FNTA

Summary

FNTA (farnesyltransferase, CAAX box, subunit alpha, HGNC:3782) is a protein-coding gene on chromosome 8p11.21, encoding Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha (P49354). Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. It is a common-essential gene (DepMap: required in 90.7% of cancer cell lines).

Prenyltransferases can attach either a farnesyl group or a geranylgeranyl group in thioether linkage to the cysteine residue of proteins with a C-terminal CAAX box. CAAX geranylgeranyltransferase and CAAX farnesyltransferase are heterodimers that share the same alpha subunit but have different beta subunits. This gene encodes the alpha subunit of these transferases. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 11 and 13.

Source: NCBI Gene 2339 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 73 total — 1 pathogenic
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 90.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_002027

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3782
Approved symbol	FNTA
Name	farnesyltransferase, CAAX box, subunit alpha
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Aliases	FPTA, PGGT1A, PTAR2
Ensembl gene	ENSG00000168522
Ensembl biotype	protein_coding
OMIM	134635
Entrez	2339

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron, 3 nonsense_mediated_decay

ENST00000302279, ENST00000524546, ENST00000525099, ENST00000525699, ENST00000526755, ENST00000527153, ENST00000528400, ENST00000529687, ENST00000531266, ENST00000533336, ENST00000533368, ENST00000533383, ENST00000533559, ENST00000533998, ENST00000903292, ENST00000903293, ENST00000903294, ENST00000903295, ENST00000903296

RefSeq mRNA: 1 — MANE Select: NM_002027 NM_002027

CCDS: CCDS6140

Canonical transcript exons

ENST00000302279 — 9 exons

Exon	Start	End
ENSE00002156549	43056323	43056546
ENSE00003467132	43059092	43059177
ENSE00003487643	43085160	43085785
ENSE00003496632	43064101	43064215
ENSE00003499158	43083118	43083180
ENSE00003500721	43069555	43069659
ENSE00003514597	43077216	43077364
ENSE00003531863	43084710	43084881
ENSE00003790940	43072181	43072307

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.2743 / max 315.5645, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88713	41.7047	1825
88714	3.5696	1547

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	99.20	gold quality
gingival epithelium	UBERON:0001949	99.19	gold quality
olfactory bulb	UBERON:0002264	99.12	gold quality
subthalamic nucleus	UBERON:0001906	99.09	gold quality
inferior vagus X ganglion	UBERON:0005363	99.07	gold quality
gingiva	UBERON:0001828	99.03	gold quality
squamous epithelium	UBERON:0006914	98.94	gold quality
pancreatic ductal cell	CL:0002079	98.84	gold quality
amniotic fluid	UBERON:0000173	98.83	gold quality
parotid gland	UBERON:0001831	98.82	gold quality
skin of hip	UBERON:0001554	98.81	gold quality
germinal epithelium of ovary	UBERON:0001304	98.80	gold quality
trigeminal ganglion	UBERON:0001675	98.76	gold quality
medulla oblongata	UBERON:0001896	98.70	gold quality
pons	UBERON:0000988	98.67	gold quality
corpus callosum	UBERON:0002336	98.63	gold quality
cranial nerve II	UBERON:0000941	98.56	gold quality
oral cavity	UBERON:0000167	98.52	gold quality
upper leg skin	UBERON:0004262	98.51	gold quality
parietal pleura	UBERON:0002400	98.50	gold quality
lateral globus pallidus	UBERON:0002476	98.50	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.48	gold quality
superior vestibular nucleus	UBERON:0007227	98.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.45	gold quality
dorsal root ganglion	UBERON:0000044	98.44	gold quality
epithelium of esophagus	UBERON:0001976	98.44	gold quality
epithelial cell of pancreas	CL:0000083	98.42	gold quality
mammalian vulva	UBERON:0000997	98.42	gold quality
pleura	UBERON:0000977	98.38	gold quality
inferior olivary complex	UBERON:0002127	98.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

44 targeting FNTA, 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-499A-5P	99.98	70.79	1323
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
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-548E-5P	99.89	72.73	4486
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-584-3P	99.35	67.69	1082

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 90.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• Results suggest that all peptide substrates adopt a common binding mode in the protein farnesyltransferase and geranylgeranyltransferase active site. (PMID:15451670)
• Geranylgeranyltransferase inhibitor-2147 (GGTI-2147), an inhibitor of protein prenylation, elicited significant inhibition of glucose-stimulated insulin secretion from INS 832/13 islet cells. (PMID:17192483)
• FTase, via its tubulin-association, is a critical upstream regulator of HDAC6 activity (PMID:19228685)
• our findings identify Geranylgeranyl transferase 1 as a key regulator of human airway smooth muscle cell viability (PMID:22160308)
• Exploring the putative self-binding property of the human farnesyltransferase alpha-subunit (PMID:28948621)
• These findings collectively suggest that the combination of farnesyltransferase inhibitors and gamma-secretase inhibitors is a promising therapeutic strategy for glioblastoma through selectively targeting the cancer stem cell subpopulation. (PMID:29198824)
• Cell-permeable CaaX-peptides affect K-Ras downstream signaling and promote cell death in cancer cells. (PMID:33112492)
• Scaffold association factor B (SAFB) is required for expression of prenyltransferases and RAS membrane association. (PMID:33257571)
• Protein farnesylation is upregulated in Alzheimer’s human brains and neuron-specific suppression of farnesyltransferase mitigates pathogenic processes in Alzheimer’s model mice. (PMID:34315531)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fnta	ENSDARG00000099143
mus_musculus	Fnta	ENSMUSG00000015994
rattus_norvegicus	Fnta	ENSRNOG00000014462
drosophila_melanogaster	Fnta	FBGN0031633
caenorhabditis_elegans		WBGENE00019823

Paralogs (2): RABGGTA (ENSG00000100949), PTAR1 (ENSG00000188647)

Protein

Protein identifiers

Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha — P49354 (reviewed: P49354)

Alternative names: CAAX farnesyltransferase subunit alpha, FTase-alpha, Ras proteins prenyltransferase subunit alpha, Type I protein geranyl-geranyltransferase subunit alpha

All UniProt accessions (7): P49354, B3KVN2, E9PK84, E9PN85, E9PPM9, E9PQP6, H0YCW1

UniProt curated annotations — full annotation on UniProt →

Function. Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. May positively regulate neuromuscular junction development downstream of MUSK via its function in RAC1 prenylation and activation.

Subunit / interactions. Heterodimer of FNTA and FNTB (farnesyltransferase). Heterodimer of FNTA and PGGT1B (geranylgeranyltransferase).

Post-translational modifications. Phosphorylated. Phosphorylation is mediated by MUSK upon AGRIN stimulation and results in the activation of FNTA.

Activity regulation. Activated by the AGRIN-induced phosphorylation which is mediated by MUSK.

Similarity. Belongs to the protein prenyltransferase subunit alpha family.

Isoforms (3)

UniProt ID	Names	Canonical?
P49354-1	1	yes
P49354-2	2
P49354-3	3

RefSeq proteins (1): NP_002018* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002088	Prenyl_trans_a	Repeat

Pfam: PF01239

Enzyme classification (BRENDA):

• EC 2.5.1.58 — protein farnesyltransferase (BRENDA: 25 organisms, 389 substrates, 803 inhibitors, 111 Km, 113 kcat entries)
• EC 2.5.1.59 — protein geranylgeranyltransferase type I (BRENDA: 18 organisms, 93 substrates, 119 inhibitors, 28 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
FARNESYL DIPHOSPHATE	—	9
GERANYLGERANYL DIPHOSPHATE	—	5
(2E,6E)-FARNESYL DIPHOSPHATE	0.0008–0.0015	3
DANSYL-GCVDS	0.003–0.011	3
YRASNRSCAIM	0.0003–0.003	3
(BIOTIN-CONH-(CH2)5-CO-)-NPFREKKFFCAI-LEU	0.0003–0.025	3
(2E,6E)-3,7-DIMETHYL-8-(PHENYLAMINO)OCTA-2,6-DIE	0.0004–0.0005	2
DANSYL-GCVKS	0.0014–0.01	2
DANSYL-GLY-CYS-LYS-THR-GLN	0.0005–0.0018	2
DANSYL-GLY-CYS-LYS-VAL-LEU	0.0007–0.0025	2
DANSYL-GLY-CYS-VAL-ILE-MET	0.0001–0.0002	2
DANSYL-GLY-CYS-VAL-LEU-SER	0.0007	2
DANSYL-GLY-CYS-ILE-ILE-LEU	0.0018–0.0024	2
RAS-CYS-VAL-LEU-LEU	0.0009–0.0012	2
(2E,6E)-3,7-DIMETHYL-8-(2,3,5,6-TETRAFLUOROPHENO	0.0512	1

Catalyzed reactions (Rhea), 2 shown:

• L-cysteinyl-[protein] + (2E,6E)-farnesyl diphosphate = S-(2E,6E)-farnesyl-L-cysteinyl-[protein] + diphosphate (RHEA:13345)
• geranylgeranyl diphosphate + L-cysteinyl-[protein] = S-geranylgeranyl-L-cysteinyl-[protein] + diphosphate (RHEA:21240)

UniProt features (41 total): helix 20, repeat 5, modified residue 3, initiator methionine 2, splice variant 2, mutagenesis site 2, turn 2, chain 1, sequence conflict 1, strand 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
2H6F	X-RAY DIFFRACTION	1.5
1LD8	X-RAY DIFFRACTION	1.8
1TN6	X-RAY DIFFRACTION	1.8
2H6H	X-RAY DIFFRACTION	1.8
2IEJ	X-RAY DIFFRACTION	1.8
3E37	X-RAY DIFFRACTION	1.8
2H6G	X-RAY DIFFRACTION	1.85
1S63	X-RAY DIFFRACTION	1.9
1LD7	X-RAY DIFFRACTION	2
1MZC	X-RAY DIFFRACTION	2
1SA4	X-RAY DIFFRACTION	2.1
1JCQ	X-RAY DIFFRACTION	2.3
2F0Y	X-RAY DIFFRACTION	2.7
2H6I	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49354-F1	89.12	0.84

Functional residue map

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

Post-translational modifications (3): 373, 2, 2

Mutagenesis-validated functional residues (2):

Position	Phenotype
164	reduced activity.
199	reduced catalytic efficiency.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-111465	Apoptotic cleavage of cellular proteins
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-9648002	RAS processing
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9953170	GBP-mediated host defense

MSigDB gene sets: 215 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TTTGTAG_MIR520D, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, HSIAO_HOUSEKEEPING_GENES, CAFFAREL_RESPONSE_TO_THC_UP, GOBP_PROTEIN_MATURATION, GOBP_CELL_JUNCTION_ORGANIZATION, MARTINEZ_RB1_TARGETS_DN, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GOBP_REGULATION_OF_RAC_PROTEIN_SIGNAL_TRANSDUCTION

GO Biological Process (14): transforming growth factor beta receptor signaling pathway (GO:0007179), peptide pheromone maturation (GO:0007323), Rac protein signal transduction (GO:0016601), protein farnesylation (GO:0018343), protein geranylgeranylation (GO:0018344), positive regulation of Rac protein signal transduction (GO:0035022), regulation of microtubule-based movement (GO:0060632), skeletal muscle acetylcholine-gated channel clustering (GO:0071340), positive regulation of skeletal muscle acetylcholine-gated channel clustering (GO:1904395), nuclear envelope organization (GO:0006998), enzyme-linked receptor protein signaling pathway (GO:0007167), neuromuscular junction development (GO:0007528), protein prenylation (GO:0018342), protein maturation (GO:0051604)

GO Molecular Function (14): protein farnesyltransferase activity (GO:0004660), protein geranylgeranyltransferase activity (GO:0004661), CAAX-protein geranylgeranyltransferase activity (GO:0004662), Rab geranylgeranyltransferase activity (GO:0004663), microtubule binding (GO:0008017), acetyltransferase activator activity (GO:0010698), enzyme binding (GO:0019899), receptor tyrosine kinase binding (GO:0030971), alpha-tubulin binding (GO:0043014), molecular adaptor activity (GO:0060090), prenyltransferase activity (GO:0004659), protein binding (GO:0005515), protein prenyltransferase activity (GO:0008318), transferase activity (GO:0016740)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule associated complex (GO:0005875), plasma membrane (GO:0005886), CAAX-protein geranylgeranyltransferase complex (GO:0005953), protein farnesyltransferase complex (GO:0005965)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Apoptotic execution phase	1
The phototransduction cascade	1
RAF/MAP kinase cascade	1
SARS-CoV Infections	1
Antimicrobial mechanism of IFN-stimulated genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein prenylation	2
protein prenyltransferase activity	2
protein geranylgeranyltransferase activity	2
tubulin binding	2
binding	2
cellular anatomical structure	2
cytoplasm	2
transferase complex	2
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
protein maturation	1
small GTPase-mediated signal transduction	1
Rac protein signal transduction	1
regulation of Rac protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
microtubule-based movement	1
regulation of microtubule-based process	1
postsynaptic membrane organization	1
neuromuscular junction development	1
receptor clustering	1
skeletal muscle acetylcholine-gated channel clustering	1
positive regulation of receptor clustering	1
regulation of skeletal muscle acetylcholine-gated channel clustering	1
nucleus organization	1
endomembrane system organization	1
membrane organization	1
cell surface receptor signaling pathway	1
synapse organization	1
protein modification process	1
prenylation	1
gene expression	1
protein metabolic process	1
enzyme activator activity	1
acetyltransferase activity	1
protein binding	1
signaling receptor binding	1
protein tyrosine kinase binding	1
molecular_function	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
prenyltransferase activity	1

Protein interactions and networks

STRING

856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FNTA	FNTB	P49356	996
FNTA	PGGT1B	P53609	986
FNTA	B4DL54	B4DL54	877
FNTA	RABGGTB	P53611	818
FNTA	TPT1	P13693	642
FNTA	RPS6KB2	Q9UBS0	636
FNTA	ICMT	O60725	627
FNTA	RABGGTA	Q92696	585
FNTA	RCE1	Q9Y256	573
FNTA	GGPS1	O95749	572
FNTA	ZMPSTE24	O75844	552
FNTA	FDFT1	P37268	525
FNTA	POMK	Q9H5K3	513
FNTA	TCP11	Q8WWU5	508
FNTA	HGSNAT	Q68CP4	503

IntAct

98 interactions, top by confidence:

A	B	Type	Score
STAG2	RAD21	psi-mi:“MI:0914”(association)	0.970
FNTA	FNTB	psi-mi:“MI:0407”(direct interaction)	0.960
FNTB	FNTA	psi-mi:“MI:0407”(direct interaction)	0.960
FNTA	FNTB	psi-mi:“MI:0914”(association)	0.960
FNTA	FNTB	psi-mi:“MI:0915”(physical association)	0.960
FNTB	FNTA	psi-mi:“MI:0915”(physical association)	0.960
FNTB	FNTA	psi-mi:“MI:0914”(association)	0.960
FNTA	PGGT1B	psi-mi:“MI:0915”(physical association)	0.840
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
KRT31	HGS	psi-mi:“MI:0914”(association)	0.780
PTK2	TGFB1I1	psi-mi:“MI:0914”(association)	0.680
HRAS	FNTA	psi-mi:“MI:0915”(physical association)	0.560
FNTA	NRAS	psi-mi:“MI:0915”(physical association)	0.560
KRAS	FNTA	psi-mi:“MI:0915”(physical association)	0.560
FNTA	KRAS	psi-mi:“MI:0915”(physical association)	0.560
AP4M1	FNTA	psi-mi:“MI:0915”(physical association)	0.560
CAPN2	MYO9A	psi-mi:“MI:0914”(association)	0.530
FAM117B	GAPDHS	psi-mi:“MI:0914”(association)	0.530
TSKS	RGPD8	psi-mi:“MI:0914”(association)	0.530
EPB41L5	SETD1A	psi-mi:“MI:0914”(association)	0.530
AMMECR1L	FNTA	psi-mi:“MI:0914”(association)	0.530
FNTB	YKT6	psi-mi:“MI:0914”(association)	0.530
FNTB	CAPN1	psi-mi:“MI:0914”(association)	0.530

BioGRID (126): FNTA (Affinity Capture-MS), FNTA (Affinity Capture-MS), FNTA (Affinity Capture-MS), FNTA (Affinity Capture-MS), FNTA (Co-fractionation), FNTA (Two-hybrid), TOP1 (Negative Genetic), FNTA (Negative Genetic), FNTA (Negative Genetic), FNTA (Negative Genetic), KDM6A (Negative Genetic), FNTA (Affinity Capture-MS), FNTA (Affinity Capture-MS), FNTA (Affinity Capture-MS), FNTA (Affinity Capture-MS)

ESM2 similar proteins: A2A432, A9X1D0, B0VX69, B1MTJ4, B2KI88, B5FW36, B7ZUF3, C1FXW2, E1C1R4, E2RBS6, E9PV86, G3V6U9, O54804, O75688, P35790, P49354, P60762, Q01134, Q09LZ8, Q0VFT9, Q13098, Q13507, Q148V7, Q5F450, Q5VWJ9, Q5ZIA0, Q5ZKV9, Q5ZML9, Q6AY57, Q6DN14, Q6GPR5, Q6NRT5, Q6P5H6, Q6PBY7, Q7SXS7, Q80W47, Q80YA3, Q86TU7, Q86W50, Q8BY87

Diamond homologs: O24304, O60052, P29702, P49354, P93227, Q04631, Q54RT9, Q61239, Q9LX33, P29703, Q55DQ4, Q9Y765, O94412, Q00618

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TP53	“up-regulates quantity by expression”	FNTA	“transcriptional regulation”
FNTA	“up-regulates activity”	MRAS
FNTA	“up-regulates activity”	KRAS
FNTA	“up-regulates activity”	HRAS
tipifarnib	“down-regulates activity”	FNTA	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
DAP12 signaling	5	32.3×	5e-05
FCERI mediated MAPK activation	5	30.4×	5e-05
Signaling by BRAF and RAF1 fusions	5	14.9×	4e-04
Regulation of expression of SLITs and ROBOs	5	6.1×	6e-03
Major pathway of rRNA processing in the nucleolus and cytosol	5	5.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	51
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4070977	NM_002027.3(FNTA):c.863del (p.Gly288fs)	Pathogenic

SpliceAI

1664 predictions. Top by Δscore:

Variant	Effect	Δscore
8:43059175:AAT:A	donor_gain	1.0000
8:43059176:AT:A	donor_gain	1.0000
8:43059178:G:GG	donor_gain	1.0000
8:43064099:A:AG	acceptor_gain	1.0000
8:43064100:G:GT	acceptor_gain	1.0000
8:43064100:GTT:G	acceptor_gain	1.0000
8:43064100:GTTA:G	acceptor_gain	1.0000
8:43064211:GTGTG:G	donor_gain	1.0000
8:43064213:GTG:G	donor_gain	1.0000
8:43064216:G:GG	donor_gain	1.0000
8:43069547:T:TA	acceptor_gain	1.0000
8:43069552:TAGG:T	acceptor_loss	1.0000
8:43069552:TAGGC:T	acceptor_loss	1.0000
8:43069553:A:AG	acceptor_gain	1.0000
8:43069553:AGGC:A	acceptor_loss	1.0000
8:43069554:G:GA	acceptor_gain	1.0000
8:43069554:G:GG	acceptor_gain	1.0000
8:43069554:GGC:G	acceptor_gain	1.0000
8:43069655:GTTTG:G	donor_gain	1.0000
8:43069656:TTTG:T	donor_gain	1.0000
8:43069659:GGTAA:G	donor_loss	1.0000
8:43069660:G:GA	donor_loss	1.0000
8:43069660:G:GG	donor_gain	1.0000
8:43069661:TAA:T	donor_loss	1.0000
8:43072171:T:A	acceptor_gain	1.0000
8:43072176:TTTA:T	acceptor_loss	1.0000
8:43072178:TA:T	acceptor_loss	1.0000
8:43072179:A:AC	acceptor_loss	1.0000
8:43072179:A:AG	acceptor_gain	1.0000
8:43072180:G:A	acceptor_loss	1.0000

AlphaMissense

2517 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:43059105:T:A	W72R	1.000
8:43059105:T:C	W72R	1.000
8:43059154:T:A	V88D	1.000
8:43059160:T:C	I90T	1.000
8:43059160:T:G	I90S	1.000
8:43059177:T:C	F96L	1.000
8:43064102:T:A	F96L	1.000
8:43064102:T:G	F96L	1.000
8:43064125:G:C	R104P	1.000
8:43064170:T:C	L119P	1.000
8:43064182:C:A	A123D	1.000
8:43064195:T:A	N127K	1.000
8:43064195:T:G	N127K	1.000
8:43064204:T:A	N130K	1.000
8:43064204:T:G	N130K	1.000
8:43064205:T:C	Y131H	1.000
8:43064214:T:A	W134R	1.000
8:43064214:T:C	W134R	1.000
8:43069644:A:T	K164I	1.000
8:43069645:A:C	K164N	1.000
8:43069645:A:T	K164N	1.000
8:43069648:C:A	N165K	1.000
8:43069648:C:G	N165K	1.000
8:43069649:T:C	Y166H	1.000
8:43069650:A:G	Y166C	1.000
8:43069654:A:C	Q167H	1.000
8:43069654:A:T	Q167H	1.000
8:43069658:T:A	W169R	1.000
8:43069658:T:C	W169R	1.000
8:43072181:G:C	W169C	1.000

dbSNP variants (sampled 300 via entrez): RS1000012828 (8:43064408 G>A,T), RS1000105422 (8:43057729 G>C), RS1000185007 (8:43080929 C>A), RS1000242759 (8:43080878 C>T), RS1000272992 (8:43063245 T>G), RS1000315693 (8:43080595 T>C), RS1000521000 (8:43086218 G>A), RS1000557796 (8:43074821 C>G), RS1000589280 (8:43079677 A>G), RS1000732747 (8:43086285 A>G), RS1000918083 (8:43079401 A>G), RS1001055923 (8:43057219 G>A), RS1001155523 (8:43074676 G>A,C), RS1001176664 (8:43068409 T>G), RS1001205913 (8:43085840 C>G,T)

Disease associations

OMIM: gene MIM:134635 | disease phenotypes: MIM:143890, MIM:615592, MIM:615249, MIM:616094, MIM:252930, MIM:616544

GenCC curated gene-disease

Mondo (6): hypercholesterolemia, familial, 1 (MONDO:0007750), severe combined immunodeficiency due to IKK2 deficiency (MONDO:0014267), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 (MONDO:0014101), limb-girdle muscular dystrophy due to POMK deficiency (MONDO:0014489), mucopolysaccharidosis type 3C (MONDO:0009657), retinitis pigmentosa 73 (MONDO:0014687)

Orphanet (7): Homozygous familial hypercholesterolemia (Orphanet:391665), Combined immunodeficiency due to IKBKB deficiency (Orphanet:397787), Limb-girdle muscular dystrophy due to POMK deficiency (Orphanet:445110), Walker-Warburg syndrome (Orphanet:899), Mucopolysaccharidosis type 3 (Orphanet:581), Retinitis pigmentosa (Orphanet:791), Sanfilippo syndrome type C (Orphanet:79271)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002934_2	Zinc levels	6.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2094108 (PROTEIN COMPLEX), CHEMBL2095164 (PROTEIN COMPLEX), CHEMBL2096991 (PROTEIN COMPLEX GROUP), CHEMBL271 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 48,306 (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
CHEMBL1650	CORTISONE ACETATE	4	15,942
CHEMBL298734	LONAFARNIB	4	12,801
CHEMBL289228	TIPIFARNIB	3	18,804
CHEMBL279433	L-778123 FREE BASE	1	324
CHEMBL3218390	GGTI-2418	1	36
CHEMBL351706	BMS-214662	1	399

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.5.1.58 Protein farnesyltransferase

Binding affinities (BindingDB)

44 measured of 59 human assays (132 total across all organisms); most potent 44 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(S)-2-[(5-{2-[4-(Adamantane-1-carbonyl)-pyridin-3-yl]-vinyl}-2’-methyl-biphenyl-2-carbonyl)-amino]-4-methylsulfanyl-butyric acid	IC50	0.12 nM
4-[3-(4-Cyano-benzyl)-3H-imidazol-4-ylmethyl]-piperazine-1-carboxylic acid adamantan-1-ylamide	IC50	0.2 nM
(S)-2-[(5-{2-[4-(Adamantan-1-yl-hydroxy-methyl)-pyridin-3-yl]-vinyl}-2’-methyl-biphenyl-2-carbonyl)-amino]-4-methylsulfanyl-butyric acid	IC50	0.37 nM
(+)-4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo-[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-(4-pyridinylacetyl)-piperidine N1-Oxide	IC50	1.3 nM
4-({[4-formyl-2-(3-methoxyphenyl)phenyl]methoxy}(1-methyl-1H-imidazol-5-yl)methyl)benzonitrile	IC50	1.6 nM
(+)-4-(3,10-Dibromo-8-chloro-6,11-dihydro-5H-benzo-[5,6]cyclohepta[1,2-b]pyridin-11(R)-yl)-4-(4-pyridinyl-acetyl)piperazine N4-Oxide	IC50	1.8 nM
4-(2-{4-[(2S)-6,12-dibromo-13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-yl]piperazin-1-yl}-2-oxoethyl)-1-oxidopyridin-1-ium	IC50	2.3 nM
SCH 66336 analog	IC50	2.5 nM
4-(2-{4-[(2S)-6,12-dibromo-13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-yl]piperidin-1-yl}-2-oxoethyl)-1-oxidopyridin-1-ium	IC50	2.6 nM
4-(2-{4-[(2S)-6,12-dibromo-13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-yl]piperazin-1-yl}-2-oxoethyl)piperidine-1-carboxamide	IC50	3.1 nM
(-)-4-[2-[4-(3,7-Dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(S)-yl)-1-piperidinyl]-2-oxoethyl]-1-piperidinecarboxamide	IC50	5 nM
(5S)-31-oxo-20-oxa-2,6,11,13-tetraazahexacyclo[19.6.2.1^{2,5}.1^{15,19}.0^{9,13}.0^{24,28}]hentriaconta-1(27),9,11,15,17,19(30),21(29),22,24(28),25-decaene-18-carbonitrile	IC50	5.5 nM
4-(2-{4-[(2S)-6-bromo-12,13-dichloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-yl]piperazin-1-yl}-2-oxoethyl)-1-oxidopyridin-1-ium	IC50	6 nM
N-[(S)-1-carbamoyl-2-phenylethyl]-4-[2-(3,4-di-chlorophenyl)-4-(2-methylsulfanylethyl)-5-pyridin-3-yl-2-H-pyrazol-3-yloxy]butyramide	IC50	8.24 nM
(+)-4-(3-Bromo-8-chloro-10-fluoro-6,11-dihydro-5H-benzo-[5,6]cyclohepta[1,2-b]pyridin-11(R)-yl)-4-(4-pyridinylacetyl)-piperazine N4-Oxide	IC50	16.7 nM
(5S)-6-methyl-31-oxo-20-oxa-2,6,11,13-tetraazahexacyclo[19.6.2.1^{2,5}.1^{15,19}.0^{9,13}.0^{24,28}]hentriaconta-1(27),9,11,15,17,19(30),21(29),22,24(28),25-decaene-18-carbonitrile	IC50	32 nM
4-(2-{4-[(2S)-6-bromo-13-chloro-15-fluoro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-yl]piperazin-1-yl}-2-oxoethyl)-1-oxidopyridin-1-ium	IC50	33.1 nM
(5R)-31-oxo-20-oxa-2,6,11,13-tetraazahexacyclo[19.6.2.1^{2,5}.1^{15,19}.0^{9,13}.0^{24,28}]hentriaconta-1(27),9,11,15,17,19(30),21(29),22,24(28),25-decaene-18-carbonitrile	IC50	35 nM
(5R)-6-methyl-31-oxo-20-oxa-2,6,11,13-tetraazahexacyclo[19.6.2.1^{2,5}.1^{15,19}.0^{9,13}.0^{24,28}]hentriaconta-1(27),9,11,15,17,19(30),21(29),22,24(28),25-decaene-18-carbonitrile	IC50	39 nM
N-(adamantan-2-yl)-10-cyano-23-oxo-8-oxa-1,15,17,21-tetraazapentacyclo[19.2.2.1^{3,7}.1^{9,13}.0^{15,19}]heptacosa-3(27),4,6,9(26),10,12,16,18-octaene-4-carboxamide	IC50	43 nM
4-[2-(4-{6-bromo-13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-yl}piperazin-1-yl)-2-oxoethyl]piperidine-1-carboxamide	IC50	49 nM
(+)-4-(8-Chloro-3,7-dibromo-6,11-dihydro-5H-benzo-[5,6]cyclohepta[1,2-b]pyridin-11(R)-yl)-1-(4-pyridinyl-acetyl)-piperidine N1-Oxide	IC50	62 nM
(+)-4-[2-[4-(3,7-Dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(R)-yl)-1-piperidinyl]-2-oxoethyl]-1-piperidinecarboxamide	IC50	78 nM
4-{[(4-cyanophenyl)(1-methyl-1H-imidazol-5-yl)methoxy]methyl}-3-(3-methoxyphenyl)benzoic acid	IC50	83 nM
4-[2-(4-{6-bromo-13-chloro-12-fluoro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-yl}piperazin-1-yl)-2-oxoethyl]-1-oxidopyridin-1-ium	IC50	86 nM
4-[2-(4-{6-bromo-13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-ylidene}piperidin-1-yl)-2-oxoethyl]-1-oxidopyridin-1-ium	IC50	90 nM
(5S)-7,31-dioxo-20-oxa-2,6,11,13-tetraazahexacyclo[19.6.2.1^{2,5}.1^{15,19}.0^{9,13}.0^{24,28}]hentriaconta-1(27),9,11,15,17,19(30),21(29),22,24(28),25-decaene-18-carbonitrile	IC50	94 nM
(5R)-7,31-dioxo-20-oxa-2,6,11,13-tetraazahexacyclo[19.6.2.1^{2,5}.1^{15,19}.0^{9,13}.0^{24,28}]hentriaconta-1(27),9,11,15,17,19(30),21(29),22,24(28),25-decaene-18-carbonitrile	IC50	150 nM
1-(4-{13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-ylidene}piperidin-1-yl)-2-(pyridin-4-yl)ethan-1-one	IC50	250 nM
(1R,2R,5R)-30-oxo-19-oxa-2,6,10,12-tetraazahexacyclo[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]triaconta-8,10,14(29),15,17,20(28),21,23(27)-octaene-17-carbonitrile	IC50	390 nM
(5S)-30-oxo-19-oxa-2,6,10,12-tetraazahexacyclo[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]triaconta-1(27),8,10,14(29),15,17,20(28),21,23,25-decaene-17-carbonitrile	IC50	650 nM
(23R)-22,23,24,25-Tetrahydro-22-oxo-16H,21H-21,23-ethano-6,10:12,16-dimethenobenz[g]-imidazo[4,3-n][1,9,12,15]oxatriazacycloheneicosine-9-carbonitrile	IC50	810 nM
(1R,2R,5R)-30-oxo-19,24-dioxa-2,6,10,12-tetraazahexacyclo[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]triaconta-8,10,14(29),15,17,20(28),21,23(27)-octaene-17-carbonitrile	IC50	1100 nM
(6R)-27-oxo-2-phenyl-20-oxa-3,7,11,13-tetraazapentacyclo[19.3.1.1^{3,6}.1^{15,19}.0^{9,13}]heptacosa-1(24),9,11,15(26),16,18,21(25),22-octaene-18-carbonitrile	IC50	1600 nM
(5S)-6-methyl-30-oxo-19-oxa-2,6,10,12-tetraazahexacyclo[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]triaconta-1(27),8,10,14(29),15,17,20(28),21,23,25-decaene-17-carbonitrile	IC50	2200 nM
(1R,2R,5S)-30-oxo-19-oxa-2,6,10,12-tetraazahexacyclo[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]triaconta-8,10,14(29),15,17,20(28),21,23(27)-octaene-17-carbonitrile	IC50	2200 nM
(5R)-30-oxo-19-oxa-2,6,10,12-tetraazahexacyclo[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]triaconta-1(27),8,10,14(29),15,17,20(28),21,23,25-decaene-17-carbonitrile	IC50	3900 nM
(1S,2S,5S)-29-oxo-19-oxa-2,6,10,12-tetraazahexacyclo[18.5.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,26}]nonacosa-8,10,14(28),15,17,20(27),21,23(26)-octaene-17-carbonitrile	IC50	4000 nM
Macrocyclic 3-Aminopyrrolidinone analog 27B	IC50	7000 nM
(6R)-24-bromo-27-oxo-20-oxa-3,7,11,13-tetraazapentacyclo[19.3.1.1^{3,6}.1^{15,19}.0^{9,13}]heptacosa-1(24),9,11,15(26),16,18,21(25),22-octaene-18-carbonitrile	IC50	9200 nM
(1R,2R,5S)-30-oxo-19,24-dioxa-2,6,10,12-tetraazahexacyclo[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]triaconta-8,10,14(29),15,17,20(28),21,23(27)-octaene-17-carbonitrile	IC50	15000 nM
7-hydroxy-11-hydroxymethyl-12-methyl-14,15-dithia-9,12-diazatetracyclo[9.2.2.01,9.03,8]pentadeca-3,5-diene-10,13-dione	IC50	17000 nM
(17R, 20R)-19,20,21,22-Tetrahydro-19-oxo-17H-15,-17:18,20-diethano-6,10:12,16-dimetheno-16H-imidazo[3,4-h][1,8,11,14]oxatriazacycloeicosine-9-carbonitrile	IC50	18000 nM
(1S,2S,5R)-29-oxo-19-oxa-2,6,10,12-tetraazahexacyclo[18.5.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,26}]nonacosa-8,10,14(28),15,17,20(27),21,23(26)-octaene-17-carbonitrile	IC50	20000 nM

ChEMBL bioactivities

2679 potent at pChembl≥5 of 3016 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL361246
10.70	IC50	0.02	nM	(1R,5R)-30-OXO-19-OXA-2,6,10,12-TETRAAZAHEXACYCLO[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]TRIACONTA-8,10,14(29),15,17,20(28),21,23(27)-OCTAENE-17-CARBONITRILE (STRUCTURAL MIX)
10.52	IC50	0.03	nM	CHEMBL426063
10.44	IC50	0.036	nM	CHEMBL128501
10.22	IC50	0.06	nM	CHEMBL310586
10.22	IC50	0.06	nM	CHEMBL294888
10.22	IC50	0.06	nM	CHEMBL4565280
10.10	IC50	0.079	nM	CHEMBL23578
10.10	IC50	0.08	nM	CHEMBL379900
10.05	IC50	0.09	nM	CHEMBL378462
10.00	IC50	0.1	nM	CHEMBL52073
10.00	EC50	0.1	nM	CHEMBL10877
10.00	EC50	0.1	nM	CHEMBL24043
10.00	IC50	0.1	nM	CHEMBL3115256
10.00	IC50	0.1	nM	CHEMBL3115255
10.00	IC50	0.1	nM	CHEMBL364792
10.00	IC50	0.1	nM	CHEMBL381360
10.00	IC50	0.1	nM	CHEMBL160223
9.96	IC50	0.11	nM	CHEMBL125162
9.92	EC50	0.12	nM	CHEMBL516874
9.92	IC50	0.12	nM	CHEMBL436440
9.92	IC50	0.12	nM	CHEMBL327106
9.92	IC50	0.12	nM	CHEMBL321252
9.92	IC50	0.12	nM	CHEMBL99901
9.91	IC50	0.123	nM	CHEMBL112189
9.91	IC50	0.123	nM	CHEMBL1790750
9.85	EC50	0.14	nM	CHEMBL399482
9.82	IC50	0.15	nM	CHEMBL526466
9.82	IC50	0.15	nM	CHEMBL163383
9.82	IC50	0.15	nM	CHEMBL252953
9.82	IC50	0.15	nM	CHEMBL322355
9.80	IC50	0.16	nM	CHEMBL438264
9.80	IC50	0.16	nM	CHEMBL324081
9.80	IC50	0.16	nM	CHEMBL64183
9.74	EC50	0.18	nM	(1R,5R)-30-OXO-19-OXA-2,6,10,12-TETRAAZAHEXACYCLO[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]TRIACONTA-8,10,14(29),15,17,20(28),21,23(27)-OCTAENE-17-CARBONITRILE (STRUCTURAL MIX)
9.74	IC50	0.18	nM	CHEMBL125558
9.74	EC50	0.18	nM	CHEMBL442552
9.74	IC50	0.18	nM	CHEMBL322435
9.72	IC50	0.19	nM	CHEMBL80702
9.72	IC50	0.19	nM	CHEMBL329932
9.72	EC50	0.19	nM	CHEMBL435247
9.72	IC50	0.19	nM	CHEMBL316673
9.70	IC50	0.2	nM	CHEMBL3115258
9.70	IC50	0.2	nM	CHEMBL377974
9.70	IC50	0.2	nM	CHEMBL424564
9.70	IC50	0.2	nM	CHEMBL159400
9.70	IC50	0.2	nM	CHEMBL52073
9.68	IC50	0.21	nM	CHEMBL205973
9.68	IC50	0.21	nM	CHEMBL159764
9.62	IC50	0.24	nM	CHEMBL380313

PubChem BioAssay actives

2654 with measured affinity, of 4402 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
(1R,5R)-30-oxo-19-oxa-2,6,10,12-tetrazahexacyclo[18.6.2.12,5.114,18.08,12.023,27]triaconta-8,10,14(29),15,17,20(28),21,23(27)-octaene-17-carbonitrile	1121277: Inhibition of human recombinant FTase using [3H]farnesyldiphosphate	ic50	<0.0001	uM
4-[[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methylamino]methyl]-3-(3-ethoxyphenyl)benzonitrile	242407: Inhibition of [3H]FPP incorporation into recombinant Ras CVIM by human Farnesyltransferase	ic50	<0.0001	uM
5-(3-chlorophenyl)-6-[[(4-cyanophenyl)-(3-methylimidazol-4-yl)methoxy]methyl]-2-oxo-1-propylpyridine-3-carbonitrile	71312: In vitro inhibitory activity against farnesyltransferase (FT)	ic50	<0.0001	uM
4-[[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methyl-methylamino]methyl]-3-(3-ethoxyphenyl)benzonitrile	242407: Inhibition of [3H]FPP incorporation into recombinant Ras CVIM by human Farnesyltransferase	ic50	<0.0001	uM
4-[[5-[[(2S)-2-butyl-4-(3-chlorophenyl)-5-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile	73130: Inhibition of [3H]FPP incorporation into recombinant human K-Ras by Farnesyltransferase	ic50	0.0001	uM
4-[(1S)-1-amino-1-(3-methylimidazol-4-yl)ethyl]-2-[3-[(3S)-3-butyl-1-methyl-2-oxoazepan-3-yl]phenoxy]benzonitrile	73259: Concentration required to inhibit recombinant human farnesyltransferase (FTase) catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0001	uM
4-[[(R)-(4-cyanophenyl)-(3-methylimidazol-4-yl)methoxy]methyl]-3-(3-methoxyphenyl)benzonitrile	143977: Effective concentration required for inhibition of farnesylation of Ras protein in NIH3T3 cells	ec50	0.0001	uM
3-(1,3-benzodioxol-5-yl)-4-[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methoxymethyl]benzonitrile	242407: Inhibition of [3H]FPP incorporation into recombinant Ras CVIM by human Farnesyltransferase	ic50	0.0001	uM
155543825	1585808: Inhibition of human recombinant FTase using [3H]FPP as substrate after 15 mins by scintillation counting analysis	ic50	0.0001	uM
5-[[3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-yl-2,4-dioxoimidazolidin-1-yl]methyl]-2-methylsulfanylbenzonitrile	263454: Inhibition of farnesyl transferase	ic50	0.0001	uM
23-oxo-4-prop-2-enyl-8-oxa-1,15,17,21-tetrazapentacyclo[19.2.2.13,7.19,13.015,19]heptacosa-3,5,7(27),9,11,13(26),16,18-octaene-10-carbonitrile	73548: Inhibition of human Farnesyltransferase -catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0001	uM
3-[[3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-yl-2,4-dioxoimidazolidin-1-yl]methyl]benzonitrile	263454: Inhibition of farnesyl transferase	ic50	0.0001	uM
lithium (2S)-2-[[4-[[5-(4-chlorophenyl)furan-2-yl]methoxymethyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoate	72945: EC50 is measured as inhibition of ras processing in a whole cell assay for farnesyltransferase (FTase)	ec50	0.0001	uM
32-oxo-25-oxa-8,12,16,18-tetrazahexacyclo[24.3.1.18,11.120,24.02,7.014,18]dotriaconta-1(30),2,4,6,14,16,20(31),21,23,26,28-undecaene-23-carbonitrile	73277: Inhibition of Farnesyltransferase in PSN-1 cells at 10 pM	ic50	0.0001	uM
(2S)-2-[[2-[[(2S)-2-[[(2R)-2-amino-3-sulfanylpropyl]amino]-3-methylpentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	168708: Inhibition of [3H]- FPP incorporation into recombinant Ha-Ras by farnesyl transferase at 10 pM	ic50	0.0001	uM
(2S)-2-[[2-[[(2S)-3-methyl-2-[[2-[3-(naphthalen-2-ylmethyl)imidazol-4-yl]acetyl]amino]pentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	73432: Inhibition of [3H]FPP incorporation into recombinant [Leu68]-RAS1CVIM by Farnesyltransferase	ic50	0.0001	uM
(2S)-2-[[2-[[(2S)-3-methyl-2-[[2-[3-(naphthalen-1-ylmethyl)imidazol-4-yl]acetyl]amino]pentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	73432: Inhibition of [3H]FPP incorporation into recombinant [Leu68]-RAS1CVIM by Farnesyltransferase	ic50	0.0001	uM
(2S)-2-[[2-[[(2S)-2-[[2-(3-benzylimidazol-4-yl)acetyl]amino]-3-methylpentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	73544: Inhibition of [3H]FPP incorporation into recombinant [Leu68]-RAS1CVIM by Farnesyltransferase	ic50	0.0001	uM
(2S)-2-[[4-[2-(1H-imidazol-5-yl)ethyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoic acid	73125: Inhibitory activity against farnesyltransferase (FT) using SPA assay	ic50	0.0001	uM
(2S)-2-[[4-[(E)-2-[4-(adamantane-1-carbonyl)-3-pyridinyl]ethenyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoic acid	73125: Inhibitory activity against farnesyltransferase (FT) using SPA assay	ic50	0.0001	uM
4-(6-bromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl)-1-N-cyclohexyl-2-N-(3-imidazol-1-ylpropyl)piperazine-1,2-dicarboxamide	259952: Inhibitory activity against Farnesyltransferase quantified by modified SPA assay with improved sensitivity	ic50	0.0001	uM
(2S)-2-[[2-[[(2S,3R)-2-[[2-[3-[(4-cyanophenyl)methyl]imidazol-4-yl]acetyl]amino]-3-methylpentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	73400: Inhibitory concentration against farnesyltransferase was determined	ic50	0.0001	uM
4-[3-(4-cyanophenyl)-3-hydroxy-3-(3-methylimidazol-4-yl)prop-1-ynyl]-3-(3-ethoxyphenyl)benzonitrile	144106: Inhibition of farnesylation in NIH-3T3H-ras cell line	ec50	0.0001	uM
4-[1-hydroxy-3-[2-(3-methoxyphenyl)-4-pentanoylphenyl]-1-(3-methylimidazol-4-yl)prop-2-ynyl]benzonitrile	144106: Inhibition of farnesylation in NIH-3T3H-ras cell line	ec50	0.0001	uM
4-[(1S)-1-amino-1-(3-methylimidazol-4-yl)ethyl]-2-[3-[(3S)-3-ethyl-1-methyl-2-oxoazepan-3-yl]phenoxy]benzonitrile	73259: Concentration required to inhibit recombinant human farnesyltransferase (FTase) catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0001	uM
(2S)-2-[[2-[[(2S,3R)-2-[[(2R)-2-amino-3-sulfanylpropyl]amino]-3-methylpentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-hydroxybutanoic acid	73128: Inhibition of [3H]FPP incorporation into recombinant human Ha-Ras by Farnesyltransferase	ic50	0.0001	uM
4-[(2S)-13-chloro-10-[(1S)-1-hydroxy-1-(3-methylimidazol-4-yl)ethyl]-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-2-yl]-N-cyclohexylpiperazine-1-carboxamide	1070173: Inhibition of FTase (unknown origin) assessed as transfer of [H3]farnesyl from [H3]farnesyl pyrophosphate to trichloroacetic acid-precipitable HaRas-CVLS	ic50	0.0001	uM
4-[(2S)-13-chloro-10-[(1S)-1-hydroxy-1-(3-methylimidazol-4-yl)ethyl]-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-2-yl]piperazine-1-carboxamide	1070173: Inhibition of FTase (unknown origin) assessed as transfer of [H3]farnesyl from [H3]farnesyl pyrophosphate to trichloroacetic acid-precipitable HaRas-CVLS	ic50	0.0001	uM
(1R,5R)-29-oxo-19-oxa-2,6,10,12-tetrazahexacyclo[18.5.2.12,5.114,18.08,12.023,26]nonacosa-8,10,14(28),15,17,20(27),21,23(26)-octaene-17-carbonitrile	73276: Inhibition of Farnesyltransferase in PSN-1 cells at 10 pM	ic50	0.0001	uM
(1R,5R)-30-oxo-19,24-dioxa-2,6,10,12-tetrazahexacyclo[18.6.2.12,5.114,18.08,12.023,27]triaconta-8,10,14(29),15,17,20(28),21,23(27)-octaene-17-carbonitrile	81892: Inhibition of HDJ2 farnesylation in PSN-1 cells over 7 hr assay	ec50	0.0001	uM
3-oxo-18-oxa-2,5,9,11-tetrazahexacyclo[17.6.2.22,5.113,17.07,11.022,26]triaconta-1(25),7,9,13(28),14,16,19(27),20,22(26),23-decaene-16-carbonitrile	73274: In vitro inhibitory activity to reduce the human farnesyltransferase catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM	ic50	0.0001	uM
4-[3-(4-cyanophenyl)-3-hydroxy-3-(3-methylimidazol-4-yl)prop-1-ynyl]-3-(3,5-dichlorophenyl)benzonitrile	72822: Inhibition of human FTase-catalyzed incorporation of [3H]FPP into recombinant Ras CVIM	ic50	0.0001	uM
4-[[(4-cyanophenyl)-(3-methylimidazol-4-yl)methoxy]methyl]-3-(3-ethoxyphenyl)benzonitrile	143977: Effective concentration required for inhibition of farnesylation of Ras protein in NIH3T3 cells	ec50	0.0002	uM
4-[(1S)-1-amino-1-(3-methylimidazol-4-yl)ethyl]-2-[3-[(3R)-3-(2-cyclopropylethyl)-1-methyl-2-oxoazepan-3-yl]phenoxy]benzonitrile	73259: Concentration required to inhibit recombinant human farnesyltransferase (FTase) catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0002	uM
4-[(1S)-1-amino-1-(3-methylimidazol-4-yl)ethyl]-2-[3-[(3R)-1-methyl-2-oxo-3-(3,3,3-trifluoropropyl)azepan-3-yl]phenoxy]benzonitrile	73259: Concentration required to inhibit recombinant human farnesyltransferase (FTase) catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0002	uM
4-[[(4-cyanophenyl)-(3-methylimidazol-4-yl)methoxy]methyl]-3-[3-(methoxymethyl)phenyl]benzonitrile	1797019: Enzyme Inhibition Assay from Article 10.1021/jm030434f: “Design, synthesis, and biological activity of 4-[(4-cyano-2-arylbenzyloxy)-(3-methyl-3H-imidazol-4-yl)methyl]benzonitriles as potent and selective farnesyltransferase inhibitors.”	ic50	0.0002	uM
4-[amino-(3-methylimidazol-4-yl)methyl]-2-[3-(3-ethyl-1-methyl-2-oxoazepan-3-yl)phenoxy]benzonitrile	73259: Concentration required to inhibit recombinant human farnesyltransferase (FTase) catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0002	uM
31-oxo-20-oxa-2,6,11,13-tetrazahexacyclo[19.6.2.12,5.115,19.09,13.024,28]hentriaconta-1(27),9,11,15(30),16,18,21(29),22,24(28),25-decaene-18-carbonitrile	73276: Inhibition of Farnesyltransferase in PSN-1 cells at 10 pM	ic50	0.0002	uM
(2S)-2-[[4-(2-imidazol-1-ylethyl)-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoic acid	73125: Inhibitory activity against farnesyltransferase (FT) using SPA assay	ic50	0.0002	uM
4-[[3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-yl-2,4-dioxoimidazolidin-1-yl]methyl]benzoic acid	263454: Inhibition of farnesyl transferase	ic50	0.0002	uM
3-(3-imidazol-1-ylpropyl)-5-methyl-1-[[4-(methylsulfanylmethyl)phenyl]methyl]-5-naphthalen-1-ylimidazolidine-2,4-dione	263454: Inhibition of farnesyl transferase	ic50	0.0002	uM
1-[(4-bromophenyl)methyl]-3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-ylimidazolidine-2,4-dione	263454: Inhibition of farnesyl transferase	ic50	0.0002	uM
1-[(3-chlorophenyl)methyl]-3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-ylimidazolidine-2,4-dione	263454: Inhibition of farnesyl transferase	ic50	0.0002	uM
(1R)-30-oxo-19-oxa-2,6,10,12-tetrazahexacyclo[18.6.2.12,5.114,18.08,12.023,27]triaconta-8,10,14(29),15,17,20(28),21,23(27)-octaene-17-carbonitrile	157058: Effective concentration required to inhibit HDJ2 farnesylation in PSN-1 cells	ec50	0.0002	uM
(2S)-2-[[2-[[(2S)-3-methyl-2-[[2-[3-[(4-nitrophenyl)methyl]imidazol-4-yl]acetyl]amino]pentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	73544: Inhibition of [3H]FPP incorporation into recombinant [Leu68]-RAS1CVIM by Farnesyltransferase	ic50	0.0002	uM
4-[[5-[[(2S)-4-(3-chlorophenyl)-2-(ethylsulfonylmethyl)-5-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile	73130: Inhibition of [3H]FPP incorporation into recombinant human K-Ras by Farnesyltransferase	ic50	0.0002	uM
propan-2-yl 4-[(2S)-13-chloro-10-[(1S)-1-hydroxy-1-(3-methylimidazol-4-yl)ethyl]-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-2-yl]piperazine-1-carboxylate	1070173: Inhibition of FTase (unknown origin) assessed as transfer of [H3]farnesyl from [H3]farnesyl pyrophosphate to trichloroacetic acid-precipitable HaRas-CVLS	ic50	0.0002	uM
N-(1-adamantyl)-4-[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methyl]piperazine-1-carboxamide	74653: Inhibitory activity against human Geranylgeranyl transferase type I	ic50	0.0002	uM
(2S)-2-[[4-[(E)-2-imidazol-1-ylethenyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoic acid	73125: Inhibitory activity against farnesyltransferase (FT) using SPA assay	ic50	0.0002	uM
[2-(trifluoromethoxy)phenyl]methyl 4-[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methyl]piperazine-1-carboxylate	74504: Inhibition of [1-3H]-GGPP incorporation into biotinylated K4B-Ras peptide by geranylgeranyl transferase in the presence of 5 mM ATP	ic50	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects expression, decreases expression	5
bisphenol A	affects expression, increases expression	2
sodium arsenite	increases expression, affects cotreatment, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Cyclosporine	increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
Sch 59228	decreases activity	1
K 7174	increases expression	1
GW 4064	affects cotreatment, decreases expression	1
GW 7647	increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Fluvastatin	increases expression, affects cotreatment	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Asbestos	affects expression	1
Benzo(a)pyrene	affects methylation	1

ChEMBL screening assays

513 unique, capped per target: 438 binding, 75 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1026658	Binding	Inhibition of human recombinant FPTase by Ras farnesyl-protein-transferase assay	Barceloneic acid A, a new farnesyl-protein transferase inhibitor from a Phoma species. — J Nat Prod
CHEMBL655474	Functional	In vitro inhibition of Ras processing by COS cells at 20 uM	Inhibitors of farnesyl protein transferase. Synthesis and biological activity of amide and cyanoguanidine derivatives containing a 5,11-dihydro[1]benzthiepin, benzoxepin, and benzazepin [4,3-b]pyridine ring system. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
NCT01753232	Not specified	COMPLETED	Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	RECRUITING	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	NOT_YET_RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab
NCT05825131	Not specified	RECRUITING	Natural History Study of Participants With Sanfilippo Syndrome Type IIIC