NISCH

Summary

NISCH (nischarin, HGNC:18006) is a protein-coding gene on chromosome 3p21.1, encoding Nischarin (Q9Y2I1). Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. It is a selective cancer dependency (DepMap: 20.0% of cell lines).

This gene encodes a nonadrenergic imidazoline-1 receptor protein that localizes to the cytosol and anchors to the inner layer of the plasma membrane. The orthologous mouse protein has been shown to influence cytoskeletal organization and cell migration by binding to alpha-5-beta-1 integrin. In humans, this protein has been shown to bind to the adapter insulin receptor substrate 4 (IRS4) to mediate translocation of alpha-5 integrin from the cell membrane to endosomes. Expression of this protein was reduced in human breast cancers while its overexpression reduced tumor growth and metastasis; possibly by limiting the expression of alpha-5 integrin. In human cardiac tissue, this gene was found to affect cell growth and death while in neural tissue it affected neuronal growth and differentiation. Alternative splicing results in multiple transcript variants encoding differerent isoforms. Some isoforms lack the expected C-terminal domains of a functional imidazoline receptor.

Source: NCBI Gene 11188 — RefSeq curated summary.

At a glance

• GWAS associations: 35
• Clinical variants (ClinVar): 252 total — 1 pathogenic
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 20.0% of screened cell lines
• MANE Select transcript: NM_007184

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18006
Approved symbol	NISCH
Name	nischarin
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0975, I-1, IRAS
Ensembl gene	ENSG00000010322
Ensembl biotype	protein_coding
OMIM	615507
Entrez	11188

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 12 protein_coding, 6 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000345716, ENST00000420808, ENST00000460759, ENST00000464280, ENST00000467594, ENST00000474188, ENST00000479054, ENST00000481211, ENST00000485765, ENST00000488157, ENST00000488243, ENST00000488380, ENST00000489895, ENST00000490425, ENST00000878264, ENST00000878265, ENST00000878266, ENST00000914221, ENST00000914222, ENST00000914223, ENST00000914224, ENST00000914225

RefSeq mRNA: 3 — MANE Select: NM_007184 NM_001276293, NM_001276294, NM_007184

CCDS: CCDS33767, CCDS63651, CCDS63652

Canonical transcript exons

ENST00000345716 — 21 exons

Exon	Start	End
ENSE00002232318	52455604	52455734
ENSE00003461122	52472303	52472398
ENSE00003463267	52471814	52471977
ENSE00003471309	52491872	52493068
ENSE00003472034	52473734	52473829
ENSE00003513961	52484513	52484637
ENSE00003529812	52491352	52491513
ENSE00003544942	52489336	52489678
ENSE00003570559	52470859	52470907
ENSE00003577769	52478449	52478577
ENSE00003610160	52478097	52478282
ENSE00003613532	52476447	52476599
ENSE00003618686	52480184	52480295
ENSE00003651247	52490705	52490833
ENSE00003652100	52477574	52477642
ENSE00003655214	52485778	52485827
ENSE00003659340	52487196	52488605
ENSE00003668029	52479749	52479862
ENSE00003889159	52490075	52490231
ENSE00003890085	52458662	52458844
ENSE00003893211	52457843	52457926

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.2899 / max 279.3523, expressed in 1804 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36860	21.6078	1792
36858	2.9042	1237
36859	0.7013	401
36864	0.0478	24
36865	0.0176	6
36861	0.0112	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.43	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.41	gold quality
cerebellar hemisphere	UBERON:0002245	99.37	gold quality
cerebellar cortex	UBERON:0002129	99.31	gold quality
cerebellum	UBERON:0002037	99.23	gold quality
pituitary gland	UBERON:0000007	99.14	gold quality
adenohypophysis	UBERON:0002196	98.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.78	gold quality
paraflocculus	UBERON:0005351	98.37	gold quality
endocervix	UBERON:0000458	98.25	gold quality
tibial nerve	UBERON:0001323	98.17	gold quality
left ovary	UBERON:0002119	98.03	gold quality
entorhinal cortex	UBERON:0002728	98.03	gold quality
right ovary	UBERON:0002118	98.02	gold quality
tibia	UBERON:0000979	98.01	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.01	gold quality
visceral pleura	UBERON:0002401	97.97	gold quality
body of uterus	UBERON:0009853	97.93	gold quality
mucosa of stomach	UBERON:0001199	97.91	gold quality
right uterine tube	UBERON:0001302	97.90	gold quality
right testis	UBERON:0004534	97.83	gold quality
right frontal lobe	UBERON:0002810	97.81	gold quality
left testis	UBERON:0004533	97.81	gold quality
upper leg skin	UBERON:0004262	97.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.73	gold quality
lower esophagus	UBERON:0013473	97.71	gold quality
parietal pleura	UBERON:0002400	97.66	gold quality
pleura	UBERON:0000977	97.65	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.63	gold quality
seminal vesicle	UBERON:0000998	97.62	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.50
E-GEOD-81547	yes	12.82
E-ANND-3	yes	8.40
E-GEOD-125970	yes	7.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF6, NR1H4

miRNA regulators (miRDB)

30 targeting NISCH, 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-8485	100.00	77.57	4731
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-9851-5P	97.57	67.49	1067
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-1231	95.10	65.63	663

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 25)

• Insulin receptor substrate 4 associates with the protein IRAS (IRAS protein) (PMID:11912194)
• The heart possesses imidazoline I1-receptors that are up-regulated in the presence of hypertension or heart failure, which suggests their involvement in cardiovascular regulation. (PMID:12021582)
• I(1)-receptors can abrogate the primary signaling cascade activated by NGF, most likely by increasing levels of a specific phosphatase to return dually phosphorylated ERK to its unphosphorylated state. (PMID:12865160)
• hIRAS expression in PC12 cells resulted in protection against apoptosis (PMID:12868002)
• Results suggest that IRAS may represent a previously unknown anti-apoptotic protein involved in the regulation of cell survival. (PMID:15028619)
• Results describe three alternatively spliced transcripts of the human I(1)-imidazoline receptor candidate gene, IRAS. (PMID:15028621)
• Results suggest that imidazoline-1 receptors (I(1)R) and alpha(2)-noradrenergic receptors (alpha(2)AR) may interact with each other. (PMID:15028622)
• platelets lacked the 170-kD form of IRAS, but 33-kD and 85-kD bands were detectable and seemed to be possible fragments of full-length IRAS (PMID:15028623)
• PX domain of imidazoline receptor antisera-selected protein(IRAS) is essential for association with phosphatidylinositol 3-phosphate-enriched endosomal membranes but is insufficient without coiled-coil domain (PMID:15475348)
• The signaling pathway of IRAS in response to I1R agonists coupled with the activation of PC-PLC and its downstream signal transduction molecule, ERK. These findings are similar to those in the signaling pathways of native I1R. (PMID:16598778)
• shows strong affinity to clonidine and regulates blood pressure. (PMID:18561481)
• Nischarin reduces alpha5 integrin expression leading to reduction of FAK phosphorylation and Rac GTP loading, which in turn reduces tumor growth. NISCH also regulates PAK and LIMK signaling. (PMID:21917605)
• Imidazoline receptor 1 gene plays a role in the development of cardiac hypertrophy and ventirular remodeling. (PMID:22483786)
• Tobacco smoke induces methylation changes in the NISCH gene promoter before any detectable cancer. (PMID:23503203)
• unctional interaction between LKB1 and Nischarin to inhibit cell migration and breast tumor progression (PMID:23572524)
• Nischarin expression may therefore be used as a marker to predict the invasiveness and metastasis of primary breast cancer (PMID:25695373)
• Data found that NISCH was significantly downregulated in ovarian neoplasm through its promotor silencing with hypermethylation and its expression was correlated with poor prognosis. (PMID:25724667)
• IRAS is a new mu opioid receptor interacting protein that regulates agonist-induced trafficking of mu opioid receptor. (PMID:26363797)
• The present data confirmed that Nishcharin might be a novel tumor suppressor and plays an important role in breast cancer cell apoptosis and metastasis, which can be used as a potential therapeutic target for breast cancer treatment. (PMID:28131840)
• In the prefrontal cortex of long-term opiate/cocaine abusers, IRAS content was increased when compared to matched controls. (PMID:28461172)
• These experiments demonstrate an important role of Nischarin in regulating cell attachment, which adds to our understanding of the early events of the metastatic process in breast cancer. (PMID:29415725)
• Transcription factor KLF15 inhibits the proliferation and migration of gastric cancer cells via regulating the TFAP2A-AS1/NISCH axis. (PMID:34727954)
• Contribution of Nischarin/IRAS in CNS development, injury and diseases. (PMID:36716956)
• Nischarin expression may have differing roles in male and female melanoma patients. (PMID:37382661)
• Identification of a psychiatric risk gene NISCH at 3p21.1 GWAS locus mediating dendritic spine morphogenesis and cognitive function. (PMID:37443018)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nisch	ENSDARG00000043077
mus_musculus	Nisch	ENSMUSG00000021910
rattus_norvegicus	Nisch	ENSRNOG00000018823
drosophila_melanogaster	CG11807	FBGN0033996
caenorhabditis_elegans		WBGENE00008750

Paralogs (1): STK11IP (ENSG00000144589)

Protein

Protein identifiers

Nischarin — Q9Y2I1 (reviewed: Q9Y2I1)

Alternative names: Imidazoline receptor 1, Imidazoline receptor antisera-selected protein, Imidazoline-1 receptor, Imidazoline-1 receptor candidate protein

All UniProt accessions (2): Q9Y2I1, C9J715

UniProt curated annotations — full annotation on UniProt →

Function. Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension. Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons. Acts as a modulator of Rac-regulated signal transduction pathways. Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity. Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation. Also inhibits LIMK1 kinase activity by reducing LIMK1 ‘Tyr-508’ phosphorylation. Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells. Inhibits lamellipodia formation, when overexpressed. Plays a role in protection against apoptosis. Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3. When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures.

Subunit / interactions. Homooligomer. Interacts with GRB2. Interacts with PIK3R1; probably associates with the PI3-kinase complex. Interacts with IRS4. Found in a complex with ITGA5 and PAK1. Found in a complex with LIMK1 and PAK1. Interacts with ITGA5 (via cytoplasmic domain); this interaction is direct. Interacts with PAK1 (via kinase domain); this interaction is direct and is increased upon activation of PAK1. Interacts with LIMK1 (via PDZ and kinase domain); this interaction is direct. Interacts with LIMK2; this interaction depends on LIMK2 activity. Interacts with RAC1 (activated state). Interacts with STK11; this interaction may increase STK11 activity.

Subcellular location. Cell membrane. Cytoplasm. Early endosome. Recycling endosome.

Tissue specificity. Isoform 1, isoform 3 and isoform 4 are expressed in brain. Isoform 1 is expressed in endocrine tissues.

Domain organisation. Both the presence of the PX domain and the coiled coil region are necessary for its endosomal targeting.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y2I1-1	1, IRAS-1, IRAS-M	yes
Q9Y2I1-2	2
Q9Y2I1-3	3, IRAS-L
Q9Y2I1-4	4, IRAS-S

RefSeq proteins (3): NP_001263222, NP_001263223, NP_009115* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR001683	PX_dom	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR037904	Nischarin_PX	Domain
IPR057288	PH_PLEKHM2	Domain
IPR057714	PH_NISCH_C	Domain

Pfam: PF00787, PF23142, PF25625

UniProt features (53 total): region of interest 10, modified residue 7, repeat 6, compositionally biased region 5, splice variant 5, strand 5, sequence conflict 4, helix 3, sequence variant 2, mutagenesis site 2, initiator methionine 1, chain 1, coiled-coil region 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3P0C	X-RAY DIFFRACTION	2.27
8ESF	X-RAY DIFFRACTION	2.56

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2I1-F1	69.86	0.23

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 (7): 2, 541, 543, 546, 1022, 1282, 1284

Mutagenesis-validated functional residues (2):

Position	Phenotype
49	inhibits targeting to endosomes.
50	inhibits targeting to endosomes.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696270	RND2 GTPase cycle

MSigDB gene sets: 0 (showing top):

GO Biological Process (4): apoptotic process (GO:0006915), Rac protein signal transduction (GO:0016601), actin cytoskeleton organization (GO:0030036), negative regulation of cell migration (GO:0030336)

GO Molecular Function (4): integrin binding (GO:0005178), phosphatidylinositol binding (GO:0035091), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (10): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), intercellular bridge (GO:0045171), recycling endosome (GO:0055037), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
endosome	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
small GTPase-mediated signal transduction	1
cytoskeleton organization	1
actin filament-based process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
anion binding	1
protein binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cytoskeleton	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NISCH	RANGAP1	P46060	863
NISCH	ITGA5	P08648	803
NISCH	RANBP2	P49792	793
NISCH	SUMO1	P55856	772
NISCH	UBE2I	P50550	714
NISCH	LIMK1	P53667	676
NISCH	GCSAM	Q8N6F7	668
NISCH	STK11	Q15831	654
NISCH	CLDN1	O95832	626
NISCH	NR1H4	Q96RI1	621
NISCH	SHARPIN	Q9H0F6	616
NISCH	SRSF1	Q07955	609
NISCH	ZNF77	Q15935	600
NISCH	CABIN1	Q9Y6J0	580
NISCH	TSPAN4	O14817	573

IntAct

183 interactions, top by confidence:

A	B	Type	Score
PIK3R1	PIK3CD	psi-mi:“MI:0914”(association)	0.890
PIK3R3	PIK3CD	psi-mi:“MI:0914”(association)	0.800
NS	PIK3R2	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NISCH	RAB9A	psi-mi:“MI:0915”(physical association)	0.690
RAB9A	NISCH	psi-mi:“MI:0403”(colocalization)	0.690
NISCH	RAB9A	psi-mi:“MI:0403”(colocalization)	0.690
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
PIK3R2	IRS4	psi-mi:“MI:0914”(association)	0.640
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
USP4	PRPF3	psi-mi:“MI:0914”(association)	0.640
NISCH	Rab14	psi-mi:“MI:0915”(physical association)	0.640
Rab14	NISCH	psi-mi:“MI:0915”(physical association)	0.640
Rab14	NISCH	psi-mi:“MI:0403”(colocalization)	0.640
NISCH	Rab14	psi-mi:“MI:0403”(colocalization)	0.640
IRS4	PIK3R2	psi-mi:“MI:0914”(association)	0.640

BioGRID (202): NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS), NISCH (Affinity Capture-MS)

ESM2 similar proteins: A0A8M3AJY3, A5WUN7, A6QLR3, B5X1P9, E2AB17, F1MJR8, F1QB81, M0R5D6, O00443, O43310, O60291, P03122, P11299, P15304, P42859, P51111, P59438, Q15018, Q1HKZ5, Q1LUT1, Q1LVP6, Q28HX0, Q2PFD7, Q2T9I9, Q3TCJ1, Q3TEL6, Q3UPF5, Q535K8, Q5E9P1, Q5I0F1, Q5RD34, Q5VUB5, Q5XIQ4, Q5ZHS0, Q61194, Q6GR31, Q6INH1, Q6P4W0, Q6PEE2, Q6UWZ7

Diamond homologs: Q17QS1, Q4G017, Q5U2S5, Q80TM9, Q96L94, Q9CRB0, Q9Y2I1, Q9Y343, Q6PHS6, Q9Y5W8, Q4FZZ1, Q559T8, Q7Z7A4, Q8BX57, Q2T9W1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 212 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	17.7×	8e-04
Regulation of signaling by CBL	5	16.9×	8e-04
EPHA-mediated growth cone collapse	6	15.5×	4e-04
Interleukin receptor SHC signaling	5	13.9×	1e-03
Interleukin-3, Interleukin-5 and GM-CSF signaling	6	12.9×	8e-04
SUMOylation of ubiquitinylation proteins	6	11.9×	8e-04
EPH-ephrin mediated repulsion of cells	7	10.5×	7e-04
PI3K Cascade	5	9.2×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	7	13.2×	1e-03
insulin receptor signaling pathway	7	8.5×	5e-03
positive regulation of MAPK cascade	11	4.9×	5e-03
positive regulation of cell migration	14	4.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	202
Likely benign	13
Benign	9

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4279103	NM_007184.4(NISCH):c.277del (p.Glu93fs)	Pathogenic

SpliceAI

4149 predictions. Top by Δscore:

Variant	Effect	Δscore
3:52457838:TTTA:T	acceptor_loss	1.0000
3:52457840:TA:T	acceptor_loss	1.0000
3:52457842:GGTTT:G	acceptor_gain	1.0000
3:52457924:AAGGT:A	donor_loss	1.0000
3:52457925:AGGTA:A	donor_loss	1.0000
3:52457926:GGTAA:G	donor_loss	1.0000
3:52457928:T:G	donor_loss	1.0000
3:52458660:A:AG	acceptor_gain	1.0000
3:52458660:A:C	acceptor_loss	1.0000
3:52458660:AGCTC:A	acceptor_gain	1.0000
3:52458661:G:GT	acceptor_gain	1.0000
3:52458661:GC:G	acceptor_gain	1.0000
3:52458661:GCTC:G	acceptor_gain	1.0000
3:52458661:GCTCG:G	acceptor_gain	1.0000
3:52458810:GA:G	donor_gain	1.0000
3:52458812:G:GG	donor_gain	1.0000
3:52458840:TCTAT:T	donor_gain	1.0000
3:52458841:CTAT:C	donor_gain	1.0000
3:52458842:TATG:T	donor_loss	1.0000
3:52458843:AT:A	donor_gain	1.0000
3:52458843:ATG:A	donor_loss	1.0000
3:52458844:TGT:T	donor_loss	1.0000
3:52458845:G:GC	donor_loss	1.0000
3:52458845:G:GG	donor_gain	1.0000
3:52458846:TAAGT:T	donor_loss	1.0000
3:52471976:AGG:A	donor_loss	1.0000
3:52472301:A:AG	acceptor_gain	1.0000
3:52472301:AG:A	acceptor_gain	1.0000
3:52472302:G:A	acceptor_loss	1.0000
3:52472302:G:GT	acceptor_gain	1.0000

AlphaMissense

9822 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:52479809:G:C	A455P	1.000
3:52487309:T:C	L606P	1.000
3:52487626:T:A	W712R	1.000
3:52487626:T:C	W712R	1.000
3:52487674:T:C	C728R	1.000
3:52487676:C:G	C728W	1.000
3:52488242:T:C	L917P	1.000
3:52488413:T:C	L974P	1.000
3:52457907:T:C	F53S	0.999
3:52458759:T:C	L92P	0.999
3:52458771:T:C	L96P	0.999
3:52478204:C:A	N365K	0.999
3:52478204:C:G	N365K	0.999
3:52479804:T:C	L453P	0.999
3:52487297:T:C	F602S	0.999
3:52487321:T:A	I610N	0.999
3:52487329:G:C	A613P	0.999
3:52487629:T:C	C713R	0.999
3:52487675:G:A	C728Y	0.999
3:52487681:T:A	V730E	0.999
3:52487684:T:C	L731P	0.999
3:52487702:C:A	A737E	0.999
3:52487705:T:A	V738D	0.999
3:52487708:T:C	F739S	0.999
3:52487795:T:C	L768P	0.999
3:52487827:T:C	C779R	0.999
3:52487831:T:C	L780P	0.999
3:52487837:T:C	L782P	0.999
3:52487912:T:C	L807P	0.999
3:52488217:T:A	W909R	0.999

dbSNP variants (sampled 300 via entrez): RS1000016273 (3:52472140 G>A), RS1000052582 (3:52457609 C>G), RS1000154179 (3:52464014 A>G), RS1000413812 (3:52458965 T>C), RS1000428834 (3:52474884 G>A), RS1000448007 (3:52457226 G>A), RS1000737872 (3:52486510 C>T), RS1000774355 (3:52469596 G>A), RS1000792011 (3:52486213 A>C,G), RS1000901710 (3:52484085 TGAG>T), RS1001038073 (3:52480990 C>T), RS1001134257 (3:52457017 G>A), RS1001165266 (3:52456757 A>G), RS1001300410 (3:52483110 G>C), RS1001388274 (3:52463532 C>A)

Disease associations

OMIM: gene MIM:615507 | disease phenotypes: MIM:120435, MIM:604370

GenCC curated gene-disease

Mondo (2): Lynch syndrome 1 (MONDO:0007356), breast-ovarian cancer, familial, susceptibility to, 1 (MONDO:0011450)

Orphanet (2): Lynch syndrome (Orphanet:144), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST000829_9	Waist-hip ratio	4.000000e-10
GCST001241_15	Bipolar disorder	2.000000e-06
GCST002149_14	Schizophrenia	1.000000e-08
GCST002539_48	Schizophrenia	4.000000e-11
GCST004521_123	Autism spectrum disorder or schizophrenia	3.000000e-12
GCST004521_201	Autism spectrum disorder or schizophrenia	4.000000e-08
GCST004902_20	Parkinson’s disease	3.000000e-08
GCST006269_818	General cognitive ability	9.000000e-09
GCST006803_55	Schizophrenia	1.000000e-11
GCST008103_3	Bipolar disorder	7.000000e-11
GCST010242_421	HDL cholesterol levels	9.000000e-23
GCST010243_132	Apolipoprotein B levels	3.000000e-09
GCST010244_63	Triglyceride levels	1.000000e-31
GCST012203_2	Colon cancer	1.000000e-08
GCST012205_2	Distal colorectal cancer	5.000000e-07
GCST90002385_431	High light scatter reticulocyte count	8.000000e-09
GCST90002386_551	High light scatter reticulocyte percentage of red cells	3.000000e-09
GCST90002405_18	Reticulocyte count	2.000000e-09
GCST90002406_37	Reticulocyte fraction of red cells	7.000000e-09
GCST90020024_1200	A body shape index	4.000000e-15
GCST90020024_1203	A body shape index	6.000000e-10
GCST90020024_1204	A body shape index	3.000000e-09
GCST90020024_1205	A body shape index	2.000000e-08
GCST90020025_1951	Waist-to-hip ratio adjusted for BMI	5.000000e-17
GCST90020025_1954	Waist-to-hip ratio adjusted for BMI	1.000000e-12
GCST90020025_1955	Waist-to-hip ratio adjusted for BMI	4.000000e-10
GCST90020025_1956	Waist-to-hip ratio adjusted for BMI	9.000000e-12
GCST90020027_109	Waist-hip index	7.000000e-17
GCST90020027_112	Waist-hip index	2.000000e-12
GCST90020027_113	Waist-hip index	8.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0004337	intelligence
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0007986	reticulocyte count
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537261	Lynch syndrome I (site-specific colonic cancer) (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3923 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 211,173 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1079	TIZANIDINE	4	12,099
CHEMBL134	CLONIDINE	4	97,993
CHEMBL19236	MOXONIDINE	4	4,405
CHEMBL289480	RILMENIDINE	4	2,657
CHEMBL420	GUANABENZ	4	16,459
CHEMBL597	PHENTOLAMINE	4	14,731
CHEMBL761	NAPHAZOLINE	4	13,060
CHEMBL762	OXYMETAZOLINE	4	13,685
CHEMBL862	GUANFACINE	4	23,781
CHEMBL10316	IDAZOXAN	3	4,279
CHEMBL13852	CIRAZOLINE	2	1,206
CHEMBL13881	PHENAMAZOLINE	2	100
CHEMBL14012	FENOXAZOLINE	2	734
CHEMBL57895	EFAROXAN	2	1,638
CHEMBL269538	HARMINE	1	4,346

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

Binding affinities (BindingDB)

1 measured of 7 human assays (7 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
SR 147778	KI	1000 nM

ChEMBL bioactivities

265 potent at pChembl≥5 of 269 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.66	Ki	0.22	nM	CHEMBL3546401
9.20	Ki	0.631	nM	BENAZOLINE
9.10	Ki	0.7943	nM	CHEMBL14097
9.00	Ki	1	nM	CHEMBL14640
8.97	Ki	1.072	nM	CHEMBL2092861
8.90	Ki	1.259	nM	CHEMBL14107
8.80	Ki	1.585	nM	CHEMBL13698
8.80	Ki	1.585	nM	CHEMBL404505
8.80	Ki	1.585	nM	CHEMBL418536
8.70	Ki	1.995	nM	FENOXAZOLINE
8.70	Ki	1.995	nM	CHEMBL279200
8.70	Ki	1.995	nM	TRACIZOLINE
8.70	Ki	1.995	nM	CHEMBL13987
8.70	Ki	1.99	nM	CHEMBL13987
8.60	Ki	2.512	nM	PHENYZOLINE
8.60	Ki	2.512	nM	CHEMBL13887
8.60	Ki	2.512	nM	CHEMBL266861
8.60	Ki	2.512	nM	CHEMBL13343
8.55	Ki	2.8	nM	CHEMBL3546402
8.55	Ki	2.8	nM	CHEMBL3546398
8.50	Ki	3.162	nM	CHEMBL267801
8.50	Ki	3.162	nM	CHEMBL13631
8.46	Ki	3.5	nM	CHEMBL60186
8.45	IC50	3.548	nM	MOXONIDINE
8.40	Ki	3.981	nM	CHEMBL13892
8.40	Ki	3.981	nM	CHEMBL276276
8.40	Ki	3.981	nM	CHEMBL14203
8.40	Ki	3.981	nM	CIRAZOLINE
8.38	Ki	4.198	nM	MOXONIDINE
8.33	Ki	4.7	nM	CHEMBL14242
8.32	Ki	4.797	nM	PI-CLONIDINE
8.32	Ki	4.8	nM	PI-CLONIDINE
8.30	Ki	5.012	nM	CHEMBL71429
8.30	Ki	5.012	nM	CHEMBL276487
8.30	Ki	5.012	nM	CHEMBL13633
8.30	Ki	5.012	nM	CHEMBL14528
8.30	Ki	5.012	nM	CHEMBL268945
8.22	Ki	6.026	nM	CHEMBL468161
8.21	Ki	6.194	nM	OXYMETAZOLINE
8.21	Ki	6.2	nM	OXYMETAZOLINE
8.20	Ki	6.31	nM	CHEMBL268734
8.20	Ki	6.31	nM	CHEMBL13917
8.15	Ki	7	nM	CHEMBL62107
8.10	Ki	7.943	nM	IDAZOXAN
8.10	Ki	7.943	nM	CHEMBL14028
8.10	Ki	7.943	nM	CHEMBL269197
8.10	Ki	8	nM	CHEMBL14028
8.09	Ki	8.1	nM	CHEMBL3547056
8.09	IC50	8.128	nM	CHEMBL4536304
8.05	Ki	8.9	nM	CLONIDINE

PubChem BioAssay actives

275 with measured affinity, of 319 total; 50 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
2-naphthalen-2-yl-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0006	uM
2-[(2-methylphenoxy)methyl]-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0008	uM
2-(phenoxymethyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0010	uM
2-[(2S)-1-phenylpropan-2-yl]-4,5-dihydro-1H-imidazole	223238: Displacement of [125I]p-iodoclonidine from imidazoline receptor I-1 in rat pheochromocytoma cells	ki	0.0011	uM
2-[(2-prop-2-enylphenoxy)methyl]-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0013	uM
2-(4,5-dihydro-1H-imidazol-2-yl)quinoline	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0016	uM
2-naphthalen-1-yl-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0016	uM
2-(1-benzofuran-2-yl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0016	uM
2-(naphthalen-1-yloxymethyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0020	uM
2-[(E)-2-phenylethenyl]-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0020	uM
2-[(2-propan-2-ylphenoxy)methyl]-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0020	uM
2-(4,5-dihydro-1H-imidazol-2-yl)-4,6-dimethyl-2,3-dihydro-1,4-benzoxazine	223246: In vitro binding affinity determined against imidazoline receptor I-2 using rabbit kidney preparation	ki	0.0020	uM
2-[(2-ethylphenoxy)methyl]-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0025	uM
2-(2-phenylethyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0025	uM
5-(4,5-dihydro-1H-imidazol-2-yl)-1H-indole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0025	uM
2-benzo[e][1]benzofuran-2-yl-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0025	uM
3-(4,5-dihydro-1H-imidazol-2-yl)quinoline	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0032	uM
2-(3-fluoro-4-methylphenyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0032	uM
10-(4,5-dihydro-1H-imidazol-2-yl)-9-oxa-1-azatricyclo[6.3.1.04,12]dodeca-2,4(12),5,7-tetraene	223246: In vitro binding affinity determined against imidazoline receptor I-2 using rabbit kidney preparation	ki	0.0035	uM
4-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxy-2-methylpyrimidin-5-amine	1561260: Displacement of [3H]clonidine from I1IR in human brain frontal cortex in presence of adrenaline incubated for 45 mins by liquid scintillation spectrometry	ic50	0.0035	uM
2-(2H-chromen-3-yl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0040	uM
2-(naphthalen-2-yloxymethyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0040	uM
2-[(2-cyclopropylphenoxy)methyl]-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0040	uM
2-(4-methylsulfanylphenyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0040	uM
2-(4,5-dihydro-1H-imidazol-2-yl)-6-fluoro-4-methyl-2,3-dihydro-1,4-benzoxazine	223246: In vitro binding affinity determined against imidazoline receptor I-2 using rabbit kidney preparation	ki	0.0047	uM
N-(2,6-dichloro-4-iodophenyl)-4,5-dihydro-1H-imidazol-2-amine	342861: Displacement of [125I]PIC from human imidazoline receptor 1 in human platelets analyzed under norepinephrine mask of alpha 2AR	ki	0.0048	uM
2-(1-phenylpropan-2-yl)-4,5-dihydro-1H-imidazole	223238: Displacement of [125I]p-iodoclonidine from imidazoline receptor I-1 in rat pheochromocytoma cells	ki	0.0050	uM
3-(4,5-dihydro-1H-imidazol-2-yl)-2-methylbenzonitrile	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0050	uM
2-(4-methoxyphenyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0050	uM
2-(1,3-benzodioxol-5-yl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0050	uM
2-(3-methylphenyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0050	uM
[4-chloro-2-iodo-5-[(2-methyl-3,4-dihydro-2H-pyrrol-5-yl)amino]phenyl]imino-iminoazanium	342862: Displacement of [125I]PIC from human imidazoline receptor 1 expressed in rat PC12 cells	ki	0.0060	uM
Oxymetazoline	342861: Displacement of [125I]PIC from human imidazoline receptor 1 in human platelets analyzed under norepinephrine mask of alpha 2AR	ki	0.0062	uM
2-(2-fluoro-5-methylphenyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0063	uM
2-[(2-propylphenoxy)methyl]-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0063	uM
methyl 2-(4,5-dihydro-1H-imidazol-2-yl)-4-methyl-2,3-dihydro-1,4-benzoxazine-6-carboxylate	223246: In vitro binding affinity determined against imidazoline receptor I-2 using rabbit kidney preparation	ki	0.0070	uM
2-(4,5-dihydro-1H-imidazol-2-yl)-4-methyl-2,3-dihydro-1,4-benzoxazine	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0079	uM
2-(4-methylphenyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0079	uM
2-(2,3-dihydro-1,4-benzodioxin-3-yl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0079	uM
3-diethoxyphosphoryl-5-(4-methoxyphenyl)-3a,6a-dihydro-3H-pyrrolo[3,4-c]pyrrole-4,6-dione	1561260: Displacement of [3H]clonidine from I1IR in human brain frontal cortex in presence of adrenaline incubated for 45 mins by liquid scintillation spectrometry	ic50	0.0081	uM
Clonidine	223225: Displacement of [3H]-clonidine from bovine imidazoline receptor I-1	ki	0.0089	uM
2-(2-methylphenyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0100	uM
2-(4H-1,3-benzodioxin-2-yl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0100	uM
3-(4,5-dihydro-1H-imidazol-2-yl)-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13)-triene	223246: In vitro binding affinity determined against imidazoline receptor I-2 using rabbit kidney preparation	ki	0.0100	uM
2-(3,4-dihydronaphthalen-2-yl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0100	uM
2-(6-methoxynaphthalen-2-yl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0100	uM
2-[(E)-1-phenylprop-1-en-2-yl]-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0100	uM
2-(4-phenylphenyl)-4,5-dihydro-1H-imidazole	91715: Binding affinity for imidazoline receptor I-2 in rabbit kidney homogenate (relative to [3H]-Idazoxan radioligand)	ki	0.0100	uM
3-diethoxyphosphoryl-3-phenyl-5-(2-phenylethyl)-3a,6a-dihydropyrrolo[3,4-c]pyrrole-4,6-dione	1561260: Displacement of [3H]clonidine from I1IR in human brain frontal cortex in presence of adrenaline incubated for 45 mins by liquid scintillation spectrometry	ic50	0.0105	uM
Phentolamine	342861: Displacement of [125I]PIC from human imidazoline receptor 1 in human platelets analyzed under norepinephrine mask of alpha 2AR	ki	0.0114	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	3
Aflatoxin B1	increases methylation	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
deguelin	decreases expression	1
pinostrobin	increases expression	1
motexafin gadolinium	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
pyrachlostrobin	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	decreases methylation	1
picoxystrobin	decreases expression	1
Temozolomide	increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1

ChEMBL screening assays

38 unique, capped per target: 38 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1248889	Binding	Binding affinity to I1 receptor by radioligand displacement assay	Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. — J Med Chem

Clinical trials (associated diseases)

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