CYTH3

Summary

CYTH3 (cytohesin 3, HGNC:9504) is a protein-coding gene on chromosome 7p22.1, encoding Cytohesin-3 (O43739). Promotes guanine-nucleotide exchange on ARF1 and ARF6.

This gene encodes a member of the PSCD (pleckstrin homology, Sec7 and coiled-coil domains) family. PSCD family members have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. This encoded protein is involved in the control of Golgi structure and function, and it may have a physiological role in regulating ADP-ribosylation factor protein 6 (ARF) functions, in addition to acting on ARF1.

Source: NCBI Gene 9265 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 57 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_004227

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9504
Approved symbol	CYTH3
Name	cytohesin 3
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	GRP1, ARNO3, cytohesin-3
Ensembl gene	ENSG00000008256
Ensembl biotype	protein_coding
OMIM	605081
Entrez	9265

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 protein_coding, 5 protein_coding_CDS_not_defined, 4 retained_intron

ENST00000350796, ENST00000461891, ENST00000465320, ENST00000466543, ENST00000478541, ENST00000481329, ENST00000482460, ENST00000488964, ENST00000491641, ENST00000495176, ENST00000898310, ENST00000898311, ENST00000898312, ENST00000898313, ENST00000898314, ENST00000949556

RefSeq mRNA: 4 — MANE Select: NM_004227 NM_001367580, NM_001367581, NM_001367582, NM_004227

CCDS: CCDS5346

Canonical transcript exons

ENST00000350796 — 13 exons

Exon	Start	End
ENSE00000670563	6187050	6187116
ENSE00003479381	6170535	6170646
ENSE00003492210	6187657	6187721
ENSE00003563350	6177823	6177941
ENSE00003570382	6165734	6165810
ENSE00003575184	6171202	6171314
ENSE00003616219	6190449	6190531
ENSE00003637792	6170830	6170978
ENSE00003675858	6173653	6173733
ENSE00003682680	6165273	6165427
ENSE00003690785	6165545	6165616
ENSE00003845322	6272474	6272624
ENSE00003846866	6161779	6165016

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 98.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8664 / max 146.2320, expressed in 1744 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82639	13.4849	1740
82638	0.2604	113
82632	0.0793	42
82631	0.0417	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.48	silver quality
visceral pleura	UBERON:0002401	97.32	gold quality
parietal pleura	UBERON:0002400	97.24	gold quality
middle temporal gyrus	UBERON:0002771	96.31	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.96	gold quality
dorsal root ganglion	UBERON:0000044	95.70	gold quality
pleura	UBERON:0000977	95.00	gold quality
trigeminal ganglion	UBERON:0001675	94.99	gold quality
saphenous vein	UBERON:0007318	94.89	gold quality
tendon of biceps brachii	UBERON:0008188	94.86	gold quality
tibia	UBERON:0000979	94.58	gold quality
synovial joint	UBERON:0002217	94.48	gold quality
sural nerve	UBERON:0015488	94.27	gold quality
pericardium	UBERON:0002407	93.81	gold quality
ascending aorta	UBERON:0001496	93.49	gold quality
thoracic aorta	UBERON:0001515	93.47	gold quality
right coronary artery	UBERON:0001625	93.22	gold quality
descending thoracic aorta	UBERON:0002345	92.92	gold quality
cardia of stomach	UBERON:0001162	92.56	gold quality
vena cava	UBERON:0004087	92.53	gold quality
primary visual cortex	UBERON:0002436	92.30	gold quality
tibial nerve	UBERON:0001323	92.20	gold quality
placenta	UBERON:0001987	92.18	gold quality
aorta	UBERON:0000947	92.10	gold quality
nipple	UBERON:0002030	91.96	gold quality
pylorus	UBERON:0001166	91.41	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.41	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.41	gold quality
amniotic fluid	UBERON:0000173	91.26	gold quality
peritoneum	UBERON:0002358	91.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting CYTH3, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-12136	99.98	72.81	5713
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-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-205-3P	99.92	69.92	3165

Literature-anchored findings (GeneRIF, showing 4)

• GRP1 is a new corepressor for thyroid hormone receptors, which modulates both positive and negative regulation by T3 by decreasing TR-complex formation on thyroid response elements (PMID:15878955)
• incorporation of the E345K charge reversal mutation into the GRP1 PH domain enhances PI(4,5)P(2) affinity 8-fold and yields constitutive plasma membrane targeting in cells (PMID:21932773)
• The PH domains of cytohesin 2/ARNO and cytohesin 3/GRP1 are responsible for the differential effects of these proteins on cell adhesion to fibronectin. (PMID:22454518)
• Cytohesin-3 was upregulated in hepatocellular carcinoma tissues, correlating with overall survival/relapse-free survival and tumor size/vascular invasion. (PMID:24966920)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyth3b	ENSDARG00000005159
danio_rerio	cyth3a	ENSDARG00000007807
danio_rerio	si:ch211-189a21.1	ENSDARG00000089829
mus_musculus	Cyth3	ENSMUSG00000018001
rattus_norvegicus	Cyth3	ENSRNOG00000001065
drosophila_melanogaster	siz	FBGN0026179
drosophila_melanogaster	Sec71	FBGN0028538
drosophila_melanogaster	garz	FBGN0264560
caenorhabditis_elegans		WBGENE00007703
caenorhabditis_elegans		WBGENE00008685
caenorhabditis_elegans	agef-1	WBGENE00012386

Paralogs (15): PSD (ENSG00000059915), MON2 (ENSG00000061987), ARFGEF1 (ENSG00000066777), CYTH4 (ENSG00000100055), CYTH2 (ENSG00000105443), GBF1 (ENSG00000107862), CYTH1 (ENSG00000108669), IQSEC3 (ENSG00000120645), ARFGEF2 (ENSG00000124198), IQSEC2 (ENSG00000124313), PSD4 (ENSG00000125637), IQSEC1 (ENSG00000144711), PSD2 (ENSG00000146005), PSD3 (ENSG00000156011), FBXO8 (ENSG00000164117)

Protein

Protein identifiers

Cytohesin-3 — O43739 (reviewed: O43739)

Alternative names: ARF nucleotide-binding site opener 3, General receptor of phosphoinositides 1, PH, SEC7 and coiled-coil domain-containing protein 3

All UniProt accessions (1): O43739

UniProt curated annotations — full annotation on UniProt →

Function. Promotes guanine-nucleotide exchange on ARF1 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. Plays a role in the epithelial polarization.

Subunit / interactions. Interacts with TAMALIN. Interacts with ARF6. Interacts with FRMD4A. Interacts with FRMD4B.

Subcellular location. Cytoplasm. Cytosol. Cell membrane. Cell junction. Adherens junction. Tight junction.

Tissue specificity. Almost absent from liver, thymus and peripheral blood lymphocytes.

Domain organisation. Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate. Autoinhibited by its C-terminal basic region.

Isoforms (2)

UniProt ID	Names	Canonical?
O43739-1	1	yes
O43739-2	2

RefSeq proteins (4): NP_001354509, NP_001354510, NP_001354511, NP_004218* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000904	Sec7_dom	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR023394	Sec7_C_sf	Homologous_superfamily
IPR035999	Sec7_dom_sf	Homologous_superfamily

Pfam: PF00169, PF01369

UniProt features (25 total): strand 10, binding site 5, helix 3, domain 2, chain 1, splice variant 1, mutagenesis site 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4KAX	X-RAY DIFFRACTION	1.85
6U3E	ELECTRON MICROSCOPY	53
6U3G	ELECTRON MICROSCOPY	53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43739-F1	84.72	0.48

Functional residue map

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

Ligand- & substrate-binding residues (5): 273–281; 285; 296; 306; 355

Mutagenesis-validated functional residues (1):

Position	Phenotype
398–400	abolishes autoinhibition and increases guanine-nucleotide exchange activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6811438	Intra-Golgi traffic

MSigDB gene sets: 271 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, NKX25_02, GOBP_ESTABLISHMENT_OF_EPITHELIAL_CELL_POLARITY, GCANCTGNY_MYOD_Q6, ATACCTC_MIR202, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, REACTOME_MEMBRANE_TRAFFICKING, CAGCTG_AP4_Q5, chr7p22, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, TCF4_Q5

GO Biological Process (4): regulation of ARF protein signal transduction (GO:0032012), positive regulation of cell adhesion (GO:0045785), Golgi vesicle transport (GO:0048193), establishment of epithelial cell polarity (GO:0090162)

GO Molecular Function (4): guanyl-nucleotide exchange factor activity (GO:0005085), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (10): Golgi membrane (GO:0000139), ruffle (GO:0001726), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), bicellular tight junction (GO:0005923), cytoplasm (GO:0005737), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	2
ARF protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
vesicle-mediated transport	1
establishment of cell polarity	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
anion binding	1
phosphatidylinositol phosphate binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cell leading edge	1
plasma membrane bounded cell projection	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
cell-cell junction	1
apical junction complex	1
tight junction	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYTH3	ARF6	P26438	903
CYTH3	ARF1	P10947	901
CYTH3	TAMALIN	Q7Z6J2	864
CYTH3	FRMD4B	Q9Y2L6	862
CYTH3	PLEK2	Q9NYT0	821
CYTH3	PLEK	P08567	814
CYTH3	CYTIP	O60759	747
CYTH3	ARL4A	P40617	718
CYTH3	RASGRP3	Q8IV61	678
CYTH3	FRMD4A	Q9P2Q2	652
CYTH3	TRIM23	P36406	640
CYTH3	DLGAP3	O95886	639
CYTH3	CDKN2A	P42771	634
CYTH3	RACK1	P25388	588
CYTH3	DOCK1	Q14185	563

IntAct

63 interactions, top by confidence:

A	B	Type	Score
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
CNKSR1	CYTH3	psi-mi:“MI:0915”(physical association)	0.740
CYTH3	CNKSR1	psi-mi:“MI:0915”(physical association)	0.740
TAX1BP3	ARVCF	psi-mi:“MI:0914”(association)	0.690
SYCE1	CYTH3	psi-mi:“MI:0915”(physical association)	0.670
CYTH3	SYCE1	psi-mi:“MI:0915”(physical association)	0.670
INAVA	CYTH3	psi-mi:“MI:0914”(association)	0.640
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
	CYTH3	psi-mi:“MI:0407”(direct interaction)	0.590
CYTH3	CCDC120	psi-mi:“MI:0915”(physical association)	0.560
CCDC120	CYTH3	psi-mi:“MI:0915”(physical association)	0.560
GPS2	DCTN6	psi-mi:“MI:0914”(association)	0.530
INAVA	DCTN6	psi-mi:“MI:0914”(association)	0.530
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
FOSL2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
OIP5	CYTH3	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
TPD52L1	TPD52L2	psi-mi:“MI:0914”(association)	0.530

BioGRID (56): CNKSR1 (Two-hybrid), CCDC120 (Two-hybrid), SYCE1 (Two-hybrid), CYTH3 (Affinity Capture-MS), CYTH3 (Affinity Capture-MS), CYTH3 (Affinity Capture-MS), CYTH3 (Affinity Capture-MS), CYTH3 (Affinity Capture-MS), CNKSR1 (Two-hybrid), CALCOCO1 (Two-hybrid), CYTH3 (PCA), CYTH3 (Affinity Capture-MS), CYTH3 (Affinity Capture-MS), CYTH3 (Affinity Capture-MS), CYTH3 (Affinity Capture-MS)

ESM2 similar proteins: A0JN86, A4IG62, B3DK16, E7F590, F4IDS7, O02697, O08967, O23617, O35099, O43739, P0CF52, P19447, P25916, P35226, P52757, P54731, P97696, Q0E908, Q0WUI9, Q1JPS1, Q28H21, Q292F9, Q2YDF9, Q32KX7, Q3UK78, Q4QR06, Q5R8L2, Q5RA62, Q5SDR3, Q640D5, Q6DLV9, Q756G9, Q7JUR6, Q7T3E6, Q7Z569, Q7ZYZ7, Q86SE9, Q8BPM2, Q8IVH8, Q8JIR0

Diamond homologs: A0A0G2JUG7, A2A5R2, A5PKW4, D4A631, E1JIT7, F1MUS9, F4IXW2, F4JN05, F4JSZ5, F4K2K3, G3X9K3, G5EET6, O08967, O13690, O13817, O43739, O46382, P11075, P34512, P39993, P47102, P63034, P63035, P97694, P97696, Q10491, Q15438, Q2KI41, Q2PFD7, Q3TES0, Q42510, Q54KA7, Q5DTT2, Q5DU25, Q5E9G6, Q5JU85, Q6DFZ1, Q6DN90, Q6P1I6, Q76M68

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
58516	GRCh38/hg38 7p22.1(chr7:6137098-6398566)x1	Pathogenic

SpliceAI

2910 predictions. Top by Δscore:

Variant	Effect	Δscore
7:6165012:TGGCT:T	acceptor_gain	1.0000
7:6165013:GGCT:G	acceptor_gain	1.0000
7:6165015:CT:C	acceptor_gain	1.0000
7:6165017:C:CA	acceptor_loss	1.0000
7:6165017:C:CC	acceptor_gain	1.0000
7:6165020:G:C	acceptor_gain	1.0000
7:6165020:G:GC	acceptor_gain	1.0000
7:6165268:CTCA:C	donor_gain	1.0000
7:6165269:TCA:T	donor_loss	1.0000
7:6165270:CACT:C	donor_loss	1.0000
7:6165271:A:AC	donor_gain	1.0000
7:6165271:AC:A	donor_loss	1.0000
7:6165272:C:CA	donor_gain	1.0000
7:6165272:CT:C	donor_gain	1.0000
7:6165272:CTTG:C	donor_gain	1.0000
7:6165272:CTTGA:C	donor_gain	1.0000
7:6165294:T:TA	donor_gain	1.0000
7:6165423:CAGTT:C	acceptor_gain	1.0000
7:6165424:AGTT:A	acceptor_gain	1.0000
7:6165425:GTT:G	acceptor_gain	1.0000
7:6165426:TT:T	acceptor_gain	1.0000
7:6165426:TTCT:T	acceptor_loss	1.0000
7:6165427:TC:T	acceptor_loss	1.0000
7:6165428:C:CA	acceptor_loss	1.0000
7:6165428:C:CC	acceptor_gain	1.0000
7:6165429:T:G	acceptor_loss	1.0000
7:6165431:G:C	acceptor_gain	1.0000
7:6165431:G:GC	acceptor_gain	1.0000
7:6165543:A:AC	donor_gain	1.0000
7:6165544:C:CC	donor_gain	1.0000

AlphaMissense

2677 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:6165287:C:A	W372C	1.000
7:6165287:C:G	W372C	1.000
7:6165288:C:G	W372S	1.000
7:6165289:A:G	W372R	1.000
7:6165289:A:T	W372R	1.000
7:6165315:G:T	A363D	1.000
7:6165328:A:C	Y359D	1.000
7:6165328:A:G	Y359H	1.000
7:6165335:A:C	H356Q	1.000
7:6165335:A:T	H356Q	1.000
7:6165337:G:C	H356D	1.000
7:6165342:C:T	G354E	1.000
7:6165343:C:A	G354W	1.000
7:6165343:C:G	G354R	1.000
7:6165343:C:T	G354R	1.000
7:6165371:C:A	K344N	1.000
7:6165371:C:G	K344N	1.000
7:6165373:T:C	K344E	1.000
7:6165375:C:T	C343Y	1.000
7:6165376:A:G	C343R	1.000
7:6165378:G:T	A342D	1.000
7:6165380:C:A	K341N	1.000
7:6165380:C:G	K341N	1.000
7:6165382:T:C	K341E	1.000
7:6165414:A:G	L330P	1.000
7:6165579:A:G	L314P	1.000
7:6165588:A:C	L311W	1.000
7:6165588:A:G	L311S	1.000
7:6165591:G:T	P310Q	1.000
7:6165594:A:C	I309S	1.000

dbSNP variants (sampled 300 via entrez): RS1000053392 (7:6267900 A>C), RS1000062575 (7:6241206 C>A), RS1000080550 (7:6186721 T>C,G), RS1000114928 (7:6180366 G>A,C), RS1000148935 (7:6223569 A>C), RS1000176287 (7:6204812 T>C), RS1000203976 (7:6191943 G>A), RS1000203981 (7:6268444 A>G), RS1000217216 (7:6189656 C>G,T), RS1000263704 (7:6202754 C>A), RS1000266231 (7:6215761 T>C), RS1000296255 (7:6202940 G>A,C,T), RS1000302917 (7:6164143 C>T), RS1000307019 (7:6254445 G>A), RS1000313779 (7:6245649 A>G)

Disease associations

OMIM: gene MIM:605081 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003831_40	Asthma	9.000000e-06
GCST005951_155	Body mass index	1.000000e-08
GCST006998_2	Cerebrospinal fluid p-tau levels in mild cognitive impairment	9.000000e-08
GCST012207_6	Shigella-associated diarrhea	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004760	t-tau measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3259466 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[(3-chloro-2-hydroxy-5-nitrophenyl)carbamothioyl]benzamide	IC50	66700 nM	US-8628961: Small molecule antagonists of phosphatidylinositol-3,4,5-triphosphate (PIP3) and uses thereof
N-[(2-hydroxy-5-nitrophenyl)carbamothioyl]-3,5-dimethylbenzamide	IC50	80500 nM	US-8628961: Small molecule antagonists of phosphatidylinositol-3,4,5-triphosphate (PIP3) and uses thereof

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Fluorouracil	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, increases methylation	1
methylmercuric chloride	increases expression	1
bisphenol A	increases expression	1
kojic acid	increases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
cylindrospermopsin	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
dorsomorphin	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Dexamethasone	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3265617	Binding	Inhibition of C-terminal 6xHis-tagged Grp1 PH domain (unknown origin) expressed in Escherichia coli BL21(DE3) RIL assessed as inhibition of interaction with PtdIns(3,4,5)P3 at 500 uM after 15 mins by SPR analysis relative to control	Elucidation of different inhibition mechanism of small chemicals on PtdInsP-binding domains using in silico docking experiments. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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