GLRB

Summary

GLRB (glycine receptor beta, HGNC:4329) is a protein-coding gene on chromosome 4q32.1, encoding Glycine receptor subunit beta (P48167). Subunit of heteromeric glycine-gated chloride channels.

This gene encodes the beta subunit of the glycine receptor, which is a pentamer composed of alpha and beta subunits. The receptor functions as a neurotransmitter-gated ion channel, which produces hyperpolarization via increased chloride conductance due to the binding of glycine to the receptor. Mutations in this gene cause startle disease, also known as hereditary hyperekplexia or congenital stiff-person syndrome, a disease characterized by muscular rigidity. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2743 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperekplexia 2 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 468 total — 18 pathogenic, 5 likely-pathogenic (top 7% of genes corpus-wide)
• Expression (HPA): Tissue enhanced — highest in frontal cortex, caudate putamen, postcentral gyrus
• GTEx eGene: eQTL in 19 tissues, sQTL in 8 (q < 0.05)
• Phenotypes (HPO): 31
• Drug target: yes — 6 via a complex or family
• Approved drugs acting on a complex or family including it: 6 — Desflurane, Enflurane, Halothane, +3 more (Glycine receptor (alpha-1/beta))
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.46 (intermediate), LOEUF 0.75 (unconstrained)
• MANE Select transcript: NM_000824

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4329
Approved symbol	GLRB
Name	glycine receptor beta
Location	4q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000109738
Ensembl biotype	protein_coding
OMIM	138492
Entrez	2743

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 17 protein_coding, 11 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000264428

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 1, TSL 4: 1, TSL 5: 2

ENST00000264428, ENST00000506411, ENST00000509282, ENST00000510970, ENST00000512619, ENST00000515642, ENST00000541722, ENST00000874195, ENST00000874196, ENST00000960007, ENST00000960008, ENST00000960009, ENST00000960010, ENST00000960011, ENST00000960012, ENST00000960013, ENST00001028403, ENST00001028404, ENST00001028405, ENST00001028407, ENST00001028408, ENST00001028409, ENST00001028410, ENST00001028411, ENST00001028412, ENST00001028413, ENST00001126197, ENST00001126198, ENST00001139492

RefSeq mRNA: 4 — MANE Select: NM_000824 NM_000824, NM_001166060, NM_001166061, NM_001440545

CCDS: CCDS3796, CCDS54813

Canonical transcript exons

ENST00000264428 — 10 exons

Exon	Start	End
ENSE00000740246	157138809	157138949
ENSE00000740252	157143807	157143959
ENSE00000740254	157152718	157153010
ENSE00000813569	157077996	157078146
ENSE00002021448	157076150	157076297
ENSE00003506646	157170432	157172090
ENSE00003560964	157136469	157136698
ENSE00003605009	157136804	157136886
ENSE00003667917	157120556	157120662
ENSE00003687462	157122330	157122397

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6660 / max 274.0311, expressed in 1159 samples.

Highest expression (Bgee): frontal pole, Brodmann (1909) area 10, middle frontal gyrus, lateral nuclear group of thalamus, pons.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GLRB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 8 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 27 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	3.2e-13	+0.71	4:157086161:G:A
Esophagus Muscularis	eqtl	1.1e-09	+0.38	4:157166133:GT:G
Artery Aorta	sqtl	4.3e-06	-1.06	4:157087744:C:G
Muscle Skeletal	eqtl	7.3e-06	+0.71	4:157076458:TGCGCGGGAGAGGG:T
Adrenal Gland	eqtl	9.3e-06	-0.53	4:156674063:G:A
Artery Aorta	eqtl	9.6e-06	+0.20	4:157054664:C:T
Pituitary	sqtl	1.1e-05	+0.67	4:157080554:A:C
Brain Cerebellar Hemisphere	eqtl	1.6e-05	-0.41	4:157084761:C:T
Artery Tibial	sqtl	3.6e-04	+0.40	4:157086161:G:A
Cells Cultured fibroblasts	eqtl	4.1e-04	-0.13	4:157169837:A:T
Liver	eqtl	2.0e-03	-0.45	4:156165511:G:T
Artery Coronary	eqtl	3.4e-03	+0.23	4:157054000:A:T
Brain Frontal Cortex BA9	eqtl	4.0e-03	-0.14	4:157178546:G:A
Brain Hypothalamus	eqtl	4.4e-03	-0.15	4:157178546:G:A
Thyroid	eqtl	5.0e-03	+0.22	4:157150530:C:A
Brain Cerebellar Hemisphere	sqtl	6.3e-03	-0.67	4:157125830:C:T
Brain Anterior cingulate cortex BA24	sqtl	6.7e-03	-0.61	4:157014871:G:A
Brain Nucleus accumbens basal ganglia	eqtl	6.7e-03	-0.16	4:157185370:A:G
Brain Cortex	eqtl	7.7e-03	-0.18	4:157095871:T:C
Brain Cortex	sqtl	1.1e-02	-0.56	4:157080554:A:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
50240	11.3905	1154
50239	0.2195	101
203396	0.0560	18

Top tissues by expression

showing 100 of 282 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	98.75	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.54	gold quality
middle frontal gyrus	UBERON:0002702	96.70	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.80	gold quality
pons	UBERON:0000988	95.55	gold quality
paraflocculus	UBERON:0005351	95.21	gold quality
prefrontal cortex	UBERON:0000451	94.35	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.93	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.51	gold quality
endothelial cell	CL:0000115	93.43	gold quality
primary visual cortex	UBERON:0002436	93.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.29	gold quality
superior frontal gyrus	UBERON:0002661	92.89	gold quality
frontal cortex	UBERON:0001870	92.67	gold quality
occipital lobe	UBERON:0002021	92.55	gold quality
postcentral gyrus	UBERON:0002581	92.37	gold quality
parietal lobe	UBERON:0001872	92.12	gold quality
neocortex	UBERON:0001950	92.09	gold quality
superior vestibular nucleus	UBERON:0007227	91.50	gold quality
orbitofrontal cortex	UBERON:0004167	91.42	gold quality
cerebral cortex	UBERON:0000956	91.40	gold quality
cingulate cortex	UBERON:0003027	90.61	gold quality
anterior cingulate cortex	UBERON:0009835	90.58	gold quality
substantia nigra pars compacta	UBERON:0001965	90.38	gold quality
telencephalon	UBERON:0001893	89.86	gold quality
cortical plate	UBERON:0005343	89.56	gold quality
cerebellar vermis	UBERON:0004720	89.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.38	gold quality
choroid plexus epithelium	UBERON:0003911	89.10	gold quality
middle temporal gyrus	UBERON:0002771	89.05	gold quality
right frontal lobe	UBERON:0002810	88.91	gold quality
entorhinal cortex	UBERON:0002728	88.90	gold quality
forebrain	UBERON:0001890	88.63	gold quality
nucleus accumbens	UBERON:0001882	88.24	gold quality
brain	UBERON:0000955	88.09	gold quality
hypothalamus	UBERON:0001898	87.99	gold quality
central nervous system	UBERON:0001017	87.84	gold quality
Ammon’s horn	UBERON:0001954	87.72	gold quality
caudate nucleus	UBERON:0001873	87.65	gold quality
temporal lobe	UBERON:0001871	86.99	gold quality
putamen	UBERON:0001874	86.99	gold quality
substantia nigra pars reticulata	UBERON:0001966	86.47	gold quality
cerebellum	UBERON:0002037	86.40	gold quality
cerebellar cortex	UBERON:0002129	86.14	gold quality
ventral tegmental area	UBERON:0002691	86.10	gold quality
cerebellar hemisphere	UBERON:0002245	86.03	gold quality
dorsal plus ventral thalamus	UBERON:0001897	85.70	gold quality
amygdala	UBERON:0001876	85.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.72	gold quality
midbrain	UBERON:0001891	84.12	gold quality
islet of Langerhans	UBERON:0000006	83.95	gold quality
substantia nigra	UBERON:0002038	83.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.78	gold quality
lateral globus pallidus	UBERON:0002476	82.67	gold quality
medulla oblongata	UBERON:0001896	82.56	gold quality
parotid gland	UBERON:0001831	82.26	gold quality
body of pancreas	UBERON:0001150	81.21	gold quality
pancreas	UBERON:0001264	81.20	gold quality
stromal cell of endometrium	CL:0002255	80.89	gold quality
corpus callosum	UBERON:0002336	80.47	gold quality
pigmented layer of retina	UBERON:0001782	80.41	gold quality
retina	UBERON:0000966	80.39	gold quality
spinal cord	UBERON:0002240	79.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.88	gold quality
ascending aorta	UBERON:0001496	79.80	gold quality
thoracic aorta	UBERON:0001515	79.67	gold quality
ganglionic eminence	UBERON:0004023	79.64	gold quality
subthalamic nucleus	UBERON:0001906	79.57	gold quality
right coronary artery	UBERON:0001625	79.54	gold quality
ventricular zone	UBERON:0003053	79.03	gold quality
buccal mucosa cell	CL:0002336	78.87	gold quality
inferior vagus X ganglion	UBERON:0005363	78.79	gold quality
adenohypophysis	UBERON:0002196	78.22	gold quality
calcaneal tendon	UBERON:0003701	78.00	gold quality
descending thoracic aorta	UBERON:0002345	77.99	gold quality
dorsal root ganglion	UBERON:0000044	77.86	gold quality
left coronary artery	UBERON:0001626	77.67	gold quality
aorta	UBERON:0000947	77.47	gold quality
coronary artery	UBERON:0001621	76.91	gold quality
heart left ventricle	UBERON:0002084	76.62	gold quality
cardiac ventricle	UBERON:0002082	76.48	gold quality
right atrium auricular region	UBERON:0006631	76.48	gold quality
heart	UBERON:0000948	76.47	gold quality
caput epididymis	UBERON:0004358	76.39	gold quality
pituitary gland	UBERON:0000007	76.27	gold quality
popliteal artery	UBERON:0002250	75.94	gold quality
tibial artery	UBERON:0007610	75.91	gold quality
CA1 field of hippocampus	UBERON:0003881	75.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.46	gold quality
cardiac atrium	UBERON:0002081	75.31	gold quality
adult organism	UBERON:0007023	75.14	gold quality
saliva-secreting gland	UBERON:0001044	74.57	gold quality
heart right ventricle	UBERON:0002080	74.56	silver quality
endocervix	UBERON:0000458	74.27	gold quality
left adrenal gland	UBERON:0001234	74.23	gold quality
right adrenal gland cortex	UBERON:0035827	73.95	gold quality
apex of heart	UBERON:0002098	73.90	gold quality
left adrenal gland cortex	UBERON:0035825	73.74	gold quality
blood vessel layer	UBERON:0004797	73.36	gold quality
adrenal cortex	UBERON:0001235	73.22	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.04

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	172.2
Caudate putamen	tissue	137.3
Postcentral gyrus	tissue	90.0
Cerebral cortex	tissue	54.0	low
Somatosensory cortex	tissue	54.0
Occipital cortex	tissue	50.6
Pons	tissue	47.2
Thalamus	tissue	45.1
Superior colliculi	tissue	42.9
Motor cortex	tissue	42.1
Hippocampal formation	tissue	41.4
Retrosplenial and cingulate cortex	tissue	39.5
Midbrain	tissue	38.6
Locus coeruleus	tissue	38.0
Retrosplenial cortex	tissue	36.3
Entorhinal cortex	tissue	35.6
Prefrontal cortex	tissue	35.5
Temporal cortex	tissue	35.3
Cerebellum	tissue	34.7	not detected
Medulla oblongata	tissue	31.3
Parathyroid gland	tissue	31.1	not detected
Hippocampus	tissue	31.1	not detected
Nucleus accumbens	tissue	29.6
Insular cortex	tissue	29.5
Substantia nigra	tissue	28.6
Septum	tissue	27.4
Putamen	tissue	27.1
Hypothalamus	tissue	26.6
Ventral forebrain	tissue	26.1
Periaqueductal gray	tissue	24.8
Amygdala	tissue	23.4
Choroid plexus	tissue	22.8
Spinal cord	tissue	20.2
Basal ganglia	tissue	19.9	not detected
Salivary gland	tissue	18.4	low
Olfactory bulb	tissue	15.3
Pancreas	tissue	14.3	low
Corpus callosum	tissue	13.2
Heart muscle	tissue	10.4	not detected
Breast	tissue	9.9	not detected
Cervix	tissue	8.4	not detected
Retina	tissue	7.8
Fallopian tube	tissue	6.9	not detected
Pituitary gland	tissue	6.8
Adrenal gland	tissue	6.6	not detected
Prostate	tissue	5.8	not detected
Epididymis	tissue	4.9	not detected
Tongue	tissue	4.6
Seminal vesicle	tissue	4.4	low
Adipose tissue	tissue	4.4	not detected
Kidney	tissue	3.6	low
Smooth muscle	tissue	3.5	not detected
Skeletal muscle	tissue	3.1	low
Lung	tissue	3.0	not detected
Gallbladder	tissue	3.0	low
Endometrium 1	tissue	2.7	not detected
Placenta	tissue	2.5	not detected
Ovary	tissue	1.7	not detected
Testis	tissue	1.5	not detected
Vagina	tissue	1.4	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Postcentral gyrus, middle (64.7), Precentral gyrus, middle (63.2), Paracentral lobule, anterior (61.5), Frontal eye field (55.9), Precentral gyrus, dorsal (55.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GLRB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 112 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3671	99.90	73.04	3897

Functional genomics

gnomAD constraint: pLI 0.463, LOEUF 0.746, missense Z 0.575 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000264428 — one region, missense o/e 0.98. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 23)

• proton modulation of glycine receptor function is determined by extracellular domain in both the alpha1 and beta subunits (PMID:14563849)
• Stoichiometry of recombinant heteromeric glycine receptors revealed by a pore-lining region point mutation (PMID:14698963)
• Report interaction of androsterone and progesterone with inhibitory ligand-gated ion channels: a patch clamp study. (PMID:19705103)
• This study presents a large family with Hereditary hyperekplexia (HH) as a result of homozygous mutation in GLRB. (PMID:21391991)
• The authors have identified a protein kinase C (PKC) phosphorylation site within the cytoplasmic domain of the beta-subunit of the GlyR (residue S403) that causes a reduction of the binding affinity between the receptor and gephyrin. (PMID:21829170)
• Hereditary hyperekplexia-causing mutations that modify alpha1 beta GlyR channel function are almost exclusively located in the alpha1 to the exclusion of the beta subunit. (PMID:22132222)
• Distinct properties of glycine receptor beta+/alpha- interface: unambiguously characterizing heteromeric interface reconstituted in homomeric protein. (PMID:22535951)
• investigated neural progenitor cells in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR (PMID:22606311)
• We report novel GLRB mutations in hyperekplexia (PMID:23182654)
• This study describes the definitive assignment of GLRB as the third major gene for hyperekplexia and impacts on the genetic stratification and biological causation of this neonatal/paediatric disorder. (PMID:23184146)
• Systematic DNA sequencing of GLRB in individuals with hyperekplexia revealed new missense mutations in GLRB, resulting in M177R, L285R and W310C substitutions. (PMID:23238346)
• p.E375X truncated subunits are incorporated into functional hGlyRs together with unmutated alpha1 or alpha1 plus beta subunits. (PMID:24108130)
• The N-terminal region of GABRA3 and the GlyR beta subunit occupies the same binding site of gephyrin. (PMID:25531214)
• Whole-exome sequencing in ASD patients from each family identified a second rare inherited genetic variant, affecting GLRB expressed in inhibitory or in excitatory synapses. (PMID:26055424)
• GLRA1 and GLRB mutations are responsible for abnormal startled reactions in humans. (Review) (PMID:26845851)
• A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, P = 3.3 x 10 - 8; rs191260602, P = 3.9 x 10- 8).GLRB gene expression was found to be modulated by rs7688285 in brain tissue, as well as cell culture. (PMID:28167838)
• GLRB variants are associated with etiopathogenesis of fear and anxiety disorders. (PMID:28872638)
• 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. (PMID:28883437)
• The association between the missense SNP rs2235371 in gene IRF6 and NSCL/P suggests that this SNP may play an important role as a risk factor for NSCL/P in the Han Chinese populations. (PMID:30462859)
• single nucleotide polymorphism of glrb interacts in a complex manner with Panic Disorder /AgoraphobiaG on a functional systems level and might be involved in the development of PD/AG but not in their treatment. (PMID:31444036)
• Clinical, genetic, and functional characterization of the glycine receptor beta-subunit A455P variant in a family affected by hyperekplexia syndrome. (PMID:35526563)
• Glycine Receptor beta-Targeting Autoantibodies Contribute to the Pathology of Autoimmune Diseases. (PMID:38215349)
• Gating mechanism of the human alpha1beta GlyR by glycine. (PMID:39146932)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	glrbb	ENSDARG00000052769
danio_rerio	glrba	ENSDARG00000052782
mus_musculus	Glrb	ENSMUSG00000028020
rattus_norvegicus	Glrb	ENSRNOG00000010199

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090), GABRA5 (ENSG00000186297), ZACN (ENSG00000186919), GABRD (ENSG00000187730), CHRNG (ENSG00000196811), GABRQ (ENSG00000268089)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95751) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 41 distinct phenotype terms.

Mouse phenotype (MP)	Records
tremors	3
impaired righting response	3
muscle spasm	2
abnormal gait	2
reduced male fertility	2
muscle hypertonia	2
hyperekplexia	2
preweaning lethality, complete penetrance	2
fragile skeleton	1
increased neutrophil cell number	1
impaired fertilization	1
enlarged adrenal glands	1
abnormal Purkinje cell morphology	1
abnormal spinal cord morphology	1
abnormal dorsal root ganglion morphology	1
abnormal spinal nerve morphology	1
decreased body size	1
abnormal maternal nurturing	1
short stride length	1
decreased exploration in new environment	1
increased startle reflex	1
abnormal posture	1
limb grasping	1
impaired swimming	1
edema	1

+16 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	D1LYT2	100.0%	Diamond
Drosophila melanogaster	P25123	99.8%	Diamond
Bos taurus	P57695	99.8%	Diamond
Pongo abelii	Q5RCC5	99.8%	Diamond
Drosophila simulans	Q9BLY8	99.8%	Diamond
Gallus gallus	P21548	92.8%	Diamond
Musca domestica	Q75NA5	84.3%	Diamond
Haemonchus contortus	P91730	81.4%	Diamond
Caenorhabditis elegans	Q17328	81.4%	Diamond
Lymnaea stagnalis	P26714	58.6%	Diamond
Anopheles gambiae	A0A1S4H2E2	48.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC02272	ncRNA	107986322
PDGFC	protein-coding	56034
GRIA2	protein-coding	2891

Protein

Protein identifiers

Glycine receptor subunit beta — P48167 (reviewed: P48167)

Alternative names: Glycine receptor 58 kDa subunit

All UniProt accessions (3): D6R9Y9, D6RD86, P48167

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of heteromeric glycine-gated chloride channels. Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents.

Subunit / interactions. Forms heteropentamers with glycin receptor alpha subunits. Heteropentamers with GLRA1 can be composed of two GLRA1 and three GLRB subunits, or three GLRA1 and two GLRB subunits, or four GLRA1 subunits and one GLRB subunit. Forms heteropentamers with GLRA2. Functional GLRB-GLRA2 heteropentamers contain four GLRA2 subunits and one GLRB subunit, although alternative subunit composition cannot be excluded. Forms a heteropentamer with GLRA3. Interacts with GPHN.

Subcellular location. Postsynaptic cell membrane. Synapse. Cell projection. Dendrite. Cell membrane. Cytoplasm.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Channel opening is triggered by extracellular glycine. Heteropentameric channels composed of GLRB and GLRA1 are activated by lower glycine levels than homopentameric GLRA1.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily. GLRB sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P48167-1	1	yes
P48167-2	2

RefSeq proteins (4): NP_000815, NP_001159532, NP_001159533, NP_001427474 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR008060	Glycine_rcpt_B	Family
IPR018000	Neurotransmitter_ion_chnl_CS	Conserved_site
IPR036719	Neuro-gated_channel_TM_sf	Homologous_superfamily
IPR036734	Neur_chan_lig-bd_sf	Homologous_superfamily
IPR038050	Neuro_actylchol_rec	Homologous_superfamily
IPR047029	GlyR_beta_TM	Domain
IPR047031	GlyR_beta__ECD	Domain

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea)

• chloride(in) = chloride(out) (RHEA:29823)

UniProt features (28 total): sequence variant 5, topological domain 4, transmembrane region 4, binding site 3, glycosylation site 2, disulfide bond 2, splice variant 2, mutagenesis site 2, signal peptide 1, chain 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

12 structures by resolution:

PDB	Title	Method	Resolution (Å)
8DN3	Cryo-EM structure of human Glycine Receptor alpha1-beta heteromer, apo state	ELECTRON MICROSCOPY	3.55
5BKF	Cyro-EM structure of human Glycine Receptor alpha2-beta heteromer, Glycine bound …	ELECTRON MICROSCOPY	3.6
7KUY	Cyro-EM structure of human Glycine Receptor alpha2-beta heteromer, strychnine bound state	ELECTRON MICROSCOPY	3.6
9BP7	Cryo-EM structure of human heteromeric Glycine Receptor alpha3S346E-beta in presence of …	ELECTRON MICROSCOPY	3.6
8DN5	Cryo-EM structure of human Glycine Receptor alpha1-beta heteromer, glycine-bound …	ELECTRON MICROSCOPY	3.63
9BP0	Cryo-EM structure of human heteromeric Glycine Receptor alpha3S346E-beta with glycine	ELECTRON MICROSCOPY	3.67
5BKG	Cyro-EM structure of human Glycine Receptor alpha2-beta heteromer, glycine bound …	ELECTRON MICROSCOPY	3.8
7L31	Cyro-EM structure of human Glycine Receptor alpha2-beta heteromer, strychnine bound …	ELECTRON MICROSCOPY	3.8
9BOY	Cryo-EM structure of human Glycine Receptor apha3-beta heteromer with glycine in nanodisc	ELECTRON MICROSCOPY	3.81
9BOZ	Cryo-EM structure of human Glycine Receptor alpha3-beta heteromer in presence of glycine	ELECTRON MICROSCOPY	3.84
8DN2	Cryo-EM structure of human Glycine Receptor alpha1-beta heteromer, glycine-bound state …	ELECTRON MICROSCOPY	3.9
8DN4	Cryo-EM structure of human Glycine Receptor alpha-1 beta heteromer, glycine-bound …	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48167-F1	78.85	0.49

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
307	important for obstruction of the ion pore in the closed conformation

Ligand- & substrate-binding residues (3)

Position	Role
108	glycine
174	glycine
250	glycine

Post-translational modifications (1)

Type	Positions
Phosphothreonine	391

Disulfide bonds (2)

Type	Positions
Disulfide bond	183–197, 243–255

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	54, 242

Mutagenesis-validated functional residues (2)

Position	Phenotype
54	prevents proper assembly of the glra2/glrb heteropentamer receptor.
242	loss of glycosylation. prevents proper assembly of the glra2/glrb heteropentamer receptor.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-112316	Neuronal System	—
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	electronic
R-HSA-112315	Transmission across Chemical Synapses	—

MSigDB gene sets: 286 (showing top): GCACCTT_MIR18A_MIR18B, GOBP_SINGLE_FERTILIZATION, chr4q32, MODULE_274, TSENG_IRS1_TARGETS_UP, GOBP_BEHAVIOR, GOBP_ADULT_BEHAVIOR, AAGCCAT_MIR135A_MIR135B, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_ADULT_LOCOMOTORY_BEHAVIOR, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_REFLEX, SMID_BREAST_CANCER_RELAPSE_IN_LIVER_DN, GOBP_CELL_CELL_SIGNALING, MODULE_66

GO Biological Process (11): startle response (GO:0001964), monoatomic ion transport (GO:0006811), neuropeptide signaling pathway (GO:0007218), chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), synaptic transmission, glycinergic (GO:0060012), chloride transmembrane transport (GO:1902476), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079)

GO Molecular Function (11): transmembrane signaling receptor activity (GO:0004888), excitatory extracellular ligand-gated monoatomic ion channel activity (GO:0005231), glycine binding (GO:0016594), extracellularly glycine-gated ion channel activity (GO:0016933), extracellularly glycine-gated chloride channel activity (GO:0016934), protein-containing complex binding (GO:0044877), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), chloride channel activity (GO:0005254), protein binding (GO:0005515)

GO Cellular Component (11): cytoplasm (GO:0005737), plasma membrane (GO:0005886), glycine-gated chloride channel complex (GO:0016935), dendrite (GO:0030425), postsynaptic membrane (GO:0045211), glycinergic synapse (GO:0098690), GABA-ergic synapse (GO:0098982), postsynaptic specialization (GO:0099572), membrane (GO:0016020), chloride channel complex (GO:0034707), synapse (GO:0045202)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Transmission across Chemical Synapses	1
Neuronal System	1

GO top-level categories

49 GO namespaces:

Category	Terms
regulation of postsynaptic membrane potential	2
binding	2
cellular anatomical structure	2
postsynapse	2
synapse	2
response to external stimulus	1
neuromuscular process	1
transport	1
G protein-coupled receptor signaling pathway	1
anterograde trans-synaptic signaling	1
system development	1
animal gross anatomical part developmental process	1
chemical synaptic transmission	1
chloride transport	1
monoatomic anion transmembrane transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of membrane potential	1
chemical synaptic transmission, postsynaptic	1
signaling receptor activity	1
extracellular ligand-gated monoatomic ion channel activity	1
excitatory postsynaptic potential	1
amino acid binding	1
carboxylic acid binding	1
cation binding	1
excitatory extracellular ligand-gated monoatomic ion channel activity	1
inhibitory extracellular ligand-gated monoatomic ion channel activity	1
chloride channel activity	1
extracellularly glycine-gated ion channel activity	1
ligand-gated monoatomic anion channel activity	1
transmitter-gated monoatomic ion channel activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
chloride channel complex	1
plasma membrane protein complex	1
neuron projection	1
dendritic tree	1
synaptic membrane	1
organelle	1
monoatomic ion channel complex	1
cell junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 33 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
chemical synaptic transmission	BP	mutant phenotype
chloride transmembrane transport	BP	mutant phenotype
monoatomic ion transport	BP	direct assay
nervous system development	BP	mutant phenotype
neuropeptide signaling pathway	BP	direct assay
startle response	BP	mutant phenotype
glycine-gated chloride channel complex	CC	direct assay
plasma membrane	CC	direct assay
extracellularly glycine-gated ion channel activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 830 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLRB	GPHN	Q9NQX3	920
GLRB	SLC6A5	Q9Y345	919
GLRB	ARHGEF9	O43307	899
GLRB	AMPH	P49418	670
GLRB	SLC6A2	P23975	644
GLRB	GRIA2	P42262	574
GLRB	NPY5R	Q15761	573
GLRB	BIN1	O00499	559
GLRB	SLC32A1	Q9H598	503
GLRB	TRAK1	Q9UPV9	496
GLRB	GASK1B	Q6UWH4	469
GLRB	MOCOS	Q96EN8	460
GLRB	XRRA1	Q6P2D8	460
GLRB	TMEM144	Q7Z5S9	437
GLRB	GAD2	Q05329	435

IntAct

Human interaction partners of GLRB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
GLRA1	physical association	0.400	2
HDLBP	physical association	0.400	1
EPHA4	physical association	0.000	1

BioGRID (58 interactions; top human partners by supporting records): BTNL8 (Affinity Capture-MS; 3 records), ASIC4 (Affinity Capture-MS; 2 records), CHRNA3 (Affinity Capture-MS; 2 records), CLEC2D (Affinity Capture-MS; 2 records), GABRA3 (Affinity Capture-MS; 2 records), GPHN (Reconstituted Complex; 2 records), GRIA3 (Affinity Capture-MS; 2 records), NRN1 (Affinity Capture-MS; 2 records), TCTN2 (Affinity Capture-MS; 2 records), TMEM194A (Affinity Capture-MS; 2 records), TMPRSS11B (Affinity Capture-MS; 2 records), APP (Reconstituted Complex), CD3D (Affinity Capture-MS), CHRNA4 (Affinity Capture-MS), CHRNB4 (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
SRC	up-regulates	GLRB	phosphorylation
glycine	“up-regulates activity”	GLRB	“chemical activation”

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexe by size:

Complex	Subunits	Members
★ Glycine receptor (GLRA11, GLRB)	2	GLRA1, GLRB

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
GLRA1;GLRB		Signaling by Glycine

Disease & clinical

Genetic variants

Variant evidence for GLRB: 468 ClinVar records (23 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

468 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	5
Uncertain significance	216
Likely benign	161
Benign	45

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 23 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1076905	NM_000824.5(GLRB):c.634C>T (p.Arg212Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
4747421	NM_000824.5(GLRB):c.298-1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	2
540368	NM_000824.5(GLRB):c.1221dup (p.Val408fs)	Pathogenic	criteria provided, single submitter	1
574411	NM_000824.5(GLRB):c.448dup (p.Ser150fs)	Pathogenic	criteria provided, single submitter	1
574419	NM_000824.5(GLRB):c.123-2A>G	Pathogenic	criteria provided, single submitter	1
582806	NM_000824.5(GLRB):c.472del (p.Gln158fs)	Pathogenic	criteria provided, single submitter	1
653331	NM_000824.5(GLRB):c.24del (p.Phe9_Leu10insTer)	Pathogenic	criteria provided, single submitter	1
802099	NM_000824.5(GLRB):c.122+1G>A	Pathogenic	criteria provided, single submitter	1
1064420	NM_000824.5(GLRB):c.1114C>T (p.Gln372Ter)	Pathogenic	criteria provided, single submitter	1
1459343	NM_000824.5(GLRB):c.371del (p.Gly124fs)	Pathogenic	criteria provided, single submitter	1
2095370	NM_000824.5(GLRB):c.618C>G (p.Tyr206Ter)	Pathogenic	criteria provided, single submitter	1
2710247	NM_000824.5(GLRB):c.704del (p.Lys235fs)	Pathogenic	criteria provided, single submitter	1
2754032	NM_000824.5(GLRB):c.84del (p.Lys31fs)	Pathogenic	criteria provided, single submitter	1
2772628	NM_000824.5(GLRB):c.449del (p.Ser150fs)	Pathogenic	criteria provided, single submitter	1
3638329	NM_000824.5(GLRB):c.756C>G (p.Tyr252Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore GLRB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 1,090):

Position(s)	Effect	Δscore	Sites
4:157076298–157076299	donor_loss	1.0000	4
4:157078114	donor_gain	1.0000
4:157122328–157122329	acceptor_loss	1.0000	4
4:157122398–157122399	donor_loss	1.0000	5
4:157138806	acceptor_gain	1.0000
4:157138807–157138808	acceptor_loss	1.0000	3
4:157138950–157138951	donor_loss	1.0000	5
4:157076298	donor_loss	0.9900
4:157077994–157077995	acceptor_loss	0.9900	6
4:157078095	donor_gain	0.9900

AlphaMissense

1,719 missense substitutions predicted likely pathogenic (of 3,273 scored), across 368 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M99	9	0.972	1.000
D193	8	0.998	1.000
D474	8	0.998	0.999
N160	8	0.997	1.000
H154	8	0.996	0.999
D113	8	0.995	0.999
D142	8	0.994	0.998
D330	8	0.993	0.997
F288	8	0.991	0.999
F145	8	0.988	0.999
D68	8	0.986	0.998
D100	8	0.986	0.997
F481	8	0.980	0.996
S203	8	0.968	1.000
S174	8	0.967	1.000
F341	8	0.967	0.997
F144	8	0.966	1.000
F106	8	0.964	0.999
F190	8	0.962	0.999
F231	8	0.960	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Rectum Adenocarcinoma (validation)	favorable	0.000514

Disease associations

OMIM: gene MIM:138492 | disease phenotypes: MIM:614619 (Hyperekplexia 2)

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
hyperekplexia 2	Definitive	Autosomal recessive	5
hereditary hyperekplexia	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
Adult-onset neurological disorders	green
Brain channelopathy	green
DDG2P	green
Dystonia, chorea or related movement disorder, childhood onset	green
Hereditary ataxia, adult onset	green
Paediatric disorders	green
Paroxysmal central nervous system disorders	green

Mondo (2): hyperekplexia 2 (MONDO:0013828), hereditary hyperekplexia (MONDO:0021022)

HPO phenotypes

31 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000483	Astigmatism
HP:0000545	Myopia
HP:0000565	Esotropia
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001270	Motor delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001373	Joint dislocation
HP:0001387	Joint stiffness
HP:0001537	Umbilical hernia
HP:0002020	Gastroesophageal reflux
HP:0002036	Hiatus hernia
HP:0002063	Rigidity
HP:0002267	Exaggerated startle response
HP:0002360	Sleep disturbance
HP:0002380	Fasciculations
HP:0002827	Hip dislocation
HP:0003552	Muscle stiffness
HP:0003577	Congenital onset
HP:0003623	Neonatal onset
HP:0010519	Increased fetal movement
HP:0030904	Glabellar reflex
HP:0100022	Abnormality of movement
HP:0100633	Esophagitis
HP:0100790	Hernia

GWAS associations

2 associations:

Study	Trait	p-value
GCST009615_7	Triglyceride levels x loop diuretics use interaction	2e-6
GCST003901_20	Cognitive decline (age-related)	6e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2363052 (PROTEIN COMPLEX), CHEMBL4106144 (PROTEIN COMPLEX), CHEMBL4296075 (PROTEIN COMPLEX)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes GLRB — the drug acts on the assembly or class, not necessarily on this subunit alone.

6 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
DESFLURANE	Glycine receptor (alpha-1/beta)	2	4
ENFLURANE	Glycine receptor (alpha-1/beta)	2	4
HALOTHANE	Glycine receptor (alpha-1/beta)	2	4
ISOFLURANE	Glycine receptor (alpha-1/beta)	2	4
METHOXYFLURANE	Glycine receptor (alpha-1/beta)	2	4
SEVOFLURANE	Glycine receptor (alpha-1/beta)	2	4

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — Glycine receptors

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
ginkgolide B	Channel blocker	6.3	pIC50
tropisetron	Antagonist	5.3	pKi
cyanotriphenylborate	Channel blocker	5.1	pIC50
pregnenolone sulphate	Antagonist	5.0	pKi
nifedipine	Antagonist	4.9	pIC50
picrotoxinin	Channel blocker	4.6	pIC50
picrotin	Channel blocker	4.6	pIC50
bilobalide	Antagonist	3.7	pIC50
picrotoxin	Channel blocker	3.7	pIC50
Zn2+	Inhibition	3.7	pIC50
ginkgolide X	Antagonist	3.5	pIC50

Binding affinities (BindingDB)

71 measured of 222 human assays (222 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4227298	EC50	13 nM
CHEMBL4079657	IC50	49 nM
CHEMBL4103909	IC50	51 nM
CHEMBL4060962	IC50	76 nM
CHEMBL4089150	IC50	82 nM
CHEMBL4102677	IC50	100 nM
CHEMBL4870499	IC50	100 nM
CHEMBL4068867	IC50	109 nM
CHEMBL4857611	IC50	130 nM
CHEBI:28973	IC50	134 nM
CHEMBL4873527	IC50	137 nM
CHEMBL4864603	IC50	158 nM
CHEMBL4086212	IC50	166 nM
CHEMBL4851242	IC50	170 nM
CHEMBL4518537	IC50	173 nM
CHEMBL4096857	IC50	201 nM
CHEMBL4096505	IC50	220 nM
CHEMBL4087535	IC50	245 nM
CHEMBL4060206	IC50	260 nM
CHEMBL4083687	EC50	300 nM
CHEMBL4074873	EC50	327 nM
CHEMBL4096154	IC50	370 nM
CHEMBL4865584	IC50	427 nM
CHEMBL4282578	EC50	500 nM
Gelsemine	EC50	590 nM
CHEMBL4227048	EC50	661 nM
CHEMBL4066164	IC50	690 nM
CHEMBL4061219	IC50	708 nM
CHEMBL4870669	IC50	730 nM
CHEMBL4849489	IC50	776 nM
CHEMBL4295252	EC50	900 nM
CHEMBL4290867	EC50	900 nM
CHEMBL4447664	IC50	1000 nM
CHEMBL4850957	IC50	1100 nM
CHEMBL4860026	IC50	1100 nM
CHEMBL4870655	IC50	1200 nM
CHEMBL4285964	EC50	1210 nM
CHEMBL4865147	IC50	1340 nM
CHEMBL4873219	IC50	1400 nM
CHEMBL4849060	IC50	1500 nM
CHEMBL4864670	IC50	1700 nM
CHEMBL4278706	EC50	2100 nM
CHEMBL4848356	IC50	2100 nM
CHEMBL4290271	EC50	2300 nM
CHEMBL4277386	EC50	2300 nM
CHEMBL4281910	EC50	2500 nM
CHEMBL4292781	EC50	2700 nM
CHEMBL4861263	IC50	2900 nM
CHEMBL4282176	EC50	3100 nM
CHEMBL4867244	IC50	3200 nM

ChEMBL bioactivities

130 potent at pChembl≥5 of 144 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.87	EC50	13.49	nM	CHEMBL4227298
7.80	EC50	16	nM	CHEMBL4070615
7.37	IC50	43	nM	CHEMBL4103909
7.34	IC50	46	nM	CHEMBL4079657
7.25	IC50	56	nM	CHEMBL4102677
7.24	IC50	58	nM	STRYCHNINE
7.22	IC50	60	nM	STRYCHNINE
7.18	EC50	66	nM	CHEMBL4070615
7.10	IC50	80	nM	CHEMBL4089150
7.01	IC50	97	nM	CHEMBL4060962
6.94	IC50	116	nM	CHEMBL4068867
6.83	IC50	147	nM	CHEMBL4518537
6.82	IC50	150	nM	CHEMBL4079657
6.80	IC50	158.5	nM	CHEMBL4079657
6.77	EC50	171	nM	CHEMBL4074873
6.75	IC50	180	nM	STRYCHNINE
6.74	IC50	182	nM	STRYCHNINE
6.69	IC50	204.2	nM	CHEMBL4865584
6.68	IC50	210	nM	CHEMBL4102677
6.68	IC50	210	nM	CHEMBL4089150
6.68	IC50	210	nM	CHEMBL4865584
6.67	IC50	213.8	nM	CHEMBL4089150
6.67	IC50	213.8	nM	CHEMBL4102677
6.62	IC50	240	nM	CHEMBL4103909
6.62	IC50	239.9	nM	CHEMBL4103909
6.57	IC50	270	nM	CHEMBL4060962
6.56	IC50	275.4	nM	CHEMBL4060962
6.52	EC50	300	nM	CHEMBL4083687
6.51	IC50	310	nM	CHEMBL4086212
6.51	IC50	309	nM	CHEMBL4086212
6.51	IC50	311	nM	CHEMBL4096857
6.48	EC50	330	nM	CHEMBL4074873
6.46	IC50	350	nM	CHEMBL4068867
6.45	IC50	354.8	nM	CHEMBL4068867
6.43	EC50	370	nM	CHEMBL4083687
6.30	EC50	500	nM	CHEMBL4282578
6.29	IC50	512.9	nM	STRYCHNINE
6.29	IC50	510	nM	STRYCHNINE
6.29	IC50	510	nM	CHEMBL4849489
6.29	IC50	512.9	nM	CHEMBL4849489
6.22	EC50	600	nM	CHEMBL4284872
6.18	IC50	660.7	nM	CHEMBL4096505
6.18	EC50	660.7	nM	CHEMBL4227048
6.17	IC50	670	nM	CHEMBL4096505
6.17	IC50	680	nM	CHEMBL4870655
6.17	IC50	676.1	nM	CHEMBL4870655
6.16	EC50	700	nM	CHEMBL4284872
6.15	IC50	710	nM	CHEMBL4087535
6.15	IC50	708	nM	CHEMBL4087535
6.11	IC50	780	nM	CHEMBL4066164

PubChem BioAssay actives

130 with measured affinity, of 407 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3,5-ditert-butyl-2,6-dihydroxybenzoic acid	1388379: Positive allosteric modulation of human GlyRalpha3beta expressed in CHO cells assessed as potentiation of EC20 glycine-induced ion flux by HT assay	ec50	0.0135	uM
(3S,3aS,9bS)-2-(1,3-benzodioxol-5-ylsulfonyl)-3,5-dimethyl-1,3,3a,9b-tetrahydropyrrolo[3,4-c][1,6]naphthyridin-4-one	1388057: Positive allosteric modulation of human glycine alpha1beta receptor expressed in HEK293T cells assessed as glycine-induced increase in current response after 18 to 24 hrs by membrane potential blue dye based FLIPR assay	ec50	0.0160	uM
(4aR,5aS,8aR,13aS,15E,15aR,15bR)-15-prop-2-ynoxyimino-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431420: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in HEK293 cells assessed as inhibition of glycine-induced current at -50mV holding potential by whole cell patch-clamp method	ic50	0.0430	uM
(4aR,5aS,8aR,13aS,15E,15aR,15bR)-15-prop-2-enoxyimino-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431420: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in HEK293 cells assessed as inhibition of glycine-induced current at -50mV holding potential by whole cell patch-clamp method	ic50	0.0460	uM
(4aR,5aS,8aR,13aS,15E,15aR,15bR)-15-methoxyimino-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431420: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in HEK293 cells assessed as inhibition of glycine-induced current at -50mV holding potential by whole cell patch-clamp method	ic50	0.0560	uM
(4aR,5aS,8aR,13aS,15aS,15bR)-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431420: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in HEK293 cells assessed as inhibition of glycine-induced current at -50mV holding potential by whole cell patch-clamp method	ic50	0.0580	uM
(4aR,5aS,8aR,13aS,15E,15aR,15bR)-15-hydroxyimino-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431420: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in HEK293 cells assessed as inhibition of glycine-induced current at -50mV holding potential by whole cell patch-clamp method	ic50	0.0800	uM
(4aR,5aS,8aR,13aS,15aS,15bR)-10-amino-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431420: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in HEK293 cells assessed as inhibition of glycine-induced current at -50mV holding potential by whole cell patch-clamp method	ic50	0.0970	uM
(4aR,5aS,8aR,13aS,15E,15aR,15bR)-15-propoxyimino-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431420: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in HEK293 cells assessed as inhibition of glycine-induced current at -50mV holding potential by whole cell patch-clamp method	ic50	0.1160	uM
N-[(4aR,5aS,8aR,13aS,15S,15aR,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-15-yl]propanamide	1545116: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in HEK293 cells assessed as reduction in glycine-induced whole cell currents by patch-clamp technique	ic50	0.1470	uM
(3aS,9bS)-2-(1-benzofuran-5-ylsulfonyl)-5-methyl-1,3,3a,9b-tetrahydropyrrolo[3,4-c][1,6]naphthyridin-4-one	1388057: Positive allosteric modulation of human glycine alpha1beta receptor expressed in HEK293T cells assessed as glycine-induced increase in current response after 18 to 24 hrs by membrane potential blue dye based FLIPR assay	ec50	0.1710	uM
N,N’-bis[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]tetradecanediamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	0.2042	uM
(3aS,9bS)-2-(1,3-benzodioxol-5-ylsulfonyl)-5-methyl-1,3,3a,9b-tetrahydropyrrolo[3,4-c]quinolin-4-one	1401008: Positive allosteric modulation of human GlyRalpha1beta assessed as increase in glycine-induced chloride ion flux by FLIPR assay	ec50	0.3000	uM
(4aR,5aS,8aR,13aS,15E,15aR,15bR)-15-phenylmethoxyimino-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431418: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in human tsA201 cells assessed as inhibition of glycine-induced receptor activation after 30 mins by FLIPR membrane potential blue assay	ic50	0.3090	uM
N-[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]propanamide	1431420: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in HEK293 cells assessed as inhibition of glycine-induced current at -50mV holding potential by whole cell patch-clamp method	ic50	0.3110	uM
1-(1,3-benzodioxol-5-ylsulfonyl)-3-(5-chloro-2-methoxyphenoxy)azetidine	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	0.5000	uM
N-[2-[[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]amino]-2-oxoethyl]octanamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	0.5100	uM
6-[3-(5-chloro-2-methoxyphenoxy)azetidin-1-yl]sulfonyl-3H-1,3-benzoxazol-2-one	1401008: Positive allosteric modulation of human GlyRalpha1beta assessed as increase in glycine-induced chloride ion flux by FLIPR assay	ec50	0.6000	uM
methyl 2-[(E)-[(4aR,5aS,8aR,13aS,15aR,15bR)-14-oxo-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-15-ylidene]amino]oxyacetate	1431418: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in human tsA201 cells assessed as inhibition of glycine-induced receptor activation after 30 mins by FLIPR membrane potential blue assay	ic50	0.6607	uM
4-[[(2R)-8-fluoro-3-oxo-4-[[2-(trifluoromethyl)phenyl]methyl]-1,4-benzothiazin-2-yl]methyl]benzoic acid	1388379: Positive allosteric modulation of human GlyRalpha3beta expressed in CHO cells assessed as potentiation of EC20 glycine-induced ion flux by HT assay	ec50	0.6607	uM
N-[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]octanamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	0.6761	uM
(4aR,5aS,8aR,13aS,15E,15aR,15bR)-15-pentoxyimino-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431418: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in human tsA201 cells assessed as inhibition of glycine-induced receptor activation after 30 mins by FLIPR membrane potential blue assay	ic50	0.7079	uM
(4aR,5aS,8aR,13aS,15E,15aR,15bR)-15-(2-phenylethoxyimino)-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431418: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in human tsA201 cells assessed as inhibition of glycine-induced receptor activation after 30 mins by FLIPR membrane potential blue assay	ic50	0.7762	uM
N,N’-bis[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]dodecanediamide	1761886: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in HEK293 cells assessed as reduction in glycine-induced currents by whole-cell patch-clamp assay	ic50	0.8000	uM
(4aR,5aS,8aR,13aS,15E,15aR,15bR)-15-butoxyimino-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431418: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in human tsA201 cells assessed as inhibition of glycine-induced receptor activation after 30 mins by FLIPR membrane potential blue assay	ic50	0.8710	uM
N,N’-bis[2-[[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]amino]-2-oxoethyl]decanediamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	0.8710	uM
5-[3-(5-chloro-2-methoxyphenoxy)azetidin-1-yl]sulfonyl-1,3-benzothiazole	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	0.9000	uM
5-[3-(5-chloro-2-methoxyphenoxy)azetidin-1-yl]sulfonyl-1H-indazole	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	0.9000	uM
(4aR,5aS,8aR,13aS,15E,15aR,15bR)-15-(2-methylpropoxyimino)-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one	1431418: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in human tsA201 cells assessed as inhibition of glycine-induced receptor activation after 30 mins by FLIPR membrane potential blue assay	ic50	1.1000	uM
1-(1,3-benzodioxol-5-ylsulfonyl)-3-(5-fluoro-2-methoxyphenoxy)azetidine	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	1.2100	uM
N,N’-bis[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]octanediamide	1761886: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in HEK293 cells assessed as reduction in glycine-induced currents by whole-cell patch-clamp assay	ic50	1.3000	uM
methyl 5-[(E)-[(4aR,5aS,8aR,13aS,15aR,15bR)-14-oxo-2,4a,5,5a,7,8,13a,15a,15b,16-decahydro4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-15-ylidene]amino]oxypentanoate	1431418: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in human tsA201 cells assessed as inhibition of glycine-induced receptor activation after 30 mins by FLIPR membrane potential blue assay	ic50	1.4791	uM
N,N’-bis[2-[[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]amino]-2-oxoethyl]nonanediamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	1.7000	uM
N-[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]-5-[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[3-[[5-[[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]amino]-5-oxopentyl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]pentanamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	1.7783	uM
N,N’-bis[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]decanediamide	1761886: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in HEK293 cells assessed as reduction in glycine-induced currents by whole-cell patch-clamp assay	ic50	1.9000	uM
N,N’-bis[2-[[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]amino]-2-oxoethyl]dodecanediamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	1.9000	uM
N,N’-bis[2-[[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]amino]-2-oxoethyl]tetradecanediamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	1.9953	uM
(2S,3S)-1-(1,3-benzodioxol-5-ylsulfonyl)-3-(5-chloro-2-methoxyphenoxy)-2-methylazetidine	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	2.1000	uM
1,1,1-trifluoro-2-[4-[[2-piperidin-1-yl-4-(trifluoromethyl)-4,5-dihydro-1,3-thiazol-5-yl]sulfonyl]phenyl]propan-2-ol	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	2.2000	uM
2-[4-[[2-ethylimino-4-(trifluoromethyl)-1,3-thiazolidin-5-yl]sulfonyl]phenyl]-1,1,1-trifluoropropan-2-ol	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	2.2000	uM
N,N’-bis[2-[[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]amino]-2-oxoethyl]heptanediamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	2.2000	uM
N,N’-bis[2-[[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]amino]-2-oxoethyl]hexadecanediamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	2.2000	uM
6-[3-(5-chloro-2-methoxyphenoxy)azetidin-1-yl]sulfonyl-1H-indazole	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	2.3000	uM
1-(1,3-benzodioxol-5-ylsulfonyl)-3-(2-methoxyphenoxy)azetidine	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	2.3000	uM
N,N’-bis[2-[[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]amino]-2-oxoethyl]octanediamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	2.3988	uM
5-[3-(5-chloro-2-methoxyphenoxy)azetidin-1-yl]sulfonyl-1-methylbenzimidazole	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	2.5000	uM
(2R,3R)-1-(1,3-benzodioxol-5-ylsulfonyl)-3-(5-chloro-2-methoxyphenoxy)-2-methylazetidine	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	2.7000	uM
1-(1,3-benzodioxol-5-ylsulfonyl)-3-(2-methoxy-5-methylphenoxy)azetidine	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	3.1000	uM
5-[3-(5-chloro-2-methoxyphenoxy)azetidin-1-yl]sulfonyl-1-methylindazole	1400990: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins by FLIPR assay	ec50	3.3000	uM
N-[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]-11-[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[3-[[11-[[(4aR,5aS,8aR,13aS,15aS,15bR)-14-oxo-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-10-yl]amino]-11-oxoundecyl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]undecanamide	1761884: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay	ic50	3.8904	uM

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	5
entinostat	decreases expression, affects cotreatment	2
Nickel	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Temozolomide	affects response to substance	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	increases abundance, increases expression	1
Carmustine	affects response to substance	1
Cyclophosphamide	increases expression	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Lead	affects expression	1
Ouabain	increases expression	1

ChEMBL screening assays

30 unique, capped per target: 29 binding, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3998488	Binding	Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in human tsA201 cells assessed as inhibition of glycine-induced receptor activation after 30 mins by FLIPR membrane potential blue assay	Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists. — *J Nat Prod*
CHEMBL6108592	Toxicity	Inhibition of glycine receptor alpha1beta (unknown origin)	Discovery of BT-114143, a Novel and Potent Phosphoric Acid-Containing Small-Molecule Plasminogen Activation Inhibitor for Hyperfibrinolysis. — *J Med Chem*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SQ06	HAP1 GLRB (-) 1	Cancer cell line	Male
CVCL_SQ07	HAP1 GLRB (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

4 trials:

NCT	Phase	Status	Title
NCT01476514	Not specified	TERMINATED	Effects of Mutations of the Glycine Gene Associated With Hyperekplexia on Central Pain Processing
NCT05168969	Not specified	COMPLETED	Hyperekplexia in Patients With CTNNB1 Mutation
NCT05652101	Not specified	RECRUITING	Hyperekplexia : Adaptative Skills and Neurodevelopmental Trajectory
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for GLRB across ~30M SureChEMBL compounds — explore on Sugi Predict.