FBP1

Summary

FBP1 (fructose-bisphosphatase 1, HGNC:3606) is a protein-coding gene on chromosome 9q22.32, encoding Fructose-1,6-bisphosphatase 1 (P09467). Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.

Fructose-1,6-bisphosphatase 1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. Fructose-1,6-diphosphatase deficiency is associated with hypoglycemia and metabolic acidosis.

Source: NCBI Gene 2203 — RefSeq curated summary.

At a glance

• Gene–disease (curated): fructose-1,6-bisphosphatase deficiency (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 360 total — 39 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000507

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3606
Approved symbol	FBP1
Name	fructose-bisphosphatase 1
Location	9q22.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165140
Ensembl biotype	protein_coding
OMIM	611570
Entrez	2203

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 nonsense_mediated_decay

ENST00000375326, ENST00000414122, ENST00000415431, ENST00000648117, ENST00000682520, ENST00000884867, ENST00000884868, ENST00000884869, ENST00000884870, ENST00000884871, ENST00000933250, ENST00000945611, ENST00000945612, ENST00000945613, ENST00000945614, ENST00000945615

RefSeq mRNA: 2 — MANE Select: NM_000507 NM_000507, NM_001127628

CCDS: CCDS6712

Canonical transcript exons

ENST00000375326 — 7 exons

Exon	Start	End
ENSE00000895736	94605457	94605576
ENSE00000895738	94609921	94610061
ENSE00001466714	94639141	94639518
ENSE00001759285	94617768	94617860
ENSE00003476614	94620329	94620491
ENSE00003789161	94606815	94606952
ENSE00003899682	94603133	94603572

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 99.28.

FANTOM5 (CAGE): breadth broad, TPM avg 31.2194 / max 945.6277, expressed in 613 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101520	29.5756	568
101519	0.4857	205
101521	0.4524	189
101524	0.1833	106
205567	0.1670	104
205566	0.1214	89
101522	0.0991	48
101525	0.0837	59
101523	0.0513	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.28	gold quality
endometrium epithelium	UBERON:0004811	99.05	gold quality
jejunal mucosa	UBERON:0000399	98.71	gold quality
ileal mucosa	UBERON:0000331	98.17	gold quality
liver	UBERON:0002107	97.95	gold quality
duodenum	UBERON:0002114	97.25	gold quality
adult mammalian kidney	UBERON:0000082	96.94	gold quality
right lung	UBERON:0002167	95.81	gold quality
upper lobe of left lung	UBERON:0008952	95.49	gold quality
nephron tubule	UBERON:0001231	95.39	gold quality
upper lobe of lung	UBERON:0008948	95.26	gold quality
monocyte	CL:0000576	95.04	gold quality
mononuclear cell	CL:0000842	94.62	gold quality
leukocyte	CL:0000738	94.43	gold quality
kidney epithelium	UBERON:0004819	94.10	gold quality
mucosa of transverse colon	UBERON:0004991	93.59	gold quality
lung	UBERON:0002048	92.98	gold quality
gall bladder	UBERON:0002110	92.97	gold quality
lower lobe of lung	UBERON:0008949	92.91	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.71	gold quality
kidney	UBERON:0002113	92.56	gold quality
granulocyte	CL:0000094	92.42	gold quality
adult organism	UBERON:0007023	92.25	gold quality
small intestine	UBERON:0002108	92.16	gold quality
metanephric glomerulus	UBERON:0004736	92.13	gold quality
renal glomerulus	UBERON:0000074	91.93	gold quality
right adrenal gland cortex	UBERON:0035827	91.82	gold quality
rectum	UBERON:0001052	91.36	gold quality
parotid gland	UBERON:0001831	91.13	gold quality
right adrenal gland	UBERON:0001233	91.04	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	2059.87
E-MTAB-6653	yes	1584.86
E-HCAD-1	yes	1538.53
E-GEOD-125970	yes	74.11
E-CURD-122	yes	72.61
E-MTAB-10553	yes	33.28
E-GEOD-130148	yes	27.57
E-HCAD-10	yes	16.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MAFB, NFKB1, NPM1, NR1H2, NR1H3, RELA, SP1, SP3, USF1, USF2, ZBTB20, ZEB1, ZFX

miRNA regulators (miRDB)

29 targeting FBP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-3059-3P	96.71	67.08	606
HSA-MIR-6828-3P	96.06	67.61	1155
HSA-MIR-6777-3P	95.35	64.30	699

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• liver fructose-1,6-bisphosphatase coupled with phosphofructokinase (PFK) plays a crucial role in the metabolism of pancreatic islet cells (PMID:15965961)
• Upregulation of FBPase in pancreatic islet beta-cells in states of lipid oversupply and type 2 diabetes, contributes to insulin secretory dysfunction. (PMID:18375435)
• Human FBP1 was found to regulate mouse endogenous glucose production and whole body glucose homeostasis in a liver-specific transgenic model. (PMID:18780768)
• first report on mutations in patients with FBP deficiency of Arab ethnicity,two novel mutations in the FBP1 gene encode for a duplication of two amino acids and a truncation in the FBP1 protein in these families. (PMID:19259699)
• Data show that EDTA and mercaptoethanol stabilized FBP-1 activity in stored urine. (PMID:19505453)
• this is the first experimental evidence confirming that the KKKGK motif can act as a functional NLS fructose 1,6-bisphosphatase . (PMID:19626708)
• Data show that NF-kappaB functions downstream of Ras to promote epigenetic downregulation of FBP1. (PMID:19881551)
• Novel compound heterozygous mutations in the fructose-1,6-bisphosphatase gene cause hypoglycemia and lactic acidosis. (PMID:20096900)
• Case Reports: present reliable diagnostic system to verify an FBPase deficiency and find the genetic aberration. (PMID:20151204)
• epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis (PMID:22039417)
• The Identification of FBPase interacting partners with mass spectrometry reveals a set of nuclear proteins involved in cell cycle regulation, mRNA processing and in stabilization of genomic DNA structure. (PMID:22057438)
• AMP binding pattern of the muscle isozyme of fructose-1,6-bisphosphatase is quite similar to that of the liver isozyme and the T conformations of the two isozymes are nearly the same (PMID:22120740)
• This is the first study to identify liver FBPase as a previously unknown regulator of appetite and adiposity and describes a novel process by which the liver participates in body weight regulation. (PMID:22517657)
• study indicates that the loss of FBP1 is a critical oncogenic event in epithelial-mesenchymal transition and basal-like breast cancer (PMID:23453623)
• LSD1 regulates transcription activation of two gluconeogenic genes, FBP1 and G6Pase. (PMID:23755305)
• A novel missense mutation (c.841G>A) in the FBP1 gene seems to be prevalent in Pakistani-Indian patients with fructose-1,6-bisphosphatase deficiency. (PMID:23881342)
• A homozygous c.658delT mutation was detected at exon 5 of the FBP1 gene in the two siblings with FBPase deficiency. (PMID:24007283)
• the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) is uniformly depleted in over six hundred clear cell renal cell carcinoma tumours examined. (PMID:25043030)
• Twelve different mutations were identified in 22 alleles: one missense mutation c.472C > T, one point deletion c.48del, one point duplication c.865dupA, one deletion-insertion, and two splice mutations (c.427-1del and c.825 + 1G > A). (PMID:25601412)
• There was a negative correlation with the level of FBP1 and recurrence of the lung cancer (PMID:25844935)
• NPM1 promotes aerobic glycolysis and tumor progression in patients with pancreatic cancer by inhibiting FBP1 (PMID:26068981)
• FBP1 expression, which is closely correlated with c-Myc expression, is an independent prognostic factor and promotes nasopharyngeal carcinoma progression. (PMID:26469968)
• identified Zinc finger E-box-binding homeobox 1 (ZEB1) bond to FBP1 promoter to enhance DNA methylation in lung cancer cells. Our findings indicate that the down-regulation of FBP1 is a critical oncogenic event in lung cancer progression (PMID:26546081)
• Cox multivariate regression analysis demonstrated that DUOX1, GLS2, FBP1 and age were independent risk factors for the prognosis of HCC patients after surgery (PMID:27079415)
• FBP1 underexpression is associated with Tumor Progression in Hepatocellular Carcinoma. (PMID:27197151)
• These findings indicate that FBP1 appears to be a tumor suppressor in hepatocellular carcinoma (HCC). Strategies to restore the levels and activities of FBP1 might be developed to treat patients with HCC. (PMID:27742690)
• Elevated FBP1 is a critical modulator in breast cancer progression by altering glucose metabolism and the activity of Wnt/beta-catenin pathway. (PMID:27780144)
• we show that EV71 viral proteinase 2A is capable of cleaving far upstream element-binding protein 1 (FBP1), a positive internal ribosome entry sitet rans-acting factor that directly binds to the EV71 5’ UTR linker region to promote viral IRES-driven translation (PMID:27780225)
• Here, the first crystal structure of human liver FBPase in the R-state conformation is presented, determined at a resolution of 2.2 A in a tetragonal setting that exhibits an unusual arrangement of noncrystallographic symmetry (NCS) elements. (PMID:27841754)
• Results identified FBP1 as a promising acute liver failure (ALF) biomarker among energy metabolism-related proteins. It may serve as a short-term prognosis indicator for ALF, with higher serum level of FBP1 correlated with higher ALF-related mortality in human studies. (PMID:28336726)
• FBP1 is highly expressed in human hypertrophic scars and increases fibroblast proliferation, apoptosis and collagen expression. (PMID:28362515)
• Studied association of fructose 1,6-bisphosphatase 1 (FBP1) expression with fluorine 18 ((18)F) fluorodeoxyglucose (FDG) accumulation in patients with hepatocellular carcinoma. Found that in patients with HCC, both 18F FDG accumulation and tumor grade (from differentiated to undifferentiated) were inversely correlated with the expression of FBP1. (PMID:28387640)
• overexpressed FBP1 may repress tumor growth, migration and glycolysis via targeting HIF-1alpha in breast cancer (PMID:28485159)
• Homozygous Alu element insertion in the FBP1 gene is associated with Fructose-1,6-bisphosphatase deficiency. (PMID:28599390)
• fructose-1,6-bisphosphatase 1 facilitated co-action between Bcl-2 and Beclin 1, which may be important in the mechanism of fructose-1,6-bisphosphatase 1-mediated mitophagy inhibition. In summary, loss of mitophagy by fructose-1,6-bisphosphatase 1-mediated repression promotes apoptosis in breast cancer (PMID:28653874)
• decreased levels of FBP1 may be used as a predictor for poor prognosis of cervical cancer patients (PMID:28990097)
• FBP1 mutation was associated with fructose-1,6-bisphosphatase deficiency (PMID:29016355)
• The expansion of CB HSPCs by PPAR-gamma antagonism was completely suppressed by removal of glucose or inhibition of glycolysis. Moreover, knockdown of FBP1 expression promoted glycolysis and ex vivo expansion of long-term repopulating CB HSPCs, whereas overexpression of FBP1 suppressed the expansion of CB HSPCs that was induced by PPARG antagonism (PMID:29377004)
• Study identified for the first time that HNF4alpha and C/EBPalpha are important transcriptional regulators for FBP1 expression in human hepatoma HepG2 cells. (PMID:29566023)
• CBX3 serves as a positive regulator of aerobic glycolysis via suppressing of the FBP1 in pancreatic cancer cells. (PMID:29678579)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fbp1	ENSMUSG00000069805
rattus_norvegicus	Fbp1	ENSRNOG00000017597
drosophila_melanogaster	fbp	FBGN0032820
caenorhabditis_elegans	fbp-1	WBGENE00001404

Paralogs (1): FBP2 (ENSG00000130957)

Protein

Protein identifiers

Fructose-1,6-bisphosphatase 1 — P09467 (reviewed: P09467)

Alternative names: D-fructose-1,6-bisphosphate 1-phosphohydrolase 1, Liver FBPase

All UniProt accessions (4): A0A3B3IUC7, A0A804HJK9, P09467, Q5VZC3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain.

Subunit / interactions. Homotetramer.

Tissue specificity. Expressed in pancreatic islets.

Disease relevance. Fructose-1,6-bisphosphatase deficiency (FBP1D) [MIM:229700] An autosomal recessive metabolic disorder characterized by impaired gluconeogenesis, and episodes of hypoglycemia and metabolic acidosis that can be lethal in newborn infants or young children. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as an allosteric inhibitor. AMP binding affects the turnover of bound substrate and not the affinity for substrate. Fructose 2,6-bisphosphate acts as a competitive inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects.

Cofactor. Binds 3 Mg(2+) ions per subunit.

Induction. Up-regulated in pancreatic islets of individuals with type 2 diabetes.

Pathway. Carbohydrate biosynthesis; gluconeogenesis.

Similarity. Belongs to the FBPase class 1 family.

RefSeq proteins (2): NP_000498, NP_001121100 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000146	FBPase_class-1	Family
IPR020548	Fructose_bisphosphatase_AS	Active_site
IPR028343	FBPtase	Family
IPR033391	FBPase_N	Domain
IPR044015	FBPase_C_dom	Domain

Pfam: PF00316, PF18913

Enzyme classification (BRENDA):

• EC 3.1.3.11 — fructose-bisphosphatase (BRENDA: 105 organisms, 146 substrates, 726 inhibitors, 228 Km, 143 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-FRUCTOSE 1,6-BISPHOSPHATE	0.0001–3.2	136
FRUCTOSE 1,6-DIPHOSPHATE	0.0005–0.057	51
SEDOHEPTULOSE 1,7-DIPHOSPHATE	0.0026–1.4	8
BETA-D-GLUCOSE 1,6-BISPHOSPHATE	0.0026–0.17	7
D-FRUCTOSE-1,6-BISPHOSPHATE	0.0018–0.035	3
D-FRUCTOSE 1,6-DIPHOSPHATE	0.0111–99.98	2
FRUCTOSE 1,6-BISPHOSPHATE	0.1–0.45	2
RIBULOSE 1,5-DIPHOSPHATE	0.0031–0.021	2
D-FRUCTOSE 1-PHOSPHATE	1	1
SEDOHEPTULOSE 1,6-DIPHOSPHATE	0.016	1
SEDOHEPTULOSE-1,7-DIPHOSPHATE	0.118	1

Catalyzed reactions (Rhea), 1 shown:

• beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6-phosphate + phosphate (RHEA:11064)

UniProt features (73 total): binding site 17, strand 16, helix 13, sequence variant 9, turn 6, modified residue 5, mutagenesis site 3, sequence conflict 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

51 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7WJV	X-RAY DIFFRACTION	1.72
7C9Q	X-RAY DIFFRACTION	1.88
5PZR	X-RAY DIFFRACTION	1.9
5Q09	X-RAY DIFFRACTION	1.9
5PZU	X-RAY DIFFRACTION	1.9
9XV1	X-RAY DIFFRACTION	1.96
2JJK	X-RAY DIFFRACTION	2
5PZV	X-RAY DIFFRACTION	2
5PZW	X-RAY DIFFRACTION	2
6LS5	X-RAY DIFFRACTION	2.03
7CVH	X-RAY DIFFRACTION	2.09
7WVB	X-RAY DIFFRACTION	2.09
5Q02	X-RAY DIFFRACTION	2.1
2Y5K	X-RAY DIFFRACTION	2.1
2VT5	X-RAY DIFFRACTION	2.2
2Y5L	X-RAY DIFFRACTION	2.2
5LDZ	X-RAY DIFFRACTION	2.2
5Q05	X-RAY DIFFRACTION	2.2
5Q08	X-RAY DIFFRACTION	2.2
5PZY	X-RAY DIFFRACTION	2.21
2WBB	X-RAY DIFFRACTION	2.22
3KC1	X-RAY DIFFRACTION	2.25
1FTA	X-RAY DIFFRACTION	2.3
5Q0A	X-RAY DIFFRACTION	2.3
5Q0B	X-RAY DIFFRACTION	2.3
5Q03	X-RAY DIFFRACTION	2.31
5PZS	X-RAY DIFFRACTION	2.37
2WBD	X-RAY DIFFRACTION	2.4
4MJO	X-RAY DIFFRACTION	2.4
5Q06	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09467-F1	94.46	0.88

Functional residue map

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

Ligand- & substrate-binding residues (17): 121; 122–125; 122; 141; 213–216; 244–249; 265; 275–277; 281; 18–22; 28–32; 69 …

Post-translational modifications (5): 2, 151, 216, 245, 265

Mutagenesis-validated functional residues (3):

Position	Phenotype
70	increased affinity towards ca(2+) and mg(2+).
119	reduced activity.
122	reduced activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-70263	Gluconeogenesis
R-HSA-9940951	Interaction of NuRD complexes with transcription factors

MSigDB gene sets: 437 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOZGIT_ESR1_TARGETS_DN, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_GROWTH, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_HYPEROSMOTIC_RESPONSE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, BROWNE_HCMV_INFECTION_12HR_UP, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (19): negative regulation of transcription by RNA polymerase II (GO:0000122), fructose metabolic process (GO:0006000), fructose 6-phosphate metabolic process (GO:0006002), gluconeogenesis (GO:0006094), regulation of gluconeogenesis (GO:0006111), negative regulation of cell growth (GO:0030308), fructose 1,6-bisphosphate metabolic process (GO:0030388), response to nutrient levels (GO:0031667), cellular response to insulin stimulus (GO:0032869), negative regulation of glycolytic process (GO:0045820), negative regulation of Ras protein signal transduction (GO:0046580), cellular response to magnesium ion (GO:0071286), cellular response to cAMP (GO:0071320), cellular response to xenobiotic stimulus (GO:0071466), cellular hyperosmotic salinity response (GO:0071475), cellular hypotonic salinity response (GO:0071477), cellular response to raffinose (GO:0097403), cellular response to phorbol 13-acetate 12-myristate (GO:1904628), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (11): AMP binding (GO:0016208), fructose 1,6-bisphosphate 1-phosphatase activity (GO:0042132), identical protein binding (GO:0042802), metal ion binding (GO:0046872), monosaccharide binding (GO:0048029), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791), phosphoric ester hydrolase activity (GO:0042578)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glucose metabolism	1
NuRD complex assembly	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organophosphate metabolic process	2
carbohydrate derivative metabolic process	2
cellular response to salt stress	2
cation binding	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
hexose metabolic process	1
glucose metabolic process	1
hexose biosynthetic process	1
gluconeogenesis	1
regulation of glucose metabolic process	1
regulation of carbohydrate biosynthetic process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
response to stimulus	1
response to insulin	1
cellular response to peptide hormone stimulus	1
glycolytic process	1
regulation of glycolytic process	1
negative regulation of purine nucleotide catabolic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of ATP metabolic process	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
response to magnesium ion	1
cellular response to metal ion	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to xenobiotic stimulus	1
cellular response to chemical stimulus	1
hyperosmotic salinity response	1
cellular hyperosmotic response	1
hypotonic salinity response	1
cellular hypotonic response	1

Protein interactions and networks

STRING

2859 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBP1	FUBP3	Q96I24	886
FBP1	FUBP1	Q96AE4	881
FBP1	G6PC1	P35575	824
FBP1	ZBTB22	O15209	811
FBP1	PCK1	P35558	805
FBP1	PCK2	Q16822	794
FBP1	KHSRP	Q92945	779
FBP1	SKP1	P34991	734
FBP1	GCK	P35557	729
FBP1	PC	P11498	715
FBP1	PFKM	P08237	700
FBP1	HNRNPF	P52597	667
FBP1	PFKP	Q01813	660
FBP1	PKM	P14618	652
FBP1	ALDOB	P05062	649

IntAct

108 interactions, top by confidence:

A	B	Type	Score
FBP1	FBP1	psi-mi:“MI:0915”(physical association)	0.950
FBP1	FBP2	psi-mi:“MI:0915”(physical association)	0.920
FBP2	FBP1	psi-mi:“MI:0915”(physical association)	0.920
MED24	MED19	psi-mi:“MI:0914”(association)	0.730
DIDO1	OGT	psi-mi:“MI:0914”(association)	0.670

BioGRID (409): BIN1 (Protein-peptide), FBP1 (Reconstituted Complex), FBP1 (Two-hybrid), FBP1 (Two-hybrid), FBP2 (Two-hybrid), FBP1 (Affinity Capture-MS), FBP1 (Affinity Capture-MS), FBP1 (Affinity Capture-MS), FBP1 (Affinity Capture-MS), PCNXL4 (Two-hybrid), FXR2 (Two-hybrid), RNF183 (Two-hybrid), LNX1 (Two-hybrid), FBP1 (Two-hybrid), FBP1 (Two-hybrid)

ESM2 similar proteins: A1AJD7, A2WXB2, A6THE3, A7MM48, A7ZVB0, A8A7Y7, A8AMG4, A9N548, B1ISX3, B1LRB5, B1XEL4, B2TZ12, B4T3H9, B5BKN5, B5FSC7, B5R0U4, B5Y2X3, B5Z3I7, O00757, P00636, P00637, P09199, P09467, P0A993, P0A994, P0A995, P14766, P46267, P46276, Q0JHF8, Q0SXH4, Q0T9F7, Q1R324, Q2KJJ9, Q31TG8, Q328V4, Q3SZB7, Q42649, Q43139, Q57GG7

Diamond homologs: A0RP36, A1APW8, A1B2P8, A1VZI4, A2RQ29, A2ST39, A2WXB2, A3QAZ7, A4XPL2, A5EVS5, A5G439, A6Q349, A6Q9C9, A6SVE7, A6VDM7, A7GXH6, A7H3L9, A7I1B8, A7I8R6, A7ZCB2, A8EU55, A8FLP9, B0C7G7, B0JH56, B0R3Y1, B1WX40, B2T699, B2U8C4, B2UVU9, B2V6E2, B3E2M3, B3R3R6, B4S2E8, B5EFV5, B5Z9G5, B7V3K3, C0QTP7, C1DHU3, O00757, O20252

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
FBP1	“down-regulates activity”	HIF1A	binding
TRIM28	“down-regulates quantity by destabilization”	FBP1	ubiquitination
NPM1	“down-regulates quantity by repression”	FBP1	“transcriptional regulation”
ZFX	“down-regulates quantity by repression”	FBP1	“transcriptional regulation”
ZEB1	“down-regulates quantity by repression”	FBP1	“transcriptional regulation”
FBP1	“down-regulates quantity”	“beta-D-fructofuranose 1,6-bisphosphate(4-)”	“chemical modification”
FBP1	“up-regulates quantity”	“β-D-fructose 6-phosphate”	“chemical modification”
ULK1	“down-regulates activity”	FBP1	phosphorylation
ULK2	“down-regulates activity”	FBP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	5	17.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	39
Likely pathogenic	17
Uncertain significance	78
Likely benign	158
Benign	26

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1322891	NM_000507.4(FBP1):c.426+1G>A	Pathogenic
1322892	NM_000507.4(FBP1):c.392del (p.Val131fs)	Pathogenic
1453508	NM_000507.4(FBP1):c.127A>T (p.Lys43Ter)	Pathogenic
1803969	NM_000507.4(FBP1):c.881G>A (p.Gly294Glu)	Pathogenic
2506540	GRCh37/hg19 9q22.32(chr9:97401423-97401592)	Pathogenic
2579730	NM_000507.4(FBP1):c.333+2T>G	Pathogenic
2719715	NM_000507.4(FBP1):c.56dup (p.Met19fs)	Pathogenic
2753761	NM_000507.4(FBP1):c.343_347del (p.Val115fs)	Pathogenic
2758463	NM_000507.4(FBP1):c.846C>A (p.Cys282Ter)	Pathogenic
2772871	NM_000507.4(FBP1):c.131_132del (p.Ala44fs)	Pathogenic
2797845	NM_000507.4(FBP1):c.960del (p.Ser321fs)	Pathogenic
2809502	NM_000507.4(FBP1):c.961dup (p.Ser321fs)	Pathogenic
2819827	NM_000507.4(FBP1):c.504T>A (p.Tyr168Ter)	Pathogenic
2828070	NM_000507.4(FBP1):c.860_863dup (p.Met289fs)	Pathogenic
2832764	NM_000507.4(FBP1):c.740dup (p.Ser248fs)	Pathogenic
2866196	NM_000507.4(FBP1):c.325G>T (p.Glu109Ter)	Pathogenic
2872419	NM_000507.4(FBP1):c.282_289del (p.Leu95fs)	Pathogenic
2875401	NM_000507.4(FBP1):c.723T>G (p.Tyr241Ter)	Pathogenic
3245071	NC_000009.11:g.(?97401403)(97401592_?)del	Pathogenic
3245072	NC_000009.11:g.(?97380030)(97382793_?)del	Pathogenic
3245073	NC_000009.11:g.(?97355088)(97365840_?)del	Pathogenic
3383389	NM_000507.4(FBP1):c.200dup (p.Gly68fs)	Pathogenic
372364	NM_000507.4(FBP1):c.960delinsGG (p.Ser321fs)	Pathogenic
403701	NM_000507.4(FBP1):c.720_729del (p.Tyr241fs)	Pathogenic
403706	NM_000507.4(FBP1):c.825+1G>A	Pathogenic
427178	NM_000507.4(FBP1):c.267del (p.Phe90fs)	Pathogenic
4731288	NM_000507.4(FBP1):c.582_585del (p.Ile195fs)	Pathogenic
526506	NM_000507.4(FBP1):c.779del (p.Gly260fs)	Pathogenic
548480	NM_000507.4(FBP1):c.841G>T (p.Glu281Ter)	Pathogenic
561988	NM_000507.4(FBP1):c.472C>T (p.Arg158Trp)	Pathogenic

SpliceAI

1166 predictions. Top by Δscore:

Variant	Effect	Δscore
9:94605451:CCTTA:C	donor_loss	1.0000
9:94605452:CTTAC:C	donor_loss	1.0000
9:94605453:TTACC:T	donor_loss	1.0000
9:94605454:TA:T	donor_loss	1.0000
9:94605455:A:AC	donor_gain	1.0000
9:94605455:A:AG	donor_loss	1.0000
9:94605456:C:A	donor_loss	1.0000
9:94605456:C:CC	donor_gain	1.0000
9:94605575:TCC:T	acceptor_loss	1.0000
9:94605576:CCTG:C	acceptor_loss	1.0000
9:94605577:C:CA	acceptor_loss	1.0000
9:94605578:T:G	acceptor_loss	1.0000
9:94606813:A:AC	donor_gain	1.0000
9:94606814:C:CC	donor_gain	1.0000
9:94609919:A:C	donor_loss	1.0000
9:94610059:TTT:T	acceptor_gain	1.0000
9:94610059:TTTCT:T	acceptor_loss	1.0000
9:94610060:TT:T	acceptor_gain	1.0000
9:94610060:TTC:T	acceptor_loss	1.0000
9:94610062:C:CC	acceptor_gain	1.0000
9:94610062:CTAGA:C	acceptor_loss	1.0000
9:94610068:C:CT	acceptor_gain	1.0000
9:94610069:A:T	acceptor_gain	1.0000
9:94617859:CC:C	acceptor_gain	1.0000
9:94617860:CC:C	acceptor_gain	1.0000
9:94620327:AC:A	donor_gain	1.0000
9:94620328:CC:C	donor_gain	1.0000
9:94620487:CATAG:C	acceptor_gain	1.0000
9:94620488:ATAG:A	acceptor_gain	1.0000
9:94620489:TAG:T	acceptor_gain	1.0000

AlphaMissense

2209 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:94603568:C:G	R277T	0.999
9:94605518:C:G	R255P	0.999
9:94605528:C:G	D252H	0.999
9:94606887:G:C	S211R	0.999
9:94606887:G:T	S211R	0.999
9:94606889:T:G	S211R	0.999
9:94617793:C:T	G134E	0.999
9:94617816:G:C	N126K	0.999
9:94617816:G:T	N126K	0.999
9:94617826:C:T	G123E	0.999
9:94617829:T:A	D122V	0.999
9:94617838:T:C	D119G	0.999
9:94603439:C:T	G320E	0.998
9:94603555:T:A	E281D	0.998
9:94603555:T:G	E281D	0.998
9:94603556:T:A	E281V	0.998
9:94605493:A:C	F263L	0.998
9:94605493:A:T	F263L	0.998
9:94605495:A:G	F263L	0.998
9:94605519:G:T	R255S	0.998
9:94609978:A:C	S170R	0.998
9:94609978:A:T	S170R	0.998
9:94609980:T:G	S170R	0.998
9:94610001:C:G	A163P	0.998
9:94617793:C:A	G134V	0.998
9:94617794:C:G	G134R	0.998
9:94617794:C:T	G134R	0.998
9:94617826:C:A	G123V	0.998
9:94617827:C:G	G123R	0.998
9:94617827:C:T	G123R	0.998

dbSNP variants (sampled 300 via entrez): RS1000006913 (9:94631844 C>T), RS1000084482 (9:94623628 C>A,T), RS1000116101 (9:94607380 G>A), RS1000179338 (9:94602874 C>T), RS1000218319 (9:94607997 C>G,T), RS1000276075 (9:94637020 G>C), RS1000405933 (9:94608539 A>G), RS1000539536 (9:94623796 G>A), RS1000623990 (9:94619226 A>G), RS1000625808 (9:94607456 T>C), RS1000698346 (9:94602631 AAAAAAAGAAAGAAAG>A), RS1000730936 (9:94612723 A>G,T), RS1000913602 (9:94619457 G>C), RS1000931619 (9:94631328 C>T), RS1000983842 (9:94631722 G>A)

Disease associations

OMIM: gene MIM:611570 | disease phenotypes: MIM:229700, MIM:181500, MIM:192350, MIM:232200

GenCC curated gene-disease

Disease	Classification	Inheritance
fructose-1,6-bisphosphatase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
fructose-1,6-bisphosphatase deficiency	Definitive	AR

Mondo (4): fructose-1,6-bisphosphatase deficiency (MONDO:0009251), schizophrenia (MONDO:0005090), VACTERL/vater association (MONDO:0008642), disorder of glycogen metabolism (MONDO:0002412)

Orphanet (4): Fructose-1,6-bisphosphatase deficiency (Orphanet:348), VACTERL/VATER association (Orphanet:887), Glycogen storage disease (Orphanet:79201), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000737	Irritability
HP:0000980	Pallor
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001259	Coma
HP:0001262	Excessive daytime somnolence
HP:0001397	Hepatic steatosis
HP:0001649	Tachycardia
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0001945	Fever
HP:0001946	Ketosis
HP:0001998	Neonatal hypoglycemia
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002094	Dyspnea
HP:0002098	Respiratory distress
HP:0002104	Apnea
HP:0002119	Ventriculomegaly
HP:0002149	Hyperuricemia
HP:0002240	Hepatomegaly
HP:0002329	Drowsiness
HP:0002876	Episodic tachypnea
HP:0002883	Hyperventilation
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003128	Lactic acidosis
HP:0003162	Fasting hypoglycemia

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001762_812	Obesity-related traits	4.000000e-06
GCST003209_11	Colorectal or endometrial cancer	4.000000e-06
GCST004490_17	Cerebrospinal fluid t-tau:AB1-42 ratio	1.000000e-08
GCST004490_18	Cerebrospinal fluid t-tau:AB1-42 ratio	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004230	endometrial neoplasm
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006008	Glycogen Storage Disease	C16.320.565.202.449; C18.452.648.202.449

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3975 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 291,931 (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
CHEMBL752	ADENOSINE PHOSPHATE	4	165,316
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL120563	THIRAM	2	79,340
CHEMBL495498	MB-05032	2	72
CHEMBL8260	BAICALEIN	2	8,592

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

Binding affinities (BindingDB)

3 measured of 4 human assays (4 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1,1’-(1,3,7,9-Tetrahydroxydibenzofuran-2,6-diyl)bis(2-methylbutan-1-one)	IC50	6000 nM	US-9273021: Dibenzofuran derivatives as inhibitors of fructose 1,6-bisphosphatase and methods of use thereof
1,1’-(1,3,7,9-Tetrahydroxydibenzofuran-2,6-diyl)bis(3-methylbutan-1-one)	IC50	8100 nM	US-9273021: Dibenzofuran derivatives as inhibitors of fructose 1,6-bisphosphatase and methods of use thereof
2,6-diacetyl-3,7,9-trihydroxy-8,9b-dimethyldibenzofuran-1-one	IC50	371000 nM	US-9273021: Dibenzofuran derivatives as inhibitors of fructose 1,6-bisphosphatase and methods of use thereof

ChEMBL bioactivities

714 potent at pChembl≥5 of 788 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL589266
9.00	IC50	1	nM	CHEMBL1173125
8.70	IC50	2	nM	CHEMBL462979
8.70	IC50	2	nM	CHEMBL597891
8.70	IC50	2	nM	CHEMBL1173126
8.52	IC50	3	nM	CHEMBL462979
8.52	IC50	3	nM	CHEMBL597692
8.40	IC50	4	nM	CHEMBL462978
8.40	IC50	4	nM	CHEMBL457189
8.30	IC50	5	nM	CHEMBL457400
8.22	IC50	6	nM	CHEMBL462978
8.22	IC50	6	nM	CHEMBL463183
8.10	IC50	8	nM	CHEMBL515042
8.10	IC50	8	nM	CHEMBL456977
8.10	IC50	8	nM	CHEMBL597282
8.10	IC50	8	nM	CHEMBL597484
8.10	IC50	8	nM	CHEMBL1173572
8.05	IC50	9	nM	CHEMBL457189
8.05	IC50	9	nM	CHEMBL592639
8.05	IC50	9	nM	CHEMBL597691
8.05	IC50	9	nM	CHEMBL605956
8.00	IC50	10	nM	CHEMBL515524
8.00	IC50	10	nM	MB-05032
8.00	IC50	10	nM	CHEMBL609616
8.00	IC50	10	nM	CHEMBL1096789
8.00	IC50	10	nM	CHEMBL1172935
8.00	IC50	10	nM	CHEMBL1172936
8.00	IC50	10	nM	CHEMBL259771
8.00	IC50	10	nM	CHEMBL1650184
7.96	IC50	11	nM	CHEMBL5271686
7.96	IC50	11	nM	CHEMBL592391
7.96	IC50	11	nM	CHEMBL1173571
7.96	IC50	11	nM	CHEMBL1173636
7.92	IC50	12	nM	CHEMBL463183
7.92	IC50	12	nM	CHEMBL457400
7.92	IC50	12	nM	CHEMBL458056
7.92	IC50	12	nM	CHEMBL456154
7.92	IC50	12	nM	CHEMBL456978
7.92	IC50	12	nM	CHEMBL592390
7.92	IC50	12	nM	CHEMBL1650181
7.92	IC50	12	nM	CHEMBL1650209
7.89	IC50	13	nM	CHEMBL565809
7.89	IC50	13	nM	CHEMBL1650205
7.85	IC50	14	nM	CHEMBL501816
7.85	IC50	14	nM	CHEMBL456564
7.85	IC50	14	nM	CHEMBL504104
7.85	IC50	14	nM	CHEMBL1650203
7.82	IC50	15	nM	CHEMBL597483
7.82	IC50	15	nM	CHEMBL1650198
7.80	IC50	16	nM	MB-05032

