transduction
  • neuropeptide signaling pathway
  • chemical synaptic transmission
  • ion transmembrane transport
  • regulation of membrane potential

Molecular Function

  • transmembrane signaling receptor activity
  • extracellular ligand-gated ion channel activity
  • chloride channel activity
  • glycine binding
  • extracellularly glycine-gated chloride channel activity

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • cell junction
  • chloride channel complex
  • neuron projection

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000218075
Coding exons
9
Length
202515
Individuals with no LoFs
125694
Homozygous LoFs
1
Heterozygous LoFs
2
Defined
125697
p
0.0000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.70781800.4340.00001432996
Missense (PolyPhen)2287.8670.250381464
Synonymous0.2646769.80.9600.00000566852
Loss of Function3.42115.60.06420.00000120264

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.0000720.000054rare
Finnish0.0000630.000046rare
European (Non-Finnish)0.0000120.0000088rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:2155780, PubMed:15302677, PubMed:16144831, PubMed:23895467, PubMed:25445488). Channel opening is also triggered by taurine and beta-alanine (PubMed:15302677). Plays a role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Plays a role in cellular responses to ethanol (PubMed:23895467). {ECO:0000269|PubMed:15302677, ECO:0000269|PubMed:16144831, ECO:0000269|PubMed:2155780, ECO:0000269|PubMed:23895467, ECO:0000269|PubMed:25445488}.;

Recessive Scores

pRec
0.311

Intolerance Scores

LoFtool
0.338
RVIS EVS
-0.1
RVIS percentile EVS
46.49

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.457

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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