ICMT

Summary

ICMT (isoprenylcysteine carboxyl methyltransferase, HGNC:5350) is a protein-coding gene on chromosome 1p36.31, encoding Protein-S-isoprenylcysteine O-methyltransferase (O60725). Catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues. It is a selective cancer dependency (DepMap: 10.4% of cell lines).

This gene encodes the third of three enzymes that posttranslationally modify isoprenylated C-terminal cysteine residues in certain proteins and target those proteins to the cell membrane. This enzyme localizes to the endoplasmic reticulum. Alternative splicing may result in other transcript variants, but the biological validity of those transcripts has not been determined.

Source: NCBI Gene 23463 — RefSeq curated summary.

At a glance

• GWAS associations: 48
• Clinical variants (ClinVar): 40 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 10.4% of screened cell lines
• MANE Select transcript: NM_012405

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5350
Approved symbol	ICMT
Name	isoprenylcysteine carboxyl methyltransferase
Location	1p36.31
Locus type	gene with protein product
Status	Approved
Aliases	PCCMT, HSTE14, PPMT
Ensembl gene	ENSG00000116237
Ensembl biotype	protein_coding
OMIM	605851
Entrez	23463

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000343813, ENST00000474756, ENST00000489498, ENST00000495791, ENST00000875198, ENST00000944941

RefSeq mRNA: 1 — MANE Select: NM_012405 NM_012405

CCDS: CCDS61

Canonical transcript exons

ENST00000343813 — 5 exons

Exon	Start	End
ENSE00001408180	6221193	6225262
ENSE00001475518	6235717	6235964
ENSE00002959560	6234886	6234974
ENSE00003483716	6233474	6233643
ENSE00003631599	6231902	6232119

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 95.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.0153 / max 151.3723, expressed in 1797 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10003	21.3405	1777
10002	11.6748	1742

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
diaphragm	UBERON:0001103	95.06	silver quality
adrenal tissue	UBERON:0018303	94.97	gold quality
stromal cell of endometrium	CL:0002255	94.67	gold quality
body of tongue	UBERON:0011876	94.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.49	gold quality
esophagus squamous epithelium	UBERON:0006920	93.08	gold quality
gastrocnemius	UBERON:0001388	92.96	gold quality
muscle of leg	UBERON:0001383	92.82	gold quality
islet of Langerhans	UBERON:0000006	92.75	gold quality
epithelium of esophagus	UBERON:0001976	92.70	gold quality
nasal cavity epithelium	UBERON:0005384	92.61	gold quality
heart right ventricle	UBERON:0002080	92.41	gold quality
gluteal muscle	UBERON:0002000	92.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.12	gold quality
muscle organ	UBERON:0001630	92.03	gold quality
left ventricle myocardium	UBERON:0006566	91.93	gold quality
biceps brachii	UBERON:0001507	91.90	gold quality
myocardium	UBERON:0002349	91.70	gold quality
secondary oocyte	CL:0000655	91.62	gold quality
tongue	UBERON:0001723	91.62	gold quality
heart left ventricle	UBERON:0002084	91.59	gold quality
cardiac ventricle	UBERON:0002082	91.57	gold quality
tibialis anterior	UBERON:0001385	91.41	gold quality
placenta	UBERON:0001987	91.27	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.27	gold quality
deltoid	UBERON:0001476	91.17	gold quality
nasal cavity mucosa	UBERON:0001826	91.13	gold quality
heart	UBERON:0000948	91.03	gold quality
skeletal muscle tissue	UBERON:0001134	90.99	gold quality
triceps brachii	UBERON:0001509	90.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting ICMT, 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-9-5P	100.00	72.28	2361
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4650-5P	99.98	64.69	999
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-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-380-3P	99.89	70.18	1978

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 23)

• modulation of pcCMT activity in retinoic acid (RA)-treated SH-SY5Y neuroblastoma cells (PMID:11906819)
• ICMTase is a critical component of the redox-sensitive VCAM-1-selective signaling pathway and appears to activate a discrete inflammatory signaling pathway, at least in part, through the methylation of Rac1 in endothelial cells. (PMID:12006387)
• findings suggest that inhibition of isoprenylcysteine-O-carboxyl methyltransferase (ICMT) causes endothelial cell apoptosis by attenuation of Ras GTPase methylation and activation and its downstream antiapoptotic signaling pathway. (PMID:12631708)
• These studies identify isoprenylcysteine carboxyl methyltransferase as a potential target for reducing the growth of K-Ras- and B-Raf-induced malignancies. (PMID:14966563)
• ICMT inhibition induces endothelial cell apoptosis through GRP94 (PMID:17347446)
• Icmt traverses the Eendoplasmic reticulum membrane eight times, with both N and C termini disposed toward the cytosol and with a helix-turn-helix structure comprising transmembrane (TM) segments 7 and 8. (PMID:19158273)
• Inhibition of isoprenylcysteine carboxylmethyltransferase (Icmt) decreases activation of RhoA and Rac1, and in the absence of Icmt activity, addition of exogenous RhoA or Rac1 partially rescues directed and random migration, respectively. (PMID:19651782)
• a role for isoprenylcysteine carboxylmethyltransferase in cell migration and adhesion. (PMID:20798596)
• Silencing ICMT in osteosarcoma cells decreased Notch1 signaling in response to stimulation with cell-surface ligands. (PMID:24216479)
• impact of Icmt on tumorigenic processes (PMID:25151967)
• simultaneous inhibition of BCR-ABL1 and Icmt may represent a potential therapeutic strategy for CML. (PMID:26706195)
• Apoptosis, but not autophagy, that is induced via p21-activated BNIP3 expression accounts for the efficacy of ICMT inhibition in sensitive pancreatic cancer cells in both in vitro and in vivo models. In contrast, cells resistant to ICMT inhibition demonstrated no mitochondria dysfunction or p21 signaling changes under ICMT suppression (PMID:28167504)
• ICMT function is critical for the tumorigenesis capacity of naturally occurring mutant KRAS human cancer cells. (PMID:28192404)
• ICMT catalyzed carboxylmethylation is critical for RAB4A activation and interaction with effectors, its localization to endosomes and recycling vesicles, and hence important for RAB4A-dependent integrin beta3 recycling to plasma membrane. (PMID:28604748)
• Using cell culturing system, mouse model and patient samples, this work is the first to demonstrate the essential roles of Icmt in ovarian cancer via Ras signaling, particularly on its response to chemotherapy. (PMID:29746868)
• ICMT expression is repressed by WT p53. This work unveils a link between postprenylation protein processing and the p53 pathway, indicating that the functional interplay between WT and mutant p53 alters ICMT levels, thereby affecting tumor aggressiveness. (PMID:30655292)
• Findings show that isoprenylcysteine carboxylmethyltransferase (Icmt)plays an important role in the development of nasopharyngeal carcinoma (NPC) chemoresistance. (PMID:31253403)
• ICMT expression is higher in hepatocellular carcinoma (HCC) tissues and cells than normal counterparts. ICMT is critical for HCC growth, migration, survival and chemoresistance. (PMID:31451223)
• Isoprenylcysteine carboxylmethyltransferase is required for the impact of mutant KRAS on TAZ protein level and cancer cell self-renewal. (PMID:32561852)
• NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane. (PMID:33579760)
• CircRNA hsa_circ_0018289 exerts an oncogenic role in cervical cancer progression through miR-1294/ICMT axis. (PMID:35312113)
• PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma. (PMID:35914811)
• Isoprenylcysteine carboxyl methyltransferase (ICMT) promotes invadopodia formation and metastasis in cancer cells. (PMID:38301884)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	icmt	ENSDARG00000020241
mus_musculus	Icmt	ENSMUSG00000039662
rattus_norvegicus	Icmt	ENSRNOG00000010953
drosophila_melanogaster	Icmt	FBGN0036336
caenorhabditis_elegans	icmt-1	WBGENE00017673
caenorhabditis_elegans	M01E11.1	WBGENE00019710

Protein

Protein identifiers

Protein-S-isoprenylcysteine O-methyltransferase — O60725 (reviewed: O60725)

Alternative names: Isoprenylcysteine carboxylmethyltransferase, Prenylated protein carboxyl methyltransferase, Prenylcysteine carboxyl methyltransferase

All UniProt accessions (3): K7EQW0, O60725, Q7Z750

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitously expressed. Expressed at higher levels in the cerebellum and putamen than in other brain regions. Abundant expression seen in the Purkinje cells and pontine neurons.

Activity regulation. Competitively inhibited by N-acetyl-S-trans,trans-farnesyl-l-cysteine (AFC).

Similarity. Belongs to the class VI-like SAM-binding methyltransferase superfamily. Isoprenylcysteine carboxyl methyltransferase family.

RefSeq proteins (1): NP_036537* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007269	ICMT_MeTrfase	Family
IPR025770	PPMT_MeTrfase	Family

Pfam: PF04140

Enzyme classification (BRENDA):

• EC 2.1.1.100 — protein-S-isoprenylcysteine O-methyltransferase (BRENDA: 14 organisms, 72 substrates, 342 inhibitors, 71 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

31 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
S-ADENOSYL-L-METHIONINE	0.0001–3.8	16
N-ACETYL-S-(E,E)-FARNESYL-L-CYSTEINE	0.0002–11.1	13
N-ACETYL-S-GERANYLGERANYL-L-CYSTEINE	0.0014–0.166	8
N-ACETYL-S-FARNESYL-L-CYSTEINE	0.003–0.0223	5
4-BENZOYL-N-([2-[2-([5-[(3AS,4S,6AR)-2-OXOHEXAHY	0.0059–0.0179	2
S-[(2E,6E)-8-(3-BENZOYLPHENOXY)-3,7-DIMETHYLOCTA	0.0034–0.0183	2
BIOTIN-PEG4-K(5-FAM)YIIKGVFWDPAC(C10-DIAZIRINE)-	0.0066	1
BIOTIN-PEG4-K(5-FAM)YIIKGVFWDPAC(C5-M-BP)-OH	0.0278	1
BIOTIN-PEG4-YIIKGVFWDPAC(C10-META-BP)	0.015	1
BIOTIN-PEG4-YIIKGVFWDPAC(C10-PARA-BP)	0.0051	1
BIOTIN-PEG4-YIIKGVFWDPAC(C5-META-BP)	0.0146	1
BIOTIN-PEG4-YIIKGVFWDPAC(C5-PARA-BP)	0.0061	1
BIOTIN-PEG4-YIIKGVFWDPAC(FR)-OH	0.0122	1
BIOTIN-S-FARNESYL-L-CYSTEINE	0.0021	1
FARNESYLATED AND RCE1-PROTEOLYZED K-RAS PROTEIN	0.0029	1

Catalyzed reactions (Rhea), 1 shown:

• [protein]-C-terminal S-[(2E,6E)-farnesyl]-L-cysteine + S-adenosyl-L-methionine = [protein]-C-terminal S-[(2E,6E)-farnesyl]-L-cysteine methyl ester + S-adenosyl-L-homocysteine (RHEA:21672)

UniProt features (24 total): topological domain 9, transmembrane region 8, binding site 6, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60725-F1	93.57	0.86

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 (6): 190; 197–200; 205; 210–213; 247; 251

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation
R-HSA-9648002	RAS processing

MSigDB gene sets: 194 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TGCGCANK_UNKNOWN, FISCHER_G1_S_CELL_CYCLE, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_PROTEIN_TARGETING, WHITE_NEUROBLASTOMA_WITH_1P36.3_DELETION, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, ATTCTTT_MIR186, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (8): C-terminal protein methylation (GO:0006481), protein targeting to membrane (GO:0006612), protein modification process (GO:0036211), obsolete S-adenosylhomocysteine metabolic process (GO:0046498), S-adenosylmethioninamine metabolic process (GO:0046499), nuclear envelope organization (GO:0006998), methylation (GO:0032259), protein maturation (GO:0051604)

GO Molecular Function (5): protein C-terminal carboxyl O-methyltransferase activity (GO:0003880), protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity (GO:0004671), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
RAF/MAP kinase cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
protein methylation	1
C-terminal protein amino acid modification	1
protein targeting	1
establishment of protein localization to membrane	1
macromolecule modification	1
sulfur compound metabolic process	1
purine ribonucleoside metabolic process	1
nucleus organization	1
endomembrane system organization	1
membrane organization	1
metabolic process	1
gene expression	1
protein carboxyl O-methyltransferase activity	1
protein C-terminal carboxyl O-methyltransferase activity	1
S-adenosylmethionine-dependent methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1226 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ICMT	RCE1	Q9Y256	986
ICMT	ZMPSTE24	O75844	963
ICMT	SUN1	O94901	680
ICMT	DNAJA1	P31689	663
ICMT	FNTB	P49356	656
ICMT	SUN2	Q9UH99	656
ICMT	FNTA	P49354	627
ICMT	LMNA	P02545	617
ICMT	PCMT1	P22061	605
ICMT	LMNB1	P20700	585
ICMT	SYNE1	Q8NF91	584
ICMT	CASP3	P42574	560
ICMT	B4DL54	B4DL54	550
ICMT	NRAS	P01111	521
ICMT	KRAS	P01116	520

IntAct

59 interactions, top by confidence:

A	B	Type	Score
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
ICMT	JAGN1	psi-mi:“MI:0915”(physical association)	0.560
ICMT	TRIM32	psi-mi:“MI:0915”(physical association)	0.560
ICMT	MUC1	psi-mi:“MI:0915”(physical association)	0.560
ICMT	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
ICMT	AQP6	psi-mi:“MI:0915”(physical association)	0.560
ICMT	RNF19B	psi-mi:“MI:0915”(physical association)	0.560
ICMT	PDZK1IP1	psi-mi:“MI:0915”(physical association)	0.560
ICMT	KCNJ6	psi-mi:“MI:0915”(physical association)	0.560
ICMT	STXBP3	psi-mi:“MI:0914”(association)	0.530
	SCD	psi-mi:“MI:0914”(association)	0.500
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
CLN6	SCAMP3	psi-mi:“MI:0914”(association)	0.350
	TSPO	psi-mi:“MI:0914”(association)	0.350
RAD51D	ICMT	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
ELK1	TPP1	psi-mi:“MI:0914”(association)	0.350
PRKCB	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
ELK1	PPP6C	psi-mi:“MI:0914”(association)	0.350
PRKCB	CHEK1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): ICMT (Affinity Capture-MS), ICMT (Affinity Capture-MS), GCA (Affinity Capture-MS), ICMT (Affinity Capture-MS), PCCA (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), OXSR1 (Affinity Capture-MS), PPM1E (Affinity Capture-MS), ICMT (Synthetic Lethality), ICMT (Synthetic Lethality), ICMT (Affinity Capture-RNA), ICMT (Affinity Capture-MS), ICMT (Affinity Capture-MS), ICMT (Affinity Capture-MS), ICMT (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2M425, A1L1J9, B0BNG2, O60725, O75908, O77759, O88269, O88908, O95255, Q0P4J9, Q290J8, Q3T1L5, Q3TAE8, Q3UV71, Q499P8, Q49LS7, Q4R4E1, Q4VV71, Q5F380, Q5KR61, Q5R8F6, Q5RAH7, Q5RKL5, Q6AZ83, Q6NVG1, Q7SXZ1, Q7T310, Q7TPN3, Q7TQM4, Q86VD9, Q8AVI9, Q8BTP0, Q8C0T0, Q8C3X8, Q8CI59, Q8IUR5, Q8K2A8, Q8L638, Q8R1J1, Q8R4P9

Diamond homologs: A2XX73, D6WJ77, O12947, O60725, P32584, P87014, Q558K8, Q7XSR9, Q8TMG0, Q93W54, Q9EQK7, Q9FMW9, Q9WVM4, P29940, B1WZQ6, Q44587

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

816 predictions. Top by Δscore:

Variant	Effect	Δscore
1:6231896:TTATA:T	donor_loss	1.0000
1:6231897:TATAC:T	donor_loss	1.0000
1:6231899:TACCT:T	donor_loss	1.0000
1:6231900:ACCTG:A	donor_loss	1.0000
1:6231917:C:CA	donor_gain	1.0000
1:6231926:C:CT	donor_gain	1.0000
1:6231927:C:CT	donor_gain	1.0000
1:6232115:CAGTT:C	acceptor_gain	1.0000
1:6232116:AGTT:A	acceptor_gain	1.0000
1:6232117:GTT:G	acceptor_gain	1.0000
1:6232118:TT:T	acceptor_gain	1.0000
1:6232118:TTCTG:T	acceptor_loss	1.0000
1:6232120:C:CA	acceptor_loss	1.0000
1:6232120:C:CC	acceptor_gain	1.0000
1:6233529:TGTA:T	donor_gain	1.0000
1:6235711:CTGCA:C	donor_loss	1.0000
1:6235712:TGCA:T	donor_loss	1.0000
1:6235713:GCAC:G	donor_loss	1.0000
1:6235714:CA:C	donor_loss	1.0000
1:6235715:ACCT:A	donor_loss	1.0000
1:6235716:C:CT	donor_loss	1.0000
1:6225137:ATACT:A	donor_gain	0.9900
1:6231969:CTGG:C	donor_gain	0.9900
1:6231970:TGGT:T	donor_gain	0.9900
1:6232122:G:C	acceptor_gain	0.9900
1:6233537:C:CA	donor_gain	0.9900
1:6234880:TCTTA:T	donor_loss	0.9900
1:6234881:CTTAC:C	donor_loss	0.9900
1:6234882:TTA:T	donor_loss	0.9900
1:6234883:T:TG	donor_loss	0.9900

AlphaMissense

1817 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:6232019:G:C	F185L	1.000
1:6232019:G:T	F185L	1.000
1:6232021:A:G	F185L	1.000
1:6225158:A:C	F259L	0.999
1:6225158:A:T	F259L	0.999
1:6225160:A:G	F259L	0.999
1:6225206:G:C	F243L	0.999
1:6225206:G:T	F243L	0.999
1:6225208:A:G	F243L	0.999
1:6231930:C:T	G215E	0.999
1:6231942:G:T	P211H	0.999
1:6232020:A:C	F185C	0.999
1:6232020:A:G	F185S	0.999
1:6232052:C:A	R174S	0.999
1:6232052:C:G	R174S	0.999
1:6232053:C:A	R174M	0.999
1:6232053:C:G	R174T	0.999
1:6233556:A:C	F124L	0.999
1:6233556:A:T	F124L	0.999
1:6233558:A:G	F124L	0.999
1:6233594:C:G	A112P	0.999
1:6225160:A:T	F259I	0.998
1:6225171:A:G	L255P	0.998
1:6225195:C:G	R247P	0.998
1:6225248:G:C	N229K	0.998
1:6225248:G:T	N229K	0.998
1:6231914:A:C	S220R	0.998
1:6231914:A:T	S220R	0.998
1:6231916:T:G	S220R	0.998
1:6231928:A:G	W216R	0.998

dbSNP variants (sampled 300 via entrez): RS1000032691 (1:6230081 G>C), RS1000138378 (1:6233094 T>C), RS1000430267 (1:6232982 C>T), RS1000521636 (1:6235958 G>A,C), RS1000763311 (1:6234166 C>A,T), RS1000849490 (1:6222873 C>T), RS1000900345 (1:6223092 C>G,T), RS1000915884 (1:6228185 C>T), RS1001309922 (1:6229709 T>A,C), RS1001581478 (1:6226368 T>C), RS1001659445 (1:6229350 T>C), RS1001914999 (1:6225164 G>C), RS1002382242 (1:6235194 T>C), RS1002407963 (1:6231260 G>A), RS1002431239 (1:6237097 C>G)

Disease associations

OMIM: gene MIM:605851 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

48 associations (top):

Study	Trait	p-value
GCST003818_24	Resting heart rate	2.000000e-11
GCST004213_1	Resting heart rate	4.000000e-08
GCST010796_1076	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-24
GCST010796_1077	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-25
GCST010796_1078	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-25
GCST010796_1079	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-25
GCST010796_1080	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-26
GCST010796_1081	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-27
GCST010796_1082	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-26
GCST010796_1083	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-26
GCST010796_1084	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-25
GCST010796_1085	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-24
GCST010796_1086	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-25
GCST010796_1088	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-25
GCST010796_1089	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-23
GCST010796_1090	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-22
GCST010796_1091	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-21
GCST010796_1092	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-20
GCST010796_1093	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-19
GCST010796_1094	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-18
GCST010796_1095	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-16
GCST010796_1096	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-15
GCST010796_1097	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-13
GCST010796_1098	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12
GCST010796_1099	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-12
GCST010796_1100	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-10
GCST010796_1101	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_1102	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_1103	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-27
GCST010796_1211	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-25

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4699 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 450 (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
CHEMBL23293	SALIRASIB	2	450

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

Binding affinities (BindingDB)

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

Ligand	Measure	Value
(R)-2-[(adamantane-1-carbonyl)-amino]-3-(3,7,11-trimethyl-dodeca-2,6,10-trienylsulfanyl)-propionic acid	IC50	12400 nM

ChEMBL bioactivities

183 potent at pChembl≥5 of 260 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	CHEMBL4583704
10.00	IC50	0.1	nM	CHEMBL4446351
9.80	IC50	0.16	nM	CHEMBL4449942
9.70	IC50	0.2	nM	CHEMBL4468997
9.70	IC50	0.2	nM	CHEMBL4446048
9.15	IC50	0.7	nM	CHEMBL4464629
9.05	IC50	0.9	nM	CHEMBL4473893
9.00	IC50	1	nM	CHEMBL1800705
8.80	IC50	1.6	nM	CHEMBL4445788
8.42	IC50	3.8	nM	CHEMBL1800516
8.10	IC50	8	nM	CHEMBL1800513
8.00	IC50	10	nM	CHEMBL1800715
7.82	IC50	15	nM	CHEMBL1800426
7.82	IC50	15	nM	CHEMBL1800522
7.72	IC50	19	nM	CHEMBL1800514
7.60	IC50	25	nM	CHEMBL1800485
7.60	IC50	25	nM	CHEMBL1800498
7.58	IC50	26	nM	CHEMBL1800501
7.51	IC50	31	nM	CHEMBL1800417
7.51	IC50	31	nM	CHEMBL1800418
7.51	IC50	31	nM	CHEMBL1800496
7.50	IC50	32	nM	CHEMBL1800499
7.40	IC50	40	nM	CHEMBL1800421
7.31	IC50	49	nM	CHEMBL1800490
7.28	IC50	52	nM	CHEMBL1800492
7.27	IC50	54	nM	CHEMBL1800420
7.18	IC50	66	nM	CHEMBL1800483
7.16	IC50	69	nM	CHEMBL1800419
7.05	IC50	90	nM	CHEMBL1800477
7.05	IC50	90	nM	CHEMBL1800479
7.00	IC50	100	nM	CHEMBL1800512
6.92	IC50	120	nM	CHEMBL1484316
6.91	IC50	123	nM	CHEMBL1800484
6.88	IC50	132	nM	CHEMBL1800423
6.88	IC50	131	nM	CHEMBL1800481
6.80	IC50	160	nM	CHEMBL1800495
6.78	IC50	167	nM	CHEMBL1800422
6.78	IC50	168	nM	CHEMBL1800493
6.77	IC50	170	nM	CHEMBL1800487
6.74	IC50	184	nM	CHEMBL1800480
6.74	IC50	181	nM	CHEMBL1800488
6.72	IC50	190	nM	CHEMBL1800511
6.64	IC50	230	nM	CHEMBL1800714
6.57	IC50	270	nM	CHEMBL1800476
6.57	IC50	270	nM	CHEMBL1800515
6.52	IC50	300	nM	CHEMBL1800494
6.51	IC50	310	nM	CHEMBL1800360
6.51	IC50	308	nM	CHEMBL1800489
6.44	IC50	360	nM	CHEMBL1800486
6.42	IC50	380	nM	CHEMBL1800500

PubChem BioAssay actives

183 with measured affinity, of 514 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
4-[(2S)-1-[3-(2-cyclopropylimidazol-1-yl)phenoxy]propan-2-yl]oxy-3-methoxybenzonitrile	1510875: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay	ic50	<0.0001	uM
4-[(2R)-1-[3-(2-cyclopropylimidazol-1-yl)phenoxy]propan-2-yl]oxy-3-fluorobenzonitrile	1510875: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay	ic50	<0.0001	uM
3-chloro-4-[2-[3-(2-cyclopropylimidazol-1-yl)phenoxy]ethoxy]benzonitrile	1510875: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay	ic50	0.0001	uM
3-methoxy-4-[(2S)-1-[3-(2-methylimidazol-1-yl)phenoxy]propan-2-yl]oxybenzonitrile	1510875: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay	ic50	0.0001	uM
4-[2-[3-(2-cyclopropylimidazol-1-yl)phenoxy]ethoxy]benzonitrile	1510875: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay	ic50	0.0002	uM
3-chloro-4-[2-[3-(2-methylimidazol-1-yl)phenoxy]ethoxy]benzonitrile	1510875: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay	ic50	0.0002	uM
3-methoxy-4-[2-[3-(2-methylimidazol-1-yl)phenoxy]ethoxy]benzonitrile	1510875: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay	ic50	0.0002	uM
3-fluoro-4-[(2S)-1-[3-(2-methylpyrazol-3-yl)phenoxy]propan-2-yl]oxybenzonitrile	1510875: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay	ic50	0.0007	uM
3-methoxy-4-[2-[3-(2-methylpyrazol-3-yl)phenoxy]ethoxy]benzonitrile	1510875: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay	ic50	0.0009	uM
3-methoxy-N-[2-(2,2,6,6-tetramethyl-4-phenyloxan-4-yl)ethyl]aniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0010	uM
3-methyl-4-[(2S)-1-[3-(2-methylpyrazol-3-yl)phenoxy]propan-2-yl]oxybenzonitrile	1510875: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay	ic50	0.0016	uM
3-chloro-N-[2-(2,2-dimethyl-4-thiophen-2-yloxan-4-yl)ethyl]aniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0038	uM
N-[2-[4-(3-fluorophenyl)-2,2-dimethyloxan-4-yl]ethyl]-3-methoxyaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0080	uM
N-[2-[(4R)-2,2-dimethyl-4-phenyloxan-4-yl]ethyl]-3-methoxyaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0100	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-methoxyaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0150	uM
N-[2-(2,2,6,6-tetramethyl-4-phenyloxan-4-yl)ethyl]aniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0150	uM
N-[2-(2,2-dimethyl-4-thiophen-2-yloxan-4-yl)ethyl]-3-methoxyaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0190	uM
3-chloro-N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]aniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0250	uM
3-chloro-N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-4-fluoroaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0250	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-nitroaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0260	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-methylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0310	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-4-methylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0310	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3,5-difluoro-4-methoxyaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0310	uM
5-chloro-N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-2-fluoroaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0320	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-ethylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0400	uM
3-chloro-N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-4-methylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0490	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-fluoroaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0520	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3,5-dimethylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0540	uM
3-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethylamino]benzonitrile	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0660	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3,4-dimethylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0690	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-methoxy-4-methylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0900	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-(trifluoromethoxy)aniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.0900	uM
N-[2-[4-(4-fluorophenyl)-2,2-dimethyloxan-4-yl]ethyl]-3-methoxyaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1000	uM
N-benzyl-N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]furan-2-carboxamide	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1200	uM
4-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethylamino]benzonitrile	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1230	uM
1-N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-N,3-N-dimethylbenzene-1,3-diamine	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1310	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-4-propan-2-ylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1320	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-fluoro-4-methoxyaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1600	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-propan-2-ylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1670	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-4-fluoroaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1680	uM
3,5-dichloro-N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]aniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1700	uM
3,4-dichloro-N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]aniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1810	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-4-(trifluoromethoxy)aniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1840	uM
N-[2-[4-(3-chlorophenyl)-2,2-dimethyloxan-4-yl]ethyl]-3-methoxyaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.1900	uM
N-[2-[(4S)-2,2-dimethyl-4-phenyloxan-4-yl]ethyl]-3-methoxyaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.2300	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-4-methoxyaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.2700	uM
N-[2-(2,2-dimethyl-4-thiophen-2-yloxan-4-yl)ethyl]aniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.2700	uM
N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-2-fluoro-4-methylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.3000	uM
4-chloro-N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]-3-methylaniline	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.3080	uM
2-[N-[2-(2,2-dimethyl-4-phenyloxan-4-yl)ethyl]anilino]-1-(furan-2-yl)ethanone	607239: Inhibition of human recombinant C-terminal His6-tagged ICMT assessed as methylation of N-acetyl-S-geranylgeranylcysteine using SAM as methyl donor substrate after 1 hr by fluorometric assay	ic50	0.3100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	4
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
Aflatoxin B1	increases expression, increases methylation	3
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
salinomycin	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
abrine	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Copper	affects binding, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Lead	affects expression	1

ChEMBL screening assays

68 unique, capped per target: 68 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1259548	Binding	Inhibition of recombinant ICMT expressed in Sf9 cells using [3H] AdoMet after 20 mins by scintillation counting	Amino derivatives of indole as potent inhibitors of isoprenylcysteine carboxyl methyltransferase. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SR96	HAP1 ICMT (-) 1	Cancer cell line	Male
CVCL_SR97	HAP1 ICMT (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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