GLRA2

glycine receptor alpha 2, the group of Glycine receptors

Basic information

Region (hg38): X:14529298-14731812

Previous symbols: [ "GLR" ]

Links

ENSG00000101958 ∙ NCBI:2742 ∙ OMIM:305990 ∙ HGNC:4327 ∙ Uniprot:P23416 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, X-linked, syndromic, Pilorge type (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndromic, Pilorge type	XL	General	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	Craniofacial; Neurologic; Ophthalmologic	20479760; 26370147; 35294868

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GLRA2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLRA2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	4	1	6
missense		2	11	1		14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)				1		1
splice region			4	1	1	6
non coding					1	1
Total	0	2	12	6	2

Variants in GLRA2

This is a list of pathogenic ClinVar variants found in the GLRA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-14532285-T-C		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
X-14532310-T-C		See cases	Likely pathogenic (Jan 10, 2022)
X-14532361-C-A		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
X-14532376-G-T			Uncertain significance (Aug 01, 2017)
X-14532380-C-T			Uncertain significance (Oct 01, 2023)
X-14574379-A-G		GLRA2-related disorder	Uncertain significance (Oct 27, 2023)
X-14581236-G-A		GLRA2-related disorder	Likely benign (Sep 10, 2019)
X-14581278-C-T		not specified	Likely benign (Nov 16, 2023)
X-14581319-A-G		Intellectual developmental disorder, X-linked, syndromic, Pilorge type	Pathogenic (Apr 26, 2022)
X-14581345-G-A		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
X-14581370-G-A		Intellectual developmental disorder, X-linked, syndromic, Pilorge type	Pathogenic (Apr 26, 2022)
X-14581408-T-TAAGC			Uncertain significance (Jun 01, 2019)
X-14581411-G-A			Uncertain significance (Jan 01, 2019)
X-14607193-G-C		Intellectual developmental disorder, X-linked, syndromic, Pilorge type	Uncertain significance (Oct 18, 2024)
X-14607212-A-C		Intellectual developmental disorder, X-linked, syndromic, Pilorge type	Uncertain significance (Dec 20, 2023)
X-14608992-A-G		GLRA2-related disorder	Likely benign (Jul 23, 2019)
X-14609029-C-T		See cases • Intellectual developmental disorder, X-linked, syndromic, Pilorge type	Uncertain significance (Mar 26, 2024)
X-14609052-C-G		See cases • Intellectual developmental disorder, X-linked, syndromic, Pilorge type	Likely pathogenic (Sep 01, 2022)
X-14609137-G-A		See cases	Likely pathogenic (Jan 10, 2022)
X-14609162-C-T		See cases • Intellectual developmental disorder, X-linked, syndromic, Pilorge type	Conflicting classifications of pathogenicity (Feb 02, 2023)
X-14690691-G-C			Benign (Feb 03, 2022)
X-14690691-GTC-G		Inborn genetic diseases	Benign (Mar 17, 2022)
X-14690691-G-GTCTC		GLRA2-related disorder	Likely benign (May 26, 2020)
X-14690744-C-T		GLRA2-related disorder	Uncertain significance (Mar 14, 2024)
X-14690789-C-T		Inborn genetic diseases	Likely benign (Jun 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLRA2	protein_coding	protein_coding	ENST00000218075	9	202515

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.973	0.0267	125694	1	2	125697	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.70	78	180	0.434	0.0000143	2996
Missense in Polyphen		22	87.867	0.25038		1464
Synonymous	0.264	67	69.8	0.960	0.00000566	852
Loss of Function	3.42	1	15.6	0.0642	0.00000120	264

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000724	0.0000544
Finnish	0.0000626	0.0000462
European (Non-Finnish)	0.0000122	0.00000880
Middle Eastern	0.0000724	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);Neuronal System;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses (Consensus)

Recessive Scores

• pRec: 0.311

Intolerance Scores

• loftool: 0.338
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.49

Haploinsufficiency Scores

• pHI: 0.667
• hipred: Y
• hipred_score: 0.800
• ghis: 0.608

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.457

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Glra2
• Phenotype: cellular 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)

Gene ontology

• Biological process: signal transduction;neuropeptide signaling pathway;chemical synaptic transmission;ion transmembrane transport;regulation of membrane potential;response to amino acid;nervous system process;synaptic transmission, glycinergic;excitatory postsynaptic potential;cellular response to amino acid stimulus;cellular response to zinc ion;cellular response to ethanol;chloride transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;cell junction;chloride channel complex;neuron projection;synapse;postsynaptic membrane;glycinergic synapse
• Molecular function: transmembrane signaling receptor activity;extracellular ligand-gated ion channel activity;chloride channel activity;glycine binding;extracellularly glycine-gated chloride channel activity;glycine-gated chloride ion channel activity;metal ion binding;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential