PFKFB4

Summary

PFKFB4 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4, HGNC:8875) is a protein-coding gene on chromosome 3p21.31, encoding 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (Q16877). Synthesis and degradation of fructose 2,6-bisphosphate.

The protein encoded by this gene is one of four bifunctional kinase/phosphatases that regulate the concentration of the glycolytic byproduct fructose-2,6-bisphosphate (F2,6BP). The encoded protein is highly expressed in cancer cells and is induced by hypoxia. This protein is essential to the survival of cancer cells under conditions of hypoxia, because it increases the amount of F2,6BP and ATP at a time when the cell cannot produce much of them. This finding suggests that this protein may be a good target for disruption in cancer cells, hopefully imperiling their survival. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5210 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 105 total
• Druggable target: yes
• MANE Select transcript: NM_004567

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8875
Approved symbol	PFKFB4
Name	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000114268
Ensembl biotype	protein_coding
OMIM	605320
Entrez	5210

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 12 protein_coding, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000232375, ENST00000383734, ENST00000412035, ENST00000416568, ENST00000417753, ENST00000422701, ENST00000445633, ENST00000452531, ENST00000467176, ENST00000468162, ENST00000471890, ENST00000478516, ENST00000490115, ENST00000490404, ENST00000496767, ENST00000877351, ENST00000919611, ENST00000919612, ENST00000919613, ENST00000919614, ENST00000956232

RefSeq mRNA: 6 — MANE Select: NM_004567 NM_001317134, NM_001317135, NM_001317136, NM_001317137, NM_001317138, NM_004567

CCDS: CCDS2771, CCDS82769, CCDS82770

Canonical transcript exons

ENST00000232375 — 14 exons

Exon	Start	End
ENSE00000877764	48517684	48519806
ENSE00003461116	48523701	48523830
ENSE00003467502	48521986	48522050
ENSE00003485285	48525565	48525669
ENSE00003492773	48539254	48539310
ENSE00003536598	48523537	48523599
ENSE00003550564	48538498	48538619
ENSE00003563432	48550118	48550234
ENSE00003583026	48536256	48536463
ENSE00003583488	48549864	48549960
ENSE00003630298	48539697	48539771
ENSE00003784213	48543580	48543646
ENSE00003787736	48535512	48535658
ENSE00003843529	48556681	48556803

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 91.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2313 / max 111.1987, expressed in 1528 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42143	3.8909	1105
42144	2.7653	1162
42145	0.5021	276
42141	0.0731	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	91.74	gold quality
monocyte	CL:0000576	90.02	gold quality
mononuclear cell	CL:0000842	89.88	gold quality
leukocyte	CL:0000738	89.57	gold quality
right testis	UBERON:0004534	89.42	gold quality
left testis	UBERON:0004533	89.28	gold quality
stromal cell of endometrium	CL:0002255	88.20	gold quality
testis	UBERON:0000473	87.25	gold quality
granulocyte	CL:0000094	86.99	gold quality
jejunal mucosa	UBERON:0000399	86.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.41	gold quality
duodenum	UBERON:0002114	83.37	gold quality
lower esophagus mucosa	UBERON:0035834	83.35	gold quality
body of pancreas	UBERON:0001150	82.06	gold quality
cortical plate	UBERON:0005343	81.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.08	gold quality
jejunum	UBERON:0002115	80.95	gold quality
triceps brachii	UBERON:0001509	80.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.92	gold quality
gluteal muscle	UBERON:0002000	80.50	gold quality
ventricular zone	UBERON:0003053	80.07	gold quality
pancreas	UBERON:0001264	79.56	gold quality
islet of Langerhans	UBERON:0000006	79.45	gold quality
small intestine	UBERON:0002108	79.41	gold quality
spleen	UBERON:0002106	79.24	gold quality
ganglionic eminence	UBERON:0004023	79.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.97	gold quality
vena cava	UBERON:0004087	78.03	gold quality
superficial temporal artery	UBERON:0001614	77.61	gold quality
bone marrow	UBERON:0002371	77.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

75 targeting PFKFB4, 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-4283	100.00	66.42	2097
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-505-3P	99.19	69.71	896

Literature-anchored findings (GeneRIF, showing 40)

• Mechanisms of hypoxic regulation of PFKFB4 gene expression were studied in several cancer cell lines. (PMID:15474002)
• A detailed analysis of the 5’-flanking region of human gene pfkfb4 using different 5’-deletion promoter constructs was carried out; this gene is activated by serum and chemical hypoxia whereas beta-estradiol decreases its expression. (PMID:15642344)
• Overexpression of PFKFB-4 transcript levels in breast & colon malignant tumors correlates with enhanced expression of PFKFB-3, hypoxia-inducible factor(HIF)-1alpha & known HIF-1 dependent genes Glut1 & VEGF (PMID:15925437)
• PFKFB-4 and PFKFB-3 genes are expressed in gastric and pancreatic cancer cells, they strongly respond to hypoxia via a HIF-1alpha dependent mechanism and possibly have a significant role in the Warburg effect which is found in malignant cells (PMID:17143338)
• PFKFB4 has an important role in the progression of non-muscle-invasive bladder cancer ( (PMID:21396842)
• Sulforaphane is a potent inducer of apoptosis in hepatocellular carcinoma cells via PFKFB4-inhibition pathways. (PMID:21640852)
• an essential role of PFKFB4 in the maintenance of brain cancer stem-like cells (PMID:22056879)
• we found that the glycolytic enzyme PFKFB4 is essential for prostate cancer cell survival by maintaining the balance between the use of glucose for energy generation and the synthesis of antioxidants. (PMID:22576210)
• Data suggest that molecular mechanism by which dihydrotestosterone induces Pfkfb4 (and thus glycolysis) during spermatogenesis involves stimulation of Sertoli cells to secrete FGF-2 (fibroblast growth factor 2); study uses recombinant human Pfkfb4. (PMID:22811469)
• PFKFB4 and HO-2 are expressed in a coordinated manner to maintain glucose homeostasis. (PMID:22892400)
• Data indicate that the PFKFB4 expressed in multiple transformed cells and tumors functions to synthesize F2,6BP. (PMID:25115398)
• PFKFB4 suppresses oxidative stress and p62 accumulation, without which autophagy is stimulated likely as a ROS detoxification response. (PMID:25772235)
• Inhibition of PFKFB4 suppresses glycolysis and proliferation of multiple human cancer cell lines. (PMID:26221874)
• HIF-1alpha transactivates hypoxia-responsive elements (HRE)-D of the promoter region of PFKFB4 in hypoxia condition. (PMID:27181362)
• The expression of PFKFB3, PFKFB4, NAMPT, and TSPAN13 is strongly up-regulated in pediatric glioma. (PMID:27491149)
• Our FD models could facilitate a better mechanistic understanding of FD and help develop effective therapeutics for FD and other fibrosis diseases. (PMID:27614159)
• Data show that PFKFB4 is the target gene of PPARgamma which modulates the transcriptional activity of its promoter. (PMID:27769068)
• High PFKFB4 expression is associated with colon and lung cancer. (PMID:28092678)
• This work has uncovered a novel function of the enzymes PFKFB3 and PFKFB4 in ovarian cancer cells during mitotic arrest (PMID:28152500)
• Epithelial and endothelial tyrosine kinase (Etk) interacts with 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) to promote small-cell lung cancer (SCLC) chemoresistance through regulation of autophagy. (PMID:29208667)
• findings suggest that the Warburg pathway enzyme PFKFB4 acts as a molecular fulcrum that couples sugar metabolism to transcriptional activation by stimulating SRC-3 to promote aggressive metastatic tumours (PMID:29615789)
• PFKFB4 enhances the invasiveness of breast cancer cells in vitro and in vivo by inducing HA production and PFKFB4-induced expression of HAS2 depends upon the activation of p38 signaling. (PMID:30415245)
• Currently available anti-melanoma therapeutic strategies may significantly benefit from agents targeting PFKFB4 activity. (PMID:30504385)
• CD44ICD interacts with CREB and binds to the promoter region of PFKFB4, thereby regulating PFKFB4 transcription and expression. (PMID:30613295)
• This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia . (PMID:30819197)
• PFKFB4 is critical for the survival of acute monocytic leukemia cells. (PMID:32299611)
• PFKFB4 promotes lung adenocarcinoma progression via phosphorylating and activating transcriptional coactivator SRC-2. (PMID:33593309)
• PFKFB4 Overexpression Facilitates Proliferation by Promoting the G1/S Transition and Is Associated with a Poor Prognosis in Triple-Negative Breast Cancer. (PMID:34211613)
• Relocation of phosphofructokinases within epithelial cells is a novel event preceding breast cancer recurrence that accurately predicts patient outcomes. (PMID:34348486)
• Expression of Alternative Splice Variants of 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase-4 in Normoxic and Hypoxic Melanoma Cells. (PMID:34445551)
• PFKFB4 is overexpressed in clear-cell renal cell carcinoma promoting pentose phosphate pathway that mediates Sunitinib resistance. (PMID:34593007)
• Loss of PFKFB4 induces cell cycle arrest and glucose metabolism inhibition by inactivating MEK/ERK/c-Myc pathway in cervical cancer cells. (PMID:35659173)
• Hypoxia-inducible CircPFKFB4 Promotes Breast Cancer Progression by Facilitating the CRL4(DDB2) E3 Ubiquitin Ligase-mediated p27 Degradation. (PMID:35813480)
• PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma. (PMID:35914811)
• PFKFB4 modulated by miR-195-5p can boost the malignant progression of cervical cancer cells. (PMID:35926796)
• Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis. (PMID:36109523)
• PFKFB4 Drives the Oncogenicity in TP53-Mutated Hepatocellular Carcinoma in a Phosphatase-Dependent Manner. (PMID:36806581)
• PFKFB4 Is a Metabolic Driver of HCC Progression and Chemoresistance Through ROS Mitigation. (PMID:36963434)
• THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification. (PMID:37500615)
• Transforming growth factor beta1 upregulates 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-4 expression in A549 and MCF-10A cells. (PMID:37707291)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pfkfb4b	ENSDARG00000029075
danio_rerio	pfkfb4a	ENSDARG00000055540
mus_musculus	Pfkfb4	ENSMUSG00000025648
rattus_norvegicus	Pfkfb4	ENSRNOG00000020656
drosophila_melanogaster	Pfrx	FBGN0027621
caenorhabditis_elegans		WBGENE00019295
caenorhabditis_elegans	pfkb-1.1	WBGENE00022456

Paralogs (3): PFKFB2 (ENSG00000123836), PFKFB1 (ENSG00000158571), PFKFB3 (ENSG00000170525)

Protein

Protein identifiers

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 — Q16877 (reviewed: Q16877)

Alternative names: 6PF-2-K/Fru-2,6-P2ase testis-type isozyme

All UniProt accessions (7): C9JJ23, C9JX77, C9K0D8, Q16877, F8WC12, F8WDY1, Q66S35

UniProt curated annotations — full annotation on UniProt →

Function. Synthesis and degradation of fructose 2,6-bisphosphate.

Subunit / interactions. Homodimer.

Activity regulation. The most important regulatory mechanism of these opposing activities is by phosphorylation and dephosphorylation of the enzyme.

Similarity. In the C-terminal section; belongs to the phosphoglycerate mutase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q16877-1	1	yes
Q16877-2	2
Q16877-3	3

RefSeq proteins (6): NP_001304063, NP_001304064, NP_001304065, NP_001304066, NP_001304067, NP_004558* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001345	PG/BPGM_mutase_AS	Active_site
IPR003094	6Pfruct_kin	Family
IPR013078	His_Pase_superF_clade-1	Family
IPR013079	6Phosfructo_kin	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR029033	His_PPase_superfam	Homologous_superfamily

Pfam: PF00300, PF01591

Enzyme classification (BRENDA):

• EC 2.7.1.105 — 6-phosphofructo-2-kinase (BRENDA: 25 organisms, 68 substrates, 145 inhibitors, 158 Km, 41 kcat entries)
• EC 3.1.3.46 — fructose-2,6-bisphosphate 2-phosphatase (BRENDA: 28 organisms, 27 substrates, 93 inhibitors, 21 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
BETA-D-FRUCTOSE 6-PHOSPHATE	0.0038–39	63
ATP	0.0009–1.62	35
MGATP2-	0.0072–2	21
FRUCTOSE 2,6-BISPHOSPHATE	0.0001–1.4	15
D-FRUCTOSE 6-PHOSPHATE	0.0094–0.1	4
BETA-D-FRUCTOSE 2,6-BISPHOSPHATE	0.0102–0.204	3
BETA-D-FRUCTOSE 2,6-BISPHOSPHATE	0.02–0.21	2
CTP	0.9–2	2
GTP	0.35–1.5	2
UTP	0.78–2.3	2
D-PSICOSE 6-PHOSPHATE	7.4	1
D-TAGATOSE 6-PHOSPHATE	15	1
ITP	0.3	1
L-SORBOSE 6-PHOSPHATE	0.175	1
D-FRUCTOSE 2,6-BISPHOSPHATE	0.0001	1

Catalyzed reactions (Rhea), 2 shown:

• beta-D-fructose 6-phosphate + ATP = beta-D-fructose 2,6-bisphosphate + ADP + H(+) (RHEA:15653)
• beta-D-fructose 2,6-bisphosphate + H2O = beta-D-fructose 6-phosphate + phosphate (RHEA:17289)

UniProt features (34 total): binding site 22, active site 4, region of interest 2, splice variant 2, chain 1, site 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16877-F1	92.64	0.80

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 (5): 391 (transition state stabilizer); 129; 159; 257 (tele-phosphohistidine intermediate); 326 (proton donor/acceptor)

Ligand- & substrate-binding residues (22): 131; 137; 168–173; 173; 194; 198; 256; 263; 269; 306; 337; 348–351 …

Post-translational modifications (1): 444

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9634600	Regulation of glycolysis by fructose 2,6-bisphosphate metabolism

MSigDB gene sets: 184 (showing top): GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, MODULE_45, MODULE_64, MENSE_HYPOXIA_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_PHOSPHORYLATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, MODULE_66, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS

GO Biological Process (5): fructose metabolic process (GO:0006000), fructose 2,6-bisphosphate metabolic process (GO:0006003), gluconeogenesis (GO:0006094), glycolytic process (GO:0006096), carbohydrate phosphorylation (GO:0046835)

GO Molecular Function (9): 6-phosphofructo-2-kinase activity (GO:0003873), fructose-2,6-bisphosphate 2-phosphatase activity (GO:0004331), ATP binding (GO:0005524), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytosol (GO:0005829), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase complex (GO:0043540)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycolysis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
hexose metabolic process	1
organophosphate metabolic process	1
carbohydrate derivative metabolic process	1
glucose metabolic process	1
hexose biosynthetic process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
carbohydrate metabolic process	1
phosphorylation	1
phosphofructokinase activity	1
sugar-phosphatase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
cytoplasm	1
cellular anatomical structure	1
cytosol	1
transferase complex, transferring phosphorus-containing groups	1

Protein interactions and networks

STRING

1450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PFKFB4	TIGAR	Q9NQ88	956
PFKFB4	PFKM	P08237	730
PFKFB4	GCK	P35557	726
PFKFB4	PKM	P14618	622
PFKFB4	FBP2	O00757	602
PFKFB4	PFKP	Q01813	578
PFKFB4	SLC2A1	P11166	574
PFKFB4	HK2	P52789	565
PFKFB4	H6PD	O95479	558
PFKFB4	LDHA	P00338	546
PFKFB4	PFKL	P17858	546
PFKFB4	PGK1	P00558	519
PFKFB4	SLC2A3	P11169	510
PFKFB4	TP53	P04637	509
PFKFB4	HIF1A	Q16665	507

IntAct

38 interactions, top by confidence:

A	B	Type	Score
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
PFKFB1	PFKFB4	psi-mi:“MI:0915”(physical association)	0.670
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
PFKFB4	LRR1	psi-mi:“MI:0915”(physical association)	0.560
PFKFB4	CCDC102B	psi-mi:“MI:0915”(physical association)	0.560
PFKFB4	CDC23	psi-mi:“MI:0915”(physical association)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PFKFB4	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
GADD45A	PFKFB4	psi-mi:“MI:0915”(physical association)	0.370
PFKFB4	GSK3B	psi-mi:“MI:0915”(physical association)	0.370
PFKFB3	PFKFB2	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAQ	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAH	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAZ	HECTD4	psi-mi:“MI:0914”(association)	0.350
PFKFB4	PFKFB2	psi-mi:“MI:0914”(association)	0.350
RRAS	KIN	psi-mi:“MI:0914”(association)	0.350
SLC2A8	FOLH1	psi-mi:“MI:0914”(association)	0.350
GNG12	GNAQ	psi-mi:“MI:0914”(association)	0.350
PFKFB1	PFKFB4	psi-mi:“MI:0915”(physical association)	0.000
LRR1	PFKFB4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (58): PFKFB4 (Affinity Capture-RNA), PFKFB4 (Affinity Capture-MS), PFKFB4 (Affinity Capture-RNA), PFKFB4 (Co-localization), PFKFB4 (Co-localization), PFKFB4 (Co-localization), PFKFB4 (Biochemical Activity), PFKFB4 (Negative Genetic), TST (Positive Genetic), PFKFB4 (Positive Genetic), PRKDC (Positive Genetic), PFKFB4 (Two-hybrid), CCDC102B (Two-hybrid), PFKFB1 (Two-hybrid), LRR1 (Two-hybrid)

ESM2 similar proteins: A0A4X1T4U3, A4IFD0, O00329, O14936, O35904, O61069, O65583, O70589, P07953, P16118, P25114, P49872, P70266, Q13057, Q16875, Q16877, Q24210, Q28901, Q298L5, Q2UM43, Q32M07, Q4R3W4, Q4R8B6, Q4V8A1, Q502L7, Q5B5L3, Q5M7G4, Q5R9C1, Q623S8, Q62915, Q68FP8, Q6DGQ8, Q6DTY7, Q6P618, Q80UN9, Q8IMX7, Q8MIR4, Q91309, Q91348, Q91YL3

Diamond homologs: A1AJW4, A1JJB8, A1TC01, A4TQH5, A4W6B3, A5VVV5, A6TI09, A6UEW3, A6WYJ2, A7FMF8, A7HZ35, A7MIJ0, A7ZVT7, A8A8C4, A8ALW1, A8G9J4, A8IGZ9, A9IXE7, A9MCX8, A9MR94, A9N7F5, A9R032, A9WW62, B0UBD4, B1IS24, B1JL20, B1LEK2, B1XFK5, B2K3K5, B2SC37, B2TZS8, B2VH13, B4EY52, B4T4I9, B4TH18, B4TU55, B5BAL1, B5F543, B5FTD9, B5R3B7

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PFKFB4	“up-regulates quantity”	“beta-D-fructofuranose 2,6-bisphosphate”	“chemical modification”
PFKFB4	“up-regulates activity”	NCOA3	phosphorylation
PFKFB4	“down-regulates quantity”	“β-D-fructose 6-phosphate”	“chemical modification”
PFKFB4	“down-regulates quantity”	“beta-D-fructofuranose 2,6-bisphosphate”	“chemical modification”
PFKFB4	“up-regulates quantity”	“β-D-fructose 6-phosphate”	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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
Activation of BAD and translocation to mitochondria	6	175.7×	5e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	155.0×	6e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	155.0×	6e-11
Activation of BH3-only proteins	6	114.6×	4e-10
RHO GTPases activate PKNs	6	73.2×	5e-09
Intrinsic Pathway for Apoptosis	6	67.6×	8e-09
Transcriptional and post-translational regulation of MITF-M expression and activity	6	41.2×	1e-07
SARS-CoV-1-host interactions	6	40.5×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	63.2×	4e-06
intracellular protein localization	6	21.7×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2609 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48523600:C:CC	acceptor_gain	1.0000
3:48523696:CACA:C	donor_loss	1.0000
3:48523697:ACAC:A	donor_loss	1.0000
3:48523700:CC:C	donor_loss	1.0000
3:48523706:G:GA	donor_gain	1.0000
3:48523826:TAGGA:T	acceptor_gain	1.0000
3:48523827:AGGA:A	acceptor_gain	1.0000
3:48523828:GGA:G	acceptor_gain	1.0000
3:48523829:GA:G	acceptor_gain	1.0000
3:48523830:ACTGC:A	acceptor_loss	1.0000
3:48523831:C:CC	acceptor_gain	1.0000
3:48523831:CTG:C	acceptor_loss	1.0000
3:48523832:T:G	acceptor_loss	1.0000
3:48523834:C:CT	acceptor_gain	1.0000
3:48523840:C:CT	acceptor_gain	1.0000
3:48525666:CGCC:C	acceptor_gain	1.0000
3:48525667:GCCC:G	acceptor_loss	1.0000
3:48525669:CCT:C	acceptor_loss	1.0000
3:48535659:C:CC	acceptor_gain	1.0000
3:48536251:CTGA:C	donor_loss	1.0000
3:48536252:TGACC:T	donor_loss	1.0000
3:48536253:GAC:G	donor_loss	1.0000
3:48536254:ACCTC:A	donor_gain	1.0000
3:48536255:CCTCC:C	donor_gain	1.0000
3:48536258:C:A	donor_gain	1.0000
3:48536277:T:TA	donor_gain	1.0000
3:48536459:GGTCC:G	acceptor_gain	1.0000
3:48536460:GTCC:G	acceptor_gain	1.0000
3:48536461:TCC:T	acceptor_gain	1.0000
3:48536462:CC:C	acceptor_gain	1.0000

AlphaMissense

3085 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48523784:A:G	L380P	1.000
3:48523817:A:G	L369P	1.000
3:48525569:C:T	G363E	1.000
3:48525570:C:A	G363W	1.000
3:48525570:C:G	G363R	1.000
3:48525570:C:T	G363R	1.000
3:48525592:C:A	K355N	1.000
3:48525592:C:G	K355N	1.000
3:48550139:A:G	W65R	1.000
3:48550139:A:T	W65R	1.000
3:48523554:A:G	L423P	0.999
3:48523563:A:T	V420D	0.999
3:48523732:G:C	C397W	0.999
3:48523737:G:T	R396S	0.999
3:48523763:A:G	L387P	0.999
3:48523805:A:G	L373P	0.999
3:48523807:T:A	R372S	0.999
3:48523807:T:G	R372S	0.999
3:48523808:C:G	R372T	0.999
3:48523820:T:A	D368V	0.999
3:48523820:T:C	D368G	0.999
3:48523820:T:G	D368A	0.999
3:48523821:C:G	D368H	0.999
3:48523827:A:G	Y366H	0.999
3:48523829:G:A	S365F	0.999
3:48523830:A:G	S365P	0.999
3:48525569:C:A	G363V	0.999
3:48525579:A:C	Y360D	0.999
3:48525579:A:G	Y360H	0.999
3:48525581:C:G	R359P	0.999

dbSNP variants (sampled 300 via entrez): RS1000003120 (3:48551728 A>G), RS1000062596 (3:48546291 C>A,G), RS1000135937 (3:48546181 G>T), RS1000174218 (3:48539048 G>A,C,T), RS1000185587 (3:48546378 T>A), RS1000214043 (3:48545323 G>A), RS1000383518 (3:48532897 T>C), RS1000454030 (3:48526933 T>C), RS1000533228 (3:48527681 CATCTTT>C), RS1000538371 (3:48540637 T>C), RS1000608351 (3:48539224 C>T), RS1000696306 (3:48546751 A>G), RS1000727868 (3:48539223 A>T), RS1000902226 (3:48521604 G>T), RS1000933173 (3:48520960 C>T)

Disease associations

OMIM: gene MIM:605320 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001725_77	Inflammatory bowel disease	1.000000e-47
GCST002548_9	Ulcerative colitis	8.000000e-07
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST007565_82	Morning person	5.000000e-14
GCST008521_9	Bitter beverage consumption	8.000000e-06
GCST008550_18	Mental health study participation (completed survey)	3.000000e-08
GCST010002_422	Refractive error	4.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST90020027_103	Waist-hip index	2.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0010089	bitter beverage consumption measurement
EFO:0010130	health study participation
EFO:0004346	neuroimaging measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3721311 (SINGLE PROTEIN), CHEMBL3832646 (PROTEIN COMPLEX)

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

Binding affinities (BindingDB)

100 measured of 100 human assays (100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[(3-methyl-5-propan-2-yl-1-benzothiophen-2-yl)sulfonylamino]benzoic acid	IC50	30 nM	US-9233946: Sulfonamide compounds
2-[(3-methyl-5-propan-2-yl-1-benzothiophen-2-yl)sulfonylamino]-1,3-thiazole-5-carboxylic acid	IC50	100 nM	US-9233946: Sulfonamide compounds
5-methyl-N-[3-(2H-tetrazol-5-yl)phenyl]-1-benzothiophene-2-sulfonamide	IC50	140 nM	US-9233946: Sulfonamide compounds
5-fluoro-3-methyl-N-[3-(2H-tetrazol-5-yl)phenyl]-1-benzothiophene-2-sulfonamide	IC50	170 nM	US-9233946: Sulfonamide compounds
3-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonylamino]benzoic acid	IC50	180 nM	US-9233946: Sulfonamide compounds
3-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonylamino]-2-hydroxybenzoic acid	IC50	180 nM	US-9233946: Sulfonamide compounds
3-[(7-chloro-3-methyl-1-benzothiophen-2-yl)sulfonylamino]benzoic acid	IC50	200 nM	US-9233946: Sulfonamide compounds
2-Hydroxyethyl 4-{[(5’-fluoro-2’-hydroxybiphenyl-3-yl)sulfonyl]amino}-2-hydroxybenzoate	IC50	200 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Butyl 4-{[(4,5-dichloro-2-thienyl)sulfonyl]amino}-2-hydroxybenzoate	IC50	200 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
3-phenyl-N-[3-(2H-tetrazol-5-yl)phenyl]benzenesulfonamide	IC50	390 nM	US-9233946: Sulfonamide compounds
5-(2-methylsulfanylpyrimidin-4-yl)-N-[3-(2H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide	IC50	420 nM	US-9233946: Sulfonamide compounds
3-[(7-methoxy-3-methyl-1-benzothiophen-2-yl)sulfonylamino]benzoic acid	IC50	420 nM	US-9233946: Sulfonamide compounds
5-(4-methylphenyl)-N-[3-(2H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide	IC50	480 nM	US-9233946: Sulfonamide compounds
2,6-dichloro-N-[3-(2H-tetrazol-5-yl)phenyl]-4-(trifluoromethyl)benzenesulfonamide	IC50	510 nM	US-9233946: Sulfonamide compounds
5-(2,4-difluorophenyl)-N-[3-(tetrazolidin-5-yl)phenyl]thiophene-2-sulfonamide	IC50	600 nM	US-9233946: Sulfonamide compounds
2-(1H-Pyrrol-1-yl)ethyl 4-{[(4,5-dichlorothiophen-2-yl)sulfonyl]amino}-2-hydroxybenzoate	IC50	600 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
3-Morpholin-4-ylpropyl 4-({[5-chloro-4-(5-fluoro-2-hydroxyphenyl)-2-thienyl]sulfonyl}amino)-2-hydroxybenzoate trifluoroacetate	IC50	600 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
5-(2-methoxyphenyl)-N-[3-(2H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide	IC50	660 nM	US-9233946: Sulfonamide compounds
5-(3-chloro-4-fluorophenyl)-N-[3-(2H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide	IC50	660 nM	US-9233946: Sulfonamide compounds
2-Methoxyethyl 4-({[3-(2,3-dihydro-1-benzofuran-5-yl)phenyl]sulfonyl}amino)-2-hydroxybenzoate	IC50	700 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
5-(2-chlorophenyl)-N-[3-(tetrazolidin-5-yl)phenyl]thiophene-2-sulfonamide	IC50	750 nM	US-9233946: Sulfonamide compounds
4-{[(5-Chloro-4-phenyl-2-thienyl)sulfonyl]amino}-2-hydroxybenzoic acid	IC50	800 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Benzyl 4-{[(4,5-dichloro-2-thienyl)sulfonyl]amino}-2-hydroxybenzoate	IC50	800 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
2-Methoxy-1-methylethyl 4-{[(4,5-dichlorothiophen-2-yl)sulfonyl]amino}-2-hydroxybenzoate	IC50	800 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
3-[(5-Methylisoxazol-3-yl)amino]propyl 4-{[(5’-fluoro-2’-hydroxybiphenyl-3-yl)sulfonyl]amino}-2-hydroxybenzoate trifluoroacetate	IC50	800 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
2-Methoxyethyl 4-({[5-chloro-4-(2,3-dihydro-1-benzofuran-5-yl)-2-thienyl]sulfonyl}amino)-2-hydroxybenzoate	IC50	900 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
General Procedure 9	IC50	1080 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
2-Methoxyethyl 4-({[5-chloro-4-(2-hydroxyphenyl)-2-thienyl]sulfonyl}amino)-2-hydroxybenzoate	IC50	1200 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
1-Methyl-3-morpholin-4-ylpropyl 4-{[(4,5-dichlorothiophen-2-yl)sulfonyl]amino}-2-hydroxybenzoate)trifluoroacetate	IC50	1200 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 2-hydroxy-4-({[(2’-hydroxybiphenyl-4-yl)methyl]sulfonyl}amino)benzoate	IC50	1400 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
2-Methoxy-1-(methoxymethyl)ethyl 4-{[(3,5-dichlorophenyl)sulfonyl]amino}-2-hydroxybenzoate	IC50	1400 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
2-Hydroxyethyl 4-{[(5-chloro-4-phenyl-2-thienyl)sulfonyl]amino}-2-hydroxybenzoate	IC50	1400 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 2-hydroxy-4-({[3-(piperidin-1-yl)phenyl]sulfonyl}amino)benzoate	IC50	1500 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 4-[(biphenyl-3-ylsulfonyl)amino]-2-hydroxybenzoate	IC50	1600 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 4-({[3-(2,3-dihydro-1-benzofuran-5-yl)-5-(trifluoromethyl)phenyl]sulfonyl}amino)-2-hydroxybenzoate	IC50	1700 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
4-{[(4-Bromo-2,5-dichlorothiophen-3-yl)sulfonyl]amino}-2-hydroxybenzoic acid	IC50	1700 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 4-({[3-(5-acetyl-2-thienyl)phenyl]sulfonyl}amino)-2-hydroxybenzoate	IC50	1700 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
1-Benzylpyrrolidin-3-yl 2-hydroxy-4-{[(2,4,5-trichloro-3-thienyl)sulfonyl]amino}benzoate	IC50	1800 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
4-bromo-2-fluoro-N-[3-(tetrazolidin-5-yl)phenyl]benzenesulfonamide	IC50	1830 nM	US-9233946: Sulfonamide compounds
Methyl 4-[(tert-butoxycarbonyl)amino]-2-hydroxybenzoate	IC50	1900 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
General Procedure 14	IC50	1900 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 4-({[5-(2,5-difluorophenyl)thiophen-2-yl]sulfonyl}amino)-2-hydroxybenzoate	IC50	2000 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 4-({[5-chloro-4-(5-fluoro-2-hydroxyphenyl)-2-thienyl]sulfonyl}amino)-2-hydroxybenzoate	IC50	2000 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
2-Methoxy-1-(methoxymethyl)ethyl 4-({[5-chloro-4-(3-fluorophenyl)-2-thienyl]sulfonyl}amino)-2-hydroxybenzoate	IC50	2000 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 4-({[5-(dimethylamino)naphthalen-1-yl]sulfonyl}amino)-2-hydroxybenzoate trifluoroacetate	IC50	2100 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 4-{[(2,5-dichloro-3-thienyl)sulfonyl]amino}-2-hydroxybenzoate	IC50	2300 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 4-[({5-chloro-4-[3-(dimethylcarbamoyl)phenyl]thiophen-2-yl}sulfonyl)amino]-2-hydroxybenzoate	IC50	2400 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 2-hydroxy-4-({[4’-(trifluoromethoxy)biphenyl-3-yl]sulfonyl}amino)benzoate	IC50	2400 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
Methyl 4-({[4-(3-aminophenyl)-5-chlorothiophen-2-yl]sulfonyl}amino)-2-hydroxybenzoate trifluoroacetate	IC50	2800 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer
3-Morpholin-4-ylpropyl 4-({[4-(1,3-benzodioxol-5-yl)-5-chloro-2-thienyl]sulfonyl}amino)-2-hydroxybenzoate trifluoroacetate	IC50	2800 nM	US-9718809: Bisarylsulfonamides useful in the treatment of inflammation and cancer

ChEMBL bioactivities

53 potent at pChembl≥5 of 55 total, top 35 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	IC50	60	nM	CHEMBL3731843
7.00	IC50	100	nM	CHEMBL3731045
6.89	IC50	130	nM	CHEMBL3728731
6.85	IC50	140	nM	CHEMBL3731894
6.77	IC50	170	nM	CHEMBL3731503
6.75	IC50	180	nM	CHEMBL3729923
6.70	IC50	200	nM	CHEMBL3727732
6.41	IC50	390	nM	CHEMBL3729559
6.38	IC50	420	nM	CHEMBL3731358
6.38	IC50	420	nM	CHEMBL3727631
6.32	IC50	480	nM	CHEMBL3732792
6.30	IC50	500	nM	CHEMBL3729840
6.29	IC50	510	nM	CHEMBL3728448
6.22	IC50	600	nM	CHEMBL3729843
6.18	IC50	660	nM	CHEMBL3728006
6.18	IC50	660	nM	CHEMBL3730654
6.12	IC50	750	nM	CHEMBL3728043
5.92	IC50	1200	nM	CHEMBL3732576
5.89	IC50	1300	nM	CHEMBL3731769
5.74	IC50	1830	nM	CHEMBL3727849
5.64	IC50	2300	nM	CHEMBL3731843
5.55	IC50	2800	nM	CHEMBL3728905
5.52	IC50	3000	nM	CHEMBL3732213
5.51	IC50	3100	nM	CHEMBL3728464
5.46	IC50	3500	nM	CHEMBL3727471
5.43	IC50	3720	nM	CHEMBL3731572
5.43	IC50	3700	nM	CHEMBL3731235
5.40	IC50	4000	nM	CHEMBL3731235
5.37	IC50	4300	nM	CHEMBL3732138
5.27	IC50	5400	nM	CHEMBL3727505
5.16	IC50	7000	nM	CHEMBL3730791
5.12	IC50	7500	nM	CHEMBL3730349
5.06	IC50	8700	nM	CHEMBL3728324
5.05	IC50	9000	nM	CHEMBL3727888
5.00	IC50	1.01e+04	nM	CHEMBL3728731

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oxygen	decreases reaction, increases expression, increases reaction	6
Cisplatin	affects expression, decreases expression, increases expression	5
Estradiol	affects cotreatment, increases expression, decreases expression	4
Cyclosporine	decreases expression, increases expression	4
cobaltous chloride	decreases reaction, decreases abundance, increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
tungsten carbide	affects cotreatment, affects binding, increases expression	2
Zoledronic Acid	increases expression	2
Ethanol	affects cotreatment, increases expression, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cobalt	affects cotreatment, affects binding, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
1-cyclopropyl-4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl)pyridin-2-yl)piperazine	increases expression, decreases reaction	1
GSK-J4	increases expression	1
4-hydroxyphenyl 4-isopropoxyphenylsulfone	decreases expression	1
PF-06840003	decreases expression, decreases reaction	1
sotorasib	affects cotreatment, decreases expression	1
bufotalin	increases expression	1
chloroacetaldehyde	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
bisphenol A	affects expression	1
sodium arsenate	increases abundance, increases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chloride	decreases reaction, increases expression	1
nickel chloride	increases expression	1
benzo(e)pyrene	decreases methylation	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3734144	Binding	Inhibition of PFKFB4 (unknown origin) expressed in Escherichia coli assessed as ADP level preincubated for 15 mins followed by addition of fructose-6-phosphate as substrate and ATP measured after 40 mins by luciferase assay	New compounds

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D6AR	HyCyte A-549 KO-hPFKFB4	Cancer cell line	Male
CVCL_D7WU	Ubigene A-549 PFKFB4 KO	Cancer cell line	Male
CVCL_D8S7	Ubigene HCT 116 PFKFB4 KO	Cancer cell line	Male
CVCL_D9MN	Ubigene HEK293 PFKFB4 KO	Transformed cell line	Female
CVCL_E0K0	Ubigene HeLa PFKFB4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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