PubChem BioAssay actives

669 with measured affinity, of 1155 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
(5-carbamoyl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0010	uM
ethyl (2S)-2-[[(5-carbamoyl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethyl-[[(2S)-1-ethoxy-1-oxopropan-2-yl]amino]phosphoryl]amino]propanoate	492056: Inhibition of human FBase	ic50	0.0010	uM
[5-(methylcarbamoyl)-4H-indeno[1,2-d][1,3]thiazol-8-yl]oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0020	uM
1-(3-methylphenyl)sulfonyl-3-[[4-[[(3-methylphenyl)sulfonylcarbamoylamino]methyl]phenyl]methyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0020	uM
ethyl (2S)-2-[[[[(2S)-1-ethoxy-1-oxopropan-2-yl]amino]-[[5-(methylcarbamoyl)-4H-indeno[1,2-d][1,3]thiazol-8-yl]oxymethyl]phosphoryl]amino]propanoate	492056: Inhibition of human FBase	ic50	0.0020	uM
(5-pyrimidin-5-yl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0030	uM
1-(3-chlorophenyl)sulfonyl-3-[7-[(3-chlorophenyl)sulfonylcarbamoylamino]heptyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0040	uM
1-(3-chlorophenyl)sulfonyl-3-[[4-[[(3-chlorophenyl)sulfonylcarbamoylamino]methyl]phenyl]methyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0040	uM
1-(3-methylphenyl)sulfonyl-3-[7-[(3-methylphenyl)sulfonylcarbamoylamino]heptyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0050	uM
1-(3-methylphenyl)sulfonyl-3-[[3-[[(3-methylphenyl)sulfonylcarbamoylamino]methyl]phenyl]methyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0060	uM
1-(3-chlorophenyl)sulfonyl-3-[6-[(3-chlorophenyl)sulfonylcarbamoylamino]hexyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0080	uM
1-(3-methylphenyl)sulfonyl-3-[8-[(3-methylphenyl)sulfonylcarbamoylamino]octyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0080	uM
(5-methyl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0080	uM
(5-chloro-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0080	uM
ethyl (2S)-2-[[[[(2S)-1-ethoxy-1-oxopropan-2-yl]amino]-[(5-methyl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethyl]phosphoryl]amino]propanoate	492056: Inhibition of human FBase	ic50	0.0080	uM
(5,6-difluoro-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0090	uM
(5-pyridin-3-yl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0090	uM
(5-pyridin-4-yl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0090	uM
[5-[2-amino-5-(2-methylpropyl)-1,3-thiazol-4-yl]furan-2-yl]phosphonic acid	446447: Inhibition of human liver FBPase	ic50	0.0100	uM
(5,6-dimethyl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0100	uM
1-(3-chlorophenyl)sulfonyl-3-[2-[2-[(3-chlorophenyl)sulfonylcarbamoylamino]ethyldisulfanyl]ethyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0100	uM
ethyl (2S)-2-[[(5,6-dimethyl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethyl-[[(2S)-1-ethoxy-1-oxopropan-2-yl]amino]phosphoryl]amino]propanoate	492056: Inhibition of human FBase	ic50	0.0100	uM
propan-2-yl (2S)-2-[[(5,6-dimethyl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethyl-[[(2S)-1-oxo-1-propan-2-yloxypropan-2-yl]amino]phosphoryl]amino]propanoate	492056: Inhibition of human FBase	ic50	0.0100	uM
ethyl 2-[[(5,6-dimethyl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethyl-[(2-ethoxy-2-oxoethyl)amino]phosphoryl]amino]acetate	492056: Inhibition of human FBase	ic50	0.0100	uM
[5-(2-amino-5-cyclohexyl-1,3-thiazol-4-yl)furan-2-yl]phosphonic acid	554209: Inhibition of human liver FBP	ic50	0.0100	uM
ethyl (2S)-2-[[[5-[2-amino-5-(2-methylpropyl)-1,3-thiazol-4-yl]furan-2-yl]-[[(2S)-1-ethoxy-1-oxopropan-2-yl]amino]phosphoryl]amino]propanoate	492056: Inhibition of human FBase	ic50	0.0100	uM
(5-ethyl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0110	uM
[5-[2-amino-5-(2-methylpentanoyl)-1,3-thiazol-4-yl]furan-2-yl]phosphonic acid	1959370: Inhibition of human liver FBPase by spectrophotometric method	ic50	0.0110	uM
ethyl (2S)-2-[[[5-(2,2-dimethylpropylcarbamoyl)-4H-indeno[1,2-d][1,3]thiazol-8-yl]oxymethyl-[[(2S)-1-ethoxy-1-oxopropan-2-yl]amino]phosphoryl]amino]propanoate	492056: Inhibition of human FBase	ic50	0.0110	uM
ethyl (2S)-2-[[[[(2S)-1-ethoxy-1-oxopropan-2-yl]amino]-[(5-ethyl-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethyl]phosphoryl]amino]propanoate	492056: Inhibition of human FBase	ic50	0.0110	uM
1-(3-methylphenyl)sulfonyl-3-[6-[(3-methylphenyl)sulfonylcarbamoylamino]hex-3-ynyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0120	uM
1-(3-methylphenyl)sulfonyl-3-[6-[(3-methylphenyl)sulfonylcarbamoylamino]hexyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0120	uM
1-(3-methylphenyl)sulfonyl-3-[2-[2-[(3-methylphenyl)sulfonylcarbamoylamino]ethyldisulfanyl]ethyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0120	uM
4H-indeno[1,2-d][1,3]thiazol-8-yloxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0120	uM
[5-(2-amino-5-naphthalen-2-yl-1,3-thiazol-4-yl)furan-2-yl]phosphonic acid	554209: Inhibition of human liver FBP	ic50	0.0120	uM
[5-[2-amino-5-(2,2-dimethylpropyl)-1,3-thiazol-4-yl]furan-2-yl]phosphonic acid	554209: Inhibition of human liver FBP	ic50	0.0120	uM
(2-amino-4,5-dihydrobenzo[e][1,3]benzothiazol-8-yl) dihydrogen phosphate	446447: Inhibition of human liver FBPase	ic50	0.0130	uM
[5-[2-amino-5-(4-chlorophenyl)-1,3-thiazol-4-yl]furan-2-yl]phosphonic acid	554209: Inhibition of human liver FBP	ic50	0.0130	uM
1-(3-chlorophenyl)sulfonyl-3-[(E)-6-[(3-chlorophenyl)sulfonylcarbamoylamino]hex-3-enyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0140	uM
[5-(2-amino-5-ethoxycarbonyl-1,3-thiazol-4-yl)furan-2-yl]phosphonic acid	1959370: Inhibition of human liver FBPase by spectrophotometric method	ic50	0.0140	uM
[5-(2-amino-5-phenyl-1,3-thiazol-4-yl)furan-2-yl]phosphonic acid	554209: Inhibition of human liver FBP	ic50	0.0140	uM
[5-[2-amino-5-(4-methoxycarbonylphenyl)-1,3-thiazol-4-yl]furan-2-yl]phosphonic acid	554209: Inhibition of human liver FBP	ic50	0.0140	uM
(5-fluoro-4H-indeno[1,2-d][1,3]thiazol-8-yl)oxymethylphosphonic acid	461157: Inhibition of human liver recombinant FBPase	ic50	0.0150	uM
[5-(2-amino-5-phenylmethoxycarbonyl-1,3-thiazol-4-yl)furan-2-yl]phosphonic acid	554209: Inhibition of human liver FBP	ic50	0.0150	uM
[5-(2-amino-5-propylsulfanyl-1,3-thiazol-4-yl)furan-2-yl]phosphonic acid	554209: Inhibition of human liver FBP	ic50	0.0160	uM
1-(3-chlorophenyl)sulfonyl-3-[[4-[[(3-chlorophenyl)sulfonylcarbamoylamino]methyl]cyclohexyl]methyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0160	uM
[5-[2-amino-5-(4-fluorophenyl)-1,3-thiazol-4-yl]furan-2-yl]phosphonic acid	554209: Inhibition of human liver FBP	ic50	0.0160	uM
[5-(2-amino-5-morpholin-4-yl-1,3-thiazol-4-yl)furan-2-yl]phosphonic acid	554209: Inhibition of human liver FBP	ic50	0.0160	uM
1-(3-chlorophenyl)sulfonyl-3-[8-[(3-chlorophenyl)sulfonylcarbamoylamino]octyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0170	uM
1-(3-methylphenyl)sulfonyl-3-[2-[2-[(3-methylphenyl)sulfonylcarbamoylamino]ethylsulfanyl]ethyl]urea	365659: Inhibition of human liver fructose-1,6-bisphosphatase in presence of fructose-2,6-bisphosphate	ic50	0.0180	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Estradiol	increases expression, decreases expression, affects cotreatment	3
Tretinoin	decreases expression, increases expression	3
Valproic Acid	decreases expression, increases methylation	3
(+)-JQ1 compound	decreases expression	2
Decitabine	affects expression, affects methylation, decreases methylation, increases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Aflatoxin B1	decreases expression	2
GSK-J4	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
kaempferol	decreases expression	1
bisphenol A	decreases expression	1
glycidyl methacrylate	decreases expression	1
trichostatin A	affects expression, affects methylation	1
sodium bichromate	increases reaction, affects response to substance, decreases expression, decreases reaction, increases expression (+1 more)	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
myricetin	decreases expression	1
chrysin	decreases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
seocalcitol	increases expression	1
vanillin	affects binding	1
obeticholic acid	decreases expression	1
Vorinostat	increases expression	1

ChEMBL screening assays

125 unique, capped per target: 125 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1031960	Binding	Inhibition of human liver FBPase	A library of novel allosteric inhibitors against fructose 1,6-bisphosphatase. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety