RGS19

Summary

RGS19 (regulator of G protein signaling 19, HGNC:13735) is a protein-coding gene on chromosome 20q13.33, encoding Regulator of G-protein signaling 19 (P49795). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.

G proteins mediate a number of cellular processes. The protein encoded by this gene belongs to the RGS (regulators of G-protein signaling) family and specifically interacts with G protein, GAI3. This protein is a guanosine triphosphatase-activating protein that functions to down-regulate Galpha i/Galpha q-linked signaling. Alternatively spliced transcript variants encoding the same protein isoform have been found for this gene.

Source: NCBI Gene 10287 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 35 total
• Druggable target: yes
• MANE Select transcript: NM_005873

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13735
Approved symbol	RGS19
Name	regulator of G protein signaling 19
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	GAIP, RGSGAIP
Ensembl gene	ENSG00000171700
Ensembl biotype	protein_coding
OMIM	605071
Entrez	10287

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000332298, ENST00000395042, ENST00000479996, ENST00000493165, ENST00000910389, ENST00000910390, ENST00000910391, ENST00000910392, ENST00000910393, ENST00000910394, ENST00000910395, ENST00000936747, ENST00000944526

RefSeq mRNA: 2 — MANE Select: NM_005873 NM_001039467, NM_005873

CCDS: CCDS13555

Canonical transcript exons

ENST00000395042 — 6 exons

Exon	Start	End
ENSE00001520399	64079294	64079518
ENSE00003526437	64074467	64074541
ENSE00003587130	64076525	64076646
ENSE00003668618	64076857	64076954
ENSE00003890024	64074144	64074378
ENSE00003893278	64073181	64074044

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 98.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1297 / max 684.2413, expressed in 1745 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188455	7.6529	700
188457	7.4799	1700
188456	0.5419	248
188454	0.4152	148
188458	0.0398	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.09	gold quality
blood	UBERON:0000178	97.25	gold quality
leukocyte	CL:0000738	96.81	gold quality
monocyte	CL:0000576	96.78	gold quality
mononuclear cell	CL:0000842	96.72	gold quality
spleen	UBERON:0002106	95.43	gold quality
bone marrow cell	CL:0002092	94.76	gold quality
bone marrow	UBERON:0002371	93.89	gold quality
parotid gland	UBERON:0001831	91.51	gold quality
lymph node	UBERON:0000029	91.21	gold quality
trabecular bone tissue	UBERON:0002483	91.21	gold quality
amniotic fluid	UBERON:0000173	91.20	gold quality
vermiform appendix	UBERON:0001154	90.95	gold quality
right coronary artery	UBERON:0001625	90.38	gold quality
lower lobe of lung	UBERON:0008949	88.96	gold quality
caecum	UBERON:0001153	88.87	gold quality
cervix squamous epithelium	UBERON:0006922	88.81	silver quality
periodontal ligament	UBERON:0008266	88.42	gold quality
epithelium of nasopharynx	UBERON:0001951	87.35	gold quality
thymus	UBERON:0002370	86.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.90	gold quality
type B pancreatic cell	CL:0000169	86.50	gold quality
coronary artery	UBERON:0001621	85.87	gold quality
left coronary artery	UBERON:0001626	85.83	gold quality
superficial temporal artery	UBERON:0001614	85.79	silver quality
upper lobe of lung	UBERON:0008948	85.47	gold quality
decidua	UBERON:0002450	85.40	gold quality
upper lobe of left lung	UBERON:0008952	85.39	gold quality
olfactory bulb	UBERON:0002264	85.36	gold quality
palpebral conjunctiva	UBERON:0001812	85.10	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	21.01
E-ANND-3	yes	9.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF263

miRNA regulators (miRDB)

34 targeting RGS19, 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-3163	100.00	77.23	8605
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-4286	97.20	64.37	1587

Literature-anchored findings (GeneRIF, showing 10)

• gene structure and transcription regulation (PMID:12507475)
• GIPC recruits GAIP (RGS19) to attenuate dopamine D2 receptor signaling (PMID:15356268)
• cyclin D1/3 and Cdk6 were upregulated in HEK293 cells overexpressing RGS19, while INK4A and INK4B were reduced (PMID:21705135)
• elevated expression of RGS19 can severely disrupt the regulation of mitogen-activated protein kinases by small GTPases (PMID:22045062)
• The RGS19 inhibits Ras signaling through a complex network involving a scaffold protein KSR1 and a nucleoside diphosphate kinase Nm23. (PMID:23416464)
• Overall methylation levels in the promoter regions of three genes (ALDH1A1, OPRL1 and RGS19) are elevated in subjects who were exposed to childhood adversity. (PMID:23799031)
• RGS19 may play an important role in controlling the degree of synergism between FGF-1 receptors and 5-HT1A receptors, that may work together to mediate an anti-depressant effect. (PMID:24793302)
• RGS19 senses cellular iron availability and is stabilized under iron-depleted conditions, resulting in the induction of a growth-inhibitory signal. (PMID:26116529)
• Genome-wide screening for the G-protein-coupled receptor (GPCR) pathway-related therapeutic gene RGS19 (regulator of G protein signaling 19) in bladder cancer. (PMID:34482807)
• RGS19 activates the MYH9/beta-catenin/c-Myc positive feedback loop in hepatocellular carcinoma. (PMID:38825640)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgs19	ENSDARG00000077385
mus_musculus	Rgs19	ENSMUSG00000002458
rattus_norvegicus	Rgs19	ENSRNOG00000016547

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), AXIN1 (ENSG00000103126), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGS4 (ENSG00000117152), 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), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Regulator of G-protein signaling 19 — P49795 (reviewed: P49795)

Alternative names: G-alpha-interacting protein

All UniProt accessions (1): P49795

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. Binds to G-alpha subfamily 1 members, with the order G(i)a3 > G(i)a1 > G(o)a » G(z)a/G(i)a2. Activity on G(z)-alpha is inhibited by phosphorylation and palmitoylation of the G-protein.

Subunit / interactions. Interacts with GIPC PDZ domain. Interacts with GNAO1.

Subcellular location. Membrane.

Tissue specificity. Highest expression in lung. Placenta, liver and heart also express high levels of GAIP.

Post-translational modifications. Fatty acylated. Heavily palmitoylated in the cysteine string motif. Phosphorylated, mainly on serine residues.

RefSeq proteins (2): NP_001034556, NP_005864* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00615

UniProt features (22 total): helix 10, modified residue 3, strand 2, region of interest 2, chain 1, domain 1, turn 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1CMZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49795-F1	79.75	0.61

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): 24, 97, 151

Mutagenesis-validated functional residues (1):

Position	Phenotype
151	diminishes gap activity towards g(i)-alpha3 and autophagy in colon cancer cells.

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: 190 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GGGTGGRR_PAX4_03, HOFMANN_MYELODYSPLASTIC_SYNDROM_RISK_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, NRF2_01, DOUGLAS_BMI1_TARGETS_UP, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GCM_VAV1, GOCC_CYTOPLASMIC_SIDE_OF_MEMBRANE, YAGI_AML_WITH_11Q23_REARRANGED, BROWNE_HCMV_INFECTION_14HR_UP

GO Biological Process (4): autophagy (GO:0006914), G protein-coupled receptor signaling pathway (GO:0007186), small GTPase-mediated signal transduction (GO:0007264), negative regulation of signal transduction (GO:0009968)

GO Molecular Function (2): GTPase activity (GO:0003924), protein binding (GO:0005515)

GO Cellular Component (3): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020)

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
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
G protein-coupled receptor activity	1
intracellular signaling cassette	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
ribonucleoside triphosphate phosphatase activity	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS19	GIPC1	O14908	998
RGS19	GNB5	O14775	873
RGS19	GNAQ	P50148	872
RGS19	SUCLG2	Q96I99	841
RGS19	ARHGEF1	Q92888	772
RGS19	GRK2	P25098	762
RGS19	ARHGEF11	O15085	754
RGS19	RGSL1	A5PLK6	746
RGS19	MYO6	Q9UM54	706
RGS19	GNA13	Q14344	706
RGS19	RGS7BP	Q6MZT1	703
RGS19	SUCLG1	P53597	702
RGS19	PLEK	P08567	683
RGS19	MCF2	P10911	672
RGS19	AKAP10	O43572	655

IntAct

50 interactions, top by confidence:

A	B	Type	Score
RGS20	GLRX3	psi-mi:“MI:0914”(association)	0.810
PSMA1	RGS19	psi-mi:“MI:0915”(physical association)	0.560
RGS19	LCE4A	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	RGS19	psi-mi:“MI:0915”(physical association)	0.560
RGS19	NUFIP2	psi-mi:“MI:0915”(physical association)	0.560
RGS19	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
OTX1	RGS19	psi-mi:“MI:0915”(physical association)	0.560
RGS19	CATSPER1	psi-mi:“MI:0915”(physical association)	0.560
ALPP	RGS19	psi-mi:“MI:0915”(physical association)	0.560
RGS19	VASN	psi-mi:“MI:0915”(physical association)	0.560
RGS19	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.560
Gnai3	RGS19	psi-mi:“MI:0915”(physical association)	0.510
RGS19	Gnai3	psi-mi:“MI:0915”(physical association)	0.510
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
RGS19	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
MZT1	ZC3H18	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
RGS20	PGP	psi-mi:“MI:0914”(association)	0.350
CYP2S1	MPP2	psi-mi:“MI:0914”(association)	0.350
CFTR	POTEF	psi-mi:“MI:0914”(association)	0.350
rep	CNK3/IPCEF1	psi-mi:“MI:0914”(association)	0.350
SLC39A7	AIP	psi-mi:“MI:0914”(association)	0.350
PSMA1	RGS19	psi-mi:“MI:0915”(physical association)	0.000
LCE4A	RGS19	psi-mi:“MI:0915”(physical association)	0.000
VASN	RGS19	psi-mi:“MI:0915”(physical association)	0.000
POU4F2	RGS19	psi-mi:“MI:0915”(physical association)	0.000
OTX1	RGS19	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (42): GNAI3 (Reconstituted Complex), RGS19 (Affinity Capture-MS), RGS19 (Affinity Capture-MS), RGS19 (Affinity Capture-MS), RGS19 (Affinity Capture-MS), GIPC1 (Reconstituted Complex), RGS19 (Reconstituted Complex), RGS19 (Two-hybrid), RGS19 (Two-hybrid), RGS19 (Two-hybrid), RGS19 (Two-hybrid), RGS19 (Two-hybrid), RGS19 (Two-hybrid), RGS19 (Two-hybrid), RGS19 (Two-hybrid)

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

4 interactions.

A	Effect	B	Mechanism
MAPK1	up-regulates	RGS19	phosphorylation
CSNK2A1	unknown	RGS19	phosphorylation
CSNK2A2	unknown	RGS19	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1034 predictions. Top by Δscore:

Variant	Effect	Δscore
20:64074040:CTCAC:C	acceptor_gain	1.0000
20:64074041:TCAC:T	acceptor_gain	1.0000
20:64074042:CAC:C	acceptor_gain	1.0000
20:64074042:CACC:C	acceptor_gain	1.0000
20:64074043:ACC:A	acceptor_loss	1.0000
20:64074044:CCTGC:C	acceptor_loss	1.0000
20:64074045:C:CC	acceptor_gain	1.0000
20:64074045:CTG:C	acceptor_loss	1.0000
20:64074046:T:C	acceptor_loss	1.0000
20:64074139:CGCA:C	donor_loss	1.0000
20:64074142:ACCT:A	donor_gain	1.0000
20:64074143:C:CG	donor_loss	1.0000
20:64074143:CCTC:C	donor_gain	1.0000
20:64074145:T:TA	donor_gain	1.0000
20:64074146:C:A	donor_gain	1.0000
20:64074170:A:AC	donor_gain	1.0000
20:64074170:AGT:A	donor_gain	1.0000
20:64074170:AGTC:A	donor_gain	1.0000
20:64074171:G:C	donor_gain	1.0000
20:64074172:T:TA	donor_gain	1.0000
20:64074374:TGGCA:T	acceptor_gain	1.0000
20:64074375:GGCA:G	acceptor_gain	1.0000
20:64074377:CA:C	acceptor_gain	1.0000
20:64074379:C:CC	acceptor_gain	1.0000
20:64074460:GACTC:G	donor_loss	1.0000
20:64074462:CT:C	donor_loss	1.0000
20:64074463:TCACC:T	donor_loss	1.0000
20:64074465:A:AC	donor_gain	1.0000
20:64074465:A:T	donor_loss	1.0000
20:64074466:C:CC	donor_gain	1.0000

AlphaMissense

1426 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:64074250:A:G	F119S	1.000
20:64074285:G:C	F107L	1.000
20:64074285:G:T	F107L	1.000
20:64074287:A:G	F107L	1.000
20:64073919:G:C	F196L	0.999
20:64073919:G:T	F196L	0.999
20:64073920:A:G	F196S	0.999
20:64073921:A:G	F196L	0.999
20:64073930:A:C	Y193D	0.999
20:64073935:T:A	D191V	0.999
20:64073935:T:G	D191A	0.999
20:64073938:C:G	R190P	0.999
20:64073944:A:G	M188T	0.999
20:64073947:A:G	L187P	0.999
20:64074039:G:C	S156R	0.999
20:64074039:G:T	S156R	0.999
20:64074041:T:G	S156R	0.999
20:64074166:A:T	V147E	0.999
20:64074238:C:T	C123Y	0.999
20:64074248:A:G	W120R	0.999
20:64074248:A:T	W120R	0.999
20:64074249:G:C	F119L	0.999
20:64074249:G:T	F119L	0.999
20:64074250:A:C	F119C	0.999
20:64074251:A:G	F119L	0.999
20:64074258:G:C	N116K	0.999
20:64074258:G:T	N116K	0.999
20:64074262:T:A	E115V	0.999
20:64074267:G:C	S113R	0.999
20:64074267:G:T	S113R	0.999

dbSNP variants (sampled 300 via entrez): RS1000465031 (20:64076446 C>T), RS1001361529 (20:64076846 A>C), RS1002015938 (20:64080082 A>C,T), RS1002416386 (20:64076537 C>T), RS1002638504 (20:64081035 G>A,T), RS1002656772 (20:64074851 C>T), RS1002757695 (20:64081543 G>A), RS1003012415 (20:64075159 T>C), RS1003758099 (20:64079626 T>G), RS1003810359 (20:64079281 G>A), RS1003824230 (20:64077426 C>T), RS10039 (20:64073301 G>A), RS1004152776 (20:64080652 C>T), RS1004832890 (20:64076111 C>T), RS1004883731 (20:64075830 G>A)

Disease associations

OMIM: gene MIM:605071 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004602_237	Mean corpuscular volume	8.000000e-09
GCST007001_16	Cerebrospinal AB1-42 levels in normal cognition	3.000000e-07
GCST007267_160	Systolic blood pressure	2.000000e-14
GCST008058_241	Estimated glomerular filtration rate	1.000000e-13
GCST008064_19	Chronic kidney disease	2.000000e-06
GCST010866_170	Coronary artery disease	2.000000e-09
GCST90002390_679	Mean corpuscular hemoglobin	2.000000e-13
GCST90002392_120	Mean corpuscular volume	5.000000e-15
GCST90002396_72	Mean reticulocyte volume	1.000000e-12
GCST90002397_294	Mean spheric corpuscular volume	1.000000e-22

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0006335	systolic blood pressure
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3707468 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6090041	Toxicity	3	opioids	Opioid-Related Disorders

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6090041	OPRL1, RGS19	3	0.50	1	opioids
rs6011280	RGS19		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — RZ family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
CCG-50014	Inhibition	5.96	pIC50

Binding affinities (BindingDB)

52 measured of 176 human assays (188 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
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
(4E)-5-methyl-4-[(3-nitroanilino)methylene]-2-phenyl-2-pyrazoline-3-thione	IC50	31100 nM
2-(5-morpholin-4-ylsulfonyl-2-pyrrolidin-1-yl-phenyl)-1,2-benzothiazol-3-one	IC50	34500 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.92	IC50	120	nM	CHEMBL1917204

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, decreases reaction, increases abundance, increases palmitoylation	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
sodium bichromate	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	increases expression	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Caffeine	increases phosphorylation	1
Choline	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	affects binding, increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Nickel	increases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3707973	Binding	Inhibitory Assay: FCPIA Characterization of RGS Inhibitory Activity: CCG-50014 (FIG. 1) was originally identified as a potential inhibitor of RGS8 and RGS16 in a polyplex high throughput screen to identify inhibitors of the RGS-Gα interacti	Small molecule inhibitors of RGS proteins

Clinical trials (associated diseases)

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