PGAM1

Summary

PGAM1 (phosphoglycerate mutase 1, HGNC:8888) is a protein-coding gene on chromosome 10q24.1, encoding Phosphoglycerate mutase 1 (P18669). Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate, a crucial step in glycolysis, by using 2,3-bisphosphoglycerate. It is a common-essential gene (DepMap: required in 93.2% of cancer cell lines).

The protein encoded by this gene is a mutase that catalyzes the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5223 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 47 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 93.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_002629

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8888
Approved symbol	PGAM1
Name	phosphoglycerate mutase 1
Location	10q24.1
Locus type	gene with protein product
Status	Approved
Aliases	PGAM-B
Ensembl gene	ENSG00000171314
Ensembl biotype	protein_coding
OMIM	172250
Entrez	5223

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000334828, ENST00000467867, ENST00000473929, ENST00000889728, ENST00000889729, ENST00000889730, ENST00000940113, ENST00000940114

RefSeq mRNA: 1 — MANE Select: NM_002629 NM_002629

CCDS: CCDS7458

Canonical transcript exons

ENST00000334828 — 4 exons

Exon	Start	End
ENSE00001367378	97432355	97433444
ENSE00001821632	97426191	97426446
ENSE00003567351	97430955	97431135
ENSE00003628907	97430379	97430653

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.0295 / max 433.7455, expressed in 1824 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106431	22.2227	1813
106429	20.0712	1791
106430	17.0255	1794
106433	0.4533	257
106432	0.2569	132

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	99.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.28	gold quality
esophagus mucosa	UBERON:0002469	99.26	gold quality
right frontal lobe	UBERON:0002810	99.26	gold quality
right adrenal gland	UBERON:0001233	99.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.23	gold quality
anterior cingulate cortex	UBERON:0009835	99.21	gold quality
lower esophagus mucosa	UBERON:0035834	99.18	gold quality
right adrenal gland cortex	UBERON:0035827	99.17	gold quality
left adrenal gland	UBERON:0001234	99.15	gold quality
hypothalamus	UBERON:0001898	99.14	gold quality
ventricular zone	UBERON:0003053	99.13	gold quality
cerebral cortex	UBERON:0000956	99.12	gold quality
putamen	UBERON:0001874	99.12	gold quality
primary visual cortex	UBERON:0002436	99.11	gold quality
esophagus	UBERON:0001043	99.09	gold quality
caudate nucleus	UBERON:0001873	99.09	gold quality
frontal cortex	UBERON:0001870	99.07	gold quality
nucleus accumbens	UBERON:0001882	99.07	gold quality
left adrenal gland cortex	UBERON:0035825	99.05	gold quality
adrenal gland	UBERON:0002369	99.02	gold quality
substantia nigra	UBERON:0002038	99.00	gold quality
temporal lobe	UBERON:0001871	98.99	gold quality
amygdala	UBERON:0001876	98.98	gold quality
brain	UBERON:0000955	98.95	gold quality
lower esophagus	UBERON:0013473	98.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.95	gold quality
prefrontal cortex	UBERON:0000451	98.92	gold quality
stromal cell of endometrium	CL:0002255	98.89	gold quality
right atrium auricular region	UBERON:0006631	98.89	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	2087.07
E-HCAD-8	yes	854.07
E-HCAD-5	yes	34.11
E-CURD-46	yes	26.28
E-CURD-122	yes	24.99
E-MTAB-10042	yes	13.34
E-MTAB-2983	no	8102.51
E-MTAB-8271	no	7.48
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting PGAM1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-7515	99.31	68.22	1795

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 37)

• Cloning, purification, crystallization and preliminary crystallographic analysis of human phosphoglycerate mutase (PMID:15388943)
• Phosphoglycerate mutase may have a role in preventing non-spherocytic anemia [case report] (PMID:15710582)
• We report two patients in whom phosphoglycerate mutase (PGAM) deficiency was associated with the triad of exercise-induced cramps, recurrent myoglobinuria, and tubular aggregates in the muscle biopsy. (PMID:16881065)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• Results identified phosphoglycerate mutase 1 that showed elevated levels of protein carbonyls in inferior parietal lobule (IPL) from subjects with early stage-Alzheimer’s disease. (PMID:19686046)
• Our studies suggested that PGAM1 plays an important role in hepatocarcinogenesis (PMID:20403181)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• histidine-phosphorylated PGAM1 correlated with expression of PKM2 in cancer cell lines; decreased pyruvate kinase activity in PKM2-expressing cells allows PEP-dependent histidine phosphorylation of PGAM1 and may provide an alternate glycolytic pathway (PMID:20847263)
• PGAM1 deacetylation and activity are directly controlled by Sirt1. (PMID:22157007)
• Phosphoglycerate mutase 1 (PGAM1) contributes to biosynthesis regulation by controlling intracellular levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2-phosphoglycerate (2-PG). (PMID:23153533)
• Tyrosine26 phosphorylation represents an additional acute mechanism underlying phosphoglycerate mutase 1 upregulation. (PMID:23653202)
• PGAM is acetylated at lysines 100/106/113/138 in its central region, and a member of the Sirtuin family (class III deacetylase), SIRT2, is responsible for its deacetylation. (PMID:25195573)
• PGAM1 correlates with spermatogenic dysfunction and affects the function of cell proliferation, apoptosis and migration. (PMID:25701843)
• PGAM1 is highly expressed in clear cell renal cell carcinoma and correlated with clinicalpathological features, which may contribute to tumor formation and progression. (PMID:26464696)
• Our finding showed that PGAM1 might serve as a promising therapeutic target for UBC. (PMID:26655504)
• PGAM1 may be associated with the grade of glioma and be involved in the biological behavior of glioma cells. PGAM1 might be a novel therapeutic target in glioma. (PMID:27572934)
• study provided the first evidence revealing a non-metabolic function of PGAM1 in promoting cell migration, and gained new insights into the role of PGAM1 in cancer progression. (PMID:27991922)
• Data show that tyrosine 26 phosphorylation enhances the binding of phosphoglycerate mutase 1 (PGAM1) to its substrates through generating electrostatic environment and structural features that are advantageous to the binding. (PMID:28076845)
• PGAM1 in promoting homologous recombination repair in tumor cell lines. Suggest potential therapeutic opportunity for PGAM1 inhibitors in combination with PARP inhibitors in cancer treatment. (PMID:28122957)
• conformation and dynamics of the C-terminal region in human phosphoglycerate mutase 1 (PMID:28748916)
• When BPGM is knocked out, 1,3-BPG can directly phosphorylate PGAM1. In this case, PGAM1 phosphorylation and activity are decreased, but nevertheless sufficient to maintain normal glycolytic flux and cellular growth rate. (PMID:28805803)
• Knockdown of PGAM1 by siRNA in PC-3 and 22Rv1 prostate cancer cell lines inhibited cell proliferation, migration, and invasion and enhanced cancer cell apoptosis. In a nude mouse xenograft model, PGAM1 knockdown markedly suppressed tumor growth. Deletion of PGAM1 resulted in decreased expression of Bcl-2, enhanced expression of Bax, caspases-3 and inhibition of MMP-2 and MMP-9 expression. (PMID:29271400)
• PGAM1 is thus a downstream effector of mTOR signaling pathway and mTOR-PGAM1 signaling cascade may contribute to the development of Warburg effect observed in cancer. (PMID:29362480)
• High PGAM1 expression is associated with Pancreatic Ductal Adenocarcinoma Metastasis. (PMID:29386088)
• The aim of this review is to update scientific research network with cancer-specific role of PGAM1 to elucidate its capability as bonafide therapeutic target for cancer therapy. (PMID:31169978)
• Circ-PGAM1 promotes malignant progression of epithelial ovarian cancer through regulation of the miR-542-3p/CDC5L/PEAK1 pathway. (PMID:32167655)
• T cell-specific deletion of Pgam1 reveals a critical role for glycolysis in T cell responses. (PMID:32709928)
• PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-beta (TGF-beta) signaling in the progression of non-small cell lung carcinoma. (PMID:32855383)
• PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway. (PMID:35674458)
• PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells. (PMID:36224008)
• Matrine induces hepatocellular carcinoma apoptosis and represses EMT and stemness through microRNA-299-3p/PGAM1 axis. (PMID:36260520)
• Circ-PGAM1 Enhances Matrine Resistance of Non-Small Cell Lung Cancer via the miR-326/CXCR5 Axis. (PMID:36576783)
• MicroRNA-324-3p inhibits osteosarcoma progression by suppressing PGAM1-mediated aerobic glycolysis. (PMID:36880587)
• Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1. (PMID:37542027)
• PGAM1 Inhibition Promotes HCC Ferroptosis and Synergizes with Anti-PD-1 Immunotherapy. (PMID:37705495)
• RFX6 facilitates aerobic glycolysis-mediated growth and metastasis of hepatocellular carcinoma through targeting PGAM1. (PMID:38093528)
• Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages. (PMID:38750301)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgam1a	ENSDARG00000005423
danio_rerio	pgam1b	ENSDARG00000014068
mus_musculus	Pgam1	ENSMUSG00000011752
rattus_norvegicus	Pgam1	ENSRNOG00000050585
drosophila_melanogaster	Pglym87	FBGN0011270
drosophila_melanogaster	Pglym78	FBGN0014869

Paralogs (3): PGAM2 (ENSG00000164708), BPGM (ENSG00000172331), PGAM4 (ENSG00000226784)

Protein

Protein identifiers

Phosphoglycerate mutase 1 — P18669 (reviewed: P18669)

Alternative names: BPG-dependent PGAM 1, Phosphoglycerate mutase isozyme B

All UniProt accessions (2): P18669, Q6FHU2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate, a crucial step in glycolysis, by using 2,3-bisphosphoglycerate. Also catalyzes the interconversion of (2R)-2,3-bisphosphoglycerate and (2R)-3-phospho-glyceroyl phosphate.

Subunit / interactions. Homodimer.

Tissue specificity. Expressed in the liver and brain. Not found in the muscle.

Post-translational modifications. Acetylated at Lys-253, Lys-253 and Lys-254 under high glucose condition. Acetylation increases catalytic activity. Under glucose restriction SIRT1 levels dramatically increase and it deacetylates the enzyme.

Similarity. Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.

RefSeq proteins (1): NP_002620* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001345	PG/BPGM_mutase_AS	Active_site
IPR005952	Phosphogly_mut1	Family
IPR013078	His_Pase_superF_clade-1	Family
IPR029033	His_PPase_superfam	Homologous_superfamily

Pfam: PF00300

Enzyme classification (BRENDA):

• EC 5.4.2.11 — phosphoglycerate mutase (2,3-diphosphoglycerate-dependent) (BRENDA: 20 organisms, 14 substrates, 85 inhibitors, 37 Km, 16 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3-PHOSPHOGLYCERATE	0.026–7.46	18
3-PHOSPHO-D-GLYCERATE	0.22–6	14
2-PHOSPHOGLYCERATE	0.041–0.067	3
2-PHOSPHO-D-GLYCERATE	0.37–0.69	2

Catalyzed reactions (Rhea), 2 shown:

• (2R)-2-phosphoglycerate = (2R)-3-phosphoglycerate (RHEA:15901)
• (2R)-3-phospho-glyceroyl phosphate = (2R)-2,3-bisphosphoglycerate + H(+) (RHEA:17765)

UniProt features (43 total): helix 13, modified residue 10, binding site 7, strand 7, active site 2, initiator methionine 1, chain 1, site 1, turn 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7XB9	X-RAY DIFFRACTION	1.58
7XB8	X-RAY DIFFRACTION	1.6
4GPZ	X-RAY DIFFRACTION	1.65
22RB	X-RAY DIFFRACTION	1.75
8ITC	X-RAY DIFFRACTION	1.88
8ITD	X-RAY DIFFRACTION	1.9
22WM	X-RAY DIFFRACTION	1.91
5Y2I	X-RAY DIFFRACTION	1.92
8IT8	X-RAY DIFFRACTION	1.95
5Y2U	X-RAY DIFFRACTION	1.98
6ISN	X-RAY DIFFRACTION	1.98
5Y35	X-RAY DIFFRACTION	1.99
9LG2	X-RAY DIFFRACTION	2.02
22TN	X-RAY DIFFRACTION	2.03
9XVS	X-RAY DIFFRACTION	2.08
4GPI	X-RAY DIFFRACTION	2.08
9XW4	X-RAY DIFFRACTION	2.11
5Y64	X-RAY DIFFRACTION	2.15
5ZS8	X-RAY DIFFRACTION	2.2
7XB7	X-RAY DIFFRACTION	2.2
8IT5	X-RAY DIFFRACTION	2.2
5ZRM	X-RAY DIFFRACTION	2.28
22RH	X-RAY DIFFRACTION	2.28
9XWT	X-RAY DIFFRACTION	2.28
8ITB	X-RAY DIFFRACTION	2.38
8IT4	X-RAY DIFFRACTION	2.4
8IT6	X-RAY DIFFRACTION	2.55
5Y65	X-RAY DIFFRACTION	2.55
5ZS7	X-RAY DIFFRACTION	2.68
1YFK	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18669-F1	94.51	0.89

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 (3): 186 (transition state stabilizer); 11 (tele-phosphohistidine intermediate); 89 (proton donor/acceptor)

Ligand- & substrate-binding residues (7): 187–188; 10–17; 23–24; 62; 89–92; 100; 116–117

Post-translational modifications (10): 14, 23, 26, 31, 106, 118, 251, 251, 253, 254

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-70171	Glycolysis
R-HSA-70263	Gluconeogenesis

MSigDB gene sets: 317 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOCC_SECRETORY_GRANULE, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, DARWICHE_SKIN_TUMOR_PROMOTER_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, KEGG_GLYCOLYSIS_GLUCONEOGENESIS

GO Biological Process (3): gluconeogenesis (GO:0006094), canonical glycolysis (GO:0061621), glycolytic process (GO:0006096)

GO Molecular Function (8): bisphosphoglycerate mutase activity (GO:0004082), phosphoglycerate mutase activity (GO:0004619), hydrolase activity (GO:0016787), protein kinase binding (GO:0019901), catalytic activity (GO:0003824), protein binding (GO:0005515), isomerase activity (GO:0016853), intramolecular phosphotransferase activity (GO:0016868)

GO Cellular Component (7): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glucose metabolism	2
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intramolecular phosphotransferase activity	2
catalytic activity	2
glucose metabolic process	1
hexose biosynthetic process	1
glucokinase activity	1
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity	1
glucose catabolic process	1
glycolytic process through glucose-6-phosphate	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
kinase binding	1
molecular_function	1
binding	1
intramolecular transferase activity	1
intracellular anatomical structure	1
cytoplasm	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

2660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGAM1	PKM	P14618	934
PGAM1	TPI1	P00938	860
PGAM1	PGK1	P00558	854
PGAM1	ENO1	P06733	853
PGAM1	ALDOA	P04075	839
PGAM1	J3KPS3	J3KPS3	837
PGAM1	UBASH3B	Q8TF42	797
PGAM1	GOT1	P17174	772
PGAM1	LDHA	P00338	731
PGAM1	GAPDH	P00354	729
PGAM1	ENO2	P09104	721
PGAM1	ENO3	P13929	706
PGAM1	PGAM2	P15259	695
PGAM1	PKLR	P11973	678
PGAM1	PFKL	P17858	662

IntAct

89 interactions, top by confidence:

A	B	Type	Score
PGAM2	BPGM	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
APP	PGAM1	psi-mi:“MI:0915”(physical association)	0.670
APP	CRYAB	psi-mi:“MI:0914”(association)	0.670
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PGAM1	UNC5CL	psi-mi:“MI:0915”(physical association)	0.560
PGAM1	PCNA	psi-mi:“MI:0915”(physical association)	0.540
PCNA	PGAM1	psi-mi:“MI:0407”(direct interaction)	0.540
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
SEC14L1	PGAM1	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
YWHAZ	PGAM1	psi-mi:“MI:0915”(physical association)	0.400
PGAM1		psi-mi:“MI:0915”(physical association)	0.370
ERBB2	PGAM1	psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
PHOSPHO1	DDX39A	psi-mi:“MI:0914”(association)	0.350
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350

BioGRID (252): PGAM1 (Affinity Capture-MS), AKR1B1 (Co-fractionation), CKMT1B (Co-fractionation), CKMT1A (Co-fractionation), FABP5 (Co-fractionation), GLO1 (Co-fractionation), NUTF2 (Co-fractionation), PGAM1 (Co-fractionation), PGAM1 (Co-fractionation), PGAM1 (Co-fractionation), PGAM1 (Co-fractionation), PGAM1 (Co-fractionation), PGAM1 (Co-fractionation), PGAM1 (Co-fractionation), PGAM1 (Co-fractionation)

ESM2 similar proteins: A1BE55, A1K9B9, A1VKR6, A4JI45, A4SDM0, B0K4E2, B0KBW9, B1JZ61, B1VS80, B1Y3R5, B1YNA6, B2AGP7, B2JC95, B2S101, B2SX15, B2VBS6, B3EFK8, B4EA64, B4S616, B4SEI0, B9MEZ2, G4VJD5, O70250, P07738, P07952, P15327, P16290, P18669, P25113, Q0BBK5, Q2FTH0, Q2T1H5, Q2Y9Z7, Q39CN6, Q39V40, Q3AU60, Q3B5J2, Q3T014, Q476J7, Q4R6L7

Diamond homologs: A0JSU9, A0PVZ3, A0QLK3, A1BE55, A1KFW3, A1SP05, A1UZX9, A1VKR6, A2S625, A3MQ23, A3N5B0, A3NR09, A4JI45, A4QB41, A4SDM0, A5CTZ0, A5TZL7, A9BUZ3, B0RAW4, B0RQR7, B1JZ61, B1VS80, B1Y3R5, B1YNA6, B2AGP7, B2FHH6, B2HQV4, B2JC95, B2SRM8, B2SX15, B2VBS6, B3DQI6, B3EFK8, B3EN99, B3QPN8, B3QVL0, B4EA64, B4RZM6, B4S616, B4SEI0

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PGAM1	“down-regulates quantity”	3-phosphonato-D-glycerate(3-)	“chemical modification”
PGAM1	“up-regulates quantity”	2-phosphonato-D-glycerate(3-)	“chemical modification”
SIRT2	“up-regulates activity”	PGAM1	deacetylation
FGFR1	“up-regulates activity”	PGAM1	phosphorylation
PAK1	down-regulates	PGAM1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1670 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:97426371:T:C	F22L	1.000
10:97426373:C:A	F22L	1.000
10:97426373:C:G	F22L	1.000
10:97430505:A:T	E89V	1.000
10:97430539:A:C	K100N	1.000
10:97430539:A:T	K100N	1.000
10:97430586:G:C	R116T	1.000
10:97430586:G:T	R116M	1.000
10:97431104:C:A	N188K	1.000
10:97431104:C:G	N188K	1.000
10:97426342:G:A	G12D	0.999
10:97426358:C:A	N17K	0.999
10:97426358:C:G	N17K	0.999
10:97426372:T:C	F22S	0.999
10:97426380:T:A	W25R	0.999
10:97426380:T:C	W25R	0.999
10:97426408:G:A	G34D	0.999
10:97430404:C:G	C55W	0.999
10:97430424:G:C	R62T	0.999
10:97430425:A:C	R62S	0.999
10:97430425:A:T	R62S	0.999
10:97430492:T:A	W85R	0.999
10:97430492:T:C	W85R	0.999
10:97430504:G:A	E89K	0.999
10:97430506:G:C	E89D	0.999
10:97430506:G:T	E89D	0.999
10:97430513:T:C	Y92H	0.999
10:97430517:G:A	G93E	0.999
10:97430537:A:C	K100Q	0.999
10:97430537:A:G	K100E	0.999

dbSNP variants (sampled 300 via entrez): RS1000228933 (10:97432670 C>T), RS1000279551 (10:97429260 T>C), RS1000438205 (10:97426855 T>TGAAA), RS1000882169 (10:97431538 G>T), RS1000882977 (10:97433563 C>T), RS1001026089 (10:97424488 T>C), RS1001058397 (10:97425990 C>G,T), RS1001286277 (10:97432242 G>A,C), RS1001386048 (10:97425591 G>A), RS1001576719 (10:97427645 C>G,T), RS1001842596 (10:97426200 C>A,G,T), RS1003255089 (10:97426502 G>A,C,T), RS1003820908 (10:97426527 G>A,C,T), RS1003849704 (10:97426923 A>G), RS1003871873 (10:97426854 G>A,T)

Disease associations

OMIM: gene MIM:172250 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3334418 (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: 22,804 (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
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804

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

ChEMBL bioactivities

67 potent at pChembl≥5 of 77 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	Kd	50.02	nM	CHEMBL5653589
7.30	ED50	50.02	nM	CHEMBL5653589
7.01	IC50	97	nM	CHEMBL4760337
6.98	IC50	105	nM	CHEMBL5270603
6.85	IC50	140	nM	CHEMBL4763924
6.72	IC50	190	nM	CHEMBL4789955
6.60	IC50	250	nM	CHEMBL4741748
6.58	IC50	260	nM	CHEMBL4784572
6.57	IC50	270	nM	CHEMBL5287487
6.48	IC50	330	nM	CHEMBL4742013
6.44	IC50	360	nM	CHEMBL4757633
6.32	IC50	480	nM	CHEMBL4759807
6.31	IC50	490	nM	EPIGALOCATECHIN GALLATE
6.31	IC50	490	nM	CHEMBL4752163
6.31	IC50	490	nM	CHEMBL5277511
6.30	IC50	500	nM	CHEMBL4228862
6.30	IC50	500	nM	XANTHONE
6.26	IC50	550	nM	CHEMBL4798515
6.26	IC50	550	nM	CHEMBL4743623
6.20	IC50	630	nM	CHEMBL4762201
6.11	IC50	770	nM	CHEMBL5274803
6.08	IC50	840	nM	CHEMBL4787732
6.07	IC50	850	nM	CHEMBL5290046
6.00	IC50	1000	nM	CHEMBL4227227
6.00	IC50	1000	nM	CHEMBL5282807
5.92	IC50	1200	nM	CHEMBL4227876
5.89	IC50	1290	nM	CHEMBL4752963
5.89	IC50	1300	nM	CHEMBL5268049
5.82	IC50	1500	nM	CHEMBL4745620
5.82	IC50	1500	nM	CHEMBL4776823
5.80	IC50	1600	nM	CHEMBL4226661
5.77	IC50	1700	nM	CHEMBL4227402
5.76	IC50	1750	nM	CHEMBL4747578
5.72	IC50	1900	nM	CHEMBL4227616
5.72	IC50	1900	nM	CHEMBL4227498
5.72	IC50	1900	nM	CHEMBL260553
5.69	IC50	2050	nM	CHEMBL4790666
5.69	IC50	2050	nM	CHEMBL4746342
5.68	IC50	2100	nM	CHEMBL4226542
5.64	IC50	2300	nM	ALIZARIN RED
5.64	IC50	2300	nM	Alizarin Red S
5.58	IC50	2600	nM	CHEMBL4225083
5.58	IC50	2600	nM	CHEMBL4793513
5.57	IC50	2700	nM	CHEMBL4227083
5.55	IC50	2800	nM	CHEMBL4228033
5.55	IC50	2810	nM	CHEMBL4756511
5.55	IC50	2800	nM	CHEMBL4748271
5.55	IC50	2800	nM	CHEMBL4775985
5.54	IC50	2900	nM	CHEMBL4226752
5.54	IC50	2860	nM	CHEMBL4782282

PubChem BioAssay actives

64 with measured affinity, of 128 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148985: Binding affinity to human PGAM1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0500	uM
4-cyclohexyl-N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)benzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.0970	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-4-pyrrolidin-1-ylbenzenesulfonamide	1944975: Inhibition of recombinant PGAM1 (unknown origin) assessed as decrease in absorbance in presence of LDH, pyruvate kinase M2 and NADH by spectroscopic analysis	ic50	0.1050	uM
4-(4-chlorophenyl)-N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)benzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.1400	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)naphthalene-2-sulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.1900	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-4-phenylbenzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.2500	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-4-(4-fluorophenyl)benzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.2600	uM
4-chloro-N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)benzenesulfonamide	1944975: Inhibition of recombinant PGAM1 (unknown origin) assessed as decrease in absorbance in presence of LDH, pyruvate kinase M2 and NADH by spectroscopic analysis	ic50	0.2700	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-4-piperidin-1-ylbenzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.3300	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-4-methylbenzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.3600	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-3-methoxybenzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.4800	uM
4-tert-butyl-N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)benzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.4900	uM
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1390564: Inhibition of recombinant human His-tagged PGAM1 expressed in Escherichia coli BL21 competent cells by kinase-glo assay	ic50	0.4900	uM
[(2R,3R)-2-(3,4-dihydroxy-5-methylphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1944989: Inhibition of His-tagged recombinant PGAM1 (unknown origin) assessed as reduction in ATP production in presence of pyruvate kinase M1 and ATP by Kinase-Glo Max luminescent kinase assay	ic50	0.4900	uM
4-cyclohexyl-N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)benzenesulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	0.5000	uM
xanthen-9-one	1708712: Inhibition of PGAM1 (unknown origin)	ic50	0.5000	uM
5-chloro-N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)thiophene-2-sulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.5500	uM
4-chloro-N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-3-(trifluoromethyl)benzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.5500	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-4-fluoro-3-(trifluoromethyl)benzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.6300	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-4-(dimethylamino)benzenesulfonamide	1944975: Inhibition of recombinant PGAM1 (unknown origin) assessed as decrease in absorbance in presence of LDH, pyruvate kinase M2 and NADH by spectroscopic analysis	ic50	0.7700	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)thiophene-2-sulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	0.8400	uM
4-(azetidin-1-yl)-N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)benzenesulfonamide	1944982: Allosteric inhibition of PGAM1 (unknown origin) assessed as decrease in absorbance in presence of LDH, pyruvate kinase M2 and NADH by spectroscopic analysis	ic50	0.8500	uM
[2-[(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)sulfamoyl]phenyl] acetate	1944988: Inhibition of His-tagged recombinant PGAM1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in absorbance from oxidation of NADH in presence of LDH, pyruvate kinase M1 and NADH by microplate reader assay	ic50	1.0000	uM
4-piperidin-1-yl-N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)benzenesulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	1.0000	uM
4-phenyl-N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)benzenesulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	1.2000	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)naphthalene-1-sulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	1.2900	uM
[2-[(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)sulfamoyl]phenyl] 5-azidopentanoate	1944988: Inhibition of His-tagged recombinant PGAM1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in absorbance from oxidation of NADH in presence of LDH, pyruvate kinase M1 and NADH by microplate reader assay	ic50	1.3000	uM
2,3,6,8-tetrahydroxy-1-(3-phenylpropyl)xanthen-9-one	1708712: Inhibition of PGAM1 (unknown origin)	ic50	1.5000	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)benzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	1.5000	uM
N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)naphthalene-2-sulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	1.6000	uM
N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)naphthalene-1-sulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	1.7000	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)cyclohexanesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	1.7500	uM
1-phenyl-N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)methanesulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	1.9000	uM
4-iodo-N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)benzenesulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	1.9000	uM
1,3,6,7-tetrahydroxy-2,8-bis(3-methylbut-2-enyl)xanthen-9-one	1708712: Inhibition of PGAM1 (unknown origin)	ic50	1.9000	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)butane-1-sulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	2.0500	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)quinoline-8-sulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	2.0500	uM
3-cyano-N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)benzenesulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	2.1000	uM
sodium 3,4-dihydroxy-9,10-dioxoanthracene-2-sulfonate	1708712: Inhibition of PGAM1 (unknown origin)	ic50	2.3000	uM
3,4-dihydroxy-9,10-dioxoanthracene-2-sulfonic acid	1390544: Inhibition of PGAM1 (unknown origin)	ic50	2.3000	uM
4-tert-butyl-N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)benzenesulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	2.6000	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-4-(3,5-dimethylpiperidin-1-yl)benzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	2.6000	uM
4-pyrrolidin-1-yl-N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)benzenesulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	2.7000	uM
3,6,7-trihydroxy-1-octoxyxanthen-9-one	1708712: Inhibition of PGAM1 (unknown origin)	ic50	2.8000	uM
N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)benzenesulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	2.8000	uM
1-hept-2-enyl-2,3,6,8-tetrahydroxyxanthen-9-one	1708712: Inhibition of PGAM1 (unknown origin)	ic50	2.8000	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-3,4-dimethoxybenzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	2.8100	uM
N-(3,4-dihydroxy-9,10-dioxoanthracen-2-yl)-2,4-dimethoxybenzenesulfonamide	1671942: Inhibition of human recombinant PGAM1 by measuring decrease in OD by enzyme based assay	ic50	2.8600	uM
4-bromo-N-(1,2,8-trihydroxy-9-oxoxanthen-3-yl)benzenesulfonamide	1390545: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition	ic50	2.9000	uM
2,3,6,8-tetrahydroxy-1-(3-methylbut-2-enyl)xanthen-9-one	1708712: Inhibition of PGAM1 (unknown origin)	ic50	3.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
sodium arsenite	increases expression, decreases expression	4
Cadmium Chloride	increases abundance, increases expression, decreases expression	3
chloropicrin	affects expression, decreases expression	2
Resveratrol	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Quercetin	increases phosphorylation, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tunicamycin	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
TAK-243	decreases sumoylation	1
PF-06840003	decreases expression, decreases reaction	1
beauvericin	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
chlorophyllin	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
sulindac sulfide	decreases expression	1
potassium chromate(VI)	increases expression	1
beta-methylcholine	affects expression	1
microcystin RR	decreases expression	1
yessotoxin	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
enniatins	affects cotreatment, increases expression	1
pterostilbene	decreases expression	1
7,3’-dihydroxy-4’-methoxyisoflavone	increases expression	1
azaspiracid	increases expression	1

ChEMBL screening assays

37 unique, capped per target: 37 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3386524	Binding	Inhibition of PGM1 (unknown origin) by enzymatic assay	An update on therapeutic opportunities offered by cancer glycolytic metabolism. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1PQ	Abcam K-562 PGAM1 KO	Cancer cell line	Female
CVCL_D2LB	Abcam Raji PGAM1 KO	Cancer cell line	Male
CVCL_WQ26	Abcam Jurkat PGAM1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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