RGS4

Summary

RGS4 (regulator of G protein signaling 4, HGNC:10000) is a protein-coding gene on chromosome 1q23.3, encoding Regulator of G-protein signaling 4 (P49798). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.

Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 4 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. Regulator of G protein signaling 4 protein is 37% identical to RGS1 and 97% identical to rat Rgs4. This protein negatively regulate signaling upstream or at the level of the heterotrimeric G protein and is localized in the cytoplasm. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 5999 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 42 total
• Druggable target: yes
• MANE Select transcript: NM_005613

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10000
Approved symbol	RGS4
Name	regulator of G protein signaling 4
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000117152
Ensembl biotype	protein_coding
OMIM	602516
Entrez	5999

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000367906, ENST00000367908, ENST00000367909, ENST00000421743, ENST00000491263, ENST00000527393, ENST00000527809, ENST00000528938, ENST00000531057, ENST00000533019

RefSeq mRNA: 4 — MANE Select: NM_005613 NM_001102445, NM_001113380, NM_001113381, NM_005613

CCDS: CCDS1243, CCDS44270, CCDS44271, CCDS44272

Canonical transcript exons

ENST00000367909 — 5 exons

Exon	Start	End
ENSE00001702189	163074321	163076802
ENSE00003569569	163073456	163073622
ENSE00003581479	163072805	163072866
ENSE00003619818	163072395	163072499
ENSE00003993184	163069361	163069528

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 99.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.0590 / max 6975.8565, expressed in 999 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6330	66.9320	991
6329	0.6590	180
6328	0.2087	91
6339	0.0951	39
6338	0.0864	44
6340	0.0521	22
6327	0.0258	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.75	gold quality
endothelial cell	CL:0000115	99.47	gold quality
frontal pole	UBERON:0002795	99.46	gold quality
orbitofrontal cortex	UBERON:0004167	99.42	gold quality
superior frontal gyrus	UBERON:0002661	99.26	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.20	gold quality
primary visual cortex	UBERON:0002436	98.55	gold quality
occipital lobe	UBERON:0002021	98.37	gold quality
prefrontal cortex	UBERON:0000451	98.13	gold quality
parietal lobe	UBERON:0001872	97.98	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.95	gold quality
postcentral gyrus	UBERON:0002581	97.81	gold quality
frontal cortex	UBERON:0001870	97.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.23	gold quality
entorhinal cortex	UBERON:0002728	96.81	gold quality
islet of Langerhans	UBERON:0000006	96.78	gold quality
cingulate cortex	UBERON:0003027	96.17	gold quality
anterior cingulate cortex	UBERON:0009835	96.10	gold quality
right frontal lobe	UBERON:0002810	96.09	gold quality
germinal epithelium of ovary	UBERON:0001304	96.00	gold quality
parietal pleura	UBERON:0002400	95.92	gold quality
neocortex	UBERON:0001950	95.66	gold quality
adult organism	UBERON:0007023	95.31	gold quality
substantia nigra pars compacta	UBERON:0001965	95.28	gold quality
cerebral cortex	UBERON:0000956	94.62	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.01	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.78	gold quality
dorsal root ganglion	UBERON:0000044	93.77	gold quality
pons	UBERON:0000988	93.67	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-124858	yes	4545.89
E-GEOD-83139	yes	1522.63
E-GEOD-81608	yes	1290.57
E-MTAB-5061	yes	1025.06
E-ENAD-27	yes	842.95
E-MTAB-9388	yes	771.35
E-HCAD-35	yes	38.54
E-HCAD-31	yes	26.24
E-GEOD-81547	yes	19.93
E-ANND-3	yes	5.50
E-HCAD-10	yes	4.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BCL6, CEBPB, FOSL2, GLI1, JUN, NFKB1, NFKB, NFYA, PITX2, PPARD, PROX1, RELA

miRNA regulators (miRDB)

141 targeting RGS4, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4514	99.99	67.10	1870
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6835-3P	99.93	70.49	2904

Literature-anchored findings (GeneRIF, showing 40)

• cytosolic and membrane levels of RGS4 may contribute to the regional differences in the coupling of muscarinic M1 receptors in Alzheimer’s disease (PMID:12422374)
• A significant decrease in the transcript encoding regulator of G-protein signaling 4 (RGS4) in the prefrontal cortex of patients with schizophrenia. (PMID:12436019)
• results suggest that palmitoylation of a Cys residue in the regulator of G protein signaling(RGS) box is critical for RGS16 and RGS4 GAPase activating protein activity and their ability to regulate G protein signaling in mammalian cells (PMID:12642592)
• The data of this research give modest support for the hypothesis that the regulator of G-protein signaling 4 is a susceptibility gene for schizophrenia. (PMID:14732600)
• RGS4 mRNA distribution in human postmortem tissue from normal persons was very dense in most cortical layers examined, with lower density in the basal ganglia and thalamus. (PMID:15182322)
• Results could be interpreted as supporting evidence for the association between RGS4 and schizophrenia. (PMID:15274033)
• RGS4 and beta-tubulin modulate Galpha-GDP and Galpha-GTP states thus modulating MT1 melatonin receptor function. (PMID:15369705)
• RGS4 polymorphisms are associated with alterations in dorsolateral prefrontal cortex (area 9) volumes among schizophrenic patients. (PMID:15381923)
• Although gross indices of signaling were unaffected by RGS4, it slowed the rate of increase in Ins(1,4,5)P3 levels. (PMID:15383626)
• In schizophrenia, significant case-control differences were not observed, though the TDT suggested transmission distortion. For bipolar disorder, an omnibus test suggested differences in the overall distribution of haplotypes bearing all four SNPs. (PMID:15660667)
• No association is identified between RGS4 single nucleotide polymorphism (SNP) markers, genotypes, or haplotypes and schizophrenia (PMID:16082709)
• Data do not directly replicate previous associations of RGS4, but association with SNP 7 in the Scottish population provides some support for a role in schizophrenia susceptibility. (PMID:16176390)
• These results provide the first demonstration of a Ca(2+)-dependent interaction between RGS4 and CaM in vivo and show that association in lipid rafts of the plasma membrane might be involved in this physiological regulation of RGS proteins. (PMID:16246308)
• Finding weakens the evidence that mutations or variation in the RGS4 gene have an effect on schizophrenia susceptibility. (PMID:16508931)
• Results fail to support the RGS4 as a candidate gene for schizophrenia when evaluated with three SNP markers from promoter region and intron 1. (PMID:16526029)
• this meta-analysis did not find statistically significant evidence for association between RGS4 and PRODH and schizophrenia on the basis of either allelic or genotypic analysis. (PMID:16791139)
• RGS4 is an example of a molecule that may underlie increased vulnerability through either genetic or non-genetic mechanisms, which we suggest may be typical of other genes in a complex, polygenic disorder such as schizophrenia. (PMID:16860780)
• Genetic polymorphisms within RGS4 are unlikely to confer an increased susceptibility to the etiology of schizophrenia. (PMID:16904822)
• RGS4 mRNA was inversely correlated with COMT enzyme activity in the dorsolateral prefrontal cortex (PMID:16905560)
• SNPs in RGS4, G72, GRM3, and DISC1 showed evidence for significant statistical epistasis with COMT. (PMID:17006672)
• examined function, receptor specificity, and expression of R4 subfamily RGS proteins, RGS2, -3, -4, -5, and -8 via missense mutations introduced (PMID:17220356)
• RGS4 single nucleotide polymorphism impacts frontal lobe blood oxygenation level-dependent response and network coupling during working memory and results in reductions in gray, white matter structural volume in individuals carrying the A allele. (PMID:17301167)
• In RGS4, the G-allele of the previously reported SNP RGS4-1 (single and as part of haplotypes with SNP RGS4-18) was associated with non-deficit schizophrenia but not with deficit schizophrenia. (PMID:17410640)
• study identified all common RGS4 polymorphisms & evaluated patterns of linkage disequilibrium in relation to schizophrenia; 2 haplotypes reported to confer liability to SZ had significant promoter activity suggesting functional role for both haplotypes (PMID:17515439)
• RGS4 genotypes predicted both the severity of baseline symptoms and relative responsiveness to antipsychotic treatment in patient with schizophrenia. (PMID:17588543)
• Full length cloning and expression analysis of splice variants of RGS4 were performed. (PMID:17707117)
• Multiple splice variant forms of RGS4 and Rgs4 are expressed in human and mouse brain and show differential expression across brain compartments. (PMID:17707117)
• the association of regulator of G-protein signalling 4 protein polymorphisms with the phenotypic subgroups of schizophrenia. (PMID:17722013)
• The isolation and characterization of a novel human RGS4 mutant which displays enhanced or gain-of-function (GOF) activity, is described. (PMID:18031991)
• RGS4 variances influence clinical manifestations of schizophrenia (PMID:18204343)
• RGS4 polymorphism was not associated with treatment response to electroconvulsive therapy in major depressive disorder (PMID:18434012)
• Transgenic overexpression of cardiac myocyte-specific RGS4 attenuates overexpression of hypertrophy-related genes in guanylyl cyclase A-knockout mice. (PMID:18443239)
• Data show that the expression of RGS4 decreases in the prefrontal cortex of postmortem brain samples spanning half a century of human aging (18-67 years). (PMID:18470533)
• Altered RGS4 expression is not universally present throughout the cortex of people with schizophrenia. (PMID:18622782)
• We found evidence of a joint effect between IL3 (rs31400) and DTNBP1 (PMID:18804346)
• results suggest the possibility that alterations in the expression of RGS4-3 contribute to the development of SCZ. (PMID:19041089)
• Regulator of G-protein signaling 4 suppresses LPS-induced MUC5AC overproduction in the airway. (PMID:19059885)
• Prostaglandin E(2) can induce MUC5AC overproduction via the EP(4) receptor and that RGS4 may have suppressive effects in controlling MUC5AC overexpression in the airway. (PMID:19201815)
• RGS4 polymorphisms are associated with variations in cognitive functions and contribute a small but statistically significant proportion of variance in a family-based sample. (PMID:19282471)
• RGS4 plays a key role in G protein coupling selectivity and signaling of the mu- and delta-opioid receptors. (PMID:19324084)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgs4	ENSDARG00000070047
mus_musculus	Rgs4	ENSMUSG00000038530
rattus_norvegicus	Rgs4	ENSRNOG00000002773

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), AXIN1 (ENSG00000103126), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGSL1 (ENSG00000121446), RGS13 (ENSG00000127074), RGS22 (ENSG00000132554), RGS8 (ENSG00000135824), RGS3 (ENSG00000138835), RGS5 (ENSG00000143248), RGS16 (ENSG00000143333), RGS20 (ENSG00000147509), RGS10 (ENSG00000148908), RGS18 (ENSG00000150681), RGS12 (ENSG00000159788), AXIN2 (ENSG00000168646), RGS14 (ENSG00000169220), RGS19 (ENSG00000171700), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Regulator of G-protein signaling 4 — P49798 (reviewed: P49798)

All UniProt accessions (3): P49798, E9PR32, E9PS05

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(z)-alpha is inhibited by phosphorylation of the G-protein. Activity on G(z)-alpha and G(i)-alpha-1 is inhibited by palmitoylation of the G-protein.

Tissue specificity. Expressed in brain and heart. Expressed in brain at protein level. Expressed in prefontal and visual cortex. Isoform 4 and isoform 5 are expressed ubiquitously. Isoform 1, isoform 2 and isoform 3 are not expressed in the cerebellum.

Post-translational modifications. Palmitoylated on Cys-2 and/or Cys-12. Phosphorylated by cyclic GMP-dependent protein kinase.

Disease relevance. Schizophrenia (SCZD) [MIM:181500] A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Isoforms (5)

UniProt ID	Names	Canonical?
P49798-1	1, B	yes
P49798-2	2, A
P49798-3	3, C
P49798-4	4
P49798-5	5

RefSeq proteins (4): NP_001095915, NP_001106851, NP_001106852, NP_005604* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016137	RGS	Domain
IPR024066	RGS_subdom1/3	Homologous_superfamily
IPR034953	RGS_RGS4	Domain
IPR036305	RGS_sf	Homologous_superfamily
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00615

UniProt features (10 total): splice variant 4, lipid moiety-binding region 3, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49798-F1	80.26	0.62

Functional residue map

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

Post-translational modifications (3): 2, 12, 95

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events

MSigDB gene sets: 367 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_RESPONSE_TO_ETHANOL, HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_COCAINE, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_AMINE, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH

GO Biological Process (17): response to amphetamine (GO:0001975), G protein-coupled receptor signaling pathway (GO:0007186), regulation of G protein-coupled receptor signaling pathway (GO:0008277), positive regulation of heart rate (GO:0010460), response to cocaine (GO:0042220), response to ethanol (GO:0045471), regulation of calcium ion transport (GO:0051924), negative regulation of dopamine receptor signaling pathway (GO:0060160), negative regulation of cell growth involved in cardiac muscle cell development (GO:0061052), regulation of actin filament organization (GO:0110053), negative regulation of glycine import across plasma membrane (GO:1900924), negative regulation of potassium ion transmembrane transport (GO:1901380), dorsal root ganglion development (GO:1990791), positive regulation of excitatory postsynaptic potential (GO:2000463), negative regulation of signal transduction (GO:0009968), negative regulation of G protein-coupled receptor signaling pathway (GO:0045744), regulation of potassium ion transmembrane transport (GO:1901379)

GO Molecular Function (5): G-protein alpha-subunit binding (GO:0001965), GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), calmodulin binding (GO:0005516), protein kinase binding (GO:0019901)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
G protein-coupled receptor signaling pathway	2
regulation of signal transduction	2
potassium ion transmembrane transport	2
protein binding	2
response to amine	1
G protein-coupled receptor activity	1
regulation of heart rate	1
positive regulation of heart contraction	1
response to alkaloid	1
response to oxygen-containing compound	1
response to alcohol	1
calcium ion transport	1
regulation of metal ion transport	1
G protein-coupled dopamine receptor signaling pathway	1
negative regulation of G protein-coupled receptor signaling pathway	1
regulation of dopamine receptor signaling pathway	1
negative regulation of cardiac muscle hypertrophy	1
negative regulation of cell growth	1
negative regulation of striated muscle cell differentiation	1
negative regulation of cardiac muscle tissue growth	1
cell growth involved in cardiac muscle cell development	1
regulation of cell growth involved in cardiac muscle cell development	1
actin filament organization	1
regulation of actin cytoskeleton organization	1
regulation of supramolecular fiber organization	1
negative regulation of organic acid transport	1
negative regulation of transmembrane transport	1
negative regulation of amino acid transport	1
regulation of glycine import across plasma membrane	1
glycine import across plasma membrane	1
negative regulation of potassium ion transport	1
regulation of potassium ion transmembrane transport	1
negative regulation of cation transmembrane transport	1
ganglion development	1
positive regulation of signal transduction	1
excitatory postsynaptic potential	1
modulation of excitatory postsynaptic potential	1
negative regulation of cell communication	1
negative regulation of signaling	1

Protein interactions and networks

STRING

2458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS4	GNAO1	P09471	971
RGS4	GNAQ	P50148	960
RGS4	GNB5	O14775	884
RGS4	PPP1R9B	Q96SB3	874
RGS4	SUCLG2	Q96I99	825
RGS4	ATE1	O95260	763
RGS4	CALML6	Q8TD86	762
RGS4	CALML3	P27482	762
RGS4	CALML5	Q9NZT1	762
RGS4	CALML4	Q96GE6	762
RGS4	GRK2	P25098	751
RGS4	ARHGEF1	Q92888	748
RGS4	DTNBP1	Q96EV8	744
RGS4	ARHGEF11	O15085	741
RGS4	SUCLG1	P53597	732

IntAct

9 interactions, top by confidence:

A	B	Type	Score
EGFR	RGS4	psi-mi:“MI:0915”(physical association)	0.550
RGS4	EGFR	psi-mi:“MI:0915”(physical association)	0.550
Gnao1	RGS4	psi-mi:“MI:0407”(direct interaction)	0.440
ADO	RGS4	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
RGS4	CHRM3	psi-mi:“MI:0915”(physical association)	0.400
RGS4	PREPL	psi-mi:“MI:0915”(physical association)	0.400
RGS4	MTHFS	psi-mi:“MI:0915”(physical association)	0.400
RGS4	PAK2	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): RGS4 (Two-hybrid), GNAI1 (FRET), RGS4 (PCA), PREPL (Affinity Capture-MS), RGS4 (Biochemical Activity), GNAQ (Reconstituted Complex), GNAO1 (Reconstituted Complex), COPB2 (Two-hybrid), GNAQ (Reconstituted Complex), GNAQ (Affinity Capture-Western), ERBB3 (Affinity Capture-Western), RGS4 (Affinity Capture-Western), GNAI1 (Reconstituted Complex), GNAI2 (Reconstituted Complex), GNAO1 (Reconstituted Complex)

ESM2 similar proteins: F1S668, O08849, O08850, O08899, O15492, O15539, O43665, O46471, O70521, O94810, P41220, P49795, P49798, P49799, P49800, P49804, P49806, P56700, P57771, P97428, P97844, Q08116, Q08DC7, Q0P5H5, Q0R4E4, Q29RM9, Q3S853, Q3T0T8, Q4L0E8, Q4R525, Q5R747, Q5RB40, Q6DGI0, Q6RG78, Q7SZC6, Q864Z2, Q8BXT1, Q92619, Q95K68, Q99PG4

Diamond homologs: A1A643, F1S668, O08773, O08774, O08849, O08850, O08899, O14921, O14924, O15169, O15492, O15539, O35625, O42400, O43566, O43665, O46469, O46470, O46471, O54828, O54829, O70239, O70240, O70521, O75916, O76081, O88566, O94810, P34295, P41220, P49758, P49795, P49796, P49797, P49798, P49799, P49800, P49802, P49803, P49804

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

567 predictions. Top by Δscore:

Variant	Effect	Δscore
1:163069525:GGAG:G	donor_gain	1.0000
1:163069526:GAGG:G	donor_gain	1.0000
1:163069529:GT:G	donor_loss	1.0000
1:163072388:T:A	acceptor_gain	1.0000
1:163072390:T:TA	acceptor_gain	1.0000
1:163072390:TGCA:T	acceptor_loss	1.0000
1:163072391:GCAGT:G	acceptor_loss	1.0000
1:163072392:CA:C	acceptor_loss	1.0000
1:163072393:A:AG	acceptor_gain	1.0000
1:163072393:A:AT	acceptor_loss	1.0000
1:163072393:AGT:A	acceptor_gain	1.0000
1:163072394:G:GA	acceptor_gain	1.0000
1:163072394:GT:G	acceptor_gain	1.0000
1:163072394:GTG:G	acceptor_gain	1.0000
1:163072394:GTGC:G	acceptor_gain	1.0000
1:163072394:GTGCA:G	acceptor_gain	1.0000
1:163072497:GAG:G	donor_gain	1.0000
1:163072499:GGTAA:G	donor_loss	1.0000
1:163072500:G:T	donor_loss	1.0000
1:163072501:T:A	donor_loss	1.0000
1:163072803:A:AG	acceptor_gain	1.0000
1:163072804:G:GG	acceptor_gain	1.0000
1:163072804:GA:G	acceptor_gain	1.0000
1:163072804:GAGT:G	acceptor_gain	1.0000
1:163072863:GAAT:G	donor_gain	1.0000
1:163072867:G:GG	donor_gain	1.0000
1:163073449:A:AG	acceptor_gain	1.0000
1:163073453:TAG:T	acceptor_loss	1.0000
1:163073454:AGGT:A	acceptor_gain	1.0000
1:163073454:AGGTG:A	acceptor_gain	1.0000

AlphaMissense

1364 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:163072852:T:C	L66P	1.000
1:163073479:T:C	F79L	1.000
1:163073481:C:A	F79L	1.000
1:163073481:C:G	F79L	1.000
1:163073515:T:C	F91L	1.000
1:163073516:T:C	F91S	1.000
1:163073517:C:A	F91L	1.000
1:163073517:C:G	F91L	1.000
1:163073596:T:C	F118L	1.000
1:163073598:C:A	F118L	1.000
1:163073598:C:G	F118L	1.000
1:163074418:T:C	L159P	1.000
1:163074444:T:C	F168L	1.000
1:163074445:T:C	F168S	1.000
1:163074446:C:A	F168L	1.000
1:163074446:C:G	F168L	1.000
1:163072830:T:A	W59R	0.999
1:163072830:T:C	W59R	0.999
1:163073458:G:T	G72W	0.999
1:163073471:T:C	F76S	0.999
1:163073480:T:C	F79S	0.999
1:163073483:T:G	L80W	0.999
1:163073497:A:C	S85R	0.999
1:163073499:T:A	S85R	0.999
1:163073499:T:G	S85R	0.999
1:163073504:A:T	E87V	0.999
1:163073508:T:A	N88K	0.999
1:163073508:T:G	N88K	0.999
1:163073518:T:A	W92R	0.999
1:163073518:T:C	W92R	0.999

dbSNP variants (sampled 300 via entrez): RS1000281080 (1:163072743 T>G), RS1000320689 (1:163066987 T>C), RS1000433031 (1:163073104 G>A), RS1000609509 (1:163072813 A>G), RS1001946049 (1:163076433 C>T), RS1002447090 (1:163070247 T>C), RS1002650657 (1:163075583 G>A,T), RS1002892493 (1:163068556 T>C), RS1002952590 (1:163075012 G>A,T), RS1002970385 (1:163069242 T>A), RS1003068809 (1:163074731 G>A), RS1003560443 (1:163070568 G>C), RS1003589627 (1:163070385 C>T), RS1003857383 (1:163068848 A>C), RS1003867833 (1:163075014 G>A)

Disease associations

OMIM: gene MIM:602516 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002156_1	Response to mTOR inhibitor (rapamycin)	4.000000e-06
GCST003488_4	Response to fenofibrate (triglyceride levels)	2.000000e-06
GCST011494_87	Daytime nap	3.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005417	response to mTOR inhibitor
EFO:0007681	triglyceride change measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795091 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2661319	Efficacy	3	risperidone	Schizophrenia
rs2842030	Efficacy	3	olanzapine;perphenazine	Schizophrenia
rs2842030	Efficacy	3	risperidone	Schizophrenia
rs951439	Efficacy	3	risperidone	Schizophrenia
rs951439	Efficacy	3	antipsychotics;olanzapine;perphenazine;quetiapine;ziprasidone	Schizophrenia

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs951436	RGS4		0.00	0
rs951439	RGS4	3	5.00	2	risperidone;antipsychotics;olanzapine;perphenazine;quetiapine;ziprasidone
rs2661319	RGS4	3	2.50	1	risperidone
rs2842030	RGS4	3	2.00	2	olanzapine;perphenazine;risperidone
rs10917670	RGS4		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — R4 family

