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): 99 total — 4 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 12 tissues, sQTL in 50 (q < 0.05)
• Phenotypes (HPO): 8
• Drug target: yes — 6 curated mechanism-of-action drugs; 12 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 6 — Alendronate Sodium, Ibandronate Sodium, Minodronic Acid, +3 more
• Cancer dependency (DepMap): dependent in 72.4% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.74 (unconstrained)
• MANE Select transcript: NM_002004
• Interaction hub: 1,842 STRING partners (top 9% of genes corpus-wide)

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: 77 — 53 protein_coding, 12 nonsense_mediated_decay, 8 retained_intron, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000368356

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 11, TSL 3: 5, TSL 5: 4

ENST00000368356, ENST00000356657, 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, ENST00000998742, ENST00000998743, ENST00000998744, ENST00000998745, ENST00000998746, ENST00000998747, ENST00000998749, ENST00000998750, ENST00001050667, ENST00001050668, ENST00001050669, ENST00001050670, ENST00001069762, ENST00001069763, ENST00001069764, ENST00001069766, ENST00001069767, ENST00001099400, ENST00001099401, ENST00001099402, ENST00001099403, ENST00001099404, ENST00001099405, ENST00001099406, ENST00001099407, ENST00001099408, ENST00001099409, ENST00001099410, ENST00001099411, ENST00001099412, ENST00001099413, ENST00001099414, ENST00001099415, ENST00001099416, ENST00001130412, ENST00001130413, ENST00001145299

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.

Highest expression (Bgee): adrenal tissue, ventricular zone, mucosa of transverse colon, ganglionic eminence, adrenal gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FDPS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 50 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 62 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	1.6e-214	+1.30	1:155319754:T:G
Thyroid	sqtl	2.7e-135	+0.98	1:155319754:T:G
Esophagus Mucosa	sqtl	3.6e-129	+1.27	1:155319754:T:G
Testis	sqtl	9.2e-128	+1.27	1:155319754:T:G
Skin Sun Exposed Lower leg	sqtl	3.4e-127	+1.12	1:155314470:C:T
Skin Not Sun Exposed Suprapubic	sqtl	4.4e-119	+1.00	1:155319754:T:G
Artery Tibial	sqtl	8.0e-114	+1.15	1:155319754:T:G
Cells EBV-transformed lymphocytes	sqtl	1.9e-112	+1.50	1:155319754:T:G
Adipose Visceral Omentum	sqtl	4.6e-109	+1.03	1:155319754:T:G
Nerve Tibial	sqtl	4.7e-109	+1.03	1:155319754:T:G
Adipose Subcutaneous	sqtl	4.1e-108	+0.96	1:155319754:T:G
Colon Transverse	sqtl	8.9e-97	+1.16	1:155319754:T:G
Esophagus Muscularis	sqtl	1.5e-84	+1.03	1:155319754:T:G
Breast Mammary Tissue	sqtl	1.2e-77	+1.02	1:155319754:T:G
Heart Atrial Appendage	sqtl	1.6e-75	+1.09	1:155319754:T:G
Lung	sqtl	1.6e-69	+0.62	1:155319754:T:G
Artery Aorta	sqtl	7.4e-66	+1.07	1:155319754:T:G
Brain Caudate basal ganglia	sqtl	1.7e-64	+1.24	1:155314470:C:T
Stomach	sqtl	1.9e-64	+1.15	1:155319754:T:G
Brain Nucleus accumbens basal ganglia	sqtl	2.6e-63	+1.28	1:155314470:C:T

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

showing 100 of 295 tissues 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
body of stomach	UBERON:0001161	97.90	gold quality
body of pancreas	UBERON:0001150	97.86	gold quality
mouth mucosa	UBERON:0003729	97.85	gold quality
metanephros cortex	UBERON:0010533	97.77	gold quality
right frontal lobe	UBERON:0002810	97.75	gold quality
tibial nerve	UBERON:0001323	97.63	gold quality
prefrontal cortex	UBERON:0000451	97.60	gold quality
esophagus	UBERON:0001043	97.60	gold quality
liver	UBERON:0002107	97.53	gold quality
apex of heart	UBERON:0002098	97.52	gold quality
small intestine	UBERON:0002108	97.52	gold quality
stromal cell of endometrium	CL:0002255	97.48	gold quality
endocervix	UBERON:0000458	97.48	gold quality
upper arm skin	UBERON:0004263	97.48	gold quality
right lobe of thyroid gland	UBERON:0001119	97.47	gold quality
pancreas	UBERON:0001264	97.47	gold quality
ectocervix	UBERON:0012249	97.47	gold quality
dorsal root ganglion	UBERON:0000044	97.46	gold quality
spinal cord	UBERON:0002240	97.39	gold quality
saliva-secreting gland	UBERON:0001044	97.37	gold quality
granulocyte	CL:0000094	97.32	gold quality
body of uterus	UBERON:0009853	97.32	gold quality
right ovary	UBERON:0002118	97.29	gold quality
right uterine tube	UBERON:0001302	97.28	gold quality
vagina	UBERON:0000996	97.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.22	gold quality
stomach	UBERON:0000945	97.21	gold quality
left lobe of thyroid gland	UBERON:0001120	97.21	gold quality
cingulate cortex	UBERON:0003027	97.18	gold quality
right atrium auricular region	UBERON:0006631	97.18	gold quality
spleen	UBERON:0002106	97.13	gold quality
anterior cingulate cortex	UBERON:0009835	97.13	gold quality
omental fat pad	UBERON:0010414	97.13	gold quality
peritoneum	UBERON:0002358	97.12	gold quality
intestine	UBERON:0000160	97.11	gold quality
lymph node	UBERON:0000029	97.10	gold quality
cortical plate	UBERON:0005343	97.07	gold quality
smooth muscle tissue	UBERON:0001135	97.06	gold quality
colon	UBERON:0001155	97.06	gold quality
large intestine	UBERON:0000059	97.02	gold quality
gingiva	UBERON:0001828	96.99	gold quality
gingival epithelium	UBERON:0001949	96.97	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.97	gold quality
mucosa of stomach	UBERON:0001199	96.95	gold quality
left uterine tube	UBERON:0001303	96.95	gold quality
adenohypophysis	UBERON:0002196	96.91	gold quality
tonsil	UBERON:0002372	96.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.90	gold quality
thyroid gland	UBERON:0002046	96.87	gold quality
pons	UBERON:0000988	96.85	gold quality
amygdala	UBERON:0001876	96.81	gold quality
left ovary	UBERON:0002119	96.81	gold quality
lower esophagus	UBERON:0013473	96.80	gold quality
cerebellar hemisphere	UBERON:0002245	96.79	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.79	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.78	gold quality
lung	UBERON:0002048	96.77	gold quality
amniotic fluid	UBERON:0000173	96.76	gold quality
cerebellar cortex	UBERON:0002129	96.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.76	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.73	gold quality
prostate gland	UBERON:0002367	96.71	gold quality
vermiform appendix	UBERON:0001154	96.70	gold quality
sigmoid colon	UBERON:0001159	96.65	gold quality
colonic epithelium	UBERON:0000397	96.63	gold quality
left coronary artery	UBERON:0001626	96.55	gold quality
cardiac atrium	UBERON:0002081	96.54	gold quality
duodenum	UBERON:0002114	96.51	gold quality
descending thoracic aorta	UBERON:0002345	96.51	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	332.6	medium
Spinal cord	tissue	186.8
Duodenum	tissue	157.7	medium
Frontal cortex	tissue	138.6
Medulla oblongata	tissue	123.8
Caudate putamen	tissue	117.9
Corpus callosum	tissue	115.2
Midbrain	tissue	109.5
Locus coeruleus	tissue	105.5
Pons	tissue	103.2
Rectum	tissue	96.6	medium
Tonsil	tissue	95.8	low
Substantia nigra	tissue	95.2
Adrenal gland	tissue	89.6	medium
Thalamus	tissue	88.5
Colon	tissue	83.2	low
Lung	tissue	81.2	medium
Periaqueductal gray	tissue	81.2
Superior colliculi	tissue	77.2
Small intestine	tissue	76.4	medium
Hypothalamus	tissue	76.0
Vagina	tissue	74.0	not detected
Kidney	tissue	72.8	medium
Esophagus	tissue	71.9	medium
Lymph node	tissue	71.1	low
Hippocampal formation	tissue	69.1
Epididymis	tissue	68.9	medium
Placenta	tissue	68.1	not detected
Thymus	tissue	67.7
Heart muscle	tissue	67.6	medium
Bone marrow	tissue	65.5	low
Skin 1	tissue	64.7	low
Breast	tissue	64.5	medium
Parathyroid gland	tissue	63.8	low
Salivary gland	tissue	63.4	not detected
Appendix	tissue	62.8	medium
Prefrontal cortex	tissue	62.4
Cerebral cortex	tissue	62.4	medium
Motor cortex	tissue	62.3
Tongue	tissue	62.2
Smooth muscle	tissue	61.6	not detected
Retrosplenial cortex	tissue	59.9
Cervix	tissue	59.5	not detected
Somatosensory cortex	tissue	59.5
Skeletal muscle	tissue	57.0	medium
Pancreas	tissue	56.6	low
Insular cortex	tissue	56.3
Ovary	tissue	56.2	not detected
Retrosplenial and cingulate cortex	tissue	56.1
Amygdala	tissue	55.4
Stomach 1	tissue	54.4	medium
Fallopian tube	tissue	54.0	medium
Occipital cortex	tissue	52.9
Prostate	tissue	52.7	low
Septum	tissue	52.5
Temporal cortex	tissue	52.3
Entorhinal cortex	tissue	51.8
Adipose tissue	tissue	50.6	not detected
Postcentral gyrus	tissue	50.4
Ventral forebrain	tissue	48.4

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Ventral spinal cord (186.8), Dorsal spinal cord (156.0), White matter (115.2), Nucleus raphe magnus (89.4), Nuclei of the trapezoid body (87.4).

Regulation

Is transcription factor: no

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

Functional genomics

gnomAD constraint: pLI 9.03e-05, LOEUF 0.744, missense Z 1.88 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000368356 — one region, missense o/e 0.79. DepMap (CRISPR cell-line fitness): dependent in 72.4% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): JH-EsoAd1 (-2.722), SNU-16 (-2.471), EWS502 (-2.316), SK-N-DZ (-2.307), NCI-H209 (-2.188), SU-DHL-10 (-2.123), LP-1 (-2.09), OE33 (-2.062), HPAF-II (-2.016), SLR 24 (-2.009), SF539 (-1.948), SW1116 (-1.948), SH-4 (-1.943), NCI-H1666 (-1.929), SU-DHL-4 (-1.836).

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104888) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged heart	1
cardiac hypertrophy	1
premature death	1
increased heart weight	1
increased myocardial fiber size	1
decreased cardiac muscle contractility	1
cardiac interstitial fibrosis	1
abnormal autophagy	1
abnormal heart echocardiography feature	1
increased cardiac stroke volume	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Artemisia annua	P49350	99.1%	Diamond
Artemisia spiciformis	Q7XYS9	99.1%	Diamond
Fusarium fujikuroi	Q92235	95.1%	Diamond
Fusarium graminearum PH-1	V6RG22	95.1%	Diamond
Parthenium argentatum	O24241	94.7%	Diamond
Helianthus annuus	O64905	93.8%	Diamond
Tanacetum cinerariifolium	P0C565	90.9%	Diamond
Arabidopsis thaliana	Q09152	90.9%	Diamond
Lupinus albus	P49351	90.6%	Diamond
Bos taurus	Q8WMY2	88.7%	Diamond
Panax ginseng	Q4JHN6	87.7%	Diamond
Murgantia histrionica	A0A343W970	86.7%	Diamond
Nezara viridula	A0A386JVA3	86.7%	Diamond
Cannabis sativa	A0A7J6HWR9	83.6%	Diamond
Neurospora crassa OR74A	Q92250	80.7%	Diamond
Saccharomyces cerevisiae S288C	P08524	75.9%	Diamond
Kluyveromyces lactis NRRL Y-1140	P49349	75.9%	Diamond
Zea mays	P49353	74.1%	Diamond
Candida albicans SC5314	A0A1D8PH78	73.4%	Diamond
Gallus gallus	P08836	70.5%	Diamond
Aspergillus fumigatus Af293	Q4WEB8	70.3%	Diamond
Dictyostelium discoideum	Q54XP1	67.5%	Diamond
Saccharolobus solfataricus P2	P95999	63.0%	Diamond
Schizosaccharomyces pombe 972h-	O14230	62.5%	Diamond
Ganoderma lucidum	B4YA15	60.8%	Diamond
Penicillium aethiopicum	D7PHZ5	55.5%	Diamond
Natronomonas pharaonis DSM 2160	Q3IPL1	49.9%	Diamond
Mycobacterium tuberculosis H37Rv	O50410	42.0%	Diamond
Ips pini	Q58GE8	32.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SCAMP3	protein-coding	10067
ENTREP3	protein-coding	10712
RUSC1-AS1	ncRNA	284618
PKLR	protein-coding	5313
HCN3	protein-coding	57657
CLK2	protein-coding	1196
RUSC1	protein-coding	23623
ASH1L	protein-coding	55870
MIR555	ncRNA	693140
MSTO1	protein-coding	55154
ASH1L-AS1	ncRNA	645676

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)

• 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)

showing 30 of 92 structures by resolution:

PDB	Title	Method	Resolution (Å)
4NUA	The effects of Lysine 200 and Phenylalanine 239 Farnesyl Pyrophosphate Synthase (FPPS) …	X-RAY DIFFRACTION	1.43
4NKE	The effects of Lysine 200 and Phenylalanine 239 Farnesyl Pyrophosphate Synthase (FPPS) …	X-RAY DIFFRACTION	1.46
4QPF	New lower bone affinity bisphosphonate drug design for effective use in diseases …	X-RAY DIFFRACTION	1.59
2QIS	Crystal structure of human farnesyl pyrophosphate synthase T210S mutant bound to …	X-RAY DIFFRACTION	1.8
4DEM	Crystal structure of human FPPS in complex with YS_04_70	X-RAY DIFFRACTION	1.85
4NFI	Crystal structure of human FPPS in complex with magnesium and JDS05120	X-RAY DIFFRACTION	1.85
4NFK	Crystal structure of human FPPS in complex with nickel, JDS05120, and sulfate	X-RAY DIFFRACTION	1.85
3N45	Human FPPS complex with FBS_04 and zoledronic acid/MG2+	X-RAY DIFFRACTION	1.88
4QXS	Crystal structure of human FPPS in complex with WC01088	X-RAY DIFFRACTION	1.9
5JA0	Crystal structure of human FPPS with allosterically bound FPP	X-RAY DIFFRACTION	1.9
2F94	Crystal structure of human FPPS in complex with ibandronate	X-RAY DIFFRACTION	1.94
3B7L	Human farnesyl diphosphate synthase complexed with MG and minodronate	X-RAY DIFFRACTION	1.95
3CP6	Crystal structure of human farnesyl diphosphate synthase (T201A mutant) complexed with Mg …	X-RAY DIFFRACTION	1.95
3S4J	Human FDPS Synthase in Complex with a Rigid Analog of Risedronate	X-RAY DIFFRACTION	1.95
4KPJ	Crystal Structure of Farnesyl Pyrophosphate Synthase (Y204A) Mutant complexed with Mg …	X-RAY DIFFRACTION	1.95
4KPD	Crystal Structure of Human Farnesyl Pyrophosphate Synthase (Y204F) Mutant Complexed with …	X-RAY DIFFRACTION	1.96
4KQS	Crystal Structure of Farnesyl Pyrophosphate Synthase Mutant (Y204A) Complexed with Mg …	X-RAY DIFFRACTION	1.97
4KFA	Crystal structure of human farnesyl pyrophosphate synthase (t201a mutant) complexed with …	X-RAY DIFFRACTION	1.98
4Q23	The role of threonine 201 and tyrosine 204 in the human farnesyl pyrophosphate synthase …	X-RAY DIFFRACTION	1.98
1YV5	Human farnesyl diphosphate synthase complexed with Mg and risedronate	X-RAY DIFFRACTION	2
2RAH	Human FDPS synthase in complex with novel inhibitor	X-RAY DIFFRACTION	2
4LFV	Crystal structure of human FPPS in complex with YS0470 and two molecules of inorganic …	X-RAY DIFFRACTION	2
4NKF	The effects of Lysine 200 and Phenylalanine 239 Farnesyl Pyrophosphate Synthase (FPPS) …	X-RAY DIFFRACTION	2
6N7Y	Crystal structure of human FPPS in complex with an allosteric inhibitor MIT-01-102	X-RAY DIFFRACTION	2
6N82	Crystal structure of human FPPS in complex with an allosteric inhibitor YF-02037	X-RAY DIFFRACTION	2
6N83	Crystal structure of human FPPS in complex with an allosteric inhibitor YF-02037	X-RAY DIFFRACTION	2
4H5C	Crystal structure of human FPPS in ternary complex with YS0470 and inorganic phosphate	X-RAY DIFFRACTION	2.02
4H5D	Crystal structure of human FPPS in ternary complex with YS0470 and inorganic pyrophosphate	X-RAY DIFFRACTION	2.02
4H5E	Crystal structure of human FPPS in ternary complex with YS0470 and isopentenyl …	X-RAY DIFFRACTION	2.04
4NFJ	Crystal structure of human FPPS in complex with magnesium, JDS05120, and sulfate	X-RAY DIFFRACTION	2.05

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital malformations, Congenital malformations of skin, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

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)

Position	Role
164	important for determining product chain length
165	important for determining product chain length

Ligand- & substrate-binding residues (14)

Position	Role
123	isopentenyl diphosphate
266	dimethylallyl diphosphate
267	dimethylallyl diphosphate
306	dimethylallyl diphosphate
323	dimethylallyl diphosphate
332	dimethylallyl diphosphate
126	isopentenyl diphosphate
162	isopentenyl diphosphate
169	Mg(2+)
173	Mg(2+)
178	dimethylallyl diphosphate
179	isopentenyl diphosphate

Post-translational modifications (4)

Type	Positions
N6-(2-hydroxyisobutyryl)lysine	123
N6-acetyllysine	123, 353
N-acetylmethionine	1

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)	curated
R-HSA-9969896	Lanosterol biosynthesis	curated
R-HSA-191273	Cholesterol biosynthesis	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-8957322	Metabolism of steroids	—
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)	—

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 (11): cholesterol biosynthetic process (GO:0006695), geranyl diphosphate biosynthetic process (GO:0033384), geranylgeranyl diphosphate biosynthetic process (GO:0033386), zymosterol biosynthetic process (GO:0036197), 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 (4): cytoplasm (GO:0005737), mitochondrial matrix (GO:0005759), peroxisome (GO:0005777), cytosol (GO:0005829)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Metabolism of steroids	2
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Cholesterol biosynthesis	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

31 GO namespaces:

Category	Terms
phospholipid biosynthetic process	3
terpenoid biosynthetic process	3
sterol biosynthetic process	2
secondary alcohol biosynthetic process	2
lipid biosynthetic process	2
sterol metabolic process	2
prenyl diphosphate synthase activity	2
cellular anatomical structure	2
cholesterol metabolic process	1
geranyl diphosphate metabolic process	1
geranylgeranyl diphosphate metabolic process	1
zymosterol 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
intracellular anatomical structure	1
mitochondrion	1
intracellular organelle lumen	1
microbody	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
cytosol	CC	direct assay
mitochondrial matrix	CC	direct assay
peroxisome	CC	direct assay
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 1,842 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FDPS	HMGCS1	Q01581	953
FDPS	HMGCR	P04035	942
FDPS	HMGCS2	P54868	921
FDPS	GGPS1	O95749	905
FDPS	FDFT1	P37268	905
FDPS	MVK	Q03426	863
FDPS	MVD	P53602	846
FDPS	PMVK	Q15126	842
FDPS	SQLE	Q14534	819
FDPS	IDI1	Q13907	819
FDPS	NSDHL	Q15738	774
FDPS	CYP51A1	Q16850	772
FDPS	HMGA1	P10910	768
FDPS	IDI2	Q9BXS1	747
FDPS	LSS	P48449	722

IntAct

Human interaction partners of FDPS in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
ATXN1	physical association	0.670	4
ABHD16A	physical association	0.560	3
RNF19B	physical association	0.560	3
SLC30A2	physical association	0.560	3
SSMEM1	physical association	0.560	3
ZMPSTE24	association	0.530	2
EIF4ENIF1	physical association	0.490	2
BCAP31	physical association	0.400	1
DHCR24	physical association	0.400	1
CREB3	physical association	0.370	1
TSG101	physical association	0.370	1
DFFA	association	0.350	1
PYGM	association	0.350	1

BioGRID (196 interactions; top human partners by supporting records): ALAS1 (Affinity Capture-MS; 2 records), ATPAF2 (Affinity Capture-MS; 2 records), FGFR1 (Reconstituted Complex; 2 records), GLDC (Affinity Capture-MS; 2 records), HSPA8 (Co-fractionation; 2 records), NDUFAF5 (Affinity Capture-MS; 2 records), PARK2 (Affinity Capture-MS; 2 records), PCYOX1 (Affinity Capture-MS; 2 records), PDSS1 (Affinity Capture-MS; 2 records), PDSS2 (Affinity Capture-MS; 2 records), PLS3 (Co-fractionation; 2 records), PPME1 (Affinity Capture-MS; 2 records), PRNP (Affinity Capture-MS; 2 records), PSME4 (Affinity Capture-MS; 2 records), RPA1 (Co-fractionation; 2 records)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ FDPS homodimer	1	FDPS

Disease & clinical

Genetic variants

Variant evidence for FDPS: 99 ClinVar records (5 pathogenic / likely pathogenic); 4 PharmGKB clinical annotations; 16 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	43
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (5)

Showing all 5 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
835300	NM_002004.4(FDPS):c.684+2T>G	Likely pathogenic	criteria provided, single submitter	1
659608	NC_000001.11:g.(?155282411)(155323834_?)del	Pathogenic	criteria provided, single submitter	1
217746	NM_002004.4(FDPS):c.536G>A (p.Arg179Gln)	Pathogenic	no assertion criteria provided	1
217747	NM_002004.4(FDPS):c.481-1776_847-143del	Pathogenic	no assertion criteria provided	1
217748	NM_002004.4(FDPS):c.684+1G>A	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore FDPS’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 907):

Position(s)	Effect	Δscore	Sites
1:155308966–155308967	donor_loss	1.0000	5
1:155310206–155310207	donor_loss	1.0000	5
1:155318022–155318023	donor_loss	1.0000	5
1:155318154	acceptor_gain	1.0000
1:155318158	acceptor_gain	1.0000
1:155318163	acceptor_gain	1.0000	2
1:155318168	acceptor_loss	1.0000	2
1:155318854–155318855	acceptor_loss	1.0000	4
1:155318929–155318930	donor_loss	1.0000	5
1:155319609–155319610	acceptor_loss	1.0000	6

AlphaMissense

745 missense substitutions predicted likely pathogenic (of 2,722 scored), across 215 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D170	8	0.984	0.993
D310	8	0.981	0.993
D169	8	0.980	0.993
D173	8	0.978	0.992
D327	8	0.974	0.987
D240	8	0.970	0.981
D309	8	0.970	0.991
D313	8	0.962	0.984
D197	8	0.948	0.967
W335	7	0.978	0.997
W184	7	0.957	0.987
K266	7	0.956	0.997
E159	7	0.953	0.975
W156	7	0.925	0.993
Q306	7	0.918	0.986
C333	7	0.907	0.971
F305	7	0.903	0.976
F380	7	0.885	0.980
F254	7	0.867	0.970
F226	7	0.851	0.948

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.24e-06

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
porokeratosis 9, multiple types	Strong	Autosomal dominant	4
disseminated superficial actinic porokeratosis	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Familial disseminated superficial actinic porokeratosis	green
Rare genetic inflammatory skin disorders	green

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 phenotypes (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:

Study	Trait	p-value
GCST007294_150	Body fat distribution (trunk fat ratio)	8e-35
GCST007295_72	Body fat distribution (leg fat ratio)	1e-28
GCST007294_159	Body fat distribution (trunk fat ratio)	6e-21
GCST007295_112	Body fat distribution (leg fat ratio)	7e-17
GCST010700_5	Cortical thickness (MOSTest)	8e-17
GCST007294_25	Body fat distribution (trunk fat ratio)	1e-15
GCST010703_205	Brain morphology (MOSTest)	4e-14
GCST007295_17	Body fat distribution (leg fat ratio)	3e-13
GCST010696_10	Cortical thickness (min-P)	2e-10
GCST010697_21	Cortical surface area (min-P)	3e-10
GCST010702_25	Subcortical volume (MOSTest)	3e-10
GCST010699_50	Brain morphology (min-P)	7e-10
GCST010698_84	Subcortical volume (min-P)	9e-10
GCST010701_97	Cortical surface area (MOSTest)	1e-9
GCST004131_70	Inflammatory bowel disease	6e-8
GCST004132_19	Crohn’s disease	2e-7

EFO canonical traits (from GWAS)

3 canonical traits:

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the FDPS protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

6 curated-mechanism drugs:

Drug	Modality	Max phase
ALENDRONATE SODIUM	Small molecule	4
IBANDRONATE SODIUM	Small molecule	4
MINODRONIC ACID	Small molecule	4
PAMIDRONATE DISODIUM	Small molecule	4
RISEDRONATE SODIUM	Small molecule	4
ZOLEDRONIC ACID	Small molecule	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 445,441 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

12 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL675	ALENDRONATE SODIUM	4	2,935
CHEMBL319144	MINODRONIC ACID	4	2,918
CHEMBL4303669	ZOLEDRONIC ACID	4	528
CHEMBL924	ZOLEDRONIC ACID ANHYDROUS	4	42,628
CHEMBL870	ALENDRONIC ACID	4	36,552
CHEMBL997	IBANDRONIC ACID	4	49,429
CHEMBL834	PAMIDRONIC ACID	4	52,731
CHEMBL923	RISEDRONIC ACID	4	22,869
CHEMBL55214	NERIDRONIC ACID	3	11,442
CHEMBL53950	INCADRONIC ACID	2	2,389
CHEMBL99369	PIRIDRONIC ACID	2	583
CHEMBL1160571	PYROPHOSPHORIC ACID	2	220,437

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

4 annotations by evidence level (1 strongest → 4):

Variant	Association	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

2 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

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

5 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2297480	atorvastatin	Toxicity	Genotype TT is associated with increased bone density when treated with atorvastatin in people with Coronary Disease as compared to genotypes GG + GT.	PMID:24311107
rs11264359	atorvastatin	Toxicity	Genotype AA is associated with increased bone density when treated with atorvastatin in people with Coronary Disease as compared to genotypes AG + GG.	PMID:24311107
rs2297480	Bisphosphonates	Efficacy	Allele T is associated with increased response to Bisphosphonates in people with Osteoporosis as compared to allele G.	PMID:21151198
rs11264359	Bisphosphonates	Efficacy	Allele A is associated with increased response to Bisphosphonates in people with Osteoporosis as compared to allele G.	PMID:21151198
rs2297480	zoledronate	Toxicity	Genotype TT is associated with increased likelihood of osteonecrosis when treated with zoledronate in people with Neoplasms as compared to genotype GG.	PMID:21196316

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)

359 measured of 428 human assays (455 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL100827	IC50	0.62 nM
[1-Hydroxy-2-(1H-imidazol-4-yl)-1-phosphono-ethyl]-phosphonic acid	IC50	1.1 nM
CHEMBL101886	IC50	1.3 nM
CHEMBL101472	IC50	1.4 nM
CHEMBL101230	IC50	1.7 nM
CHEMBL100508	IC50	1.8 nM
CHEMBL101207	IC50	2 nM
{1-Hydroxy-3-[methyl-(3-phenyl-propyl)-amino]-1-phosphono-propyl}-phosphonic acid	IC50	2.6 nM
[1-Hydroxy-3-(4-phenyl-butylamino)-1-phosphono-propyl]-phosphonic acid	IC50	2.7 nM
CHEMBL98476	IC50	2.7 nM
CHEMBL316913	IC50	2.8 nM
CHEMBL101407	IC50	3.1 nM
[1-Hydroxy-3-(3-phenoxy-propylamino)-1-phosphono-propyl]-phosphonic acid	IC50	3.3 nM
1-hydroxy-3-(methyl(phenethyl)amino)propane-1,1-diyldiphosphonic acid	IC50	3.9 nM
CHEMBL100441	IC50	3.9 nM
[1-hydroxy-3-[methyl(2-phenoxyethyl)amino]propylidene-1,1-bisphosphonate	IC50	4 nM
CHEMBL319519	IC50	4.1 nM
CHEMBL100835	IC50	4.3 nM
Hydroxy phosphonate, 1	KI	4.7 nM
CHEMBL100830	IC50	4.8 nM
CHEMBL98703	IC50	5 nM
CHEMBL100335	IC50	5.1 nM
CHEMBL317646	IC50	5.1 nM
CHEMBL100295	IC50	6.2 nM
CHEMBL101539	IC50	7.1 nM
[2-(Imidazol-1-yl)ethyl]-bisphosphonic acid	IC50	9.03 nM
CHEMBL318071	IC50	10 nM
CHEMBL316663	IC50	10 nM
CHEMBL408608	IC50	10.3 nM
CHEMBL3087938	IC50	11 nM
[Phosphono-(pyridin-2-ylamino)-methyl]-phosphonic acid	IC50	11.7 nM
CHEMBL2088336	IC50	12 nM
CHEMBL259729	IC50	13.7 nM
[[[6-(4-cyclopropyloxyphenyl)thieno[2,3-d]pyrimidin-4-yl]amino]-phosphonomethyl]phosphonic acid	IC50	14 nM	US-11279719: Substituted bicyclic pyrimidine-based compounds and compositions and uses thereof
CHEMBL3087933	IC50	15 nM
CHEMBL2088339	IC50	16 nM
[2-(Benzoimidazol-1-yl)ethyl]-bisphosphonic acid	IC50	16.1 nM
1-fluoro-2-(3-pyridinyl)-ethylidene-1,1-bisphosphonic acid	IC50	16.4 nM
CHEMBL5285501	IC50	17 nM
CHEMBL97911	IC50	18 nM
CHEMBL323300	IC50	18 nM
CHEMBL100232	IC50	18 nM
CHEMBL102209	IC50	18 nM
CHEMBL100831	IC50	18 nM
[phosphono-[[6-[4-(trifluoromethyl)phenyl]thieno[2,3-d]pyrimidin-4-yl]amino]methyl]phosphonic acid	IC50	21 nM	US-11279719: Substituted bicyclic pyrimidine-based compounds and compositions and uses thereof
[2-(2-amino-phenyl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acid	IC50	21.6 nM
CHEMBL406820	IC50	23.8 nM
CHEMBL5276276	IC50	24 nM
CHEMBL318861	IC50	24 nM
[2-(Imidazol-2-yl-thio)ethyl]-bisphosphonic acid	IC50	28.1 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 1269 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	affects methylation, decreases expression, increases expression	5
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	5
bisphenol A	affects expression, decreases expression	3
sodium arsenite	increases abundance, increases expression, decreases 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	increases expression, decreases reaction, affects cotreatment	2
Pamidronate	decreases activity	2
Ibandronic Acid	decreases activity	2
Acetaminophen	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Okadaic Acid	decreases expression	2
afuresertib	increases expression	1
2,4,6-tribromophenol	decreases expression	1
bufotalin	decreases expression	1
isopentenyl pyrophosphate	decreases activity, increases abundance	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FDPS across ~30M SureChEMBL compounds — explore on Sugi Predict.