GABRR2

Summary

GABRR2 (gamma-aminobutyric acid type A receptor subunit rho2, HGNC:4091) is a protein-coding gene on chromosome 6q15, encoding Gamma-aminobutyric acid receptor subunit rho-2 (P28476). Rho subunit of the pentameric ligand-gated chloride channels responsible for mediating the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain.

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability.

Source: NCBI Gene 2570 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 99 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002043

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4091
Approved symbol	GABRR2
Name	gamma-aminobutyric acid type A receptor subunit rho2
Location	6q15
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000111886
Ensembl biotype	protein_coding
OMIM	137162
Entrez	2570

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000402938, ENST00000602432, ENST00000602808

RefSeq mRNA: 1 — MANE Select: NM_002043 NM_002043

CCDS: CCDS5020

Canonical transcript exons

ENST00000402938 — 9 exons

Exon	Start	End
ENSE00000760414	89269011	89269234
ENSE00000798183	89254464	89257981
ENSE00003605857	89315053	89315299
ENSE00003624291	89264412	89264608
ENSE00003625760	89265613	89265765
ENSE00003633619	89268014	89268096
ENSE00003641133	89271655	89271722
ENSE00003672158	89299759	89299865
ENSE00003679631	89267679	89267819

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 86.91.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0160 / max 10.3375, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74687	0.0077	3
74686	0.0056	3
74685	0.0027	3

Top tissues by expression

276 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	86.91	gold quality
olfactory bulb	UBERON:0002264	86.55	gold quality
diaphragm	UBERON:0001103	78.96	gold quality
cervix squamous epithelium	UBERON:0006922	78.27	gold quality
vena cava	UBERON:0004087	76.93	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.77	gold quality
quadriceps femoris	UBERON:0001377	74.79	gold quality
vastus lateralis	UBERON:0001379	74.52	gold quality
oocyte	CL:0000023	74.23	gold quality
thymus	UBERON:0002370	73.87	gold quality
body of tongue	UBERON:0011876	73.14	gold quality
dorsal plus ventral thalamus	UBERON:0001897	72.75	gold quality
cardia of stomach	UBERON:0001162	72.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.65	gold quality
nasal cavity epithelium	UBERON:0005384	72.62	gold quality
subthalamic nucleus	UBERON:0001906	72.37	gold quality
pharyngeal mucosa	UBERON:0000355	72.30	gold quality
ileal mucosa	UBERON:0000331	72.05	silver quality
male germ cell	CL:0000015	72.03	silver quality
saphenous vein	UBERON:0007318	71.94	gold quality
cervix epithelium	UBERON:0004801	71.80	gold quality
upper arm skin	UBERON:0004263	71.55	gold quality
skeletal muscle tissue	UBERON:0001134	71.48	gold quality
secondary oocyte	CL:0000655	71.25	gold quality
biceps brachii	UBERON:0001507	71.18	gold quality
cerebellar vermis	UBERON:0004720	71.15	gold quality
nipple	UBERON:0002030	71.04	gold quality
trachea	UBERON:0003126	70.95	gold quality
deltoid	UBERON:0001476	70.88	silver quality
pericardium	UBERON:0002407	70.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting GABRR2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728

Literature-anchored findings (GeneRIF, showing 8)

• Molecular modeling of ligand-receptor interactions of gamma-aminobutyric acid type C receptor rho1, human. (PMID:19167917)
• GABRR1 and GABRR2 encode the GABA-A receptor subunits rho1 and rho2 and are associated with alcohol dependence (PMID:19536785)
• association between serum creatinine level and polymorphisms in the collagen type XXII alpha 1 (COL22A1) gene, on chromosome 8, and in the synaptotagmin-1 (SYT1) gene, on chromosome 12 (PMID:20222955)
• found no significant differences in either the frequencies of the GABRR1-M26V, GABRR1- H27R, GABRR2-T455M, and GABRR3-Y205X genotypes or in the frequencies of the allelic variants of these polymorphisms in patients with essential tremor (PMID:20820800)
• significant involvement of alpha (GABRA6) and beta (GABRB2) subunits of GABA(A) receptor in epilepsy susceptibility in north Indian population (PMID:21420396)
• GABRR2 and CHRNA3 were found to be differentially expressed after risperidone treatment. These genes may be regulated by antipsychotic use. (PMID:24113126)
• The genetic variant of GABRR2 gene contributes to the difference of individuals’ general cognitive ability in a Chinese Han population. (PMID:26922432)
• GABAergic genes interacting with parenting in adolescent depressive symptoms: GABRR2 X perceived parental support interaction. (PMID:28660714)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabrr2b	ENSDARG00000014057
danio_rerio	gabrr2a	ENSDARG00000052982
mus_musculus	Gabrr2	ENSMUSG00000023267
rattus_norvegicus	Gabrr2	ENSRNOG00000007490

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), 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)

Protein

Protein identifiers

Gamma-aminobutyric acid receptor subunit rho-2 — P28476 (reviewed: P28476)

Alternative names: GABA(A) receptor subunit rho-2, GABA(C) receptor

All UniProt accessions (1): P28476

UniProt curated annotations — full annotation on UniProt →

Function. Rho subunit of the pentameric ligand-gated chloride channels responsible for mediating the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain. Rho-containing GABA-gated chloride channels are a subclass of GABA(A) receptors (GABAARs) entirely composed of rho subunits, where GABA molecules bind at the rho intersubunit interfaces. When activated by GABA, rho-GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. Rho-2 GABAARs may contribute to the regulation of glial development in the cerebellum by controlling extrasynaptic transmission. Rho-2 GABAARs are also involved in neuronal tonic (extrasynaptic) and phasic (synaptic) transmission in the Purkinje neurons of the cerebellum. Rho-2 GABAARs expressed in retina may play a role in retinal neurotransmission.

Subunit / interactions. Three rho subunits (rho-1/GBRR1, rho-2/GBRR2 and rho-3/GBRR3) coassemble either to form functional homopentamers or heteropentamers. Rho-2 is unable to form a functional homopentamer. Interacts with SQSTM1.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Domain organisation. GABAARs subunits share a common topological structure: a peptide sequence made up of a long extracellular N-terminal, four transmembrane domains, intracellular or cytoplasmic domain located between the third and the fourth transmembrane domains.

Miscellaneous. Isoform 2 could be translated from an upstream initiator ATG located in frame within the first coding exon. The probability of a signal peptide within this isoform is very low.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRR2 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P28476-1	1	yes
P28476-2	2

RefSeq proteins (1): NP_002034* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006028	GABAA/Glycine_rcpt	Family
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR008057	GABAAa_rho_rcpt	Family
IPR008059	GABAAa_rho2_rcpt	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

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (19 total): topological domain 5, transmembrane region 4, binding site 3, glycosylation site 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28476-F1	77.00	0.48

Functional residue map

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

Ligand- & substrate-binding residues (3): 105 (in chain a); 169 (in chain a); 197 (in chain b)

Disulfide bonds (1): 178–192

Glycosylation sites (2): 120, 254

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-977443	GABA receptor activation

MSigDB gene sets: 166 (showing top): chr6q15, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, GOBP_CELL_CELL_SIGNALING, GOBP_CHLORIDE_TRANSPORT, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, MODULE_99, GOBP_SYNAPTIC_SIGNALING, GOBP_SENSORY_PERCEPTION, CREBP1_01, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES, GOBP_TRANSMEMBRANE_TRANSPORT, LIU_CDX2_TARGETS_UP

GO Biological Process (10): signal transduction (GO:0007165), gamma-aminobutyric acid signaling pathway (GO:0007214), chemical synaptic transmission (GO:0007268), visual perception (GO:0007601), synaptic transmission, GABAergic (GO:0051932), chloride transmembrane transport (GO:1902476), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (8): GABA-A receptor activity (GO:0004890), protein domain specific binding (GO:0019904), GABA-gated chloride ion channel activity (GO:0022851), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), chloride channel activity (GO:0005254)

GO Cellular Component (8): plasma membrane (GO:0005886), chloride channel complex (GO:0034707), postsynaptic membrane (GO:0045211), intracellular vesicle (GO:0097708), GABA-ergic synapse (GO:0098982), GABA-A receptor complex (GO:1902711), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GABA receptor activity	2
transmitter-gated monoatomic ion channel activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell-cell signaling	1
anterograde trans-synaptic signaling	1
sensory perception of light stimulus	1
chemical synaptic transmission	1
chloride transport	1
monoatomic anion transmembrane transport	1
transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of membrane potential	1
protein binding	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
regulation of postsynaptic membrane potential	1
signaling receptor 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
membrane	1
cell periphery	1
monoatomic ion channel complex	1
synaptic membrane	1
postsynapse	1
intracellular anatomical structure	1
vesicle	1
intracellular membrane-bounded organelle	1
synapse	1
GABA receptor complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

710 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRR2	EYS	Q5T1H1	547
GABRR2	GABBR2	O75899	447
GABRR2	PM20D2	Q8IYS1	429
GABRR2	GABRG2	P18507	408
GABRR2	GABRQ	Q9UN88	408
GABRR2	CHRNA2	Q15822	364
GABRR2	CDC45	O75419	363
GABRR2	MTMR4	Q9NYA4	353
GABRR2	KCNV2	Q8TDN2	339
GABRR2	TMEM145	Q8NBT3	323
GABRR2	CARMIL3	Q8ND23	323
GABRR2	RUNDC3A	Q59EK9	321
GABRR2	GRIN2C	Q14957	307
GABRR2	NRSN2	Q9GZP1	307
GABRR2	RNGTT	O60942	305

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A8MPY1, F1R8P4, O75311, O93430, P02713, P02714, P02715, P02716, P02717, P02718, P04759, P05376, P09628, P09660, P09690, P20782, P22770, P22771, P23415, P23416, P24046, P24524, P25110, P26714, P28476, P43144, P47742, P49580, P49582, P50572, P50573, P54244, P56475, P56476, P57695, Q05941, Q07001, Q08832, Q0II76, Q24352

Diamond homologs: A8MPY1, D1LYT2, F1R8P4, G5EBR3, O00591, O09028, O14764, O18276, O75311, O93430, P07727, P08219, P08220, P0C2W5, P10063, P10064, P14867, P15431, P16305, P18505, P18506, P18507, P18508, P19019, P19150, P19969, P20236, P20237, P20781, P21548, P22300, P22723, P22771, P22933, P23415, P23416, P23574, P23576, P24045, P24046

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1955 predictions. Top by Δscore:

Variant	Effect	Δscore
6:89257982:C:CC	acceptor_gain	1.0000
6:89264408:TCAC:T	donor_loss	1.0000
6:89264409:CACCT:C	donor_loss	1.0000
6:89264410:A:AC	donor_gain	1.0000
6:89264410:A:AT	donor_loss	1.0000
6:89264411:C:CC	donor_gain	1.0000
6:89264411:C:T	donor_loss	1.0000
6:89264411:CCTT:C	donor_gain	1.0000
6:89264606:TACCT:T	acceptor_loss	1.0000
6:89264607:ACCTG:A	acceptor_loss	1.0000
6:89264608:CCT:C	acceptor_loss	1.0000
6:89264609:C:A	acceptor_loss	1.0000
6:89264610:T:G	acceptor_loss	1.0000
6:89270034:C:T	acceptor_gain	1.0000
6:89271627:CG:C	donor_gain	1.0000
6:89271720:GGCCT:G	acceptor_loss	1.0000
6:89271722:CCT:C	acceptor_loss	1.0000
6:89271723:C:CC	acceptor_gain	1.0000
6:89271724:T:C	acceptor_loss	1.0000
6:89257990:A:T	acceptor_gain	0.9900
6:89259124:T:TA	donor_gain	0.9900
6:89264426:T:TA	donor_gain	0.9900
6:89264431:T:A	donor_gain	0.9900
6:89264606:TAC:T	acceptor_gain	0.9900
6:89264609:C:CC	acceptor_gain	0.9900
6:89265761:CCAGC:C	acceptor_gain	0.9900
6:89265762:CAGCC:C	acceptor_gain	0.9900
6:89267756:T:C	donor_gain	0.9900
6:89269007:CTAC:C	donor_loss	0.9900
6:89269010:C:CA	donor_loss	0.9900

AlphaMissense

3100 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:89269123:A:G	W134R	1.000
6:89269123:A:T	W134R	1.000
6:89264505:G:C	S331R	0.999
6:89264505:G:T	S331R	0.999
6:89264507:T:G	S331R	0.999
6:89267785:C:A	W210C	0.999
6:89267785:C:G	W210C	0.999
6:89267787:A:G	W210R	0.999
6:89267787:A:T	W210R	0.999
6:89267798:A:G	L206P	0.999
6:89268015:G:C	S198R	0.999
6:89268015:G:T	S198R	0.999
6:89268017:T:G	S198R	0.999
6:89269016:G:C	S169R	0.999
6:89269016:G:T	S169R	0.999
6:89269018:T:G	S169R	0.999
6:89269023:A:G	L167P	0.999
6:89269121:C:A	W134C	0.999
6:89269121:C:G	W134C	0.999
6:89269199:C:A	W108C	0.999
6:89269199:C:G	W108C	0.999
6:89269201:A:G	W108R	0.999
6:89269201:A:T	W108R	0.999
6:89269209:C:G	R105P	0.999
6:89264474:A:G	Y342H	0.998
6:89265613:C:G	G297R	0.998
6:89265653:G:C	F283L	0.998
6:89265653:G:T	F283L	0.998
6:89265655:A:G	F283L	0.998
6:89265664:A:G	W280R	0.998

dbSNP variants (sampled 300 via entrez): RS1000026747 (6:89283259 A>G), RS1000136585 (6:89289045 A>G), RS1000172919 (6:89266816 C>G,T), RS1000220423 (6:89305840 T>G), RS1000275558 (6:89308966 G>A), RS1000303870 (6:89288708 A>G), RS1000363965 (6:89301949 C>T), RS1000411057 (6:89296028 G>A,T), RS1000651232 (6:89299916 G>A,T), RS1000717363 (6:89301249 C>T), RS1000724860 (6:89272611 G>A), RS1000727771 (6:89287723 C>G), RS1000782658 (6:89254605 G>T), RS1000838118 (6:89271359 G>A), RS1000860490 (6:89301784 T>C,G)

Disease associations

OMIM: gene MIM:137162 | disease phenotypes: MIM:190300

GenCC curated gene-disease

Mondo (1): essential tremor (MONDO:0003233)

Orphanet (1): NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009214_2	Third ventricle volume	4.000000e-07
GCST011426_22	Systemic lupus erythematosus	2.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020329	Essential Tremor	C10.228.662.350

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2109242 (PROTEIN COMPLEX GROUP), CHEMBL2375 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 165,947 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1	160,188
CHEMBL273481	MUSCIMOL	1	5,759

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

ChEMBL bioactivities

5 potent at pChembl≥5 of 11 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.40	EC50	400	nM	t-4-AMINOCROTONIC ACID (TACA)
6.22	Kd	600	nM	t-4-AMINOCROTONIC ACID (TACA)
5.85	Kd	1400	nM	MUSCIMOL
5.77	Kd	1700	nM	GAMMA-AMINOBUTYRIC ACID
5.52	EC50	3000	nM	IMIDAZOLE ACETIC ACID

PubChem BioAssay actives

5 with measured affinity, of 22 total; 4 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
(E)-4-aminobut-2-enoic acid	71532: Partial agonist activity against homomeric rho-2 subunit GABA-C receptor expressed in Xenopus oocytes	ec50	0.4000	uM
5-(aminomethyl)-1,2-oxazol-3-one	71414: Partial agonist activity against human rho-2 subunit GABA-C receptor expressed in Xenopus oocytes	kd	1.4000	uM
.gamma.-aminobutyric acid	71408: Agonist activity against Gamma-aminobutyric acid type C (GABA-C) receptor derived from bovine retinal RNA expressed in Xenopus oocytes	kd	1.7000	uM
2-(1H-imidazol-5-yl)acetic acid	71534: Partial agonist activity against rho-2 subunit GABA-C receptor expressed in Xenopus oocytes, higher intrinsic activity (Im 38%)	ec50	3.0000	uM

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aminomethylphosphonic acid (AMPA)	increases expression	1
di-n-butylphosphoric acid	affects expression	1
licochalcone B	increases expression	1
Fulvestrant	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Lead	decreases expression	1
Theophylline	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
2,4-Dichlorophenoxyacetic Acid	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, decreases expression	1
Okadaic Acid	increases expression	1
Acrylamide	increases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 14 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL679661	Functional	Agonist activity against Gamma-aminobutyric acid C (GABA-C) receptor derived from bovine retinal RNA expressed in Xenopus oocytes	GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology. — J Med Chem
CHEMBL679664	Binding	Activation of human rho2 GABA-C receptor at 34% of maximal GABA-induced response	GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology. — J Med Chem

Clinical trials (associated diseases)

235 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00439699	PHASE4	COMPLETED	A Pilot Clinical Trial Of Memantine for Essential Tremor
NCT00584376	PHASE4	COMPLETED	Pregabalin (Lyrica) for the Treatment of Essential Tremor
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02111369	PHASE4	COMPLETED	Propranolol and Botulinum Toxin for Essential Vocal Tremor
NCT02495883	PHASE4	COMPLETED	Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
NCT00018564	PHASE3	COMPLETED	Novel Therapies for Essential Tremor
NCT00236496	PHASE3	COMPLETED	A Comparison of the Efficacy and Safety of Topiramate Versus Placebo in Treating Tremor of Unknown Cause.
NCT01441284	PHASE3	WITHDRAWN	Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
NCT04265209	PHASE3	COMPLETED	[18F] LBT-999 PET Compared to [123I]-FP/CIT SPECT to Distinguish Between Parkinson’s Diseases and Essential Tremor
NCT06087276	PHASE3	ENROLLING_BY_INVITATION	Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET)
NCT00080366	PHASE2	COMPLETED	Octanol to Treat Essential Tremor
NCT00102596	PHASE2	COMPLETED	Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor
NCT00223743	PHASE2	COMPLETED	A Safety/Efficacy Trial of Zonisamide for Essential Tremor
NCT00321087	PHASE2	TERMINATED	A Study of T2000 in Essential Tremor
NCT00598078	PHASE2	COMPLETED	Multiple-dose,Double-blind,Placebo-controlled Study of Sodium Oxybate in Patients With Essential Tremor
NCT00655278	PHASE2	TERMINATED	T2000 in Essential Tremor - Open Label Continuation
NCT01332695	PHASE2	COMPLETED	A Pilot Efficacy and Safety Study of ST101 in Essential Tremor
NCT02277106	PHASE2	COMPLETED	Evaluate SAGE-547 in Participants With Essential Tremor
NCT02551848	PHASE2	UNKNOWN	Kinematic-based BoNT-A Injections for Bilateral ET
NCT02668146	PHASE2	UNKNOWN	An Efficacy/Safety Study of Perampanel for Reducing Essential Tremor
NCT02978781	PHASE2	COMPLETED	A Study to Evaluate SAGE-217 in Participants With Essential Tremor
NCT03101241	PHASE2	COMPLETED	A Phase 2 RCT Study of CX-8998 for Essential Tremor
NCT03688685	PHASE2	COMPLETED	A Clinical Study to Evaluate CAD-1883 in Essential Tremor
NCT03780426	PHASE2	COMPLETED	tSMS in Essential Tremor
NCT04305275	PHASE2	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor
NCT04727658	PHASE2	TERMINATED	Linac FRACtionated Radiosurgical THALamotomie in Tremors (FRACTHAL)
NCT04880616	PHASE2	COMPLETED	Safety, Efficacy, and Tolerability of NBI-827104 for the Treatment of Essential Tremor
NCT05021978	PHASE2	COMPLETED	A Clinical Trial of PRAX-944 in Participants With Essential Tremor
NCT05021991	PHASE2	COMPLETED	A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor
NCT05122650	PHASE2	COMPLETED	A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET)
NCT05173012	PHASE2	COMPLETED	Study to Evaluate SAGE-324 in Participants With Essential Tremor
NCT05387642	PHASE2	WITHDRAWN	A Clinical Trial of PRAX-114 in Participants With Essential Tremor
NCT06312800	PHASE2	WITHDRAWN	Acamprosate and Methazolamide for Essential Tremor
NCT06821906	PHASE2	RECRUITING	Stereotactic Radiosurgery in the Treatment of Essential Tremor
NCT07074002	PHASE2	RECRUITING	Proof of Concept Study on BP1.4979 Effect on Essential Tremor
NCT07103265	PHASE2	NOT_YET_RECRUITING	Developing a New LIFU Neuromodulation Method to Suppress Tremor
NCT00001986	PHASE1	COMPLETED	1-Octanol to Treat Essential Tremor
NCT00016679	PHASE1	COMPLETED	1-Octanol to Treat Essential Tremor
NCT01304758	PHASE1	COMPLETED	ExAblate Transcranial MR Guided Focused Ultrasound in the Treatment of Essential Tremor