RGS16

Summary

RGS16 (regulator of G protein signaling 16, HGNC:9997) is a protein-coding gene on chromosome 1q25.3, encoding Regulator of G-protein signaling 16 (O15492). Regulates G protein-coupled receptor signaling cascades.

The protein encoded by this gene belongs to the ‘regulator of G protein signaling’ family. It inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits. It also may play a role in regulating the kinetics of signaling in the phototransduction cascade.

Source: NCBI Gene 6004 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 32 total
• Druggable target: yes
• MANE Select transcript: NM_002928

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9997
Approved symbol	RGS16
Name	regulator of G protein signaling 16
Location	1q25.3
Locus type	gene with protein product
Status	Approved
Aliases	A28-RGS14, RGS-r
Ensembl gene	ENSG00000143333
Ensembl biotype	protein_coding
OMIM	602514
Entrez	6004

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000367558, ENST00000898513, ENST00000921546

RefSeq mRNA: 1 — MANE Select: NM_002928 NM_002928

CCDS: CCDS1348

Canonical transcript exons

ENST00000367558 — 5 exons

Exon	Start	End
ENSE00000959303	182601966	182602132
ENSE00000959323	182603229	182603339
ENSE00000959324	182602420	182602484
ENSE00001445025	182598623	182600513
ENSE00001445026	182604216	182604389

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 99.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7148 / max 1170.5843, expressed in 1192 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16160	14.7148	1192

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.50	gold quality
vena cava	UBERON:0004087	97.47	gold quality
oocyte	CL:0000023	95.57	gold quality
tendon of biceps brachii	UBERON:0008188	93.15	gold quality
cartilage tissue	UBERON:0002418	92.26	gold quality
left lobe of thyroid gland	UBERON:0001120	92.07	gold quality
thyroid gland	UBERON:0002046	91.69	gold quality
right lobe of thyroid gland	UBERON:0001119	89.85	gold quality
adenohypophysis	UBERON:0002196	89.80	gold quality
pituitary gland	UBERON:0000007	89.11	gold quality
saphenous vein	UBERON:0007318	88.83	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.14	gold quality
mucosa of stomach	UBERON:0001199	87.72	gold quality
omental fat pad	UBERON:0010414	87.18	gold quality
peritoneum	UBERON:0002358	87.12	gold quality
secondary oocyte	CL:0000655	86.88	gold quality
buccal mucosa cell	CL:0002336	86.69	silver quality
substantia nigra pars reticulata	UBERON:0001966	86.07	gold quality
gall bladder	UBERON:0002110	86.02	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.42	gold quality
lymph node	UBERON:0000029	84.75	gold quality
left uterine tube	UBERON:0001303	83.51	gold quality
upper lobe of left lung	UBERON:0008952	83.10	gold quality
layer of synovial tissue	UBERON:0007616	83.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.99	gold quality
ventricular zone	UBERON:0003053	82.95	gold quality
type B pancreatic cell	CL:0000169	82.23	gold quality
spinal cord	UBERON:0002240	82.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.21	gold quality
upper lobe of lung	UBERON:0008948	82.09	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-6911	yes	3279.41
E-CURD-126	yes	2859.44
E-MTAB-11121	yes	1645.66
E-HCAD-56	yes	1216.12
E-MTAB-10485	yes	804.35
E-MTAB-7316	yes	45.48
E-HCAD-11	yes	27.84
E-GEOD-135922	yes	25.38
E-GEOD-137537	yes	21.43
E-GEOD-81608	yes	18.68
E-MTAB-5061	yes	14.33
E-MTAB-9388	yes	13.48
E-GEOD-81547	yes	10.32
E-MTAB-10137	no	7.34
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1, STAT5A, STAT5B, TCF3, YY1

miRNA regulators (miRDB)

88 targeting RGS16, 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-5692A	100.00	74.40	6850
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4267	99.96	66.53	2368
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-11181-3P	99.75	66.38	2205

Literature-anchored findings (GeneRIF, showing 26)

• Src mediates RGS16 tyrosine phosphorylation, which may promote RGS16 stability. (PMID:12588871)
• 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)
• results suggest that the amino-terminal palmitoylation of regulator of G-protein signaling 16 protein(RGS16) promotes its lipid raft targeting that allows palmitoylation of a poorly accessible cysteine residue (PMID:12642593)
• RGS16 inhibits G alpha 13-mediated, RhoA-dependent reversal of stellation and Serum Response Element activation, thus regulating G alpha 13-mediated signal transduction independently of the RGS box. (PMID:14634662)
• RGS16 is a negative regulator of SDF-1-CXCR4 signaling in megakaryocytes (PMID:15998835)
• G alpha(i2) is specifically localized in human Fallopian tube epithelial cells, particularly in cilia, & is likely to have cilia-specific role in reproduction. (PMID:17347170)
• B4GALT3, DAP3, RGS16, TMEM183A and UCK2–were significantly overexpressed in dup(1q)-positive ALLs compared with high hyperdiploid ALLs without dup(1q). (PMID:17613536)
• Regulator of G Signaling 16 has a role in the distinct endoplasmic reticulum stress state associated with aggregated mutant alpha1-antitrypsin Z in the classical form of alpha1-antitrypsin deficiency (PMID:17635928)
• The promoter region of RGS16 was found to be methylated in 10% human breast carcinomas (PMID:18521847)
• the loss of RGS16 in some breast tumors enhances PI3K signaling elicited by growth factors and thereby promotes proliferation and TKI evasion downstream of HER activation (PMID:19509421)
• Increased RGS16 levels are associated with colorectal cancer. (PMID:19760045)
• RGS16 and FosB are underexpressed in pancreatic cancer with lymph node metastasis and associated with reduced survival (PMID:20571966)
• Missense mutations in RGS16 gene is associated with breast cancer. (PMID:21135262)
• Data indicate that multiplex ligation-dependent probe amplification (MLPA) probes (Fig. 2) corresponding to the RGSL2, RGSL1 and RGS16 genes showed 64.5 % tumour samples with copy number gains and 5 % tumour samples with copy number losses. (PMID:23248035)
• cotreatment with RGS16 siRNA reversed the downregulation of nuclear factor-kappaB expression induced by combined inhibition of LSD1 and HDACs, suggesting a crucial role of RGS16 in controlling key pathways of cell death in response to combination therapy. (PMID:23354309)
• these results indicate that RGS16 restricts the activation-induced pro-inflammatory profile in myeloid cells. (PMID:25366993)
• The data establish miR-181a as an oncomiR that promotes chondrosarcoma progression through a new mechanism involving enhancement of CXCR4 signaling by inhibition of RGS16. (PMID:26013170)
• suggest that deltaEF1 family proteins promote cell motility of breast cancer cells directly or indirectly through repressing expression of RGS16 (PMID:26823172)
• Data suggest that RGS16 functions as a GAP (GTPase accelerating protein) in the SCN (suprachiasmatic nucleus) and is required for circadian timing. [REVIEW] (PMID:28502923)
• Data show that bothregulator of G protein signaling (RGS16 and RGS18) inhibit protease-activated receptor 2 (PAR2)/G-protein, Gi-Go subunits (Galphai/o) -mediated signaling. (PMID:30117167)
• RGS16 promotes glioma progression and serves as a prognostic factor. (PMID:32319728)
• Critical roles of RGS16 in the mucosal inflammation of ulcerative colitis. (PMID:35830366)
• RGS16 regulated by let-7c-5p promotes glioma progression by activating PI3K-AKT pathway. (PMID:36414916)
• Gene expression meta-analysis in patients with schizophrenia reveals up-regulation of RGS2 and RGS16 in Brodmann Area 10. (PMID:36443250)
• RGS16 regulates Hippo-YAP activity to promote esophageal cancer cell proliferation and migration. (PMID:37473526)
• Regulator of G protein signaling 16 restrains apoptosis in colorectal cancer through disrupting TRAF6-TAB2-TAK1-JNK/p38 MAPK signaling. (PMID:38906869)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgs8	ENSDARG00000070037
mus_musculus	Rgs16	ENSMUSG00000026475
rattus_norvegicus	Rgs16	ENSRNOG00000027024

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), 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 16 — O15492 (reviewed: O15492)

Alternative names: A28-RGS14P, Retinal-specific RGS, Retinally abundant regulator of G-protein signaling

All UniProt accessions (1): O15492

UniProt curated annotations — full annotation on UniProt →

Function. Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Plays an important role in the phototransduction cascade by regulating the lifetime and effective concentration of activated transducin alpha. May regulate extra and intracellular mitogenic signals.

Subunit / interactions. Interacts with GNAI1 and GNAQ. Interacts with GNAI2, GNAI3 and GNAO1.

Subcellular location. Membrane.

Tissue specificity. Abundantly expressed in retina with lower levels of expression in most other tissues.

Post-translational modifications. Palmitoylated on Cys-2 and/or Cys-12. Phosphorylated. Phosphorylation at Tyr-168 by EGFR enhances GTPase accelerating (GAP) activity toward GNAI1.

