FDPS

Summary

FDPS (farnesyl diphosphate synthase, HGNC:3631) is a protein-coding gene on chromosome 1q22, encoding Farnesyl pyrophosphate synthase (P14324). Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. It is a selective cancer dependency (DepMap: 72.4% of cell lines).

This gene encodes an enzyme that catalyzes the production of geranyl pyrophosphate and farnesyl pyrophosphate from isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The resulting product, farnesyl pyrophosphate, is a key intermediate in cholesterol and sterol biosynthesis, a substrate for protein farnesylation and geranylgeranylation, and a ligand or agonist for certain hormone receptors and growth receptors. Drugs that inhibit this enzyme prevent the post-translational modifications of small GTPases and have been used to treat diseases related to bone resorption. Multiple pseudogenes have been found on chromosomes 1, 7, 14, 15, 21 and X. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2224 — RefSeq curated summary.

At a glance

• Gene–disease (curated): porokeratosis 9, multiple types (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 16
• Clinical variants (ClinVar): 95 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 72.4% of screened cell lines
• MANE Select transcript: NM_002004

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3631
Approved symbol	FDPS
Name	farnesyl diphosphate synthase
Location	1q22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000160752
Ensembl biotype	protein_coding
OMIM	134629
Entrez	2224

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 27 protein_coding, 8 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000356657, ENST00000368356, ENST00000447866, ENST00000461507, ENST00000465559, ENST00000467076, ENST00000468479, ENST00000470171, ENST00000471117, ENST00000474345, ENST00000477057, ENST00000487002, ENST00000489003, ENST00000489324, ENST00000490140, ENST00000491013, ENST00000492244, ENST00000492887, ENST00000495308, ENST00000611010, ENST00000612683, ENST00000851540, ENST00000851541, ENST00000851542, ENST00000851543, ENST00000851544, ENST00000851545, ENST00000851546, ENST00000851547, ENST00000851548, ENST00000851549, ENST00000851550, ENST00000851551, ENST00000851552, ENST00000851554, ENST00000930252, ENST00000930253, ENST00000930254, ENST00000930255, ENST00000947439

RefSeq mRNA: 7 — MANE Select: NM_002004 NM_001135821, NM_001135822, NM_001242824, NM_001242825, NM_001378424, NM_001378425, NM_002004

CCDS: CCDS1110, CCDS44241, CCDS72940

Canonical transcript exons

ENST00000368356 — 11 exons

Exon	Start	End
ENSE00001446957	155309789	155309965
ENSE00001876084	155308866	155308965
ENSE00003488850	155318665	155318753
ENSE00003495546	155319611	155319688
ENSE00003498928	155310043	155310205
ENSE00003534119	155317941	155318021
ENSE00003604439	155319794	155319928
ENSE00003609371	155312255	155312395
ENSE00003618706	155318169	155318291
ENSE00003635449	155320409	155320665
ENSE00003652873	155318856	155318928

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 115.4719 / max 1020.5149, expressed in 1824 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5597	112.5141	1824
5598	1.2800	424
5595	1.0697	753
5594	0.5739	340
201750	0.0342	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.44	gold quality
ventricular zone	UBERON:0003053	98.81	gold quality
mucosa of transverse colon	UBERON:0004991	98.73	gold quality
ganglionic eminence	UBERON:0004023	98.65	gold quality
right adrenal gland	UBERON:0001233	98.60	gold quality
upper leg skin	UBERON:0004262	98.60	gold quality
embryo	UBERON:0000922	98.59	gold quality
tendon of biceps brachii	UBERON:0008188	98.58	gold quality
right adrenal gland cortex	UBERON:0035827	98.53	gold quality
right lobe of liver	UBERON:0001114	98.49	gold quality
upper lobe of left lung	UBERON:0008952	98.49	gold quality
esophagus mucosa	UBERON:0002469	98.45	gold quality
mammalian vulva	UBERON:0000997	98.42	gold quality
left adrenal gland	UBERON:0001234	98.40	gold quality
adrenal gland	UBERON:0002369	98.39	gold quality
upper lobe of lung	UBERON:0008948	98.37	gold quality
right lung	UBERON:0002167	98.34	gold quality
lower esophagus mucosa	UBERON:0035834	98.31	gold quality
islet of Langerhans	UBERON:0000006	98.29	gold quality
left adrenal gland cortex	UBERON:0035825	98.29	gold quality
adrenal cortex	UBERON:0001235	98.24	gold quality
skin of abdomen	UBERON:0001416	98.21	gold quality
skin of leg	UBERON:0001511	98.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.13	gold quality
rectum	UBERON:0001052	98.10	gold quality
minor salivary gland	UBERON:0001830	98.08	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.03	gold quality
transverse colon	UBERON:0001157	97.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.92	gold quality
zone of skin	UBERON:0000014	97.91	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	36.87
E-MTAB-6701	yes	13.71
E-CURD-88	yes	4.02
E-GEOD-86618	no	243.64
E-MTAB-6678	no	3.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CNBP, CREBBP, GATA2, NFYA, NFYC, NR1H3, PAX5, POU2F1, PPARA, SREBF1, SREBF2, YY1

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 34)

• This study provides the first evidence of the presence of FPPs activity in human CRC. Moreover, FPPs enzyme was found to play a significant role in colon cancer proliferation. (PMID:15713990)
• mitochondrial targeting of FPS may be widespread among eukaryotes (PMID:17198737)
• findings suggest that a single nucleotide polymorphism in the FDPS gene (rs2297480) may be a genetic marker for lower bone mineral density in postmenopausal Caucasian women (PMID:17368768)
• FDPS is involved in the resistance to zoledronic acid of osteosarcoma cells. (PMID:18494934)
• characterized functionally the minimal basal promoter of the human FDPS gene by means of deletion mutants and we have identified two cis-acting elements which modulate the FDPS gene expression and are recognized by Pax5 and OCT-1 transcription factors (PMID:19056481)
• FPPS knockdown cells activated Vgamma9Vdelta2 T cells, as measured by increased levels of CD69 and CD107a, killing of FPPS knockdown cells, and induction of IFN-gamma secretion (PMID:19494338)
• characterized the sterol-response-element-binding protein 2 and nuclear factor Y-binding site in the farnesyl diphosphate synthase promoter (PMID:20450493)
• Common polymorphisms of the FDPS gene influence the response to bisphosphonates in osteoporotic women. (PMID:21151198)
• The A/C rs2297480 polymorphism of FDPS was highly differently distributed among osteonecrosis-of-the-jaw patients and controls, with a correlation between AA carrier status and occurrence of ONJ after 18-24 months of treatment with bisphosphonates. (PMID:21196316)
• findings reveal a FDPS-dependent mechanism in the internalization and down-regulation of beta2AR, identify FDPS as a potential target for improving the therapeutic efficacy of beta-agonists (PMID:22278941)
• first study on the gene FDPS rs2297480 SNP in postmenopausal Thai women.The effect did not contribute to the baseline of bone mineral density nor bone turnover markers. (PMID:22338925)
• FPPS was more highly expressed in prostate cancer vs. normal prostate tissue. The association of FPPS with established histopathological risk parameters and biochemical recurrence implicates a contribution of the mevalonate pathway to PC progression. (PMID:22407328)
• The crystal structure of human FPPS in complex with a novel bisphosphonate YS0470 and in the absence of a second substrate showed partial ordering of the tail in the closed conformation. (PMID:23234314)
• LRP5 and FDPS loci age-specifically affect skeletal traits in healthy fertile women. (PMID:23238007)
• FPPS might play an important role in Ang II-induced cardiac hypertrophy and fibrosis in vivo, at least in part through RhoA, p-38 MAPK and TGF-beta1. (PMID:23277274)
• The iPA-driven modulation of FDPS can cause an enhancement of post-translational prenylation essential for the biological activity of key proteins in NK signaling and effector functions, such as Ras. (PMID:23847096)
• Data indicate compounds represent a new structural class of farnesyl pyrophosphate synthase (hFPPS) inhibitors and suggest a development of therapeutics. (PMID:23998921)
• Results suggest that polymorphisms of the FDPS gene may influence the bone response to drugs targeting the mevalonate pathway, like statins. (PMID:24311107)
• These observations suggest that an increase in the expression of endogenous FPPS could confer at least partial resistance to the pharmacological effect of N-BP drugs such as ZOL in vivo (PMID:24369118)
• our study indicated that DR patients have higher VEGF levels than diabetic patients without retinopathy, and -2578A/C (rs699947) and +405C/G (rs2010963) may be important factors in determining serum VEGF levels. (PMID:24534219)
• A co-crystal structure of human farnesyl pyrophosphate synthase in complex with a bisphosphonate and two molecules of inorganic phosphate. (PMID:24598914)
• The results identify new classes of FPPS inhibitors, diterpenoids and sesquiterpenoids, that bind to the IPP site and may be of interest as anticancer and antiinfective drug leads. (PMID:24927548)
• These results are consistent with the previously proposed hypothesis that the allosteric pocket of human FPPS, located near the active site, plays a feed-back regulatory role for this enzyme. (PMID:25630225)
• Farnesyl pyrophosphate (FPP) allosterically regulated the activity of farnesyl pyrophosphate synthase. (PMID:28098152)
• Crystallographic and thermodynamic characterization of phenylaminopyridine bisphosphonates binding to human farnesyl pyrophosphate synthase (PMID:29036218)
• Deregulated expression and activity of Farnesyl Diphosphate Synthase (FDPS) in Glioblastoma (PMID:29075041)
• FPPS mediates TGF-beta1-induced lung cancer cell invasion and epithelial-to-mesenchymal transition via the RhoA/Rock1 pathway. (PMID:29337059)
• A novel premature termination mutation in FDPS in a Chinese family with disseminated superficial actinic porokeratosis. (PMID:30561051)
• FDPS plays an oncogenic role in PTEN-deficient Prostate cancer through GTPase/AKT axis. Identifying mevalonate pathway proteins could serve as a therapeutic target in PTEN dysregulated tumors. (PMID:30914801)
• FDPS rs2297480 is associated with postmenopausal osteoporosis. (PMID:31774873)
• Novel missense mutations of MVK and FDPS gene in Chinese patients with disseminated superficial actinic porokeratosis. (PMID:34751146)
• Towards an Improvement of Anticancer Activity of Benzyl Adenosine Analogs. (PMID:34885721)
• Farnesyl diphosphate synthase exacerbates nonalcoholic steatohepatitis via the activation of AHR-CD36 axis. (PMID:37310396)
• Farnesyl Diphosphate Synthase Gene Associated with Loss of Bone Mass Density and Alendronate Treatment Failure in Patients with Primary Osteoporosis. (PMID:38891810)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fdps	ENSDARG00000040890
mus_musculus	Fdps	ENSMUSG00000059743
rattus_norvegicus	Fdps	ENSRNOG00000077379
drosophila_melanogaster	Fpps	FBGN0025373
caenorhabditis_elegans	fdps-1	WBGENE00011058

Protein

Protein identifiers

Farnesyl pyrophosphate synthase — P14324 (reviewed: P14324)

Alternative names: (2E,6E)-farnesyl diphosphate synthase, Dimethylallyltranstransferase, Farnesyl diphosphate synthase, Geranyltranstransferase

All UniProt accessions (5): P14324, A0A087WTP2, A0A087WVN4, A0A087X090, A0A087X1D8

UniProt curated annotations — full annotation on UniProt →

Function. Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate.

Subunit / interactions. Homodimer. Interacts with RSAD2. (Microbial infection) Interacts with HTLV-1 protein p13(II).

Subcellular location. Cytoplasm.

Disease relevance. Porokeratosis 9, multiple types (POROK9) [MIM:616631] A form of porokeratosis, a disorder of faulty keratinization characterized by one or more atrophic patches surrounded by a distinctive hyperkeratotic ridgelike border called the cornoid lamella. The keratotic lesions can progress to overt cutaneous neoplasms, typically squamous cell carcinomas. Multiple clinical variants of porokeratosis are recognized, including porokeratosis of Mibelli, linear porokeratosis, disseminated superficial actinic porokeratosis, palmoplantar porokeratosis, and punctate porokeratosis. Different clinical presentations can be observed among members of the same family. Individuals expressing more than one variant have also been reported. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inactivated by interferon-induced RSAD2. This inactivation may result of disruption of lipid rafts at the plasma membrane, and thus have an antiviral effect since many enveloped viruses need lipid rafts to bud efficiently out of the cell.

Cofactor. Binds 2 Mg(2+) ions per subunit.

Pathway. Isoprenoid biosynthesis; farnesyl diphosphate biosynthesis; farnesyl diphosphate from geranyl diphosphate and isopentenyl diphosphate: step 1/1. Isoprenoid biosynthesis; geranyl diphosphate biosynthesis; geranyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate: step 1/1.

Similarity. Belongs to the FPP/GGPP synthase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P14324-1	1	yes
P14324-2	2

RefSeq proteins (7): NP_001129293, NP_001129294, NP_001229753, NP_001229754, NP_001365353, NP_001365354, NP_001995* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000092	Polyprenyl_synt	Family
IPR008949	Isoprenoid_synthase_dom_sf	Homologous_superfamily
IPR033749	Polyprenyl_synt_CS	Conserved_site
IPR039702	FPS1-like	Family

Pfam: PF00348

Enzyme classification (BRENDA):

• EC 2.5.1.1 — dimethylallyltranstransferase (BRENDA: 25 organisms, 58 substrates, 48 inhibitors, 15 Km, 7 kcat entries)
• EC 2.5.1.10 — (2E,6E)-farnesyl diphosphate synthase (BRENDA: 58 organisms, 91 substrates, 232 inhibitors, 47 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ISOPENTENYL DIPHOSPHATE	0.0015–130	18
GERANYL DIPHOSPHATE	0.0012–8.4	17
DIMETHYLALLYL DIPHOSPHATE	0.0045–0.0666	8
DIMETHYLALLYL DIPHOSPHATE	0.008–1.103	6
ISOPENTENYL DIPHOSPHATE	0.0008–0.163	5
GERANYL DIPHOSPHATE	0.008–0.012	2
(2E,6E)-FARNESYL DIPHOSPHATE	0.019	1
FARNESYL DIPHOSPHATE	0.02	1
FARNESYL DIPHOSPHATE	0.0705	1
MG2+	0.0712	1
MN2+	0.0445	1

Catalyzed reactions (Rhea), 2 shown:

• isopentenyl diphosphate + (2E)-geranyl diphosphate = (2E,6E)-farnesyl diphosphate + diphosphate (RHEA:19361)
• isopentenyl diphosphate + dimethylallyl diphosphate = (2E)-geranyl diphosphate + diphosphate (RHEA:22408)

UniProt features (56 total): helix 23, binding site 14, modified residue 4, sequence variant 3, sequence conflict 3, strand 3, site 2, turn 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

92 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4NUA	X-RAY DIFFRACTION	1.43
4NKE	X-RAY DIFFRACTION	1.46
4QPF	X-RAY DIFFRACTION	1.59
2QIS	X-RAY DIFFRACTION	1.8
4DEM	X-RAY DIFFRACTION	1.85
4NFI	X-RAY DIFFRACTION	1.85
4NFK	X-RAY DIFFRACTION	1.85
3N45	X-RAY DIFFRACTION	1.88
4QXS	X-RAY DIFFRACTION	1.9
5JA0	X-RAY DIFFRACTION	1.9
2F94	X-RAY DIFFRACTION	1.94
3B7L	X-RAY DIFFRACTION	1.95
3CP6	X-RAY DIFFRACTION	1.95
3S4J	X-RAY DIFFRACTION	1.95
4KPJ	X-RAY DIFFRACTION	1.95
4KPD	X-RAY DIFFRACTION	1.96
4KQS	X-RAY DIFFRACTION	1.97
4KFA	X-RAY DIFFRACTION	1.98
4Q23	X-RAY DIFFRACTION	1.98
1YV5	X-RAY DIFFRACTION	2
2RAH	X-RAY DIFFRACTION	2
4LFV	X-RAY DIFFRACTION	2
4NKF	X-RAY DIFFRACTION	2
6N7Y	X-RAY DIFFRACTION	2
6N82	X-RAY DIFFRACTION	2
6N83	X-RAY DIFFRACTION	2
4H5C	X-RAY DIFFRACTION	2.02
4H5D	X-RAY DIFFRACTION	2.02
4H5E	X-RAY DIFFRACTION	2.04
4NFJ	X-RAY DIFFRACTION	2.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14324-F1	85.27	0.77

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 (2): 164 (important for determining product chain length); 165 (important for determining product chain length)

Ligand- & substrate-binding residues (14): 123; 266; 267; 306; 323; 332; 126; 162; 169; 169; 173; 173 …

Post-translational modifications (4): 123, 123, 353, 1

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-9969896	Lanosterol biosynthesis
R-HSA-191273	Cholesterol biosynthesis

MSigDB gene sets: 289 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, MODULE_52, HORIUCHI_WTAP_TARGETS_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, JI_RESPONSE_TO_FSH_UP, MODULE_151, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (9): cholesterol biosynthetic process (GO:0006695), geranyl diphosphate biosynthetic process (GO:0033384), trans, trans-farnesyl diphosphate biosynthetic process (GO:0045337), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), isoprenoid biosynthetic process (GO:0008299), sterol biosynthetic process (GO:0016126)

GO Molecular Function (8): RNA binding (GO:0003723), dimethylallyltranstransferase activity (GO:0004161), (2E,6E)-farnesyl diphosphate synthase activity (GO:0004337), metal ion binding (GO:0046872), prenyltransferase activity (GO:0004659), protein binding (GO:0005515), transferase activity (GO:0016740), transferase activity, transferring alkyl or aryl (other than methyl) groups (GO:0016765)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrial matrix (GO:0005759), peroxisome (GO:0005777), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Cholesterol biosynthesis	1
Metabolism of steroids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
phospholipid biosynthetic process	2
terpenoid biosynthetic process	2
lipid biosynthetic process	2
sterol metabolic process	2
prenyl diphosphate synthase activity	2
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
geranyl diphosphate metabolic process	1
farnesyl diphosphate metabolic process	1
dimethylallyl diphosphate metabolic process	1
primary metabolic process	1
steroid metabolic process	1
lipid metabolic process	1
secondary alcohol metabolic process	1
isoprenoid metabolic process	1
steroid biosynthetic process	1
nucleic acid binding	1
cation binding	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
binding	1
catalytic activity	1
transferase activity	1
nuclear lumen	1
intracellular anatomical structure	1
mitochondrion	1
intracellular organelle lumen	1
microbody	1
cytoplasm	1

Protein interactions and networks

STRING

2514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FDPS	HMGCS1	Q01581	973
FDPS	RSAD2	Q8WXG1	952
FDPS	HMGCR	P04035	949
FDPS	GGPS1	O95749	943
FDPS	HMGCS2	P54868	929
FDPS	FDFT1	P37268	910
FDPS	SQLE	Q14534	893
FDPS	MVK	Q03426	871
FDPS	MVD	P53602	857
FDPS	PMVK	Q15126	836
FDPS	IDI1	Q13907	825
FDPS	CYP51A1	Q16850	774
FDPS	HMGA1	P10910	771
FDPS	SREBF2	Q12772	761
FDPS	IDI2	Q9BXS1	742

IntAct

65 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FDPS	ATXN1	psi-mi:“MI:0915”(physical association)	0.670
FDPS	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
FDPS	RNF19B	psi-mi:“MI:0915”(physical association)	0.560
FDPS	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	FDPS	psi-mi:“MI:0915”(physical association)	0.560
NDUFAF5	XRCC2	psi-mi:“MI:0914”(association)	0.530
FDPS	ZMPSTE24	psi-mi:“MI:0914”(association)	0.530
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
EIF4ENIF1	FDPS	psi-mi:“MI:0915”(physical association)	0.490
LILRB3	KRT18	psi-mi:“MI:0914”(association)	0.430
FDPS	BCAP31	psi-mi:“MI:0915”(physical association)	0.400
DHCR24	FDPS	psi-mi:“MI:0915”(physical association)	0.400
CREB3	FDPS	psi-mi:“MI:0915”(physical association)	0.370
FDPS	TSG101	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
BCL2L14		psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
DDR1		psi-mi:“MI:0914”(association)	0.350

BioGRID (192): FDPS (Affinity Capture-RNA), FDPS (Affinity Capture-RNA), FDPS (Affinity Capture-MS), BASP1 (Co-fractionation), CLIC4 (Co-fractionation), DPH2 (Co-fractionation), FDPS (Co-fractionation), FDPS (Co-fractionation), FDPS (Co-fractionation), FDPS (Co-fractionation), FDPS (Co-fractionation), FDPS (Co-fractionation), FDPS (Co-fractionation), FDPS (Co-fractionation), FDPS (Co-fractionation)

ESM2 similar proteins: A0A1V0QSA8, A0A1V0QSH7, A0A2I6PJ05, A0A7D0AGU9, A0A7J6HWR9, A0A858E6N7, A0A858E7G0, E9F5E9, F9WZD2, H1VQB1, O14230, O24241, O24242, O64905, O95749, P05369, P08524, P08836, P14324, P49349, P49350, P49351, P49352, P49353, P56966, P9WEQ2, P9WEW8, P9WEX3, P9WEX9, Q09152, Q33DR2, Q43315, Q4JHN6, Q4WBI4, Q4WEB8, Q56RZ3, Q56RZ7, Q5HZ00, Q5T2R2, Q653T6

Diamond homologs: A0A1D8PH78, A0A1V0QSH7, A0A343W970, A0A386JVA3, A0A7J6HWR9, B4YA15, D7PHZ5, O14230, O24241, O24242, O59703, O64905, P05369, P08524, P08836, P0C565, P14324, P49349, P49350, P49351, P49352, P49353, Q09152, Q43315, Q4JHN6, Q4WEB8, Q54XP1, Q55EU7, Q58GE8, Q7XYS8, Q7XYS9, Q7XYT0, Q8WMY2, Q920E5, Q92235, Q92250, Q9LJY2, Q9NH03, V6RG22, P39464

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	43
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
217746	NM_002004.4(FDPS):c.536G>A (p.Arg179Gln)	Pathogenic
217747	NM_002004.4(FDPS):c.481-1776_847-143del	Pathogenic
217748	NM_002004.4(FDPS):c.684+1G>A	Pathogenic
659608	NC_000001.11:g.(?155282411)(155323834_?)del	Pathogenic
835300	NM_002004.4(FDPS):c.684+2T>G	Likely pathogenic

SpliceAI

1662 predictions. Top by Δscore:

Variant	Effect	Δscore
1:155308961:AACAG:A	donor_loss	1.0000
1:155308963:CAGGT:C	donor_loss	1.0000
1:155308965:GGTG:G	donor_loss	1.0000
1:155308966:G:GC	donor_loss	1.0000
1:155308967:T:A	donor_loss	1.0000
1:155310041:A:AG	acceptor_gain	1.0000
1:155310042:G:GG	acceptor_gain	1.0000
1:155310042:GA:G	acceptor_gain	1.0000
1:155310042:GAGCC:G	acceptor_gain	1.0000
1:155310202:GGAG:G	donor_gain	1.0000
1:155310203:G:GT	donor_gain	1.0000
1:155310207:T:A	donor_loss	1.0000
1:155312345:G:GT	donor_gain	1.0000
1:155317939:A:AG	acceptor_gain	1.0000
1:155317940:G:GG	acceptor_gain	1.0000
1:155318019:AAGG:A	donor_loss	1.0000
1:155318022:G:A	donor_loss	1.0000
1:155318023:T:A	donor_loss	1.0000
1:155318154:T:A	acceptor_gain	1.0000
1:155318158:T:TA	acceptor_gain	1.0000
1:155318162:A:AG	acceptor_gain	1.0000
1:155318162:AT:A	acceptor_gain	1.0000
1:155318163:T:A	acceptor_gain	1.0000
1:155318163:T:G	acceptor_gain	1.0000
1:155318163:TGACA:T	acceptor_loss	1.0000
1:155318164:GACAG:G	acceptor_loss	1.0000
1:155318165:ACAGC:A	acceptor_loss	1.0000
1:155318166:CA:C	acceptor_loss	1.0000
1:155318167:A:AC	acceptor_loss	1.0000
1:155318167:A:AG	acceptor_gain	1.0000

AlphaMissense

2722 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:155318880:G:C	K266N	0.997
1:155318880:G:T	K266N	0.997
1:155319872:T:A	W335R	0.997
1:155319872:T:C	W335R	0.997
1:155317992:C:A	R178S	0.995
1:155318879:A:T	K266M	0.995
1:155319869:A:C	S334R	0.994
1:155319871:C:A	S334R	0.994
1:155319871:C:G	S334R	0.994
1:155312381:T:A	W156R	0.993
1:155312381:T:C	W156R	0.993
1:155317966:A:T	D169V	0.993
1:155317968:G:C	D170H	0.993
1:155317969:A:C	D170A	0.993
1:155317969:A:T	D170V	0.993
1:155318879:A:C	K266T	0.993
1:155319798:A:C	D310A	0.993
1:155317965:G:C	D169H	0.992
1:155317967:T:A	D169E	0.992
1:155317967:T:G	D169E	0.992
1:155317977:G:C	D173H	0.992
1:155318009:C:G	C183W	0.992
1:155318687:G:A	G236E	0.991
1:155318878:A:G	K266E	0.991
1:155319794:G:C	D309H	0.991
1:155319797:G:C	D310H	0.991
1:155319798:A:T	D310V	0.991
1:155312379:G:A	G155D	0.990
1:155319668:G:T	G302W	0.990
1:155319864:A:T	K332I	0.990

dbSNP variants (sampled 300 via entrez): RS1000809053 (1:155314299 C>T), RS1000841666 (1:155314475 G>A), RS1001040398 (1:155307411 T>A,C), RS1001051292 (1:155310799 G>A), RS1001376831 (1:155315038 C>T), RS1001469823 (1:155307720 T>G), RS1001603532 (1:155309188 C>A,T), RS1002171247 (1:155308180 C>G), RS1002718620 (1:155314761 C>G), RS1002732783 (1:155315330 A>G), RS1002812807 (1:155311110 G>A,C,T), RS1003591394 (1:155313578 G>T), RS1003686300 (1:155316433 C>A,T), RS1004733312 (1:155311662 G>A), RS1005172195 (1:155317558 G>A)