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
RGS4 inhibitor 11b	Inhibition	7.84	pIC50
CCG-50014	Inhibition	7.52	pIC50
CCG-203920	Inhibition	7.27	pIC50
CCG-63808	Inhibition	5.85	pIC50
CCG-63802	Inhibition	5.72	pIC50
CCG-4986	Inhibition	5.38	pIC50
(4Z)-1-(3-fluorophenyl)-4-(2-oxo-1H-indol-3-ylidene)pyrazolidine-3,5-dione	Inhibition	5.09	pIC50
YJ34	Inhibition	5.05	pIC50
(5Z)-5-[(5-bromothiophen-2-yl)methylidene]-1-methyl-2-sulfanylidene-1,3-diazinane-4,6-dione	Inhibition	4.82	pIC50
(5E)-1-(4-fluorophenyl)-5-[(5-methylthiophen-2-yl)methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	Inhibition	4.74	pIC50
(5Z)-1-(2-fluorophenyl)-2-sulfanylidene-5-(thiophen-2-ylmethylidene)-1,3-diazinane-4,6-dione	Inhibition	4.56	pIC50
5nd	Inhibition	4.55	pIC50

Binding affinities (BindingDB)

59 measured of 184 human assays (196 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2E)-3-(2-chloroanilino)-2-(3,3-dimethyl-2,4-dihydroisoquinolin-1-ylidene)-3-keto-propionic acid ethyl ester	EC50	10 nM
(3R)-2-(4-fluorophenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-3-carboxylic acid	EC50	10 nM
2,4-dimethyl-6-[2-oxidanylidene-2-(4-phenylpiperazin-1-yl)ethyl]-1,6-naphthyridin-5-one	EC50	18 nM
MLS000093573	IC50	23 nM
1-(1-adamantyl)-3-(1,3-benzodioxol-5-ylmethyl)urea	EC50	60 nM
2,5-bis(chloranyl)-3-(4-methylpiperazin-1-yl)-6-(2-piperidin-1-yl-1,3-thiazol-5-yl)cyclohexa-2,5-diene-1,4-dione	EC50	160 nM
2,5-bis(chloranyl)-3-[2-(dimethylamino)-1,3-thiazol-5-yl]-6-pyrrolidin-1-yl-cyclohexa-2,5-diene-1,4-dione	EC50	210 nM
MLS000114722	EC50	820 nM
MLS000689390	EC50	880 nM
3-chloranyl-N-(3-morpholin-4-ylpropyl)-6-nitro-1-benzothiophene-2-carboxamide	EC50	950 nM
3,4,5-trihydroxybenzoic acid [(3R,4S,5S,6S)-3,4,5,6-tetragalloyloxytetrahydropyran-2-yl]methyl ester	EC50	951 nM
2-[2-oxidanylidene-2-[2-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]hydrazinyl]ethoxy]-N’’-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]benzohydrazide	IC50	1070 nM
1,6,6-triphenyl-3-(p-tolyl)-3-azabicyclo[3.1.0]hexane-2,4-quinone	EC50	1160 nM
2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)sulfanyl]-1-oxidopyridin-1-ium	EC50	1320 nM
cid_25227363	EC50	1430 nM
Chebulinic acid	IC50	1520 nM
MLS000697664	IC50	1560 nM
4-chloranyl-6-(4,6-dimethylpyrimidin-2-yl)sulfanyl-N-methyl-1,3,5-triazin-2-amine	EC50	1630 nM
2-(4,6-dimethyl-3-oxidanylidene-[1,2]thiazolo[5,4-b]pyridin-2-yl)-N-(3-fluorophenyl)ethanamide	EC50	1720 nM
2-(3-keto-4,6-dimethyl-isothiazolo[5,4-b]pyridin-2-yl)-N-propyl-acetamide	EC50	1750 nM
MLS000689393	EC50	1750 nM
DEFEROXAMINE	EC50	1850 nM
1,12,23-trihydroxy-1,6,12,17,23,28-hexazacyclotritriacontane-2,5,13,16,24,27-hexone	EC50	2240 nM
2,5-bis(chloranyl)-3-piperidin-1-yl-6-(2-piperidin-1-yl-1,3-thiazol-5-yl)cyclohexa-2,5-diene-1,4-dione	EC50	2320 nM
3-chloranyl-N-(3,3-dimethylbutan-2-yl)-6-nitro-1-benzothiophene-2-carboxamide	EC50	2470 nM
MLS000544577	IC50	2630 nM
(4E)-2,3-dihydroxy-4-[[(4-methyl-2-methylimino-1,3-thiazol-3-yl)amino]methylidene]cyclohexa-2,5-dien-1-one	IC50	2720 nM
4-[(4-fluorophenyl)methyl]-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	IC50	3500 nM	US-8865750: Small molecule inhibitors of RGS proteins
MLS000759648	IC50	3520 nM
5-acetyl-2-[[5-(4-ketocyclohexa-2,5-dien-1-ylidene)-3-isoxazoline-3-carbonyl]amino]-4-methyl-thiophene-3-carboxylic acid ethyl ester	IC50	3690 nM
MLS000757112	IC50	4290 nM
(1R,19R,21S,22R,23R)-6,7,8,11,12,13,22,23-octahydroxy-3,16-dioxo-2,17,20-trioxatetracyclo[17.3.1.0^{4,9}.0^{10,15}]tricosa-4(9),5,7,10,12,14-hexaen-21-yl 3,4,5-trihydroxybenzoate	IC50	4480 nM
3-[[[(E)-(2,3-dihydroxy-4-keto-cyclohexa-2,5-dien-1-ylidene)methyl]amino]carbamoyl]-N,N-diethyl-benzenesulfonamide	EC50	5130 nM
MLS000390238	EC50	5260 nM
2-(4-Methoxy-phenyl)-[1,4]benzoquinone	IC50	5430 nM
3,4,5-trihydroxy-N’-[(1Z)-1-(4-nitrophenyl)ethylidene]benzohydrazide	EC50	5960 nM
4-[(3-carbamoyl-4,5-dimethyl-2-thienyl)amino]-4-keto-butyric acid methyl ester	EC50	6560 nM
(2Z)-3-ethyl-2-[(2E,4E)-5-(3-ethyl-1,3-benzothiazol-3-ium-2-yl)penta-2,4-dienylidene]-1,3-benzothiazole;iodide	EC50	6670 nM
(E)-3-(2-furanyl)-N-[(4-sulfamoylphenyl)methyl]-2-propenamide	EC50	7670 nM
4-(2-methylphenyl)-3-pyridin-4-yl-1H-1,2,4-triazole-5-thione	EC50	7760 nM
(4E)-5-methyl-4-[[3-[[(Z)-(3-methyl-1-phenyl-5-sulfanylidene-4-pyrazolylidene)methyl]amino]propylamino]methylidene]-2-phenyl-3-pyrazolethione	EC50	8790 nM
MLS000553854	EC50	11700 nM
4-[5-[(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)methyl]-2-furanyl]benzenesulfonamide	EC50	11900 nM
3-(3-keto-1,2-benzothiazol-2-yl)-N,N-dimethyl-benzenesulfonamide	IC50	13000 nM
1-[3-(4-nitrophenyl)-5,6-dihydroimidazo[2,1-b][1,3]thiazol-7-ium-7-yl]ethanone;bromide	EC50	13500 nM
(2Z)-3-ethyl-2-[(E)-3-(3-ethyl-1,3-benzothiazol-3-ium-2-yl)-2-methyl-prop-2-enylidene]-1,3-benzothiazole;iodide	EC50	22400 nM
(2Z,4S,6S,12aS)-4-(dimethylamino)-6,10,11,12a-tetrahydroxy-2-[hydroxy-(1-pyrrolidinylmethylamino)methylidene]-6-methyl-4,4a,5,5a-tetrahydrotetracene-1,3,12-trione	EC50	23700 nM
(4E)-4-[[(2-ethylimino-4-methyl-1,3-thiazol-3-yl)amino]methylidene]-2,3-bis(oxidanyl)cyclohexa-2,5-dien-1-one	EC50	29400 nM
UNM-0000305796	EC50	30000 nM
2,4-dimethyl-6-[2-[3-methyl-4-(3-methylphenyl)piperazin-1-yl]-2-oxidanylidene-ethyl]-1,6-naphthyridin-5-one	EC50	30000 nM

ChEMBL bioactivities

40 potent at pChembl≥5 of 43 total, top 40 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.27	IC50	5.4	nM	CHEMBL2037351
8.14	IC50	7.2	nM	CHEMBL2037350
8.07	IC50	8.6	nM	CHEMBL2037352
7.96	IC50	10.9	nM	CHEMBL2037229
7.89	IC50	12.9	nM	CHEMBL2037234
7.87	IC50	13.5	nM	CHEMBL2037228
7.85	IC50	14	nM	CHEMBL2037365
7.84	IC50	14.4	nM	CHEMBL2037235
7.84	IC50	14.5	nM	CHEMBL2037354
7.84	IC50	14.4	nM	CHEMBL24773
7.81	IC50	15.6	nM	CHEMBL2035006
7.79	IC50	16.3	nM	CHEMBL2037227
7.76	IC50	17.4	nM	CHEMBL2037353
7.72	IC50	18.9	nM	CHEMBL2037358
7.71	IC50	19.7	nM	CHEMBL2037362
7.65	IC50	22.3	nM	CHEMBL2037357
7.65	IC50	22.3	nM	CHEMBL2037359
7.63	IC50	23.5	nM	CHEMBL2037236
7.63	IC50	23.5	nM	CHEMBL2037360
7.62	IC50	23.9	nM	CHEMBL2037238
7.58	IC50	26.3	nM	CHEMBL2037366
7.56	IC50	27.8	nM	CHEMBL2037361
7.54	IC50	28.7	nM	CHEMBL2037237
7.54	IC50	29.1	nM	CHEMBL2037368
7.53	IC50	29.8	nM	CHEMBL2037363
7.52	IC50	30.1	nM	CHEMBL1917204
7.52	IC50	30	nM	CHEMBL1917204
7.49	IC50	32.5	nM	CHEMBL2037349
7.47	IC50	34.2	nM	CHEMBL2037356
7.45	IC50	35.7	nM	CHEMBL2037230
7.42	IC50	38.2	nM	CHEMBL2037348
7.41	IC50	38.6	nM	CHEMBL2037367
7.28	IC50	52.3	nM	CHEMBL2037233
7.27	IC50	53.6	nM	CHEMBL2037364
7.26	IC50	54.3	nM	CHEMBL2037369
7.24	IC50	57.4	nM	CHEMBL2037347
7.10	IC50	79.3	nM	CHEMBL2037231
7.05	IC50	88.9	nM	CHEMBL2037346
6.92	IC50	121	nM	CHEMBL2037232
6.75	IC50	176	nM	CHEMBL2037355

PubChem BioAssay actives

39 with measured affinity, of 55 total; 39 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
4-[(4-chlorophenyl)methyl]-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0054	uM
4-benzyl-2-[(4-methylphenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0072	uM
2-(4-methylphenyl)-4-[(4-methylphenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0086	uM
4-[(4-fluorophenyl)methyl]-2-(4-methoxyphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0109	uM
4-[(4-fluorophenyl)methyl]-2-[(4-methylphenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0129	uM
2-(4-chlorophenyl)-4-[(4-fluorophenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0135	uM
2-(4-methylphenyl)-4-(2-methylpropyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0140	uM
4-butyl-2-ethyl-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0144	uM
4-benzyl-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0144	uM
2-(4-methylphenyl)-4-[(3-methylphenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0145	uM
2-butyl-4-[(4-fluorophenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0156	uM
4-[(4-fluorophenyl)methyl]-2-phenyl-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0163	uM
4-[(3-chlorophenyl)methyl]-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0174	uM
4-methyl-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0189	uM
4-butyl-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0197	uM
2-ethyl-4-methyl-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0223	uM
2-ethyl-4-[(4-fluorophenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0223	uM
2-butyl-4-methyl-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0235	uM
4-benzyl-2-phenyl-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0235	uM
4-benzyl-2-(4-methoxyphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0239	uM
2-ethyl-4-(2-methylpropyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0263	uM
2-tert-butyl-4-methyl-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0278	uM
4-benzyl-2-(4-chlorophenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0287	uM
2-tert-butyl-4-(2-methylpropyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0291	uM
2,4-dibutyl-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0298	uM
4-[(4-fluorophenyl)methyl]-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0301	uM
4-benzyl-2-(3-chlorophenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0325	uM
4-[(3,4-dichlorophenyl)methyl]-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0342	uM
2-(3,4-dichlorophenyl)-4-[(4-fluorophenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0357	uM
4-benzyl-2-(3-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0382	uM
2-butyl-4-(2-methylpropyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0386	uM
2-(3-chlorophenyl)-4-[(4-fluorophenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0523	uM
4-butyl-2-tert-butyl-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0536	uM
2-ethyl-4-(2-methoxyethyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0543	uM
4-benzyl-2-[3-(trifluoromethyl)phenyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0574	uM
4-[(4-fluorophenyl)methyl]-2-[3-(trifluoromethyl)phenyl]-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0793	uM
4-benzyl-2-(3,4-dichlorophenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.0889	uM
4-[(4-fluorophenyl)methyl]-2-(3-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.1210	uM
4-[(4-methoxyphenyl)methyl]-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663946: Inhibition of RGS4 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	0.1760	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	8
(+)-JQ1 compound	decreases expression	3
Progesterone	affects cotreatment, decreases expression	3
Particulate Matter	increases expression, decreases expression, increases abundance, affects cotreatment	3
mono-(2-ethylhexyl)phthalate	decreases expression, increases expression	2
sodium arsenite	increases expression, decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Cisplatin	decreases expression, increases reaction	2
Methotrexate	decreases expression	2
Piroxicam	decreases expression, increases reaction	2
Tamoxifen	affects expression, affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
afuresertib	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
deoxynivalenol	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
cobaltous chloride	decreases expression	1
didecyldimethylammonium	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 3 functional, 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1794499	Functional	PUBCHEM_BIOASSAY: Inhibitors of Regulator of G Protein Signaling (RGS) 4: qHTS. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID504856]	PubChem BioAssay data set
CHEMBL1920074	Binding	Inhibition of RGS4 GTPase accelrating activity	Regulators of G protein signaling (RGS) proteins as drug targets: modulating G-protein-coupled receptor (GPCR) signal transduction. — J Med Chem

Clinical trials (associated diseases)

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