RefSeq proteins (1): NP_002919* (*=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 (21 total): helix 10, modified residue 2, lipid moiety-binding region 2, mutagenesis site 2, chain 1, domain 1, turn 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2BT2	X-RAY DIFFRACTION	1.9
2IK8	X-RAY DIFFRACTION	2.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15492-F1	82.21	0.66

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 (4): 168, 177, 2, 12

Mutagenesis-validated functional residues (2):

Position	Phenotype
168	30% decrease in gap activity.
177	no effect on gap activity.

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: 335 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, WALLACE_PROSTATE_CANCER_RACE_UP, MODULE_169, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, ENK_UV_RESPONSE_KERATINOCYTE_UP, ATACCTC_MIR202, MODULE_64, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_GTPASE_ACTIVITY, TAKADA_GASTRIC_CANCER_COPY_NUMBER_DN, LA_MEN1_TARGETS, MODULE_118, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION

GO Biological Process (5): G protein-coupled receptor signaling pathway (GO:0007186), visual perception (GO:0007601), regulation of G protein-coupled receptor signaling pathway (GO:0008277), negative regulation of signal transduction (GO:0009968), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (4): GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), calmodulin binding (GO:0005516), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), 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
regulation of signal transduction	2
GTPase activity	2
cellular anatomical structure	2
G protein-coupled receptor activity	1
sensory perception of light stimulus	1
G protein-coupled receptor signaling pathway	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
ribonucleoside triphosphate phosphatase activity	1
enzyme activator activity	1
GTPase regulator activity	1
protein binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS16	GNAO1	P09471	952
RGS16	GDE1	Q9NZC3	905
RGS16	GNB5	O14775	872
RGS16	GNAQ	P50148	853
RGS16	SUCLG2	Q96I99	841
RGS16	RGSL1	A5PLK6	792
RGS16	ARHGEF1	Q92888	765
RGS16	ARHGEF11	O15085	764
RGS16	ATE1	O95260	745
RGS16	GRK2	P25098	737
RGS16	GNA13	Q14344	706
RGS16	RGS7BP	Q6MZT1	679
RGS16	MCF2	P10911	678
RGS16	PLEK	P08567	667
RGS16	AKAP10	O43572	642

IntAct

4 interactions, top by confidence:

A	B	Type	Score
Gnao1	RGS16	psi-mi:“MI:0407”(direct interaction)	0.440
RGS16	ST14	psi-mi:“MI:0915”(physical association)	0.370
RGS16	CREB3L2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (20): RGS16 (Affinity Capture-RNA), RGS16 (Affinity Capture-Western), RGS16 (Biochemical Activity), GNAQ (Reconstituted Complex), GNA13 (Reconstituted Complex), GNAQ (Affinity Capture-Western), GNAI3 (Reconstituted Complex), GNAI2 (Reconstituted Complex), GNAO1 (Reconstituted Complex), GNAI3 (Affinity Capture-Western), GNAI1 (Biochemical Activity), GDE1 (Two-hybrid), GDE1 (Reconstituted Complex), EGFR (Affinity Capture-Western), RGS16 (Affinity Capture-RNA)

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

6 interactions.

A	Effect	B	Mechanism
EGFR	up-regulates	RGS16	phosphorylation
hsa-miR-181a-5p	“down-regulates quantity by repression”	RGS16	“post transcriptional regulation”
SRC	up-regulates	RGS16	phosphorylation
LYN	“up-regulates activity”	RGS16	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

447 predictions. Top by Δscore:

Variant	Effect	Δscore
1:182600509:TTGAC:T	acceptor_gain	1.0000
1:182600510:TGAC:T	acceptor_gain	1.0000
1:182600511:GAC:G	acceptor_gain	1.0000
1:182600512:AC:A	acceptor_gain	1.0000
1:182600513:CC:C	acceptor_gain	1.0000
1:182600514:C:CC	acceptor_gain	1.0000
1:182601963:AAC:A	donor_loss	1.0000
1:182601964:A:C	donor_loss	1.0000
1:182601965:CCT:C	donor_gain	1.0000
1:182601965:CCTCT:C	donor_loss	1.0000
1:182601967:T:TA	donor_gain	1.0000
1:182601981:A:AC	donor_gain	1.0000
1:182601982:C:CC	donor_gain	1.0000
1:182601994:T:TA	donor_gain	1.0000
1:182601995:C:CA	donor_gain	1.0000
1:182602129:CCAT:C	acceptor_gain	1.0000
1:182602130:CAT:C	acceptor_gain	1.0000
1:182602130:CATC:C	acceptor_gain	1.0000
1:182602131:AT:A	acceptor_gain	1.0000
1:182602131:ATCT:A	acceptor_loss	1.0000
1:182602132:TC:T	acceptor_loss	1.0000
1:182602133:C:CC	acceptor_gain	1.0000
1:182602134:T:A	acceptor_loss	1.0000
1:182602139:T:C	acceptor_gain	1.0000
1:182602139:T:TC	acceptor_gain	1.0000
1:182602142:C:CT	acceptor_gain	1.0000
1:182602143:G:T	acceptor_gain	1.0000
1:182602414:A:AC	donor_gain	1.0000
1:182602415:C:CC	donor_gain	1.0000
1:182602415:CT:C	donor_gain	1.0000

AlphaMissense

1324 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:182602107:G:C	F82L	0.991
1:182602107:G:T	F82L	0.991
1:182602109:A:G	F82L	0.991
1:182601990:G:C	F121L	0.990
1:182601990:G:T	F121L	0.990
1:182601992:A:G	F121L	0.990
1:182600388:G:C	F171L	0.987
1:182600388:G:T	F171L	0.987
1:182600390:A:G	F171L	0.987
1:182602071:G:C	F94L	0.984
1:182602071:G:T	F94L	0.984
1:182602073:A:G	F94L	0.984
1:182602092:G:C	F87L	0.984
1:182602092:G:T	F87L	0.984
1:182602094:A:G	F87L	0.984
1:182600389:A:G	F171S	0.979
1:182602072:A:G	F94S	0.969
1:182602116:G:C	F79L	0.969
1:182602116:G:T	F79L	0.969
1:182602118:A:G	F79L	0.969
1:182600399:A:C	Y168D	0.968
1:182602456:A:G	W62R	0.959
1:182602456:A:T	W62R	0.959
1:182603324:C:A	K20N	0.959
1:182603324:C:G	K20N	0.959
1:182602117:A:G	F79S	0.958
1:182600389:A:C	F171C	0.954
1:182602105:A:G	L83P	0.949
1:182600437:G:T	A155D	0.948
1:182600445:A:C	F152L	0.946

dbSNP variants (sampled 300 via entrez): RS1000005165 (1:182604678 G>A), RS1001125357 (1:182605817 T>C), RS1001417214 (1:182606254 A>C), RS1001949693 (1:182600208 C>A,G,T), RS1002647252 (1:182604407 G>A,T), RS1003659135 (1:182602953 C>T), RS1004570356 (1:182600156 A>C,T), RS1005239279 (1:182602969 A>C), RS1005746041 (1:182603991 T>G), RS1005813318 (1:182603425 G>A), RS1006820703 (1:182605143 T>C), RS1006936645 (1:182604859 C>T), RS1007011183 (1:182603859 A>T), RS1007942720 (1:182606303 G>A), RS1008279037 (1:182605175 A>C,G)

Disease associations

OMIM: gene MIM:602514 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003429_2	Morning vs. evening chronotype	7.000000e-18
GCST003453_6	Chronotype	3.000000e-14
GCST003454_5	Morning vs. evening chronotype	1.000000e-08
GCST003837_1	Chronotype	7.000000e-28
GCST003838_1	Morning vs. evening chronotype	3.000000e-12
GCST003982_3	Sleep traits (multi-trait analysis)	3.000000e-11
GCST007565_109	Morning person	2.000000e-95
GCST007576_301	Chronotype	2.000000e-95

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007875	excessive daytime sleepiness measurement
EFO:0007876	insomnia measurement
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3707469 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — R4 family

Binding affinities (BindingDB)

57 measured of 181 human assays (193 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

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
5.46	IC50	3500	nM	CHEMBL1917204

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression, increases expression	6
Cyclosporine	decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
methylmercuric chloride	affects expression, increases expression	2
sodium arsenite	increases expression, decreases expression	2
dinophysistoxin 1	increases expression	2
Acetaminophen	increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Doxorubicin	affects expression, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Formaldehyde	increases expression	2
Nickel	increases expression	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	increases expression	2
Aflatoxin B1	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
N(6)-(delta(2)-isopentenyl)adenine	decreases expression, increases expression	1
lasiocarpine	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
beta-lapachone	increases expression	1
afimoxifene	increases expression, affects reaction	1
butyraldehyde	increases expression	1
sulindac sulfide	increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression, 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
CHEMBL3707995	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.