Disease associations

OMIM: gene MIM:134629 | disease phenotypes: MIM:616631

GenCC curated gene-disease

Disease	Classification	Inheritance
porokeratosis 9, multiple types	Strong	Autosomal dominant
disseminated superficial actinic porokeratosis	Supportive	Autosomal dominant

Mondo (2): porokeratosis 9, multiple types (MONDO:0014713), disseminated superficial actinic porokeratosis (MONDO:0019212)

Orphanet (1): Disseminated superficial actinic porokeratosis (Orphanet:79152)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000989	Pruritus
HP:0000992	Cutaneous photosensitivity
HP:0002860	Squamous cell carcinoma
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0011462	Young adult onset
HP:0200044	Porokeratosis

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST004131_70	Inflammatory bowel disease	6.000000e-08
GCST004132_44	Crohn’s disease	2.000000e-07
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST010696_19	Cortical thickness (min-P)	2.000000e-10
GCST010697_10	Cortical surface area (min-P)	3.000000e-10
GCST010698_59	Subcortical volume (min-P)	9.000000e-10
GCST010699_20	Brain morphology (min-P)	7.000000e-10
GCST010700_5	Cortical thickness (MOSTest)	8.000000e-17
GCST010701_66	Cortical surface area (MOSTest)	1.000000e-09
GCST010702_43	Subcortical volume (MOSTest)	3.000000e-10
GCST010703_253	Brain morphology (MOSTest)	4.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1782 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 441,134 (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
CHEMBL319144	MINODRONIC ACID	4	2,895
CHEMBL4303669	ZOLEDRONIC ACID	4	523
CHEMBL675	ALENDRONATE SODIUM	4	2,813
CHEMBL834	PAMIDRONIC ACID	4	52,185
CHEMBL870	ALENDRONIC ACID	4	36,141
CHEMBL923	RISEDRONIC ACID	4	22,719
CHEMBL924	ZOLEDRONIC ACID ANHYDROUS	4	42,100
CHEMBL997	IBANDRONIC ACID	4	48,864
CHEMBL55214	NERIDRONIC ACID	3	11,356
CHEMBL1160571	PYROPHOSPHORIC ACID	2	218,576
CHEMBL53950	INCADRONIC ACID	2	2,379
CHEMBL99369	PIRIDRONIC ACID	2	583

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11264359	Efficacy	3	atorvastatin;Bisphosphonates	Coronary Disease;Osteoporosis
rs2297480	Toxicity	3	zoledronate	Neoplasms;Osteonecrosis
rs2297480	Other	3	atorvastatin	Coronary Disease
rs2297480	Efficacy	3	Bisphosphonates	Osteoporosis;Osteoporosis;Postmenopausal

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2297480	FDPS, PKLR	3	2.00	3	zoledronate;Bisphosphonates;atorvastatin
rs11264359	FDPS, RUSC1	3	3.75	1	atorvastatin;Bisphosphonates
rs17367421	FDPS, RUSC1-AS1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Lanosterol biosynthesis pathway

Most potent curated ligand interactions (23 total), top 23:

Ligand	Action	Affinity	Parameter
zoledronic acid	Inhibition	10.15	pKi
minodronic acid	Inhibition	8.52	pIC50
compound 5e [PMID: 17975902]	Inhibition	7.79	pIC50
NE97220	Inhibition	7.12	pIC50
NE58043	Inhibition	6.76	pIC50
NE11808	Inhibition	6.72	pIC50
ibandronic acid	Inhibition	6.71	pKi
pamidronic acid	Inhibition	6.7	pIC50
piridronic acid	Inhibition	6.59	pIC50
compound 31 [PMID: 17963374]	Inhibition	6.5	pIC50
NE58018	Inhibition	6.46	pIC50
cimadronate	Inhibition	6.44	pIC50
NE21650	Inhibition	6.43	pIC50
alendronate	Inhibition	6.34	pIC50
risedronate	Inhibition	6.34	pIC50
NE58062	Inhibition	6.27	pIC50
NE58027	Inhibition	6.23	pIC50
isopentenyl diphosphate	Inhibition	6.15	pKi
NE10575	Inhibition	5.77	pIC50
compound 2 [PMID: 18295483]	Inhibition	5.1	pIC50
geranyl biphosphonate	Inhibition	4.7	pIC50
diphosphoric acid	Inhibition	4.53	pKi
NE10790	Inhibition	4.21	pKi

Binding affinities (BindingDB)

3 measured of 26 human assays (40 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
[1-hydroxy-2-(1H-imidazol-1-yl)-1-phosphonoethyl]phosphonic acid	IC50	4 nM
Hydroxy phosphonate, 1	KI	4.7 nM
CHEMBL4458054	IC50	473 nM

ChEMBL bioactivities

693 potent at pChembl≥5 of 780 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.15	Ki	0.07	nM	ZOLEDRONIC ACID
9.62	IC50	0.2399	nM	ZOLEDRONIC ACID
9.44	IC50	0.36	nM	RISEDRONIC ACID
9.44	Ki	0.36	nM	RISEDRONIC ACID
9.21	IC50	0.618	nM	CHEMBL100827
9.13	Ki	0.74	nM	CHEMBL434024
9.00	Ki	1	nM	CHEMBL408608
8.98	IC50	1.047	nM	CHEMBL56073
8.96	Ki	1.09	nM	CHEMBL55140
8.96	IC50	1.102	nM	CHEMBL301247
8.89	IC50	1.288	nM	CHEMBL101886
8.84	IC50	1.445	nM	CHEMBL101472
8.80	Ki	1.6	nM	CHEMBL259729
8.78	IC50	1.66	nM	CHEMBL101230
8.74	IC50	1.816	nM	CHEMBL100508
8.72	IC50	1.9	nM	MINODRONIC ACID
8.71	IC50	1.972	nM	CHEMBL101207
8.70	IC50	2	nM	ZOLEDRONIC ACID
8.64	Ki	2.3	nM	CHEMBL291736
8.64	Ki	2.3	nM	CHEMBL294192
8.59	IC50	2.594	nM	CHEMBL54537
8.57	IC50	2.692	nM	CHEMBL98476
8.57	IC50	2.692	nM	CHEMBL55464
8.55	IC50	2.818	nM	CHEMBL316913
8.52	IC50	3	nM	ZOLEDRONIC ACID
8.52	IC50	3	nM	MINODRONIC ACID
8.51	IC50	3.119	nM	CHEMBL101407
8.49	IC50	3.251	nM	CHEMBL316844
8.48	Ki	3.28	nM	CHEMBL406820
8.47	Ki	3.4	nM	CHEMBL414849
8.44	Ki	3.6	nM	IBANDRONIC ACID
8.41	Ki	3.9	nM	CHEMBL99553
8.41	IC50	3.9	nM	RISEDRONIC ACID
8.41	IC50	3.89	nM	CHEMBL100441
8.41	IC50	3.917	nM	CHEMBL301244
8.40	IC50	4	nM	CHEMBL434024
8.40	IC50	3.981	nM	CHEMBL53982
8.39	IC50	4.1	nM	ZOLEDRONIC ACID
8.39	IC50	4.074	nM	CHEMBL319519
8.37	IC50	4.266	nM	CHEMBL100835
8.35	Ki	4.45	nM	PIRIDRONIC ACID
8.32	IC50	4.819	nM	CHEMBL100830
8.30	IC50	5	nM	CHEMBL98703
8.29	IC50	5.129	nM	CHEMBL100335
8.29	IC50	5.129	nM	CHEMBL317646
8.28	IC50	5.2	nM	RISEDRONIC ACID
8.24	IC50	5.7	nM	RISEDRONIC ACID
8.22	IC50	6	nM	RISEDRONIC ACID
8.21	IC50	6.2	nM	CHEMBL55140
8.21	IC50	6.152	nM	CHEMBL100295

PubChem BioAssay actives

707 with measured affinity, of 1267 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
(1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid;hydrate	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0001	uM
risedronic acid	1205923: Inhibition of human FPPS using pre-incubation of compound with enzyme	ic50	0.0004	uM
[1-hydroxy-3-[methyl(3-phenylsulfanylpropyl)amino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0006	uM
(1-hydroxy-1-phosphono-2-pyridin-2-ylethyl)phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0007	uM
[[(5-methyl-2,3,4,5-tetrahydropyridin-6-yl)amino]-phosphonomethyl]phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0010	uM
[1-hydroxy-3-[methyl(4-phenylbutyl)amino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0010	uM
[1-hydroxy-2-(1H-imidazol-5-yl)-1-phosphonoethyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0011	uM
[[(3-methyl-2-pyridinyl)amino]-phosphonomethyl]phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0011	uM
[1-hydroxy-3-[methyl(3-phenoxypropyl)amino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0013	uM
[3-[3-(4-fluorophenoxy)propyl-methylamino]-1-hydroxy-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0014	uM
(1-hydroxy-1-phosphono-2-piperidin-2-ylethyl)phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0016	uM
[3-[3-(4-chlorophenyl)propyl-methylamino]-1-hydroxy-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0017	uM
[1-hydroxy-3-[methyl(2-phenylsulfanylethyl)amino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0018	uM
(1-hydroxy-2-imidazo[1,2-a]pyridin-3-yl-1-phosphonoethyl)phosphonic acid	1197852: Inhibition of human FPPS	ic50	0.0019	uM
[1-hydroxy-2-(1-methylimidazol-2-yl)-1-phosphonoethyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0020	uM
[1-phosphono-2-(pyridin-2-ylamino)ethyl]phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0023	uM
[phosphono-(pyridin-2-ylamino)methyl]phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0023	uM
[1-hydroxy-3-[methyl(3-phenylpropyl)amino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0026	uM
[[(5-butyl-1,3-thiazol-2-yl)amino]-phosphonomethyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0027	uM
[1-hydroxy-3-(4-phenylbutylamino)-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0027	uM
[1-hydroxy-3-[3-(4-methoxyphenoxy)propyl-methylamino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0028	uM
[3-[3-(4-chlorophenoxy)propyl-methylamino]-1-hydroxy-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0031	uM
[1-hydroxy-3-(3-phenoxypropylamino)-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0033	uM
(1-phosphono-2-piperidin-2-ylethyl)phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0033	uM
[2-(2-aminophenyl)-1-hydroxy-1-phosphonoethyl]phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0034	uM
ibandronic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0036	uM
[1-hydroxy-3-[methyl-[3-(3-methylphenyl)propyl]amino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0039	uM
[1-hydroxy-3-[methyl(2-phenylethyl)amino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0039	uM
[1-hydroxy-2-(1-methylpyridin-1-ium-3-yl)-1-phosphonoethyl]phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0039	uM
[1-hydroxy-3-[methyl(2-phenoxyethyl)amino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0040	uM
Zoledronic Acid	1801915: Radioactive Assay from Article 10.1021/acs.biochem.6b00486: “Fluorescent Farnesyl Diphosphate Analogue: A Probe To Validate trans-Prenyltransferase Inhibitors.”	ic50	0.0040	uM
[3-[2-(4-chlorophenoxy)ethyl-methylamino]-1-hydroxy-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0041	uM
[1-hydroxy-3-[methyl-[3-(3-methylphenoxy)propyl]amino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0043	uM
(1-phosphono-2-pyridin-2-ylethyl)phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0044	uM
[(6E)-3,7,11-trimethyldodeca-6,10-dienoyl]phosphonic acid	1799869: CVLS Assay from Article 10.1021/bi00130a010: “Steady-state kinetic mechanism of Ras farnesyl:protein transferase.”	ki	0.0047	uM
[[(5-ethyl-1,3-thiazol-2-yl)amino]-phosphonomethyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0048	uM
[2-(4,5-dimethylimidazol-1-yl)-1-hydroxy-1-phosphonoethyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0050	uM
[[(5-methyl-1,3-thiazol-2-yl)amino]-phosphonomethyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0051	uM
[1-hydroxy-2-(5-methyl-1H-imidazol-4-yl)-1-phosphonoethyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0051	uM
[phosphono-[(5-propyl-1,3-thiazol-2-yl)amino]methyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0062	uM
[[[5-(2-phenylethyl)-1,3-thiazol-2-yl]amino]-phosphonomethyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0071	uM
(1-phosphono-2-pyridin-3-ylethyl)phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0074	uM
(2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid	390282: Inhibition of human FPP synthase expressed in Escherichia coli BL21 (DE3)	ic50	0.0090	uM
[(cyclohexylamino)-phosphonomethyl]phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0100	uM
[1-hydroxy-2-(1H-imidazol-3-ium-3-yl)-1-phosphonoethyl]phosphonic acid	72668: Binding affinity towards farnesyl Pyrophosphate Synthase using [14C]- isopentenyl pyrophosphate as radioligand	ki	0.0100	uM
[1-hydroxy-3-[methyl(4-phenoxybutyl)amino]-1-phosphonopropyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0101	uM
[1-hydroxy-2-(2-methylimidazol-1-yl)-1-phosphonoethyl]phosphonic acid	197532: Negative logarithm of inhibitory concentration against bone resorption	ic50	0.0105	uM
[[[6-[4-(2,2-difluorocyclopropyl)phenyl]thieno[2,3-d]pyrimidin-4-yl]amino]-phosphonomethyl]phosphonic acid	1054150: Inhibition of human recombinant FPPS using GPP/[3H]IPP as substrate incubated for 10 mins prior to substrate addition measured after 8 mins by scintillation counting analysis	ic50	0.0110	uM
[[hydroxy(methyl)phosphoryl]-[(3-methyl-2-pyridinyl)amino]methyl]phosphonic acid	318594: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	ki	0.0116	uM
[[[4-(4-cyclopropyloxyphenyl)-2-pyridinyl]amino]-phosphonomethyl]phosphonic acid	685336: Inhibition of human His6-tagged recombinant FPPS expressed in Escherichia coli BL21(DE3) using GPP and [3H]IPP as substrate incubated for 5 mins prior to substrate addition measured after 20 mins by liquid scintillation counting	ic50	0.0120	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Zoledronic Acid	increases abundance, increases activity, increases expression, affects binding, decreases activity	8
Benzo(a)pyrene	increases expression, affects methylation, decreases expression	5
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	5
bisphenol A	affects expression, decreases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
perfluorooctane sulfonic acid	decreases expression	3
Tetrachlorodibenzodioxin	decreases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
Cyclosporine	affects cotreatment, affects expression, decreases expression	3
deoxynivalenol	decreases expression	2
Risedronic Acid	affects binding, decreases activity	2
Resveratrol	affects cotreatment, increases expression, decreases reaction	2
Pamidronate	decreases activity	2
Ibandronic Acid	decreases activity	2
Acetaminophen	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
Okadaic Acid	decreases expression	2
afuresertib	increases expression	1
2,4,6-tribromophenol	decreases expression	1
bufotalin	decreases expression	1
isopentenyl pyrophosphate	increases abundance, decreases activity	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
isoquercitrin	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1

ChEMBL screening assays

182 unique, capped per target: 177 binding, 3 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1036745	Binding	Inhibition of human FPP synthase expressed in Escherichia coli BL21 (DE3)	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism. — J Med Chem
CHEMBL4029425	ADMET	Inhibition of human FPPS	Phenylthiazole Antibacterial Agents Targeting Cell Wall Synthesis Exhibit Potent Activity in Vitro and in Vivo against Vancomycin-Resistant Enterococci. — J Med Chem
CHEMBL799889	Functional	Negative logarithm of inhibitory concentration against bone resorption	A quantitative structure-activity relationship and pharmacophore modeling investigation of aryl-X and heterocyclic bisphosphonates as bone resorption agents. — J Med Chem

Clinical trials (associated diseases)

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