GLRB

glycine receptor beta, the group of Glycine receptors

Basic information

Region (hg38): 4:157076125-157172090

Links

ENSG00000109738 ∙ NCBI:2743 ∙ OMIM:138492 ∙ HGNC:4329 ∙ Uniprot:P48167 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperekplexia 2 (Strong), mode of inheritance: AR
• hereditary hyperekplexia (Supportive), mode of inheritance: AD
• hyperekplexia 2 (Definitive), mode of inheritance: AR
• hyperekplexia 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperekplexia 2	AR	Neurologic	Neonates are at risk of sudden death from apnea/aspiration, and surveillance, as well as primary prevention with medical treatments (eg, clonazepam) may be beneficial	Neurologic	11929858; 21391991; 20301437

ClinVar

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

• Hyperekplexia 2 (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLRB 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				80	3	83
missense		1	138	5	2	146
nonsense	3		2			5
start loss						0
frameshift	7		3			10
inframe indel			6			6
splice donor/acceptor (+/-2bp)	2	1	1			4
splice region		1	10	14	3	28
non coding			17	37	38	92
Total	12	2	167	122	43

Highest pathogenic variant AF is 0.0000197

Variants in GLRB

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

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

Position	Type	Phenotype	Significance	ClinVar
4-157076145-C-G		Hyperekplexia 2	Benign (Jan 13, 2018)
4-157076145-C-T		Hyperekplexia 2	Uncertain significance (Jan 12, 2018)
4-157076225-T-C		Hyperekplexia 2	Benign (Jan 12, 2018)
4-157076238-C-T		Hyperekplexia 2	Uncertain significance (Jan 12, 2018)
4-157076258-C-T		Hyperekplexia 2	Benign (Jan 13, 2018)
4-157077988-T-C		Hyperekplexia 2	Benign (Jan 13, 2018)
4-157077999-G-T		Hyperekplexia 2	Benign (May 19, 2021)
4-157078009-A-T		Hyperekplexia 2	Benign (May 12, 2021)
4-157078030-G-A		Hyperekplexia 2	Likely benign (Nov 16, 2022)
4-157078031-T-G		Hyperekplexia 2 • Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
4-157078032-T-A		Hyperekplexia 2	Uncertain significance (May 28, 2022)
4-157078039-G-A		Hyperekplexia 2	Likely benign (Mar 09, 2023)
4-157078046-G-C		Hyperekplexia 2	Uncertain significance (Oct 05, 2022)
4-157078046-GC-G		Hyperekplexia 2	Pathogenic (Jan 28, 2024)
4-157078058-T-G		Hyperekplexia 2	Uncertain significance (Mar 15, 2021)
4-157078061-A-G		Hyperekplexia 2	Uncertain significance (Aug 22, 2022)
4-157078069-G-A		Hyperekplexia 2	Likely benign (Apr 17, 2022)
4-157078073-G-A		Hyperekplexia 2	Uncertain significance (Mar 08, 2021)
4-157078073-G-T		Hyperekplexia 2	Uncertain significance (Mar 29, 2022)
4-157078076-G-A		Hyperekplexia 2	Uncertain significance (Sep 12, 2022)
4-157078078-A-G		Hyperekplexia 2	Likely benign (Sep 29, 2023)
4-157078083-C-T		Hyperekplexia 2	Uncertain significance (May 12, 2021)
4-157078084-C-T		Hyperekplexia 2	Likely benign (Jun 14, 2023)
4-157078090-T-C		Hyperekplexia 2	Likely benign (Nov 08, 2023)
4-157078107-AG-A		Hyperekplexia 2	Pathogenic (May 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLRB	protein_coding	protein_coding	ENST00000264428	9	96034

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00142	0.997	125724	0	22	125746	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.830	220	257	0.854	0.0000124	3260
Missense in Polyphen		73	106.22	0.68722		1352
Synonymous	0.966	83	95.0	0.874	0.00000488	941
Loss of Function	2.80	9	23.7	0.380	0.00000128	295

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000546	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.0000546	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Glycine receptors are ligand-gated chloride channels. GLRB does not form ligand-gated ion channels by itself, but is part of heteromeric ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:8717357, PubMed:15302677, PubMed:16144831, PubMed:22715885, PubMed:25445488, PubMed:11929858, PubMed:23238346). Heteropentameric channels composed of GLRB and GLRA1 are activated by lower glycine levels than homopentameric GLRA1 (PubMed:8717357). Plays an important role in the down-regulation of neuronal excitability (PubMed:11929858, PubMed:23238346). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). {ECO:0000269|PubMed:11929858, ECO:0000269|PubMed:15302677, ECO:0000269|PubMed:16144831, ECO:0000269|PubMed:22715885, ECO:0000269|PubMed:23238346, ECO:0000269|PubMed:25445488, ECO:0000269|PubMed:8717357}.
• Disease: DISEASE: Hyperekplexia 2 (HKPX2) [MIM:614619]: A neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli. {ECO:0000269|PubMed:11929858, ECO:0000269|PubMed:21391991, ECO:0000269|PubMed:23238346}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);Neuronal System;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses (Consensus)

Recessive Scores

• pRec: 0.148

Intolerance Scores

• loftool: 0.342
• rvis_EVS: -1
• rvis_percentile_EVS: 8.32

Haploinsufficiency Scores

• pHI: 0.721
• hipred: Y
• hipred_score: 0.604
• ghis: 0.655

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.837

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Glrb
• Phenotype: skeleton 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); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: glrbb
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: startle response;ion transport;signal transduction;neuropeptide signaling pathway;chemical synaptic transmission;acrosome reaction;nervous system development;visual perception;adult walking behavior;ion transmembrane transport;regulation of membrane potential;response to amino acid;nervous system process;protein heterooligomerization;synaptic transmission, glycinergic;righting reflex;excitatory postsynaptic potential;gamma-aminobutyric acid receptor clustering;chloride transmembrane transport
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;glycine-gated chloride channel complex;cell junction;dendrite;neuron projection;synapse;postsynaptic membrane;glycinergic synapse;GABA-ergic synapse
• Molecular function: transmembrane signaling receptor activity;extracellular ligand-gated ion channel activity;chloride channel activity;protein binding;glycine binding;extracellularly glycine-gated ion channel activity;extracellularly glycine-gated chloride channel activity;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential