PGK1

Summary

PGK1 (phosphoglycerate kinase 1, HGNC:8896) is a protein-coding gene on chromosome Xq21.1, encoding Phosphoglycerate kinase 1 (P00558). Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. It is a selective cancer dependency (DepMap: 86.6% of cell lines).

The protein encoded by this gene is a glycolytic enzyme that catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. The encoded protein may also act as a cofactor for polymerase alpha. Additionally, this protein is secreted by tumor cells where it participates in angiogenesis by functioning to reduce disulfide bonds in the serine protease, plasmin, which consequently leads to the release of the tumor blood vessel inhibitor angiostatin. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Deficiency of the enzyme is associated with a wide range of clinical phenotypes hemolytic anemia and neurological impairment. Pseudogenes of this gene have been defined on chromosomes 19, 21 and the X chromosome.

Source: NCBI Gene 5230 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycogen storage disease due to phosphoglycerate kinase 1 deficiency (Definitive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 379 total — 16 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 86.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000291

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8896
Approved symbol	PGK1
Name	phosphoglycerate kinase 1
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000102144
Ensembl biotype	protein_coding
OMIM	311800
Entrez	5230

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000373316, ENST00000474281, ENST00000476531, ENST00000477335, ENST00000491291, ENST00000644362, ENST00000878877, ENST00000878878, ENST00000878879, ENST00000925019, ENST00000925020, ENST00000925021, ENST00000925022, ENST00000925023, ENST00000925024, ENST00000951220, ENST00000951221

RefSeq mRNA: 1 — MANE Select: NM_000291 NM_000291

CCDS: CCDS14438

Canonical transcript exons

ENST00000373316 — 11 exons

Exon	Start	End
ENSE00000672994	78125327	78125425
ENSE00000672995	78124874	78125051
ENSE00000672996	78123195	78123374
ENSE00000672997	78122835	78122949
ENSE00001600900	78104248	78104405
ENSE00001948816	78125790	78129295
ENSE00003502842	78113744	78113899
ENSE00003506377	78109867	78109917
ENSE00003512377	78114016	78114160
ENSE00003581136	78117312	78117415
ENSE00003597777	78118051	78118170

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4042 / max 278.7995, expressed in 1728 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196779	407.1318	1827
196777	9.4042	1728
196780	9.3745	1759

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	99.75	gold quality
epithelium of esophagus	UBERON:0001976	99.69	gold quality
tibia	UBERON:0000979	99.60	gold quality
germinal epithelium of ovary	UBERON:0001304	99.59	gold quality
heart right ventricle	UBERON:0002080	99.57	gold quality
squamous epithelium	UBERON:0006914	99.56	gold quality
pericardium	UBERON:0002407	99.50	gold quality
parotid gland	UBERON:0001831	99.49	gold quality
pons	UBERON:0000988	99.48	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.48	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.48	gold quality
trabecular bone tissue	UBERON:0002483	99.46	gold quality
palpebral conjunctiva	UBERON:0001812	99.44	gold quality
gingival epithelium	UBERON:0001949	99.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.43	gold quality
renal medulla	UBERON:0000362	99.42	gold quality
biceps brachii	UBERON:0001507	99.42	gold quality
gingiva	UBERON:0001828	99.42	gold quality
colonic mucosa	UBERON:0000317	99.40	gold quality
epithelium of nasopharynx	UBERON:0001951	99.40	gold quality
oral cavity	UBERON:0000167	99.35	gold quality
middle temporal gyrus	UBERON:0002771	99.35	gold quality
tongue squamous epithelium	UBERON:0006919	99.35	gold quality
amniotic fluid	UBERON:0000173	99.34	gold quality
bone marrow	UBERON:0002371	99.33	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.33	gold quality
pharyngeal mucosa	UBERON:0000355	99.29	gold quality
jejunal mucosa	UBERON:0000399	99.27	gold quality
penis	UBERON:0000989	99.26	gold quality
type B pancreatic cell	CL:0000169	99.25	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	2899.65
E-GEOD-124472	yes	2541.99
E-MTAB-8142	yes	52.36
E-CURD-88	yes	46.55
E-MTAB-10042	yes	16.78
E-MTAB-7249	no	16872.65
E-MTAB-6819	no	7060.59
E-MTAB-6524	no	1917.58
E-MTAB-8559	no	1357.46
E-MTAB-6108	no	1287.36
E-HCAD-8	no	41.58
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, EGR1, ENO1, HIF1A, LEF1, MYC, PHF20, PPARG

miRNA regulators (miRDB)

55 targeting PGK1, 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-4713-3P	100.00	65.92	505
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-4635	98.74	67.63	1339

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 86.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Phosphoglycerate kinase is a moonlighting protein that functions as both a glycolytic enzyme and a disulfide reductase. (PMID:11130727)
• Phosphorylates pyrimidine L-deoxynucleoside analog diphosphaates (PMID:12080078)
• Overexpression induces a multidrug resistance phenotype. (PMID:12174867)
• 3-phosphoglycerate kinase has a role in the activation of L-nucleoside analogs (PMID:12869554)
• These results demonstrate that phosphpglycerate kinase regulates uPAR expression at the post-transcriptional level. (PMID:14764427)
• production and secretion of PGK are regulated separately and oxygen and the protein hydroxylases can control not only gene expression but also protein secretion (PMID:15053920)
• phosphoglycerate kinase does not appear to have a role in the development or progression of neoplasms [letter] (PMID:15255553)
• During domain closure, Lys 215 in 3-phosphoglycerate kinase possibly moves together with the transferring phosphate, and this group is being positioned properly for catalysis. (PMID:16363799)
• The impact of hypoxic treatment on the expression of PGK1 and the cytotoxicity of troxacitabine and gemcitabine are reported. (PMID:17565005)
• our study indicates that inhibition of the transcription mechanism is the cause of PGK deficiency. (PMID:17661373)
• Aa steady state kinetic and biophysical study of the interaction of the model compound l-MgADP with hPGK, is presented. (PMID:18096512)
• Although L-ADP is almost as catalytically competent as D-ADP, under our experimental conditions (buffer containing 30% methanol, 4 degrees C) phosphoglycerate kinase binds D- and L-ADP with similar kinetics. (PMID:18288812)
• overexpression of PGK1 and its signalling targets may be a expression-pathway in diffuse primary gastric carcinomas promoting peritoneal dissemination (PMID:18453750)
• transmission path of the nucleotide effect toward the main hinge of phosphoglycerate kinase is described for the first time at the level of interactions existing in the tertiary structure[ 3-phosphoglycerate kinase] (PMID:18540639)
• PGK1 was selectively overexpressed in human colon tumor cells by treating with hydrogen peroxide as oxidative stress, while its expression was suppressed by co-treatment with antioxidants. (PMID:18603805)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• Data show that PGK1 regulates the expression of CXCR4 and beta-catenin at the mRNA and protein levels. (PMID:19688824)
• Phosphoglycerate kinase 1 (PGK1) showed a difference between follicular cells from follicles leading to a pregnancy or developmental failure. (PMID:19778949)
• Results suggest that conformational rearrangements in the hinge generated by binding of both substrates provide the main driving force for domain closure overcoming the slightly unfavourable contact interactions between the domains. (PMID:19854185)
• PGK domain movement and catalysis is regulated by a spring-loaded release mechanism (PMID:21349853)
• enzyme kinetics studies show that the absence of the ribose OH-groups with is better tolerated for the purine than for the pyrimidine containing compounds in phosphoglycerate kinase 1 (PMID:21505655)
• Molecular dynamics simulations were carried out with four different nucleotides (D-/L-ADP and D-/L-CDP) in complex with PGK and 1,3-bisphospho-d-glycerate. The binding affinities of CDPs were very weak while D- and L-ADP were better substrates. (PMID:21549683)
• two key (hub) PPARgamma direct target genes, PRKCZ and PGK1, were experimentally validated to be repressed upon PPARgamma activation by its natural ligand, 15d-PGJ2 in three prostrate cancer cell lines (PMID:21780947)
• All findings indicate that the different clinical manifestations associated with PGK1 deficiency chiefly depend on the distinctive type of perturbations caused by mutations in the PGK1 gene (PMID:22348148)
• carbonic anhydrase I, phosphoglycerate kinase 1 and apolipoprotein A-I appeared to be the most significant variations of proteins in patients with osteopenia and osteoarthritis (PMID:22619369)
• Phosphoglycerate kinase 1 was up-regulated significantly in radioresistant astrocytomas and also seems to be correlated with the negative prognosis following radiotherapy. (PMID:22742733)
• Glycolytic enzymes PGK1 and PKM2 are novel transcriptional targets of PPARgamma in breast cancer. (PMID:23130662)
• Generif: Phosphoglycerate kinase is a moonlighting protein that functions as both a glycolytic enzyme and a primer recognition protein of DNA polymerase alpha. (PMID:2324090)
• the low kinetic stability displayed by PGK1 protein mutations is causing human PGK1 deficiency (PMID:23336698)
• Conformational dynamics in the catalytic cycle of phosphoglycerate kinase, molecular details provided by structural analysis. [Review] (PMID:23684636)
• increased expression of PGK1 in colon cancer tissue is associated with metastasis. (PMID:23727790)
• PGK1 could promote radioresistance in U251 human cells. (PMID:24284928)
• PGK1 appears to play an important role for neuroblastoma (PMID:24376734)
• different factors contributing to hPGK1 thermodynamic and kinetic stability (PMID:24721582)
• mutations associated with hPGK1 deficiency lead to increased aggregation and proteolysis rates in vitro and inside cells due to protein thermodynamic destabilization (PMID:24838780)
• Phosphoglycerate kinase deficiency due to a novel mutation (c. 1180A>G) manifesting as chronic hemolytic anemia in a Japanese boy. (PMID:24934115)
• Suppression of PGK1 enhanced the radiosensitivity of U251 xenografts and suggest that PGK1 may serve as a useful target in the treatment of radioresistant glioma. (PMID:25175369)
• Results show that PGK1 mRNA and protein expression were significantly increased in breast cancer tissues and can be considered as a prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer. (PMID:25867275)
• PI3K/AKT/mTOR pathway regulates HDAC3 S424 phosphorylation, which promotes HDAC3-PGK1 interaction and PGK1 K220 deacetylation (PMID:26356530)
• Retinal dystrophy may be one of the clinical manifestations of phosphoglycerate kinase deficiency. (PMID:26396085)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgk1	ENSDARG00000054191
mus_musculus	Pgk1	ENSMUSG00000062070
rattus_norvegicus	Pgk1	ENSRNOG00000058249
drosophila_melanogaster	CG9961	FBGN0031451
drosophila_melanogaster	Pgk	FBGN0250906
caenorhabditis_elegans	pgk-1	WBGENE00020185

Paralogs (1): PGK2 (ENSG00000170950)

Protein

Protein identifiers

Phosphoglycerate kinase 1 — P00558 (reviewed: P00558)

Alternative names: Cell migration-inducing gene 10 protein, Primer recognition protein 2

All UniProt accessions (2): P00558, V9HWF4

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. Both L- and D- forms of purine and pyrimidine nucleotides can be used as substrates, but the activity is much lower on pyrimidines. In addition to its role as a glycolytic enzyme, it seems that PGK1 acts as a polymerase alpha cofactor protein (primer recognition protein). Acts as a protein kinase when localized to the mitochondrion where it phosphorylates pyruvate dehydrogenase kinase PDK1 to inhibit pyruvate dehydrogenase complex activity and suppress the formation of acetyl-coenzyme A from pyruvate, and consequently inhibit oxidative phosphorylation and promote glycolysis. May play a role in sperm motility.

Subunit / interactions. Monomer. Interacts with kinase MAPK1/ERK2; the interaction is direct, occurs under hypoxic conditions, and promotes its interaction with PIN1. Interacts with peptidyl-prolyl cis-trans isomerase PIN1; the interaction is direct, occurs under hypoxic conditions, and targets the protein to the mitochondrion by promoting interactions with the TOM complex. Interacts with mitochondrial circRNA mcPGK1 (via its 2nd stem-loop); the interaction is direct and targets the protein to the mitochondrion by promoting interactions with the TOM complex. Interacts with pyruvate dehydrogenase kinase PDK1; the interaction is direct, occurs under hypoxic conditions and leads to PDK1-mediated inhibition of pyruvate dehydrogenase complex activity.

Subcellular location. Cytoplasm. Cytosol. Mitochondrion matrix.

Tissue specificity. Mainly expressed in spermatogonia. Localized on the principle piece in the sperm (at protein level). Expression significantly decreased in the testis of elderly men.

Post-translational modifications. Phosphorylated at Ser-203 by MAPK1/ERK2 under hypoxic conditions, which promotes its mitochondrial targeting.

Disease relevance. Phosphoglycerate kinase 1 deficiency (PGK1D) [MIM:300653] A condition with a highly variable clinical phenotype that includes hemolytic anemia, rhabdomyolysis, myopathy and neurologic involvement. Patients can express one or more of these manifestations, and some affected individuals develop parkinsonian symptoms. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Specifically inhibited by heterocyclic compound CBR-470-0.

Pathway. Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 2/5.

Miscellaneous. Dysregulated mitochondrial targeting of PGK1 may contribute to the elevation of aerobic glycolysis seen in tumor cells, a phenomenon known as the Warburg effect.

Similarity. Belongs to the phosphoglycerate kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P00558-1	1	yes
P00558-2	2

RefSeq proteins (1): NP_000282* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001576	Phosphoglycerate_kinase	Family
IPR015824	Phosphoglycerate_kinase_N	Homologous_superfamily
IPR015911	Phosphoglycerate_kinase_CS	Conserved_site
IPR036043	Phosphoglycerate_kinase_sf	Homologous_superfamily

Pfam: PF00162

Catalyzed reactions (Rhea), 2 shown:

• (2R)-3-phosphoglycerate + ATP = (2R)-3-phospho-glyceroyl phosphate + ADP (RHEA:14801)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)

UniProt features (133 total): binding site 40, modified residue 26, helix 24, strand 21, sequence variant 12, turn 3, sequence conflict 2, initiator methionine 1, chain 1, region of interest 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
9FDF	X-RAY DIFFRACTION	1.44
2WZB	X-RAY DIFFRACTION	1.47
2WZC	X-RAY DIFFRACTION	1.5
2WZD	X-RAY DIFFRACTION	1.56
9FDN	X-RAY DIFFRACTION	1.58
5M1R	X-RAY DIFFRACTION	1.64
5M6Z	X-RAY DIFFRACTION	1.67
2X13	X-RAY DIFFRACTION	1.74
2XE6	X-RAY DIFFRACTION	1.74
4AXX	X-RAY DIFFRACTION	1.74
9FDH	X-RAY DIFFRACTION	1.76
2XE8	X-RAY DIFFRACTION	1.79
3C3B	X-RAY DIFFRACTION	1.8
5M3U	X-RAY DIFFRACTION	1.81
5O7D	X-RAY DIFFRACTION	1.84
3C39	X-RAY DIFFRACTION	1.85
2X14	X-RAY DIFFRACTION	1.9
5NP8	X-RAY DIFFRACTION	1.9
3ZOZ	X-RAY DIFFRACTION	1.95
8YHP	X-RAY DIFFRACTION	1.95
2YBE	X-RAY DIFFRACTION	2
2ZGV	X-RAY DIFFRACTION	2
5MXM	X-RAY DIFFRACTION	2.05
2X15	X-RAY DIFFRACTION	2.1
4O33	X-RAY DIFFRACTION	2.1
2XE7	X-RAY DIFFRACTION	2.2
3C3A	X-RAY DIFFRACTION	2.3
3C3C	X-RAY DIFFRACTION	2.4
9KER	X-RAY DIFFRACTION	2.5
2Y3I	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00558-F1	96.48	0.93

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 (40): 63; 65; 66; 122; 123; 170; 171; 214; 214; 215; 215; 215 …

Post-translational modifications (26): 2, 2, 4, 6, 11, 48, 48, 75, 76, 86, 91, 97, 97, 131, 131, 146, 191, 196, 199, 203 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
378	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-165159	MTOR signalling
R-HSA-70171	Glycolysis
R-HSA-70263	Gluconeogenesis
R-HSA-9636667	Manipulation of host energy metabolism

MSigDB gene sets: 492 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_EPITHELIUM_DEVELOPMENT, HORIUCHI_WTAP_TARGETS_DN, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, HARRIS_HYPOXIA, KAAB_FAILED_HEART_ATRIUM_DN, MORF_UBE2I, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MENSE_HYPOXIA_UP, MORF_HDAC1, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, HSIAO_HOUSEKEEPING_GENES, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, DARWICHE_SKIN_TUMOR_PROMOTER_UP

GO Biological Process (8): gluconeogenesis (GO:0006094), glycolytic process (GO:0006096), negative regulation of angiogenesis (GO:0016525), epithelial cell differentiation (GO:0030855), plasminogen activation (GO:0031639), canonical glycolysis (GO:0061621), cellular response to hypoxia (GO:0071456), negative regulation of pyruvate decarboxylation to acetyl-CoA (GO:0160218)

GO Molecular Function (12): phosphoglycerate kinase activity (GO:0004618), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), ADP binding (GO:0043531), transmembrane transporter binding (GO:0044325), metal ion binding (GO:0046872), protein-disulfide reductase [NAD(P)H] activity (GO:0047134), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), membrane (GO:0016020), membrane raft (GO:0045121), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), mitochondrion (GO:0005739)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glucose metabolism	2
Signal Transduction	1
Response of Mtb to phagocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein kinase activity	2
adenyl ribonucleotide binding	2
cytoplasm	2
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
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cell differentiation	1
epithelium development	1
zymogen activation	1
glucokinase activity	1
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity	1
glucose catabolic process	1
glycolytic process through glucose-6-phosphate	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
pyruvate decarboxylation to acetyl-CoA	1
regulation of pyruvate decarboxylation to acetyl-CoA	1
negative regulation of acetyl-CoA biosynthesis	1
kinase activity	1
phosphotransferase activity, carboxyl group as acceptor	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein binding	1

Protein interactions and networks

STRING

6740 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGK1	GAPDH	P00354	983
PGK1	ENO1	P06733	928
PGK1	TPI1	P00938	917
PGK1	J3KPS3	J3KPS3	888
PGK1	ALDOA	P04075	870
PGK1	PGAM1	P18669	854
PGK1	PGAM4	Q8N0Y7	846
PGK1	LDHA	P00338	801
PGK1	H6PD	O95479	800
PGK1	VASP	P50552	794
PGK1	ENO2	P09104	789
PGK1	TALDO1	P37837	780
PGK1	PLG	P00747	770
PGK1	PKM	P14618	768
PGK1	ACTB	P02570	767
PGK1	GPI	P06744	767

IntAct

131 interactions, top by confidence:

A	B	Type	Score
PRKAG1	PRKAB2	psi-mi:“MI:0914”(association)	0.940
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PGK2	PGK1	psi-mi:“MI:0915”(physical association)	0.690
PGK1	PGK2	psi-mi:“MI:0915”(physical association)	0.690
PCNA	PGK1	psi-mi:“MI:0915”(physical association)	0.570
GAPDH	PGK1	psi-mi:“MI:0915”(physical association)	0.540
PGK1	GAPDH	psi-mi:“MI:0407”(direct interaction)	0.540
HDAC3	PGK1	psi-mi:“MI:0915”(physical association)	0.520
PGK1	NEK7	psi-mi:“MI:0915”(physical association)	0.500
rep	ACTN4	psi-mi:“MI:0914”(association)	0.480
TNFAIP3	LRRIQ3	psi-mi:“MI:2364”(proximity)	0.420
Cdk1		psi-mi:“MI:0915”(physical association)	0.400
Csnk1e		psi-mi:“MI:0915”(physical association)	0.400
Bles03		psi-mi:“MI:0915”(physical association)	0.400
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
PGK1	YWHAZ	psi-mi:“MI:0915”(physical association)	0.400
PGK1		psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
MYO5C	CLIC1	psi-mi:“MI:0914”(association)	0.350
Rfx5	MRPL27	psi-mi:“MI:0914”(association)	0.350
CENPA	ATP5PD	psi-mi:“MI:0914”(association)	0.350

BioGRID (612): PGK1 (Affinity Capture-MS), PGK1 (Affinity Capture-MS), PGK1 (Affinity Capture-MS), PGK1 (Affinity Capture-MS), AKR1A1 (Co-fractionation), AKR1B1 (Co-fractionation), AKR1B10 (Co-fractionation), ALDOA (Co-fractionation), ALDOC (Co-fractionation), ARPC3 (Co-fractionation), CSE1L (Co-fractionation), EEF1A1 (Co-fractionation), EEF2 (Co-fractionation), ENO1 (Co-fractionation), ENO2 (Co-fractionation)

ESM2 similar proteins: A0A7G5KET3, A0KGD3, A4SRF1, A5A6K4, A5U9X0, A8A466, B7K9Q5, C4LE53, O60101, O61471, O74233, P00558, P00559, P07205, P09041, P09411, P0A7A1, P11977, P14228, P16617, P24590, P29405, P29406, P29407, P29408, P33161, P38667, P41756, P41757, P41759, P50310, P50311, P51903, P74421, P91427, Q01604, Q0I6M5, Q31WI5, Q3AVX6, Q3T0P6

Diamond homologs: A0A7G5KET3, A0PYP1, A1BJZ1, A4SH15, A5A6K4, A5HYC0, A5IJ98, A5N2N8, A6LMG3, A7FQN7, A7G9Y0, A7HCN7, A7HL11, A8F5X9, A9WKE4, B0CD95, B1IDB6, B1KTJ5, B1L8B8, B3EIM1, B3EQD1, B3QLX7, B3QWD9, B4S6S2, B4SHF6, B7IDG7, B7K9Q5, B8G4H3, B9E6B4, C1F1M9, C1FQW3, C3KYR4, O00852, O00869, O00871, O00940, O02608, O02609, O52632, O60101

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
HIF1A	“up-regulates quantity by expression”	PGK1	“transcriptional regulation”
PGK1	“down-regulates quantity”	“3-phosphonato-D-glyceroyl phosphate(4-)”	“chemical modification”
PGK1	“up-regulates quantity”	3-phosphonato-D-glycerate(3-)	“chemical modification”
PDPK1	“up-regulates activity”	PGK1	phosphorylation
PGK1	“up-regulates activity”	PDK1	phosphorylation
PGK1	“up-regulates activity”	PDPK1	phosphorylation
PGK1	“up-regulates activity”	PGK1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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
Dengue Virus Genome Translation and Replication	5	14.0×	8e-03
Oncogenic MAPK signaling	5	11.0×	8e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	8.2×	8e-03
Macroautophagy	7	7.2×	8e-03
Signaling by Interleukins	10	5.7×	8e-03
Organelle biogenesis and maintenance	9	5.3×	8e-03
Cytokine Signaling in Immune system	11	4.0×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	7	15.1×	4e-04
response to xenobiotic stimulus	11	5.6×	2e-03
protein phosphorylation	10	5.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	6
Uncertain significance	177
Likely benign	86
Benign	28

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
3764516	PGK1, IVS4, G-T, 417+1	Pathogenic
3764517	G213G	Pathogenic
3764518	G372S	Pathogenic
3764519	A353P	Pathogenic
3764520	G317D	Pathogenic
9942	NM_000291.4(PGK1):c.802G>A (p.Asp268Asn)	Pathogenic
9943	NM_000291.4(PGK1):c.617G>C (p.Arg206Pro)	Pathogenic
9944	NM_000291.4(PGK1):c.796_798delinsATG (p.Val266Met)	Pathogenic
9946	NM_000291.4(PGK1):c.263T>C (p.Leu88Pro)	Pathogenic
9947	NM_000291.4(PGK1):c.473G>T (p.Gly158Val)	Pathogenic
9948	NM_000291.4(PGK1):c.946T>C (p.Cys316Arg)	Pathogenic
9951	NM_000291.4(PGK1):c.854A>T (p.Asp285Val)	Pathogenic
9952	NM_000291.4(PGK1):c.140T>A (p.Ile47Asn)	Pathogenic
9953	NM_000291.4(PGK1):c.959G>A (p.Ser320Asn)	Pathogenic
9954	NM_000291.4(PGK1):c.491A>T (p.Asp164Val)	Pathogenic
9956	NM_000291.4(PGK1):c.1132A>C (p.Thr378Pro)	Pathogenic
1506855	NM_000291.4(PGK1):c.943G>A (p.Asp315Asn)	Likely pathogenic
1506865	NM_000291.4(PGK1):c.1060G>C (p.Ala354Pro)	Likely pathogenic
1687119	NM_000291.4(PGK1):c.150C>G (p.Cys50Trp)	Likely pathogenic
391568	NM_000291.4(PGK1):c.185G>A (p.Ser62Asn)	Likely pathogenic
625219	NM_000291.4(PGK1):c.89A>C (p.Lys30Thr)	Likely pathogenic
9955	NM_000291.4(PGK1):c.756+5G>A	Likely pathogenic

SpliceAI

5891 predictions. Top by Δscore:

Variant	Effect	Δscore
X:77910833:CAGGT:C	donor_loss	1.0000
X:77910834:AGG:A	donor_loss	1.0000
X:77910835:GGTA:G	donor_loss	1.0000
X:77910837:T:A	donor_loss	1.0000
X:77923053:G:GG	donor_gain	1.0000
X:77971615:TAACA:T	acceptor_loss	1.0000
X:77971616:A:AG	acceptor_gain	1.0000
X:77971616:AACAG:A	acceptor_gain	1.0000
X:77971618:CAGG:C	acceptor_loss	1.0000
X:77971619:A:AG	acceptor_gain	1.0000
X:77971619:A:T	acceptor_loss	1.0000
X:77971619:AG:A	acceptor_gain	1.0000
X:77971620:G:GT	acceptor_gain	1.0000
X:77971620:GG:G	acceptor_gain	1.0000
X:77971620:GGA:G	acceptor_gain	1.0000
X:77971620:GGAA:G	acceptor_gain	1.0000
X:77971620:GGAAT:G	acceptor_gain	1.0000
X:77971758:TAAGG:T	donor_loss	1.0000
X:77971762:G:GG	donor_gain	1.0000
X:77971762:GT:G	donor_loss	1.0000
X:77988238:AAAGG:A	acceptor_loss	1.0000
X:77988239:AAGGT:A	acceptor_loss	1.0000
X:77988240:A:AG	acceptor_loss	1.0000
X:77988732:G:C	donor_loss	1.0000
X:77988733:T:A	donor_loss	1.0000
X:77989231:A:AG	acceptor_gain	1.0000
X:77989232:G:GG	acceptor_gain	1.0000
X:78003232:TTGTT:T	donor_gain	1.0000
X:78003234:GTT:G	donor_gain	1.0000
X:78003235:TTGTA:T	donor_loss	1.0000

AlphaMissense

2757 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:78109871:G:C	D24H	1.000
X:78109872:A:T	D24V	1.000
X:78109873:C:A	D24E	1.000
X:78109873:C:G	D24E	1.000
X:78109879:T:A	N26K	1.000
X:78109879:T:G	N26K	1.000
X:78109917:G:T	R39M	1.000
X:78113744:G:C	R39S	1.000
X:78113744:G:T	R39S	1.000
X:78113814:C:A	H63N	1.000
X:78113814:C:G	H63D	1.000
X:78113815:A:G	H63R	1.000
X:78113816:C:A	H63Q	1.000
X:78113816:C:G	H63Q	1.000
X:78114106:C:A	N121K	1.000
X:78114106:C:G	N121K	1.000
X:78117390:T:C	F166L	1.000
X:78117392:T:A	F166L	1.000
X:78117392:T:G	F166L	1.000
X:78117393:G:C	G167R	1.000
X:78117394:G:A	G167D	1.000
X:78117400:C:A	A169D	1.000
X:78117402:C:G	H170D	1.000
X:78117404:C:A	H170Q	1.000
X:78117404:C:G	H170Q	1.000
X:78117405:A:G	R171G	1.000
X:78117406:G:C	R171T	1.000
X:78117406:G:T	R171I	1.000
X:78117407:A:C	R171S	1.000
X:78117407:A:T	R171S	1.000

dbSNP variants (sampled 300 via entrez): RS1000299577 (X:78104489 C>A,T), RS1000552519 (X:78112290 A>T), RS1000886642 (X:78128068 T>C), RS1000937971 (X:78118899 A>G), RS1001146354 (X:78110511 A>G), RS1001210366 (X:78121629 A>C), RS1001719870 (X:78112878 C>A), RS1002059632 (X:78128634 T>C), RS1002162313 (X:78119250 C>T), RS1002322859 (X:78110940 T>C), RS1002424601 (X:78103872 T>A,C), RS1002779786 (X:78111252 T>C), RS1002834943 (X:78123443 C>A,G,T), RS1003154472 (X:78106805 C>A), RS1003838286 (X:78121052 C>A,T)

Disease associations

OMIM: gene MIM:311800 | disease phenotypes: MIM:300653

GenCC curated gene-disease

Disease	Classification	Inheritance
glycogen storage disease due to phosphoglycerate kinase 1 deficiency	Definitive	X-linked

Mondo (5): glycogen storage disease due to phosphoglycerate kinase 1 deficiency (MONDO:0010392), hereditary skeletal muscle disorder (MONDO:0700223), optic atrophy (MONDO:0003608), epilepsy (MONDO:0005027), intellectual disability (MONDO:0001071)

Orphanet (3): Glycogen storage disease due to phosphoglycerate kinase 1 deficiency (Orphanet:713), Male infertility due to obstructive azoospermia (Orphanet:98343), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

HPO	Term
HP:0000083	Renal insufficiency
HP:0000556	Retinal dystrophy
HP:0000572	Visual loss
HP:0000618	Blindness
HP:0000712	Emotional lability
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001337	Tremor
HP:0001419	X-linked recessive inheritance
HP:0001878	Hemolytic anemia
HP:0001923	Reticulocytosis
HP:0002076	Migraine
HP:0002904	Hyperbilirubinemia
HP:0002913	Myoglobinuria
HP:0003198	Myopathy
HP:0003201	Rhabdomyolysis
HP:0003394	Muscle spasm
HP:0003546	Exercise intolerance
HP:0003621	Juvenile onset
HP:0003710	Exercise-induced muscle cramps
HP:0003738	Exercise-induced myalgia
HP:0008305	Exercise-induced myoglobinuria
HP:0009020	Exercise-induced muscle fatigue
HP:0012132	Erythroid hyperplasia
HP:0012638	Abnormal nervous system physiology
HP:0020062	Decreased hemoglobin concentration

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002395_641	Mean platelet volume	3.000000e-14

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
C567067	Phosphoglycerate Kinase 1 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096677 (PROTEIN FAMILY), CHEMBL2886 (SINGLE PROTEIN)

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

ChEMBL bioactivities

118 potent at pChembl≥5 of 146 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL3731422
8.30	IC50	5	nM	CHEMBL3730386
8.10	IC50	8	nM	CHEMBL3728435
8.05	IC50	9	nM	CHEMBL1995927
7.92	IC50	12	nM	CHEMBL3732725
7.82	IC50	15	nM	CHEMBL3731664
7.80	IC50	16	nM	CHEMBL3731002
7.72	IC50	19	nM	CHEMBL3729175
7.44	IC50	36	nM	CHEMBL3730091
7.42	IC50	38	nM	CHEMBL3732027
7.39	IC50	41	nM	CHEMBL3729776
7.38	IC50	42	nM	CHEMBL3731566
7.27	IC50	54	nM	CHEMBL3732479
7.24	Kd	57.22	nM	CHEMBL5653589
7.24	ED50	57.22	nM	CHEMBL5653589
7.18	IC50	66	nM	CHEMBL3731179
7.18	IC50	66	nM	CHEMBL3730455
7.15	IC50	71	nM	CHEMBL3732615
7.12	IC50	75	nM	CHEMBL3732983
7.11	IC50	78	nM	CHEMBL3731721
7.04	IC50	91	nM	CHEMBL3732218
7.01	IC50	98	nM	CHEMBL3733318
6.99	IC50	103	nM	CHEMBL3733323
6.91	IC50	122	nM	CHEMBL3733024
6.90	IC50	125	nM	CHEMBL3732229
6.89	IC50	129	nM	CHEMBL3728250
6.76	IC50	173	nM	CHEMBL3727706
6.72	IC50	190	nM	CHEMBL3727770
6.71	IC50	195	nM	CHEMBL3730838
6.68	IC50	210	nM	CHEMBL3731570
6.66	IC50	220	nM	CHEMBL3730400
6.62	IC50	240	nM	CHEMBL3727820
6.60	IC50	252	nM	CHEMBL3728634
6.59	IC50	257	nM	CHEMBL3731180
6.57	IC50	270	nM	CHEMBL3729424
6.50	IC50	320	nM	CHEMBL3731979
6.48	Ki	330	nM	CHEMBL348433
6.46	IC50	346	nM	CHEMBL3727853
6.44	IC50	366	nM	CHEMBL3730512
6.42	IC50	385	nM	CHEMBL3727920
6.41	IC50	393	nM	CHEMBL3732267
6.29	IC50	515	nM	CHEMBL3731901
6.26	IC50	550	nM	CHEMBL3732863
6.25	IC50	556	nM	CHEMBL3732931
6.24	IC50	570	nM	CHEMBL3728714
6.22	IC50	596	nM	CHEMBL3731055
6.20	IC50	633	nM	CHEMBL3728173
6.18	IC50	665	nM	CHEMBL3733215
6.16	Ki	690	nM	CHEMBL356436
6.15	IC50	710	nM	CHEMBL3728456

PubChem BioAssay actives

22 with measured affinity, of 276 total; 20 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	2148988: Binding affinity to human PGK1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0572	uM
[chloro-[6-[chloro(phosphono)methyl]-2-pyridinyl]methyl]phosphonic acid	3271: Binding affinity was evaluated towards 3-phosphoglycerate kinase at 37 degrees Celsius in 0.1 m NaCl pH 7.1	ki	0.3300	uM
[fluoro-[3-[fluoro(phosphono)methyl]phenyl]methyl]phosphonic acid	3271: Binding affinity was evaluated towards 3-phosphoglycerate kinase at 37 degrees Celsius in 0.1 m NaCl pH 7.1	ki	0.6900	uM
[[5-[difluoro(phosphono)methyl]-2,4-dimethylphenyl]-difluoromethyl]phosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	0.8400	uM
[[3-[difluoro(phosphono)methyl]-5-methylphenyl]-difluoromethyl]phosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	0.8800	uM
[[3-[difluoro(phosphono)methyl]phenyl]-difluoromethyl]phosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	0.9600	uM
[[4-[difluoro(phosphono)methyl]phenyl]-difluoromethyl]phosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	0.9800	uM
[3-[difluoro(phosphono)methyl]phenyl]phosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	1.0000	uM
[chloro-[3-[chloro(phosphono)methyl]phenyl]methyl]phosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	1.0000	uM
[chloro-[4-[chloro(phosphono)methyl]phenyl]methyl]phosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	1.0800	uM
[fluoro-[4-[fluoro(phosphono)methyl]phenyl]methyl]phosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	1.1500	uM
[[6-[difluoro(phosphono)methyl]-2-pyridinyl]-difluoromethyl]phosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	1.1700	uM
[3-[difluoro(phosphono)methyl]phenyl]methylphosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	1.8000	uM
[4-[difluoro(phosphono)methyl]phenyl]methylphosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	1.9800	uM
[dichloro-[3-[dichloro(phosphono)methyl]phenyl]methyl]phosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	3.6000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148988: Binding affinity to human PGK1 incubated for 45 mins by Kinobead based pull down assay	kd	5.2056	uM
[5-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]-1,1,5,5-tetrafluoropentyl]phosphonic acid	158480: Dissociation constant for binding with Phosphoglycerate kinase (PGK) enzyme is evaluated	kd	6.0000	uM
[3-[chloro(phosphono)methyl]phenyl]methylphosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	8.0000	uM
[3-[fluoro(phosphono)methyl]phenyl]methylphosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	8.3500	uM
[4-[chloro(phosphono)methyl]phenyl]methylphosphonic acid	3270: Inhibitory activity against 3-phosphoglycerate kinase.	ic50	9.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oxygen	increases expression, increases reaction, affects reaction, affects cotreatment, decreases reaction	10
sodium arsenite	affects expression, affects cotreatment, increases abundance, increases expression	6
cobaltous chloride	increases expression, increases reaction, decreases reaction	5
Valproic Acid	decreases expression, increases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
Arsenic Trioxide	affects binding, decreases reaction, decreases expression, increases reaction, increases expression (+1 more)	3
Benzo(a)pyrene	decreases methylation, increases mutagenesis, affects methylation, decreases expression	3
Deferoxamine	decreases expression, increases expression, decreases reaction	3
Quercetin	decreases expression, increases expression	3
methylmercuric chloride	decreases expression	2
nickel sulfate	affects expression, increases expression	2
chloropicrin	affects expression, decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Arsenic	increases expression, affects methylation, affects cotreatment, increases abundance	2
Cadmium	decreases reaction, increases expression, decreases expression	2
Cisplatin	decreases expression, affects response to substance	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
PF-06840003	decreases expression, decreases reaction	1
aminomethylphosphonic acid (AMPA)	increases expression	1
beauvericin	increases expression, affects cotreatment	1
quinone	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, decreases expression, affects cotreatment	1

ChEMBL screening assays

22 unique, capped per target: 22 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL615425	Binding	Binding affinity was evaluated towards 3-phosphoglycerate kinase at 37 degrees Celsius in 0.1 m NaCl pH 7.1	Novel bisphosphonate inhibitors of phosphoglycerate kinase. — Bioorg Med Chem Lett

Cellosaurus cell lines

6 cell lines: 3 cancer cell line, 1 finite cell line, 1 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_BW98	GM00743	Finite cell line	Male
CVCL_BX00	GM14889	Transformed cell line	Male
CVCL_D1YA	Abcam A-549 PGK1 KO	Cancer cell line	Male
CVCL_D2CH	Abcam HCT 116 PGK1 KO	Cancer cell line	Male
CVCL_D2NV	Abcam THP-1 PGK1 KO	Cancer cell line	Male
CVCL_E6X2	NIMHi016-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
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NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
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NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
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NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
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