PFKP

Summary

PFKP (phosphofructokinase, platelet, HGNC:8878) is a protein-coding gene on chromosome 10p15.2, encoding ATP-dependent 6-phosphofructokinase, platelet type (Q01813). Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.

This gene encodes a member of the phosphofructokinase A protein family. The encoded enzyme is the platelet-specific isoform of phosphofructokinase and plays a key role in glycolysis regulation. This gene may play a role in metabolic reprogramming in some cancers, including clear cell renal cell carcinomas, and cancer of the bladder, breast, and lung. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5214 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 208 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002627

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8878
Approved symbol	PFKP
Name	phosphofructokinase, platelet
Location	10p15.2
Locus type	gene with protein product
Status	Approved
Aliases	PFK-C, PFKF
Ensembl gene	ENSG00000067057
Ensembl biotype	protein_coding
OMIM	171840
Entrez	5214

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 22 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000381072, ENST00000381075, ENST00000381125, ENST00000407806, ENST00000413079, ENST00000415005, ENST00000421751, ENST00000433193, ENST00000460445, ENST00000468050, ENST00000495715, ENST00000607886, ENST00000676796, ENST00000677351, ENST00000678089, ENST00000678206, ENST00000699222, ENST00000867378, ENST00000867379, ENST00000867380, ENST00000867381, ENST00000867382, ENST00000867383, ENST00000963518, ENST00000963519, ENST00000963520, ENST00000963521, ENST00000963522, ENST00000963523

RefSeq mRNA: 12 — MANE Select: NM_002627 NM_001242339, NM_001323067, NM_001323068, NM_001323069, NM_001323070, NM_001323071, NM_001323072, NM_001323073, NM_001323074, NM_001345944, NM_001410880, NM_002627

CCDS: CCDS7059, CCDS91202, CCDS91203, CCDS91204

Canonical transcript exons

ENST00000381125 — 22 exons

Exon	Start	End
ENSE00001606866	3133203	3133314
ENSE00001634832	3132380	3132441
ENSE00001638550	3109355	3109480
ENSE00001643566	3119892	3120044
ENSE00001690153	3134483	3134582
ENSE00001712413	3118782	3118869
ENSE00001722279	3113372	3113518
ENSE00001753049	3135736	3135838
ENSE00001754765	3112222	3112286
ENSE00001784119	3103779	3103944
ENSE00001791419	3113119	3113188
ENSE00001797079	3116776	3116846
ENSE00002182236	3129819	3129983
ENSE00003475963	3105115	3105159
ENSE00003507485	3082388	3082461
ENSE00003703345	3108701	3108793
ENSE00003707565	3105393	3105501
ENSE00003709765	3099275	3099352
ENSE00003710369	3107214	3107309
ENSE00003785562	3101365	3101554
ENSE00003976001	3067548	3067707
ENSE00003976003	3136450	3136802

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 99.6653 / max 567.6150, expressed in 1819 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103478	96.5696	1819
103479	1.5204	917
103484	0.3594	84
103477	0.3031	129
103482	0.2649	88
103476	0.2076	114
103486	0.1669	56
103485	0.1423	56
103483	0.0798	45
103487	0.0512	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.58	gold quality
saphenous vein	UBERON:0007318	98.23	gold quality
dorsal root ganglion	UBERON:0000044	98.20	gold quality
right frontal lobe	UBERON:0002810	97.99	gold quality
left testis	UBERON:0004533	97.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.80	gold quality
apex of heart	UBERON:0002098	97.59	gold quality
right testis	UBERON:0004534	97.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.54	gold quality
cerebellar hemisphere	UBERON:0002245	97.39	gold quality
cerebellar cortex	UBERON:0002129	97.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.25	gold quality
sperm	CL:0000019	97.23	gold quality
cingulate cortex	UBERON:0003027	97.22	gold quality
anterior cingulate cortex	UBERON:0009835	97.19	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.18	gold quality
prefrontal cortex	UBERON:0000451	97.14	gold quality
cerebellum	UBERON:0002037	97.11	gold quality
heart left ventricle	UBERON:0002084	97.11	gold quality
pons	UBERON:0000988	97.09	gold quality
frontal cortex	UBERON:0001870	97.06	gold quality
cardiac ventricle	UBERON:0002082	97.05	gold quality
lower esophagus mucosa	UBERON:0035834	97.05	gold quality
cartilage tissue	UBERON:0002418	97.04	gold quality
lower esophagus	UBERON:0013473	96.82	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.82	gold quality
male germ cell	CL:0000015	96.80	gold quality
ascending aorta	UBERON:0001496	96.79	gold quality
neocortex	UBERON:0001950	96.79	gold quality
thoracic aorta	UBERON:0001515	96.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, KLF4, PPARG, TGFB1, THRB, ZBTB7A

miRNA regulators (miRDB)

25 targeting PFKP, 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-512-3P	99.97	67.35	1049
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-3198	97.84	65.64	579
HSA-MIR-4309	97.84	65.45	588
HSA-MIR-4678	97.59	68.31	902
HSA-MIR-4536-3P	97.06	66.88	175
HSA-MIR-331-5P	96.59	67.94	705
HSA-MIR-6082	96.40	70.86	216
HSA-MIR-6828-3P	96.06	67.61	1155

Literature-anchored findings (GeneRIF, showing 33)

• PFKP was identified using a trifunctional phenyl sulfonate probe. (PMID:12438565)
• The transcription start point was determined at 48 bp upstream of the start codon. the region -65 to +48 turned out to be sufficient for promoter activity (PMID:15716112)
• Two phosphofructokinase (PFK) chimeras were constructed by exchanging the N- and C-terminal halves of the mammalian M- and C-type isozymes. (PMID:17544406)
• PFKP polymorphisms play no apparent role in the development of common forms of obesity in the Danish population. (PMID:18682847)
• KLF4 plays a role in maintenance of high glycolytic metabolism by transcriptional activation of the PFKP gene in breast cancer cells. (PMID:21586797)
• expression of TARDBP is significantly elevated in HCC and it regulates the expression of PFKP, the rate-limiting enzyme for glycolysis, through negative regulation of microRNA 520s (miR-520s). (PMID:23389994)
• Anti-human protein S antibody induces tissue factor expression through a direct interaction with PFKP and ERK1/2 activation in coronary artery endothelial cells. (PMID:24331211)
• The crystallized PFKP is permanently activated by a deletion of the 22 C-terminal residues. (PMID:26205495)
• Data indicate that platelet isoform of phosphofructokinase (PFKP) not only is required for metabolic reprogramming and maintaining cell proliferation, but also may be a valid target for anti-renal cancer pharmaceutical agents. (PMID:27049827)
• Snail functions as a metabolic switch between aerobic glycolysis and pentose phosphate pathway by repressing PFKP, a cancer-specific PFK-1, allowing cancer cell survival under metabolic stress. (PMID:28176759)
• Here the authors show that PFK1 platelet isoform is upregulated in Glioblastoma and is required for tumor growth mechanistically, such upregulation is due to an increased stability induced by AKT activation via phosphorylation on residue S386. (PMID:29038421)
• EGFR-phosphorylated platelet isoform of phosphofructokinase 1 promotes PI3K activation, promoting the Warburg effect, tumor cell proliferation, and brain tumorigenesis. (PMID:29677490)
• PFKP expression was significantly increased in OSCC patients. (PMID:29894707)
• The observed changes are suggestive of compositional changes in the subunit makeup of HK and PFK. The implication of these findings in relation to energy status of the diabetic erythrocyte and its interrelationship with loss of cell deformability are discussed here. (PMID:31520487)
• PFKP is highly expressed in lung cancer and regulates glucose metabolism. (PMID:32219704)
• PFKP phenotype in lung cancer: prognostic potential and beyond. (PMID:32915402)
• Prognostic and therapeutic relevance of phosphofructokinase platelet-type (PFKP) in breast cancer. (PMID:32919954)
• Biochemical and transcript level differences between the three human phosphofructokinases show optimisation of each isoform for specific metabolic niches. (PMID:33141153)
• Platelet isoform of phosphofructokinase promotes aerobic glycolysis and the progression of nonsmall cell lung cancer. (PMID:33236133)
• PFKP facilitates ATG4B phosphorylation during amino acid deprivation-induced autophagy. (PMID:33607258)
• Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer. (PMID:33849067)
• Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia. (PMID:34255748)
• Silencing PFKP restrains the stemness of hepatocellular carcinoma cells. (PMID:34418458)
• Platelet isoform of phosphofructokinase accelerates malignant features in breast cancer. (PMID:34751415)
• PFKP Activation Ameliorates Foot Process Fusion in Podocytes in Diabetic Kidney Disease. (PMID:35095764)
• Phosphofructokinase 1 platelet isoform induces PD-L1 expression to promote glioblastoma immune evasion. (PMID:35917090)
• Mutual regulation between phosphofructokinase 1 platelet isoform and VEGF promotes glioblastoma tumor growth. (PMID:36435833)
• Phosphofructokinase 1 Platelet Isoform Enhances VEGF Expression in Part Through HIF-1alpha Up-regulation in Breast Cancer. (PMID:36585185)
• Glycolysis regulator PFKP induces human melanoma cell proliferation and tumor growth. (PMID:36792847)
• p53-responsive CMBL reprograms glucose metabolism and suppresses cancer development by destabilizing phosphofructokinase PFKP. (PMID:37967006)
• Inhibition of PFKP in renal tubular epithelial cell restrains TGF-beta induced glycolysis and renal fibrosis. (PMID:38086793)
• PFKP deubiquitination and stabilization by USP5 activate aerobic glycolysis to promote triple-negative breast cancer progression. (PMID:38217030)
• A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression. (PMID:38982480)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pfkpb	ENSDARG00000012801
danio_rerio	pfkpa	ENSDARG00000028000
mus_musculus	Pfkp	ENSMUSG00000021196
rattus_norvegicus	Pfkp	ENSRNOG00000017163
drosophila_melanogaster	Pfk	FBGN0003071
caenorhabditis_elegans		WBGENE00022199

Paralogs (2): PFKL (ENSG00000141959), PFKM (ENSG00000152556)

Protein

Protein identifiers

ATP-dependent 6-phosphofructokinase, platelet type — Q01813 (reviewed: Q01813)

Alternative names: 6-phosphofructokinase type C, Phosphofructo-1-kinase isozyme C, Phosphohexokinase

All UniProt accessions (11): Q01813, A0A7I2V3Z0, A0A7I2V5S1, A0A7I2YQB6, A0A8V8TMY4, B1APP6, H0Y3Y3, H0Y757, Q5VSR5, V9GY25, V9GYV7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.

Subunit / interactions. Homo- and heterotetramers. Phosphofructokinase (PFK) enzyme functions as a tetramer composed of different combinations of 3 types of subunits, called PFKM (where M stands for Muscle), PFKL (Liver) and PFKP (Platelet). The composition of the PFK tetramer differs according to the tissue type it is present in. In muscles, it is composed of 4 PFKM subunits (also called M4). In the liver, the predominant form is a tetramer of PFKL subunits (L4). In erythrocytes, both PFKM and PFKL subunits randomly tetramerize to form M4, L4 and other combinations (ML3, M2L2, M3L). In platelets, brain and fibroblasts, PFK contains a higher proportion of PFKP subunits. The kinetic and regulatory properties of the tetrameric enzyme are dependent on the subunit composition, hence can vary across tissues. Interacts with ATG4B; promoting phosphorylation of ATG4B.

Subcellular location. Cytoplasm.

Post-translational modifications. Phosphorylation at Ser-386 promotes interaction with ATG4B. GlcNAcylation decreases enzyme activity.

Activity regulation. Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.

Pathway. Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 3/4.

Miscellaneous. In human PFK exists as a system of 3 types of subunits, PFKM (muscle), PFKL (liver) and PFKP (platelet) isoenzymes.

Similarity. Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade ‘E’ sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q01813-1	1	yes
Q01813-2	2

RefSeq proteins (12): NP_001229268, NP_001309996, NP_001309997, NP_001309998, NP_001309999, NP_001310000, NP_001310001, NP_001310002, NP_001310003, NP_001332873, NP_001397809, NP_002618* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000023	Phosphofructokinase_dom	Domain
IPR009161	6-Pfructokinase_euk	Family
IPR015912	Phosphofructokinase_CS	Conserved_site
IPR022953	ATP_PFK	Family
IPR035966	PKF_sf	Homologous_superfamily
IPR041914	PFK_vert-type	Family

Pfam: PF00365

Enzyme classification (BRENDA):

• EC 2.7.1.11 — 6-phosphofructokinase (BRENDA: 98 organisms, 152 substrates, 280 inhibitors, 278 Km, 43 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ATP	0.005–0.82	125
D-FRUCTOSE 6-PHOSPHATE	0.007–254	69
GTP	0.0006–4.3	9
CTP	0.018–11	8
UTP	0.009–5.1	8
ITP	0.003–2.2	6
ADP	0.32–1.4	5
FRUCTOSE 6-PHOSPHATE	0.01–0.2	4
D-FRUCTOSE 1,6-BISPHOSPHATE	0.7–16.7	3
MG2+	0.01–0.025	2
2-DEHYDRO-3-DEOXY-D-GLUCONATE	8.8	1
ADENOSINE	1	1
AMP	1.57	1
D-GLUCOSE	90	1
D-GLUCOSE 6-PHOSPHATE	0.6	1

Catalyzed reactions (Rhea), 1 shown:

• beta-D-fructose 6-phosphate + ATP = beta-D-fructose 1,6-bisphosphate + ADP + H(+) (RHEA:16109)

UniProt features (118 total): helix 37, strand 33, binding site 18, modified residue 11, turn 7, sequence conflict 4, region of interest 3, chain 1, glycosylation site 1, splice variant 1, mutagenesis site 1, active site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4XZ2	X-RAY DIFFRACTION	2.67
4U1R	X-RAY DIFFRACTION	2.8
4WL0	X-RAY DIFFRACTION	2.89
4RH3	X-RAY DIFFRACTION	3.02
4XYJ	X-RAY DIFFRACTION	3.1
4XYK	X-RAY DIFFRACTION	3.4
7TFF	X-RAY DIFFRACTION	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01813-F1	92.15	0.82

Functional residue map

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

Catalytic / active sites (1): 175 (proton acceptor)

Ligand- & substrate-binding residues (18): 210; 217–219 (in other chain); 273 (in other chain); 301; 307–310 (in other chain); 481 (in other chain); 538–542 (in other chain); 576; 583–585 (in other chain); 639 (in other chain); 665; 671–674 (in other chain) …

Post-translational modifications (11): 1, 6, 12, 21, 142, 386, 395, 486, 651, 688, 783

Glycosylation sites (1): 540

Mutagenesis-validated functional residues (1):

Position	Phenotype
386	decreased interaction with atg4b.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70171	Glycolysis

MSigDB gene sets: 368 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, HARRIS_HYPOXIA, GOBP_RESPONSE_TO_PEPTIDE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (6): fructose 6-phosphate metabolic process (GO:0006002), fructose 1,6-bisphosphate metabolic process (GO:0030388), canonical glycolysis (GO:0061621), cellular response to leukemia inhibitory factor (GO:1990830), glycolytic process (GO:0006096), glycolytic process through fructose-6-phosphate (GO:0061615)

GO Molecular Function (12): 6-phosphofructokinase activity (GO:0003872), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), cadherin binding (GO:0045296), metal ion binding (GO:0046872), fructose-6-phosphate binding (GO:0070095), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), 6-phosphofructokinase complex (GO:0005945), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glucose metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
organophosphate metabolic process	2
carbohydrate derivative metabolic process	2
binding	2
glucokinase activity	1
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity	1
glucose catabolic process	1
glycolytic process through glucose-6-phosphate	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	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
6-phosphofructokinase activity	1
fructose-bisphosphate aldolase activity	1
triose-phosphate isomerase activity	1
glycolytic process	1
phosphofructokinase activity	1
glycolytic process through fructose-6-phosphate	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
cell adhesion molecule binding	1
cation binding	1
anion binding	1
carbohydrate derivative binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
transferase activity, transferring phosphorus-containing groups	1

Protein interactions and networks

STRING

3078 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PFKP	HK1	P19367	948
PFKP	ALDOA	P04075	812
PFKP	J3KPS3	J3KPS3	791
PFKP	LDHA	P00338	790
PFKP	VDAC2	P45880	751
PFKP	PKM	P14618	743
PFKP	ALDOB	P05062	733
PFKP	TPI1	P00938	695
PFKP	PGAM4	Q8N0Y7	680
PFKP	PGK1	P00558	677
PFKP	ENO1	P06733	668
PFKP	ALDOC	P09972	666
PFKP	PGAM1	P18669	662
PFKP	FBP1	P09467	660
PFKP	PFKL	P17858	654

IntAct

148 interactions, top by confidence:

A	B	Type	Score
WDR19	TULP3	psi-mi:“MI:0914”(association)	0.860
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
PFKP	PFKM	psi-mi:“MI:0915”(physical association)	0.590
NUTF2	PFKP	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
PFKL	PFKP	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
IFT122	CDC7	psi-mi:“MI:0914”(association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
	MYL12B	psi-mi:“MI:0914”(association)	0.460
TUBA1A	TUBAL3	psi-mi:“MI:0914”(association)	0.420
TGOLN2	PGRMC1	psi-mi:“MI:0914”(association)	0.420
ALK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
FLT4	ILVBL	psi-mi:“MI:0914”(association)	0.420
AATK	NDUFA4	psi-mi:“MI:0914”(association)	0.420
MET	NDUFA4	psi-mi:“MI:2364”(proximity)	0.420
MIA2	PFKP	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
PFKP	YWHAZ	psi-mi:“MI:0915”(physical association)	0.400
TERF1	PFKP	psi-mi:“MI:0915”(physical association)	0.370
TINF2	PFKP	psi-mi:“MI:0915”(physical association)	0.370
ACD	PFKP	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (439): PFKP (Affinity Capture-MS), PFKP (Affinity Capture-MS), PFKP (Affinity Capture-MS), ALDH16A1 (Co-fractionation), ARFIP1 (Co-fractionation), ARHGAP1 (Co-fractionation), CCDC22 (Co-fractionation), DNAJC9 (Co-fractionation), EEF1A1 (Co-fractionation), MCFD2 (Co-fractionation), MCMBP (Co-fractionation), MTHFD1 (Co-fractionation), NMD3 (Co-fractionation), NPEPL1 (Co-fractionation), OXSR1 (Co-fractionation)

ESM2 similar proteins: A1A4J1, A2E9H3, A2EF58, C4QXA5, O42938, O61068, O83146, O94200, O94201, P00511, P08237, P12382, P16862, P17858, P30835, P47857, P47858, P47859, P47860, P51553, P52034, P52784, P59680, P78985, Q01813, Q03216, Q0IIG5, Q27483, Q27665, Q27705, Q27778, Q2HYU2, Q2RNU4, Q4W9B8, Q5R636, Q5R7V5, Q5RAG9, Q60HD9, Q867C9, Q8TGA0

Diamond homologs: A0PYC8, A0RJJ6, A1A4J1, A5I798, A5IKL2, A6TVD3, A7FYW7, A7GIW9, A7GTP4, A7Z7K6, A8FG55, A8MLY0, A9VJR1, B0K6L2, B0K7U7, B1IFV9, B1L266, B1L9U3, B2A6Y0, B7GGT1, B7HFB3, B7HRN9, B7IJZ8, B7JRX2, B8D1K5, B9DN94, B9J099, B9K6R9, C0Z7W7, C1EUU3, C1FM55, C3KV06, C3L8X8, C3PAI8, C4K7E1, C4LEQ5, C4QXA5, C5D663, O34529, O42938

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
PFKP	“down-regulates quantity”	“β-D-fructose 6-phosphate”	“chemical modification”
PFKP	“up-regulates quantity”	“beta-D-fructofuranose 1,6-bisphosphate(4-)”	“chemical modification”
“beta-D-fructofuranose 2,6-bisphosphate”	“up-regulates activity”	PFKP	binding
OGT	“down-regulates activity”	PFKP	glycosylation
OGA	“up-regulates activity”	PFKP	deglycosylation
CyclinD3/CDK6	“down-regulates activity”	PFKP	phosphorylation
PFKP	“up-regulates activity”	ATG4B	phosphorylation
PTEN	“down-regulates activity”	PFKP	dephosphorylation
AKT1	“up-regulates quantity”	PFKP	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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
Telomere Extension By Telomerase	5	19.4×	1e-03
RHO GTPases activate PKNs	5	13.4×	2e-03
Defective CFTR causes cystic fibrosis	6	11.2×	1e-03
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	6	9.8×	2e-03
Constitutive Signaling by Aberrant PI3K in Cancer	9	9.7×	9e-05
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	9.7×	6e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	9.2×	1e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	11	9.0×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	8	24.8×	1e-06
protein autophosphorylation	11	11.8×	2e-06
cell surface receptor protein tyrosine kinase signaling pathway	9	11.5×	3e-05
positive regulation of MAPK cascade	13	7.7×	7e-06
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	11	6.3×	4e-04
protein phosphorylation	11	5.5×	8e-04
cell migration	10	4.5×	6e-03
negative regulation of apoptotic process	16	4.1×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	127
Likely benign	24
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

4267 predictions. Top by Δscore:

Variant	Effect	Δscore
10:3067704:CAAGG:C	donor_loss	1.0000
10:3067705:AAGG:A	donor_loss	1.0000
10:3067706:AGGTG:A	donor_loss	1.0000
10:3067707:GGTG:G	donor_loss	1.0000
10:3067708:GTGC:G	donor_loss	1.0000
10:3082381:A:AG	acceptor_gain	1.0000
10:3082382:CTGCA:C	acceptor_loss	1.0000
10:3082383:T:A	acceptor_gain	1.0000
10:3082383:TGCAG:T	acceptor_loss	1.0000
10:3082384:GCA:G	acceptor_loss	1.0000
10:3082385:CAGG:C	acceptor_loss	1.0000
10:3082386:A:AG	acceptor_gain	1.0000
10:3082386:AG:A	acceptor_gain	1.0000
10:3082387:G:GG	acceptor_gain	1.0000
10:3082387:G:GT	acceptor_loss	1.0000
10:3082387:GG:G	acceptor_gain	1.0000
10:3082387:GGT:G	acceptor_gain	1.0000
10:3082387:GGTA:G	acceptor_gain	1.0000
10:3082387:GGTAT:G	acceptor_gain	1.0000
10:3082457:ACGAG:A	donor_loss	1.0000
10:3082461:GGT:G	donor_loss	1.0000
10:3082462:G:GA	donor_loss	1.0000
10:3082463:T:A	donor_loss	1.0000
10:3099270:CCTA:C	acceptor_loss	1.0000
10:3099271:CTA:C	acceptor_loss	1.0000
10:3099272:TAGG:T	acceptor_loss	1.0000
10:3099273:A:AG	acceptor_gain	1.0000
10:3099273:A:G	acceptor_loss	1.0000
10:3099273:AG:A	acceptor_gain	1.0000
10:3099274:G:GG	acceptor_gain	1.0000

AlphaMissense

5149 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:3067707:G:C	G38R	1.000
10:3103841:T:C	S173P	1.000
10:3103848:A:T	D175V	1.000
10:3103851:A:T	N176I	1.000
10:3103852:T:A	N176K	1.000
10:3103852:T:G	N176K	1.000
10:3103854:A:C	D177A	1.000
10:3103854:A:G	D177G	1.000
10:3103854:A:T	D177V	1.000
10:3103875:C:T	T184I	1.000
10:3103880:G:C	G186R	1.000
10:3103881:G:A	G186D	1.000
10:3103881:G:T	G186V	1.000
10:3103938:C:A	A205D	1.000
10:3105116:C:G	H208D	1.000
10:3105123:G:T	R210M	1.000
10:3105128:T:C	F212L	1.000
10:3105130:C:A	F212L	1.000
10:3105130:C:G	F212L	1.000
10:3105146:G:A	G218R	1.000
10:3105146:G:C	G218R	1.000
10:3105157:T:G	C221W	1.000
10:3108747:G:A	G306E	1.000
10:3108757:G:C	Q309H	1.000
10:3108757:G:T	Q309H	1.000
10:3108786:G:T	R319M	1.000
10:3113417:G:T	G424W	1.000
10:3116809:T:A	W469R	1.000
10:3116809:T:C	W469R	1.000
10:3129844:C:A	A570D	1.000

dbSNP variants (sampled 300 via entrez): RS1000093095 (10:3118258 A>G), RS1000187549 (10:3100310 G>C), RS1000189029 (10:3070958 G>A), RS1000229266 (10:3125473 G>A,T), RS1000235685 (10:3100087 A>G), RS1000261630 (10:3136221 C>T), RS1000300602 (10:3087343 A>C,G), RS1000317729 (10:3098901 G>A,C), RS1000324748 (10:3124116 T>C), RS1000338956 (10:3091151 G>A,C,T), RS1000371409 (10:3132672 C>A,T), RS1000405025 (10:3103302 C>G), RS1000425293 (10:3132537 C>A,T), RS1000462925 (10:3121985 C>A), RS1000474608 (10:3109212 G>A)

Disease associations

OMIM: gene MIM:171840 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (2): Microphthalmia-anophthalmia-coloboma (Orphanet:98555), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001687_7	Disc degeneration (lumbar)	2.000000e-06
GCST002337_57	Amyotrophic lateral sclerosis (sporadic)	2.000000e-09
GCST003474_6	Scalp hair shape	3.000000e-06
GCST004527_1	Subclinical trait of interstitial lung disease (percentage of high attenuation areas on CT scan)	3.000000e-10
GCST007013_5	Hippocampal volume in mild cognitive impairment	7.000000e-07
GCST010989_82	Body size at age 10	5.000000e-20
GCST011743_50	HDL cholesterol levels in HIV infection	3.000000e-06
GCST90002395_67	Mean platelet volume	1.000000e-10
GCST90002395_68	Mean platelet volume	6.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007627	airway imaging measurement
EFO:0005035	hippocampal volume
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2972 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,961 (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
CHEMBL2336325	VISTUSERTIB	2	1,961

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.24	Kd	5.711	nM	CHEMBL5653589
8.24	ED50	5.711	nM	CHEMBL5653589
6.01	Kd	983	nM	VISTUSERTIB
5.02	Kd	9488	nM	CHEMBL3752910
5.02	ED50	9488	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 226 total; 3 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148983: Binding affinity to human PFKP incubated for 45 mins by Kinobead based pull down assay	kd	0.0057	uM
3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide	1425108: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.9830	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148983: Binding affinity to human PFKP incubated for 45 mins by Kinobead based pull down assay	kd	9.4879	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
Aflatoxin B1	affects expression, increases expression, increases methylation	5
bisphenol A	decreases expression, increases expression, affects cotreatment	4
Tetrachlorodibenzodioxin	increases expression, affects cotreatment	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	4
methylmercuric chloride	decreases expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	increases expression, increases methylation	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	affects cotreatment, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Endosulfan	affects cotreatment, increases expression	2
Estradiol	increases expression, decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	increases expression	2
Rotenone	increases expression	2
Cyclosporine	increases expression	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
PF-06840003	decreases expression, decreases reaction	1
2,4,6-tribromophenol	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
scoparone	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991821	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2AH	Abcam HeLa PFKP KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists