FNTB

Summary

FNTB (farnesyltransferase, CAAX box, subunit beta, HGNC:3785) is a protein-coding gene on chromosome 14q23.3, encoding Protein farnesyltransferase subunit beta (P49356). Essential subunit of the farnesyltransferase complex. In precision oncology, FNTB RS11623866 is associated with resistance to Lonafarnib in Ovarian Cancer (CIViC Level B). It is a selective cancer dependency (DepMap: 90.0% of cell lines).

Enables acetyltransferase activator activity; enzyme binding activity; and zinc ion binding activity. Contributes to protein farnesyltransferase activity. Involved in protein farnesylation and regulation of microtubule-based movement. Part of microtubule associated complex and protein farnesyltransferase complex. Implicated in anxiety disorder.

Source: NCBI Gene 2342 — RefSeq curated summary.

At a glance

• GWAS associations: 38
• Clinical variants (ClinVar): 3 total — 1 likely-pathogenic
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer dependency (DepMap): dependent in 90.0% of screened cell lines
• MANE Select transcript: NM_002028

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3785
Approved symbol	FNTB
Name	farnesyltransferase, CAAX box, subunit beta
Location	14q23.3
Locus type	gene with protein product
Status	Approved
Aliases	FPTB
Ensembl gene	ENSG00000257365
Ensembl biotype	protein_coding
OMIM	134636
Entrez	2342

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000246166, ENST00000554210, ENST00000554334, ENST00000555372, ENST00000555618, ENST00000555742, ENST00000556709, ENST00000557300, ENST00000880245, ENST00000880246, ENST00000916263, ENST00000916264, ENST00000947324, ENST00000947325

RefSeq mRNA: 2 — MANE Select: NM_002028 NM_001202558, NM_002028

CCDS: CCDS9769

Canonical transcript exons

ENST00000246166 — 12 exons

Exon	Start	End
ENSE00000859806	64986895	64987097
ENSE00001013638	65061181	65062650
ENSE00003703846	65012317	65012389
ENSE00003704096	65027698	65027781
ENSE00003704144	65004249	65004313
ENSE00003706171	65032610	65032696
ENSE00003706291	65053238	65053349
ENSE00003706380	65054575	65054689
ENSE00003708004	65015625	65015716
ENSE00003709149	65040790	65040919
ENSE00003709581	65044311	65044443
ENSE00003710298	65027453	65027599

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 97.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.3621 / max 306.7156, expressed in 1810 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140139	21.6950	1806
140140	0.2525	58
140141	0.1719	57
140143	0.1373	46
140142	0.0588	32
140138	0.0466	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.85	gold quality
corpus callosum	UBERON:0002336	92.57	gold quality
substantia nigra	UBERON:0002038	92.32	gold quality
apex of heart	UBERON:0002098	89.38	gold quality
gastrocnemius	UBERON:0001388	89.08	gold quality
skin of leg	UBERON:0001511	89.06	gold quality
muscle of leg	UBERON:0001383	88.81	gold quality
zone of skin	UBERON:0000014	88.68	gold quality
tibial nerve	UBERON:0001323	88.67	gold quality
ventricular zone	UBERON:0003053	88.53	gold quality
lower esophagus mucosa	UBERON:0035834	88.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.24	gold quality
skin of abdomen	UBERON:0001416	88.23	gold quality
right testis	UBERON:0004534	88.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.05	gold quality
right uterine tube	UBERON:0001302	88.01	gold quality
sural nerve	UBERON:0015488	87.92	gold quality
left testis	UBERON:0004533	87.59	gold quality
esophagus mucosa	UBERON:0002469	87.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.34	gold quality
cerebellar hemisphere	UBERON:0002245	87.17	gold quality
cerebellum	UBERON:0002037	87.16	gold quality
cerebellar cortex	UBERON:0002129	87.13	gold quality
right adrenal gland cortex	UBERON:0035827	87.06	gold quality
testis	UBERON:0000473	87.03	gold quality
right adrenal gland	UBERON:0001233	86.93	gold quality
pituitary gland	UBERON:0000007	86.63	gold quality
primary visual cortex	UBERON:0002436	86.57	gold quality
Ammon’s horn	UBERON:0001954	86.17	gold quality
vagina	UBERON:0000996	86.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6, TP53

miRNA regulators (miRDB)

73 targeting FNTB, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-199A-5P	99.51	69.71	1107

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 90.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• farnesyl:protein transferase and geranylgeranyl:protein transferase inhibitor combinations in preclinical models. (PMID:11751396)
• The level of FTase mRNA expression in cancer tissues is much higher than in normal tissues. FTase may play an important role in the genesis and development of PLC and may be one of the markers for the metastatic activity gained by liver tumor cells. (PMID:22882915)
• Data show that protein farnesyltransferase (FTase) specificity can be “tuned” using a small number of active site contacts that play essential roles in discriminating against non-substrates in the wild-type enzyme. (PMID:22992747)
• The results of this study show that activation in Ras signaling cascade may be implicated in the METH-induced death signaling pathway in neuroblastoma SH-SY5Y cells. (PMID:23643986)
• 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)
• Characterization of the promoter of the human farnesyltransferase beta subunit and the impact of the transcription factor OCT-1 on its expression. (PMID:35167937)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fntb	ENSDARG00000027916
mus_musculus	Fntb	ENSMUSG00000033373
rattus_norvegicus	Fntb	ENSRNOG00000071324
drosophila_melanogaster	Fntb	FBGN0038424
caenorhabditis_elegans		WBGENE00006465

Paralogs (2): RABGGTB (ENSG00000137955), PGGT1B (ENSG00000164219)

Protein

Protein identifiers

Protein farnesyltransferase subunit beta — P49356 (reviewed: P49356)

Alternative names: CAAX farnesyltransferase subunit beta, Ras proteins prenyltransferase subunit beta

All UniProt accessions (2): A0A384MEJ5, P49356

UniProt curated annotations — full annotation on UniProt →

Function. Essential subunit of the farnesyltransferase complex. Catalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X.

Subunit / interactions. Heterodimer of FNTA and FNTB.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the protein prenyltransferase subunit beta family.

Isoforms (2)

UniProt ID	Names	Canonical?
P49356-1	1	yes
P49356-2	2

RefSeq proteins (2): NP_001189487, NP_002019* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001330	Prenyltrans	Domain
IPR008930	Terpenoid_cyclase/PrenylTrfase	Homologous_superfamily
IPR026872	FTB	Family
IPR045089	PGGT1B-like	Family

Pfam: PF00432

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), 1 shown:

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

UniProt features (53 total): helix 21, strand 8, binding site 6, repeat 5, mutagenesis site 4, turn 4, chain 1, site 1, modified residue 1, splice variant 1, sequence conflict 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-P49356-F1	94.72	0.91

Functional residue map

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

Catalytic / active sites (1): 102 (important for selectivity against geranylgeranyl diphosphate)

Ligand- & substrate-binding residues (6): 300–303; 362; 248–251; 291–294; 297; 299

Post-translational modifications (1): 436

Mutagenesis-validated functional residues (4):

Position	Phenotype
102	removes the steric hindrance that normally precludes geranylgeranyl diphosphate binding. reduces farnesyltransferase act
200	reduced catalytic efficiency.
249	reduced catalytic efficiency.
349	reduced catalytic efficiency.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
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: 226 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, MORF_FLT1, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, MORF_MSH3, GCM_GSPT1, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MORF_BRCA1, MORF_ATRX, MORF_ESR1, GGAMTNNNNNTCCY_UNKNOWN, MORF_RAD51L3, MORF_PPP5C, MODULE_256, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (6): lipid metabolic process (GO:0006629), positive regulation of cell population proliferation (GO:0008284), protein farnesylation (GO:0018343), positive regulation of cell cycle (GO:0045787), regulation of microtubule-based movement (GO:0060632), prenylation (GO:0097354)

GO Molecular Function (11): protein farnesyltransferase activity (GO:0004660), zinc ion binding (GO:0008270), acetyltransferase activator activity (GO:0010698), enzyme binding (GO:0019899), peptide binding (GO:0042277), catalytic activity (GO:0003824), prenyltransferase activity (GO:0004659), protein binding (GO:0005515), protein prenyltransferase activity (GO:0008318), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): cytosol (GO:0005829), microtubule associated complex (GO:0005875), protein farnesyltransferase complex (GO:0005965)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
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
positive regulation of cellular process	2
binding	2
cytoplasm	2
primary metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
protein prenylation	1
cell cycle	1
regulation of cell cycle	1
microtubule-based movement	1
regulation of microtubule-based process	1
metabolic process	1
protein prenyltransferase activity	1
transition metal ion binding	1
enzyme activator activity	1
acetyltransferase activity	1
protein binding	1
molecular_function	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
prenyltransferase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
microtubule cytoskeleton	1
protein-containing complex	1
transferase complex	1

Protein interactions and networks

STRING

720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FNTB	FNTA	P49354	996
FNTB	RCE1	Q9Y256	659
FNTB	ICMT	O60725	656
FNTB	ZMPSTE24	O75844	646
FNTB	RABGGTA	Q92696	638
FNTB	GGPS1	O95749	570
FNTB	HRAS	P01112	570
FNTB	DHDDS	Q86SQ9	522
FNTB	FDPS	P14324	513
FNTB	KRAS	P01116	500
FNTB	PCYOX1	Q9UHG3	484
FNTB	HMGCR	P04035	450
FNTB	PGGT1B	P53609	430
FNTB	PDSS1	Q5T2R2	423
FNTB	SMARCA5	O60264	404

IntAct

125 interactions, top by confidence:

A	B	Type	Score
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
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
KRT31	HGS	psi-mi:“MI:0914”(association)	0.780
KRT34	TXLNA	psi-mi:“MI:0914”(association)	0.670
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
AUP1	APOB	psi-mi:“MI:0914”(association)	0.610
TLX3	FNTB	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	FNTB	psi-mi:“MI:0915”(physical association)	0.560
KRBA1	FNTB	psi-mi:“MI:0915”(physical association)	0.560
FNTB	CCDC24	psi-mi:“MI:0915”(physical association)	0.560
FNTB	SMG9	psi-mi:“MI:0915”(physical association)	0.560
AGXT	FNTB	psi-mi:“MI:0915”(physical association)	0.560
FNTB	APOL6	psi-mi:“MI:0915”(physical association)	0.560
FNTB	ATPAF2	psi-mi:“MI:0915”(physical association)	0.560
DMWD	FNTB	psi-mi:“MI:0915”(physical association)	0.560
FNTB	SPRED1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (182): FNTB (Affinity Capture-MS), FNTB (Affinity Capture-MS), FNTB (Affinity Capture-MS), UBB (Affinity Capture-MS), SPDL1 (Affinity Capture-MS), YKT6 (Affinity Capture-MS), HOOK3 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), CENPF (Affinity Capture-MS), DYRK1A (Affinity Capture-MS), FNTA (Affinity Capture-MS), CAPN1 (Affinity Capture-MS), GRIP1 (Affinity Capture-MS), DHX57 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E0SP71, A0A348FUE1, A3LQF9, B0G172, C4YSU5, O13782, O80642, O93830, P0DPA1, P18898, P20133, P22007, P32073, P32434, P38604, P41992, P46960, P49355, P49356, P53609, P53610, P53611, P53612, Q02293, Q04782, Q04903, Q08603, Q10231, Q2V0C9, Q38920, Q4WES9, Q54MJ7, Q55D51, Q55D85, Q55DA3, Q55FS0, Q59LF2, Q59M69, Q5E9B3, Q5EAD5

Diamond homologs: G4MY67, O13782, P22007, P49355, P49356, P53611, P53612, Q02293, Q04903, Q08603, Q38920, Q5E9B3, Q8K2I1, Q9LHL5, B0G172, O80642, P20133, P32434, O93830, P53609, P53610, Q55DA3, Q5EAD5, Q84J75, Q8BUY9, Q55D51, P18898, P41992, P46960

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
TP53	“up-regulates quantity by expression”	FNTB	“transcriptional regulation”
FNTB	“up-regulates activity”	KRAS
FNTB	“up-regulates activity”	MRAS
FNTB	“up-regulates activity”	HRAS

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by BRAF and RAF1 fusions	5	12.2×	1e-03
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	5	7.0×	6e-03
Major pathway of rRNA processing in the nucleolus and cytosol	6	5.3×	8e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
980604	GRCh37/hg19 14q23.1-23.3(chr14:61409856-65742610)x3	Likely pathogenic

SpliceAI

2579 predictions. Top by Δscore:

Variant	Effect	Δscore
14:64987093:AACAG:A	donor_loss	1.0000
14:64987097:GGTG:G	donor_loss	1.0000
14:64987098:G:GA	donor_loss	1.0000
14:64987099:T:A	donor_loss	1.0000
14:65004230:T:G	acceptor_gain	1.0000
14:65004235:T:A	acceptor_gain	1.0000
14:65011739:G:GT	donor_gain	1.0000
14:65011775:GGGCT:G	donor_gain	1.0000
14:65011776:GGCTG:G	donor_gain	1.0000
14:65012316:GGCTT:G	acceptor_gain	1.0000
14:65012385:ATGAG:A	donor_loss	1.0000
14:65012386:TGAG:T	donor_loss	1.0000
14:65012387:GAGGT:G	donor_loss	1.0000
14:65012388:AG:A	donor_loss	1.0000
14:65012388:AGGTA:A	donor_loss	1.0000
14:65012389:GGTAA:G	donor_loss	1.0000
14:65012390:G:GA	donor_loss	1.0000
14:65012390:GT:G	donor_loss	1.0000
14:65012391:T:A	donor_loss	1.0000
14:65015715:GA:G	donor_gain	1.0000
14:65015717:G:GG	donor_gain	1.0000
14:65027438:T:TA	acceptor_gain	1.0000
14:65027451:A:AG	acceptor_gain	1.0000
14:65027452:G:GG	acceptor_gain	1.0000
14:65027452:GTGT:G	acceptor_gain	1.0000
14:65032608:A:AG	acceptor_gain	1.0000
14:65032609:G:GG	acceptor_gain	1.0000
14:65040785:CTTA:C	acceptor_loss	1.0000
14:65040786:TTA:T	acceptor_loss	1.0000
14:65040787:TAG:T	acceptor_loss	1.0000

AlphaMissense

2850 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:65015646:T:A	W102R	1.000
14:65015646:T:C	W102R	1.000
14:65015658:T:A	W106R	1.000
14:65015658:T:C	W106R	1.000
14:65044370:G:C	K294N	1.000
14:65044370:G:T	K294N	1.000
14:65044377:G:C	D297H	1.000
14:65044378:A:T	D297V	1.000
14:65044379:T:A	D297E	1.000
14:65044379:T:G	D297E	1.000
14:65044383:T:C	C299R	1.000
14:65044384:G:A	C299Y	1.000
14:65044385:C:G	C299W	1.000
14:65044386:T:C	Y300H	1.000
14:65044395:T:A	W303R	1.000
14:65044395:T:C	W303R	1.000
14:65053336:G:C	D352H	1.000
14:65053337:A:T	D352V	1.000
14:65053339:A:G	K353E	1.000
14:65053341:A:C	K353N	1.000
14:65053341:A:T	K353N	1.000
14:65054583:A:C	D359A	1.000
14:65054583:A:T	D359V	1.000
14:65054588:T:G	Y361D	1.000
14:65054591:C:A	H362N	1.000
14:65054591:C:G	H362D	1.000
14:65054593:C:A	H362Q	1.000
14:65054593:C:G	H362Q	1.000
14:65012352:T:C	L82P	0.999
14:65015629:T:C	L96P	0.999

dbSNP variants (sampled 300 via entrez): RS1000004753 (14:64997092 C>T), RS1000009374 (14:65039915 G>A), RS1000029483 (14:65011742 A>G,T), RS1000089134 (14:65059549 ATTGTT>A), RS1000120893 (14:65061045 T>C), RS1000130981 (14:64994581 A>G), RS1000141550 (14:64998051 G>A), RS1000162937 (14:65037376 T>A,C,G), RS1000173519 (14:65052765 T>C), RS1000210670 (14:64991292 TAGAG>T), RS1000224666 (14:64994228 G>C), RS1000225434 (14:65013556 C>G,T), RS1000283969 (14:65045926 A>C,T), RS1000310971 (14:65004404 G>A), RS1000323746 (14:65033911 C>T)

Disease associations

OMIM: gene MIM:134636 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST000503_3	Mean corpuscular volume	5.000000e-08
GCST001765_13	Red blood cell traits	2.000000e-12
GCST002040_9	Blood trace element (Zn levels)	1.000000e-07
GCST004004_1	Mean corpuscular volume	1.000000e-08
GCST004006_25	Mean corpuscular hemoglobin	1.000000e-10
GCST004599_165	Mean platelet volume	7.000000e-12
GCST004601_174	Red blood cell count	2.000000e-14
GCST004602_204	Mean corpuscular volume	4.000000e-52
GCST004603_134	Platelet count	1.000000e-11
GCST004605_3	Mean corpuscular hemoglobin concentration	9.000000e-26
GCST004630_200	Mean corpuscular hemoglobin	2.000000e-74
GCST004862_27	Itch intensity from mosquito bite adjusted by bite size	6.000000e-07
GCST005992_18	Mean corpuscular hemoglobin concentration	2.000000e-11
GCST009391_1147	Metabolite levels	7.000000e-06
GCST009391_2006	Metabolite levels	6.000000e-06
GCST009391_2016	Metabolite levels	3.000000e-06
GCST010083_251	Hemoglobin levels	1.000000e-11
GCST90002381_601	Eosinophil count	4.000000e-10
GCST90002384_340	Hemoglobin	4.000000e-11
GCST90002385_28	High light scatter reticulocyte count	2.000000e-22
GCST90002386_172	High light scatter reticulocyte percentage of red cells	2.000000e-30
GCST90002387_144	Immature fraction of reticulocytes	1.000000e-14
GCST90002390_265	Mean corpuscular hemoglobin	2.000000e-140
GCST90002390_266	Mean corpuscular hemoglobin	4.000000e-27
GCST90002391_143	Mean corpuscular hemoglobin concentration	4.000000e-16
GCST90002391_144	Mean corpuscular hemoglobin concentration	8.000000e-35
GCST90002392_452	Mean corpuscular volume	3.000000e-26
GCST90002392_453	Mean corpuscular volume	1.000000e-12
GCST90002395_201	Mean platelet volume	2.000000e-23
GCST90002396_567	Mean reticulocyte volume	3.000000e-16

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0010457	Alpha ketoglutarate measurement
EFO:0010347	cholesteryl ester 20:3 measurement
EFO:0010348	cholesteryl ester 20:4 measurement
EFO:0004509	hemoglobin measurement
EFO:0004842	eosinophil count
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2094108 (PROTEIN COMPLEX), CHEMBL2096991 (PROTEIN COMPLEX GROUP), CHEMBL272 (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

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
FNTB RS11623866	Lonafarnib	Ovarian Cancer	Resistance	CIViC B	EID815

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11623866	Efficacy	3	carboplatin;lonafarnib;paclitaxel	Ovarian Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11623866	FNTB	3	3.00	1	carboplatin;lonafarnib;paclitaxel

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.5.1.58 Protein farnesyltransferase

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
FTI 276	Inhibition	9.3	pIC50
tipifarnib	Inhibition	9.07	pIC50
LB42908	Inhibition	9.05	pIC50
BMS-214662	Inhibition	8.87	pIC50
L-739,750	Inhibition	8.74	pIC50
darlifarnib	Inhibition	8.0	pIC50

Binding affinities (BindingDB)

48 measured of 63 human assays (93 total across all organisms); most potent 48 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
(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-(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
(+/-)-11-[2-(2-methoxyphenyl)acryloyl]-1-(4-methylphenyl)-(1R,8R,9S,13S)-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-carboxylic acid (RPR130401)	IC50	8 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
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
(+/-)-11-[2-(2-methoxyphenyl)acryloyl]-1-phenyl-(1R,8R,9S,13S)-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-carboxylic acid (RPR115135)	IC50	50 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-[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
(+/-)-11-[2-(2-methoxyphenyl)acetyl]-1-phenyl-(1R,8R,9S,13S)-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-carboxylic acid (RPR104213)	KI	140 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
11-[2-(2-methoxyphenyl)acetyl]-1-phenyl-(1R,8R,9S,13S)-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-methoxycarboxamide (RPR113401)	KI	420 nM
1-(2,3-dihydrobenzo[b]furan-5-yl)-11-[2-(2-methoxyphenyl)acryloyl]-(1R,8R,9S,13S)-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-carboxylic acid (RPR208287)	KI	420 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
2-[11-[2-(2-methoxyphenyl)acetyl]-1-phenyl-(1R,8R,9S,13S)-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-trien-9-ylcarboxamido]acetic acid (RPR113258)	KI	738 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
(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
1-(4-carboxymethoxyphenyl)-11-[2-(2-methoxyphenyl)acryloyl]-(1R,8R,9S,13S)-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-carboxylic acid (RPR132506)	KI	25500 nM
11-[2-(2-benzyloxyphenyl)acetyl]-1-phenyl-(1R,8R,9S,13S)-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-carboxylic acid (RPR109043)	KI	32000 nM
6-hydroxy-11-[2-(2-methoxyphenyl)acetyl]-1-phenyl-(1R,8R,9S,13S)-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-carboxylic acid (RPR131168)	KI	50000 nM

ChEMBL bioactivities

2265 potent at pChembl≥5 of 2529 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
10.30	IC50	0.05	nM	ABT-100
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
9.74	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	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
9.60	EC50	0.25	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)

PubChem BioAssay actives

3672 with measured affinity, of 6100 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-[[(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-[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
4-[(1S)-1-amino-1-(3-methylimidazol-4-yl)ethyl]-2-[3-[(3R)-3-(cyclopropylmethyl)-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	0.0003	uM
N-[6-cyano-1-[(3-methylimidazol-4-yl)methyl]-3,4-dihydro-2H-quinolin-3-yl]-1-methyl-N-(2-methylprop-2-enyl)imidazole-4-sulfonamide	240938: Inhibition of human farnesyltransferase	ic50	0.0003	uM
1-[4-[(2S)-6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-2-yl]piperidin-1-yl]-2-(1-oxidopyridin-1-ium-4-yl)ethanone	240768: Inhibition of [3H]FPP incorporation into H-ras CVLS by Farnesyltransferase	ic50	0.0003	uM
23-oxo-4-propyl-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	0.0003	uM
4-methyl-23-oxo-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	73547: Displacement of radiolabeled FTI from Farnesyltransferase in cultured Ha-ras transformed RAT1 cells.	ic50	0.0003	uM
N-[[4-[[3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-yl-2,4-dioxoimidazolidin-1-yl]methyl]phenyl]methyl]methanesulfonamide	263454: Inhibition of farnesyl transferase	ic50	0.0003	uM
4-[(4-cyanophenyl)methoxy-(3-methylimidazol-4-yl)methyl]-2-naphthalen-1-ylbenzonitrile	71309: Inhibition of Farnesyltransferase	ic50	0.0003	uM
lithium (2S)-2-[[2-(2-methylphenyl)-4-[(5-pyridin-3-ylfuran-2-yl)methoxymethyl]benzoyl]amino]-4-methylsulfanylbutanoate	72945: EC50 is measured as inhibition of ras processing in a whole cell assay for farnesyltransferase (FTase)	ec50	0.0003	uM
4-[3-(4-cyanophenyl)-1-hydroxy-1-(3-methylimidazol-4-yl)prop-2-ynyl]-2-naphthalen-1-ylbenzonitrile	72822: Inhibition of human FTase-catalyzed incorporation of [3H]FPP into recombinant Ras CVIM	ic50	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
GW 4064	decreases expression, affects cotreatment	1
abrine	decreases expression	1
NSC 689534	increases 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	increases expression	1
Temozolomide	increases expression	1
Atrazine	decreases expression	1
Cisplatin	increases expression	1
Curcumin	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Farnesol	decreases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	increases expression, affects cotreatment	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Theophylline	affects cotreatment, increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression	1
Oleic Acid	affects cotreatment, decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

425 unique, capped per target: 366 binding, 59 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)

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