ENO1

Summary

ENO1 (enolase 1, HGNC:3350) is a protein-coding gene on chromosome 1p36.23, encoding Alpha-enolase (P06733). Enolase that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in glycolysis and the reverse reaction in gluconeogenesis. It is a selective cancer dependency (DepMap: 55.0% of cell lines).

This gene encodes alpha-enolase, one of three enolase isoenzymes found in mammals. Each isoenzyme is a homodimer composed of 2 alpha, 2 gamma, or 2 beta subunits, and functions as a glycolytic enzyme. Alpha-enolase in addition, functions as a structural lens protein (tau-crystallin) in the monomeric form. Alternative splicing of this gene results in a shorter isoform that has been shown to bind to the c-myc promoter and function as a tumor suppressor. Several pseudogenes have been identified, including one on the long arm of chromosome 1. Alpha-enolase has also been identified as an autoantigen in Hashimoto encephalopathy.

Source: NCBI Gene 2023 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polymicrogyria (Limited, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 88 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 55.0% of screened cell lines
• Transcription factor: yes — 20 downstream targets (CollecTRI)
• MANE Select transcript: NM_001428

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3350
Approved symbol	ENO1
Name	enolase 1
Location	1p36.23
Locus type	gene with protein product
Status	Approved
Aliases	PPH, MBP-1
Ensembl gene	ENSG00000074800
Ensembl biotype	protein_coding
OMIM	172430
Entrez	2023

Gene structure

Transcript identifiers

Ensembl transcripts: 52 — 44 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000234590, ENST00000414948, ENST00000464920, ENST00000486051, ENST00000489867, ENST00000492343, ENST00000497492, ENST00000643438, ENST00000645600, ENST00000645609, ENST00000646156, ENST00000646370, ENST00000646660, ENST00000646680, ENST00000646906, ENST00000647408, ENST00000879694, ENST00000879695, ENST00000879696, ENST00000879697, ENST00000879698, ENST00000879699, ENST00000879700, ENST00000879701, ENST00000879702, ENST00000879703, ENST00000879704, ENST00000879705, ENST00000879706, ENST00000879707, ENST00000935293, ENST00000935294, ENST00000935295, ENST00000935296, ENST00000935297, ENST00000935298, ENST00000935299, ENST00000935300, ENST00000935301, ENST00000935302, ENST00000935303, ENST00000935304, ENST00000935305, ENST00000935306, ENST00000935307, ENST00000971792, ENST00000971793, ENST00000971794, ENST00000971795, ENST00000971796, ENST00000971797, ENST00000971798

RefSeq mRNA: 3 — MANE Select: NM_001428 NM_001201483, NM_001353346, NM_001428

CCDS: CCDS85924, CCDS97

Canonical transcript exons

ENST00000234590 — 12 exons

Exon	Start	End
ENSE00001839322	8878580	8878686
ENSE00002805668	8870452	8870510
ENSE00003462332	8863891	8864092
ENSE00003470857	8874824	8874917
ENSE00003473774	8862887	8862945
ENSE00003508132	8867988	8868057
ENSE00003526899	8863235	8863343
ENSE00003539462	8866279	8866501
ENSE00003558670	8867117	8867250
ENSE00003576214	8865285	8865482
ENSE00003615230	8871891	8871986
ENSE00003818962	8861000	8861429

Expression profiles

Bgee: expression breadth ubiquitous, 311 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1233.4097 / max 23910.4196, expressed in 1828 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10172	1081.7292	1828
10173	71.0270	1819
10171	66.6125	1814
10164	3.8745	1383
10158	1.7654	1044
10156	1.3998	849
10177	1.3253	839
10157	1.2229	743
201342	1.1001	677
10159	0.8573	545

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	99.76	gold quality
ventricular zone	UBERON:0003053	99.72	gold quality
nucleus accumbens	UBERON:0001882	99.66	gold quality
right frontal lobe	UBERON:0002810	99.66	gold quality
calcaneal tendon	UBERON:0003701	99.62	gold quality
renal medulla	UBERON:0000362	99.61	gold quality
putamen	UBERON:0001874	99.60	gold quality
esophagus mucosa	UBERON:0002469	99.60	gold quality
esophagus	UBERON:0001043	99.57	gold quality
embryo	UBERON:0000922	99.56	gold quality
smooth muscle tissue	UBERON:0001135	99.56	gold quality
ascending aorta	UBERON:0001496	99.55	gold quality
thoracic aorta	UBERON:0001515	99.55	gold quality
caudate nucleus	UBERON:0001873	99.55	gold quality
lower esophagus	UBERON:0013473	99.55	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.55	gold quality
amygdala	UBERON:0001876	99.53	gold quality
descending thoracic aorta	UBERON:0002345	99.53	gold quality
prefrontal cortex	UBERON:0000451	99.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.51	gold quality
monocyte	CL:0000576	99.50	gold quality
skin of leg	UBERON:0001511	99.50	gold quality
granulocyte	CL:0000094	99.49	gold quality
aorta	UBERON:0000947	99.49	gold quality
cingulate cortex	UBERON:0003027	99.49	gold quality
skin of abdomen	UBERON:0001416	99.48	gold quality
minor salivary gland	UBERON:0001830	99.48	gold quality
anterior cingulate cortex	UBERON:0009835	99.48	gold quality
mouth mucosa	UBERON:0003729	99.46	gold quality
leukocyte	CL:0000738	99.45	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	7738.75
E-MTAB-6819	yes	6398.23
E-CURD-89	yes	2966.04
E-MTAB-9841	yes	1841.78
E-HCAD-56	yes	1682.29
E-HCAD-8	yes	1539.96
E-CURD-122	yes	1110.73
E-HCAD-4	yes	811.03
E-HCAD-5	yes	50.31
E-GEOD-137537	yes	43.49
E-MTAB-7316	yes	35.65
E-HCAD-31	yes	27.29
E-CURD-46	yes	26.19
E-HCAD-10	yes	23.14
E-MTAB-9067	yes	22.76

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

20 targets.

Target	Regulation
BCL2L1
CASP3
CCND1	Activation
CXCL2
ENO2
ERBB2
FOXN1
GNAS
HSD3B2	Unknown
HSPA4
IL6
JUN
LCT
MAP2K5
MBL2
MYC	Repression
MYCN	Unknown
PGK1
PTGS2	Unknown
TH

Upstream regulators (CollecTRI, top): ATF1, CREB1, EPAS1, HIF1A, MAP2K1, MYC

miRNA regulators (miRDB)

14 targeting ENO1, 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-3119	99.92	71.34	2390
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-4305	97.94	68.63	533
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4521	97.73	67.64	684
HSA-MIR-8055	97.62	66.09	1023
HSA-MIR-558	97.50	67.16	977
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-552-3P	96.68	64.12	1026

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 55.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Proteomic analysis of human brain identifies alpha-enolase as a novel autoantigen in Hashimoto’s encephalopathy. (PMID:12297304)
• A target of excess protein nitration in Alzheimer disease (AD) brain, providing evidence of the importance of oxidative stress in AD progression (PMID:12787059)
• The alpha-enolase protein is the target protein of serum anti-endothelial antibody in Behcet’s disease patients. (PMID:12847697)
• antibodies against human alpha-enolase target antigens in retinal ganglion cells and inner nuclear layer cells and induce the apoptotic death of sensitive cells in rat retinal explants (PMID:15324934)
• Results suggest a novel role of c-myc promoter-binding protein 1 for suppression of prostate cancer cell growth by regulating the MEK5-mediated signaling pathway. (PMID:15805119)
• ENO1 has tumour suppressor activity and high level of ENO1 expression has growth inhibitory effects (PMID:16359544)
• Depletion of MBP-1 in prostate cancer cells perturbs cell proliferation by inhibiting cyclin A and cyclin B1 expression. (PMID:16762917)
• Our results indicate that differential subcellular localization of ENO1 products may be closely related to carcinogenesis of the oral epithelium (PMID:17284257)
• alpha-crystallin B, glyceraldehyde phosphate dehydrogenase (GAPDH), and alpha-enolase identified as significantly S-glutathionylated in Alzheimer’s disease infeior parietal lobule (PMID:17387692)
• These findings further support the distinct roles of alpha-enolase and its MBP-1 variant in maintaining cell homeostasis. Moreover, these data suggest a novel function for NS1-BP in the control of cell proliferation. (PMID:17996313)
• alpha-enolase and MBP-1 associate with the kelch protein NS1-BP. c-Myc gene transcriptional repression exerted by MBP-1 is enhanced by NS1-BP. (PMID:17996313)
• Enolase on the surface of cells may be a receptor for plasminogen. The enolase/plasminogen (plasmin) system is one of the mechanisms facilitating the invasiveness of pathogens and it plays a role in myogenesis and in the development of tumor tissues. (PMID:18033204)
• TGF-beta1-induced growth arrest was associated with notable downregulation of the myc-binding protein-1 (MBP-1). (PMID:18070418)
• These results indicate that the activated Notch1 receptor and alpha-enolase or MBP-1 cooperate in controlling c-myc expression through binding the YY1 response element of the c-myc promoter to regulate tumorigenesis. (PMID:18490439)
• Crystal structure of ENO1 is presented at 2.2 A resolution. Despite its high sequence similarity to other enolases, the ENO1 structure exhibits distinct surface properties, explaining its various activities, including plasmin(ogen) and DNA binding. (PMID:18560153)
• Alpha-enolase was citrullinated in rheumatoid arthritis synovial fluid. (PMID:18668562)
• demonstration that IL8, DES and ENO1 act as the central elements in colon cancer susceptibility, and protein biosynthesis and the ribosome-associated function categories largely account for the colon cancer tumuorigenesis (PMID:18691435)
• HIF-1alpha-regulated glycolysis module is closely related to the aggressive phenotype of hepatocellular carcinoma, and ENO1, a glycolysis module gene, might have a role in preventing metastasis (PMID:18813785)
• An important mechanism of inflammatory cell invasion mediated by increased cell-surface expression of ENO-1. (PMID:19182206)
• Crystals of alpha-Enolase from human liver were obtained by the hanging-drop vapour-diffusion method and diffracted to 2.5 A resolution. (PMID:19255486)
• fatty acid-binding protein-5, squamous cell carcinoma antigens 2, alpha-enolase, annexin II, apolipoprotein A-I and albumin were detected at a high level in Atopic dermatitis skin lesions, but scarcely in the normal controls (PMID:19339807)
• Results indicate that alpha-enolase elicits a PDAC-specific, integrated humoral and cellular response (proliferative response by T-cells). (PMID:19425054)
• Isozymes alpha- and gamma-enolases were identified as targets for cathepsin X. (PMID:19433310)
• Inhibition of ENO-1 expression significantly augmented 4-OHT cytotoxicity in tamoxifen-resistant breast cancer cells. (PMID:19655245)
• Association of upregulated ACLY and ENO1 expression by chi square for all probe sets (reporters) combined and correlation for numbers of probe sets indicating shared upregulation of these genes. (PMID:19795461)
• These results suggest that MBP-1-suppressed COX-2 expression plays an important role in the inhibition of growth and progression of gastric cancer. (PMID:19846662)
• melanoma antigen expressed in G361, a representative melanoma cell line/ reacted with autoantibodies in patient sera (PMID:20181627)
• a prognostic role of ENO1 overexpression was demonstrated in head and neck cancer and ENO1-mediated promotion of cell transformation and invasion partly via induced CCL20 expression. (PMID:20435467)
• SEDLIN is present in the nucleus, forms homodimers and that SEDT-associated mutations cause a loss of interaction with the transcription factors MBP1, PITX1 and SF1. (PMID:20498720)
• Overexpression of ENO1 is associated with recurrences in chordomas. (PMID:20721957)
• novel transcript was alternatively transcribed from intron III of the ENO1 gene and was feasible for MBP-1 production (PMID:20849415)
• Loss of nuclear MBP-1 expression is associated with the progression of invasive ductal breast carcinoma. (PMID:20886042)
• The elevated levels of ENO1 protein in the tumor tissues and the plasma samples from NSCLC patients indicate ENO1 may be a candidate biomarker of lung cancer. (PMID:21159241)
• These results extend, confirm, and generalize the evidence supporting the specificity of the anti-CEP-1 antibody-positive subgroup of patients with rheumatoid arthritis among anti-CCP antibody-positive patients with RA. (PMID:21360494)
• glomerular alpha-enolase is a target antigen of autoimmunity in human MGN. Circulating anti alpha-enolase auto-antibodies can be detected in sera of a significant quota of membranous glomerulonephritis patients. (PMID:21640210)
• Silencing of ENO1 resulted in growth inhibition and cell cycle arrest of gastric cancer cells. (PMID:21751384)
• Data show six differentially expressed proteins were identified as HSP70, PPIA and alpha-Enolase (up-regulated) S100-A9, PIMT and beta-5 tubulin (down-regulated), most of which had been shown to play a potential role in the pathogenesis of atherosclerosis. (PMID:21839816)
• ENO1 over expression may play a important role in cell proliferation and progression of nasopharyngeal cancer. (PMID:21950004)
• Data show that ENOA, PARK7 and Beta-actin are proper reference standards in obesity studies based on omental fat. (PMID:22272336)
• Increased citrullination of Arg9 in ENO1 is associated with Creutzfeldt-Jakob disease and Alzheimer’s disease. (PMID:22551201)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	eno1b	ENSDARG00000013750
danio_rerio	eno1a	ENSDARG00000022456
mus_musculus	Eno1b	ENSMUSG00000059040
mus_musculus	Eno1	ENSMUSG00000063524
rattus_norvegicus	Eno1	ENSRNOG00000017895
rattus_norvegicus	Eno1-ps1	ENSRNOG00000028543
rattus_norvegicus	Eno1-ps20	ENSRNOG00000049269
drosophila_melanogaster	Eno	FBGN0000579
caenorhabditis_elegans		WBGENE00011884

Paralogs (3): ENO3 (ENSG00000108515), ENO2 (ENSG00000111674), ENO4 (ENSG00000188316)

Protein

Protein identifiers

Alpha-enolase — P06733 (reviewed: P06733)

Alternative names: 2-phospho-D-glycerate hydro-lyase, C-myc promoter-binding protein, Enolase 1, MBP-1, MPB-1, Non-neural enolase, Phosphopyruvate hydratase, Plasminogen-binding protein

All UniProt accessions (10): P06733, A0A024R4F1, A0A2R8Y6G6, A0A2R8Y6I8, A0A2R8Y798, A0A2R8Y879, A0A2R8YEG5, A0A2R8YEM5, K7EM90, K7ERS8

UniProt curated annotations — full annotation on UniProt →

Function. Enolase that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in glycolysis and the reverse reaction in gluconeogenesis. Also involved in various processes such as growth control, hypoxia tolerance and allergic responses. May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons. Stimulates immunoglobulin production. Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor.

Subunit / interactions. Mammalian enolase is composed of 3 isozyme subunits, alpha, beta and gamma, which can form homodimers or heterodimers which are cell-type and development-specific. ENO1 interacts with PLG in the neuronal plasma membrane and promotes its activation. The C-terminal lysine is required for this binding. Isoform MBP-1 interacts with TRAPPC2B. Interacts with ENO4 and PGAM2. Interacts with CMTM6.

Subcellular location. Cytoplasm. Cell membrane. Myofibril. Sarcomere. M line Nucleus.

Tissue specificity. The alpha/alpha homodimer is expressed in embryo and in most adult tissues. The alpha/beta heterodimer and the beta/beta homodimer are found in striated muscle, and the alpha/gamma heterodimer and the gamma/gamma homodimer in neurons.

Post-translational modifications. ISGylated. Lysine 2-hydroxyisobutyrylation (Khib) by p300/EP300 activates the phosphopyruvate hydratase activity.

Cofactor. Binds two Mg(2+) per subunit. Required for catalysis and for stabilizing the dimer.

Induction. Induced in diffuse large cell lymphoma (DLCL) after treatment with the natural biological agent, Bryo1. Up-regulated in response to enterovirus 71 (EV71) infection (at protein level).

Pathway. Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 4/5.

Miscellaneous. Used as a diagnostic marker for many tumors and, in the heterodimeric form, alpha/gamma, as a marker for hypoxic brain injury after cardiac arrest. Also marker for endometriosis. Antibodies against alpha-enolase are present in sera from patients with cancer-associated retinopathy syndrome (CAR), a progressive blinding disease which occurs in the presence of systemic tumor growth, primarily small-cell carcinoma of the lung and other malignancies. Is identified as an autoantigen in Hashimoto encephalopathy (HE) a rare autoimmune disease associated with Hashimoto thyroiditis (HT). HT is a disorder in which destructive processes overcome the potential capacity of thyroid replacement leading to hypothyroidism. It is uncertain whether the alternative initiation site is at Met-94 or at Met-97.

Similarity. Belongs to the enolase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P06733-1	alpha-enolase	yes
P06733-2	MBP-1

RefSeq proteins (3): NP_001188412, NP_001340275, NP_001419* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000941	Enolase	Family
IPR020809	Enolase_CS	Conserved_site
IPR020810	Enolase_C	Domain
IPR020811	Enolase_N	Domain
IPR029017	Enolase-like_N	Homologous_superfamily
IPR036849	Enolase-like_C_sf	Homologous_superfamily

Pfam: PF00113, PF03952

Enzyme classification (BRENDA):

• EC 4.2.1.11 — phosphopyruvate hydratase (BRENDA: 121 organisms, 78 substrates, 91 inhibitors, 111 Km, 13 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
2-PHOSPHO-D-GLYCERATE	0.025–6.053	70
PHOSPHOENOLPYRUVATE	0.07–43	31
(25R)-3BETA-HYDROXYCHOLEST-5-EN-27-OATE	0.041–0.25	2
3-PHOSPHO-D-GLYCERATE	0.39–1.281	2

Catalyzed reactions (Rhea), 1 shown:

• (2R)-2-phosphoglycerate = phosphoenolpyruvate + H2O (RHEA:10164)

UniProt features (105 total): modified residue 35, helix 21, strand 12, binding site 10, sequence conflict 6, mutagenesis site 5, region of interest 4, turn 4, sequence variant 2, active site 2, initiator methionine 1, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5NI9	X-RAY DIFFRACTION	1.33
5NIG	X-RAY DIFFRACTION	1.35
5OCK	X-RAY DIFFRACTION	1.6
5JLZ	X-RAY DIFFRACTION	1.99
2PSN	X-RAY DIFFRACTION	2.2
3B97	X-RAY DIFFRACTION	2.2
8TRL	X-RAY DIFFRACTION	2.4
5LAX	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06733-F1	97.68	0.98

Antibody-complex structures (SAbDab): 1 — 5OCK

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 (2): 210 (proton donor); 343 (proton acceptor)

Ligand- & substrate-binding residues (10): 167; 245; 293; 293; 318; 318; 370–373; 394; 40; 158

Post-translational modifications (36): 2, 5, 27, 44, 60, 60, 64, 71, 89, 89, 92, 126, 193, 199, 202, 228, 228, 228, 233, 233 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
94	mbp1 protein production. no mbp1 protein production; when associated with i-97.
97	mbp1 protein production. no mbp1 protein production; when associated with i-94.
281	decreased 2-hydroxyisobutyrylation leading to decreased phosphopyruvate hydratase activity.
384	loss of transcriptional repression and cell growth inhibition; when associated with a-388.
388	loss of transcriptional repression and cell growth inhibition; when associated with a-384.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 496 (showing top): GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, AP1_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HONMA_DOCETAXEL_RESISTANCE, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, HARRIS_HYPOXIA, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, MATTIOLI_MGUS_VS_PCL, GOBP_GROWTH, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), gluconeogenesis (GO:0006094), glycolytic process (GO:0006096), response to virus (GO:0009615), positive regulation of plasminogen activation (GO:0010756), negative regulation of cell growth (GO:0030308), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of muscle contraction (GO:0045933), canonical glycolysis (GO:0061621), negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway (GO:1903298), positive regulation of ATP biosynthetic process (GO:2001171)

GO Molecular Function (14): magnesium ion binding (GO:0000287), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), transcription corepressor binding (GO:0001222), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), phosphopyruvate hydratase activity (GO:0004634), protein homodimerization activity (GO:0042803), cadherin binding (GO:0045296), GTPase binding (GO:0051020), DNA binding (GO:0003677), protein binding (GO:0005515), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (12): phosphopyruvate hydratase complex (GO:0000015), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nuclear outer membrane (GO:0005640), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), cell surface (GO:0009986), membrane (GO:0016020), M band (GO:0031430), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glucose metabolism	2
Response of Mtb to phagocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
negative regulation of DNA-templated transcription	2
nucleic acid binding	2
cytoplasm	2
cell periphery	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
glucose metabolic process	1
hexose biosynthetic process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
response to other organism	1
regulation of plasminogen activation	1
positive regulation of protein processing	1
plasminogen activation	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
muscle contraction	1
regulation of muscle contraction	1
positive regulation of multicellular organismal process	1
glucokinase activity	1
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity	1
glucose catabolic process	1
glycolytic process through glucose-6-phosphate	1

Protein interactions and networks

STRING

6826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENO1	PLG	P00747	996
ENO1	PGK1	P00558	928
ENO1	GAPDH	P00354	925
ENO1	TPI1	P00938	899
ENO1	ALDOA	P04075	870
ENO1	PKM	P14618	869
ENO1	J3KPS3	J3KPS3	866
ENO1	PGM1	P36871	857
ENO1	PGAM1	P18669	853
ENO1	PGAM4	Q8N0Y7	836
ENO1	AK2	P54819	826
ENO1	EGFR	P00533	816
ENO1	PGD	P52209	812
ENO1	GPI	P06744	812
ENO1	LDHA	P00338	801

IntAct

272 interactions, top by confidence:

A	B	Type	Score
ENO2	ENO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ENO1	ENO2	psi-mi:“MI:0914”(association)	0.710
ENO2	ENO1	psi-mi:“MI:0915”(physical association)	0.710
ENO1	HTT	psi-mi:“MI:0915”(physical association)	0.670
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640

BioGRID (998): ENO1 (Affinity Capture-MS), ENO1 (Affinity Capture-MS), SZRD1 (Affinity Capture-RNA), NUDC (Affinity Capture-RNA), RCC1 (Affinity Capture-RNA), YARS (Affinity Capture-RNA), LRRC42 (Affinity Capture-RNA), MRPL37 (Affinity Capture-RNA), DPH5 (Affinity Capture-RNA), GSTM3 (Affinity Capture-RNA), STRIP1 (Affinity Capture-RNA), HIST2H2AB (Affinity Capture-RNA), CDC42SE1 (Affinity Capture-RNA), POGZ (Affinity Capture-RNA), LMNA (Affinity Capture-RNA)

ESM2 similar proteins: A0KU82, A3QC77, A5FRM5, A6GZ69, A8FSS8, A9NF93, B0S8S8, B0SRL5, B1JB38, B1KPT6, B3PJB3, B5DGQ7, I0J1J1, P04764, P06733, P13929, P17182, P26300, P30575, P33676, P42896, P51913, Q01YD1, Q04SI9, Q050L5, Q0HL72, Q0HXH0, Q12PZ4, Q15QR6, Q27655, Q27877, Q3KH92, Q3Z8W4, Q3ZX11, Q48F79, Q4KHF6, Q4R5L2, Q4ZWQ8, Q5R6Y1, Q6MPQ2

Diamond homologs: A0A509AQ68, A6LJF0, A6TU30, B5DGQ7, B6YUB8, B7IFN4, C1KY94, C5A2S7, I0J1J1, O02654, O57391, O59605, O74286, P00924, P00925, P04764, P06733, P07322, P07323, P08734, P09104, P0CX10, P0CX11, P13929, P15007, P15429, P17182, P17183, P19140, P21550, P25696, P25704, P26300, P26301, P30575, P31683, P33676, P40370, P42040, P42222

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	ENO1	phosphorylation
ENO1	“up-regulates quantity”	phosphonatoenolpyruvate	“chemical modification”
ENO1	“down-regulates quantity”	2-phosphonato-D-glycerate(3-)	“chemical modification”
ULK1	“down-regulates activity”	ENO1	phosphorylation
ULK2	“down-regulates activity”	ENO1	phosphorylation
MYC	“up-regulates quantity”	ENO1	“transcriptional regulation”
ENO1	“down-regulates quantity by repression”	MYC	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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.

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	7	19.0×	1e-04
positive regulation of G1/S transition of mitotic cell cycle	5	15.2×	3e-03
autophagosome maturation	5	13.3×	4e-03
JNK cascade	6	12.3×	1e-03
receptor internalization	5	12.3×	5e-03
mitophagy	5	12.0×	5e-03
cellular response to UV	5	11.2×	7e-03
G1/S transition of mitotic cell cycle	7	10.6×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1590 predictions. Top by Δscore:

Variant	Effect	Δscore
1:8861454:A:C	acceptor_gain	1.0000
1:8862882:CTTAC:C	donor_loss	1.0000
1:8862884:TACC:T	donor_loss	1.0000
1:8862885:A:AC	donor_gain	1.0000
1:8862885:A:AG	donor_loss	1.0000
1:8862886:C:CC	donor_gain	1.0000
1:8862886:C:CG	donor_loss	1.0000
1:8862943:GATC:G	acceptor_loss	1.0000
1:8862945:TCTAG:T	acceptor_loss	1.0000
1:8862946:C:CC	acceptor_gain	1.0000
1:8862946:CTA:C	acceptor_loss	1.0000
1:8862947:T:C	acceptor_loss	1.0000
1:8863229:TCTTA:T	donor_loss	1.0000
1:8863230:CTTAC:C	donor_loss	1.0000
1:8863231:TTACC:T	donor_loss	1.0000
1:8863232:TA:T	donor_loss	1.0000
1:8863233:A:AC	donor_gain	1.0000
1:8863233:A:C	donor_loss	1.0000
1:8863233:ACCTG:A	donor_gain	1.0000
1:8863234:C:CA	donor_loss	1.0000
1:8863234:C:CC	donor_gain	1.0000
1:8863234:CCTG:C	donor_gain	1.0000
1:8863234:CCTGC:C	donor_gain	1.0000
1:8863237:G:A	donor_gain	1.0000
1:8863339:TGCAC:T	acceptor_gain	1.0000
1:8863340:GCAC:G	acceptor_gain	1.0000
1:8863341:CAC:C	acceptor_gain	1.0000
1:8863341:CACC:C	acceptor_gain	1.0000
1:8863343:CCTGG:C	acceptor_loss	1.0000
1:8863344:C:CC	acceptor_gain	1.0000

AlphaMissense

2862 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:8862940:C:A	K394N	1.000
1:8862940:C:G	K394N	1.000
1:8863291:C:A	G374W	1.000
1:8863297:G:T	R372S	1.000
1:8863920:C:A	Q346H	1.000
1:8863920:C:G	Q346H	1.000
1:8863929:T:A	K343N	1.000
1:8863929:T:G	K343N	1.000
1:8863930:T:A	K343I	1.000
1:8864001:A:C	D319E	1.000
1:8864001:A:T	D319E	1.000
1:8864002:T:A	D319V	1.000
1:8864002:T:C	D319G	1.000
1:8864002:T:G	D319A	1.000
1:8864003:C:G	D319H	1.000
1:8864005:T:A	D318V	1.000
1:8864005:T:G	D318A	1.000
1:8864006:C:G	D318H	1.000
1:8864078:C:G	D294H	1.000
1:8864079:T:A	E293D	1.000
1:8864079:T:G	E293D	1.000
1:8865415:G:C	D245E	1.000
1:8865415:G:T	D245E	1.000
1:8865416:T:A	D245V	1.000
1:8865416:T:G	D245A	1.000
1:8865417:C:G	D245H	1.000
1:8866311:C:T	G212E	1.000
1:8866315:C:G	G211R	1.000
1:8866317:T:A	E210V	1.000
1:8866323:C:T	G208E	1.000

dbSNP variants (sampled 300 via entrez): RS1000039412 (1:8864779 C>A), RS1000224184 (1:8880218 A>G), RS1000296452 (1:8880428 G>A), RS1000533487 (1:8861566 T>C,G), RS1000744012 (1:8874996 G>A,C), RS1000800309 (1:8867742 G>A), RS1001058942 (1:8877988 G>A), RS1001348095 (1:8877566 T>A), RS1001571104 (1:8871466 G>A), RS1001859718 (1:8867118 G>A), RS1001872302 (1:8878008 A>C,G), RS1002005100 (1:8872242 T>C), RS1002135002 (1:8870445 G>T), RS1002166224 (1:8870652 C>G,T), RS1002281863 (1:8877707 C>T)

Disease associations

OMIM: gene MIM:172430 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
polymicrogyria	Limited	Autosomal dominant

Mondo (1): polymicrogyria (MONDO:0000087)

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001877_69	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	5.000000e-07
GCST003995_27	Tonsillectomy	6.000000e-09
GCST004607_4	Plateletcrit	3.000000e-16
GCST004618_23	White blood cell count (basophil)	1.000000e-09
GCST005014_33	Tonsillectomy	6.000000e-09
GCST006585_638	Blood protein levels	6.000000e-06
GCST006952_12	Feeling tense	8.000000e-10
GCST007798_2	Asthma	2.000000e-09
GCST90002400_12	Plateletcrit	5.000000e-52
GCST90002402_526	Platelet count	8.000000e-30
GCST90002407_385	White blood cell count	9.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007924	tonsillectomy risk measurement
EFO:0007985	platelet crit
EFO:0005090	basophil count
EFO:0009596	feeling tense measurement
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065706	Polymicrogyria	C10.500.507.500.500; C16.131.666.507.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3298 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,202 (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
CHEMBL260046	EVOFOSFAMIDE	3	664
CHEMBL1232461	MOLIBRESIB	2	1,538

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

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
SF2312	IC50	37.9 nM
phosphonoacetohydroxamate (PhAH)	IC50	53.2 nM

ChEMBL bioactivities

25 potent at pChembl≥5 of 27 total, top 25 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.92	IC50	1.2	nM	CHEMBL5185604
8.20	IC50	6.3	nM	CHEMBL5187779
7.29	IC50	51	nM	PHOSPHONOACETOHYDROXAMATE
7.28	Kd	52.99	nM	CHEMBL5653589
7.28	ED50	52.99	nM	CHEMBL5653589
6.52	IC50	301	nM	EVOFOSFAMIDE
6.24	IC50	576	nM	CHEMBL3335790
6.22	IC50	604	nM	CHEMBL4647008
6.14	IC50	720	nM	CHEMBL4647008
6.05	IC50	897	nM	EVOFOSFAMIDE
5.74	IC50	1814	nM	CHEMBL4647008
5.67	IC50	2148	nM	CHEMBL4647008
5.62	IC50	2406	nM	CHEMBL4647008
5.59	IC50	2554	nM	EVOFOSFAMIDE
5.57	IC50	2691	nM	CHEMBL5193347
5.55	IC50	2806	nM	CHEMBL4647008
5.46	IC50	3450	nM	MOLIBRESIB
5.40	IC50	3945	nM	CHEMBL4633981
5.40	IC50	4020	nM	CHEMBL4633981
5.36	Kd	4368	nM	CHEMBL3752910
5.36	ED50	4368	nM	CHEMBL3752910
5.32	IC50	4838	nM	EVOFOSFAMIDE
5.24	IC50	5764	nM	CHEMBL4643988
5.23	IC50	5900	nM	CHEMBL4647387
5.11	IC50	7840	nM	CHEMBL4643988

PubChem BioAssay actives

25 with measured affinity, of 41 total; 14 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
(1,5-dihydroxy-2-oxopyrrolidin-3-yl)phosphonic acid	1852635: Inhibition of ENO1 (unknown origin)	ic50	0.0012	uM
[(3S,5S)-1,5-dihydroxy-3-methyl-2-oxopyrrolidin-3-yl]phosphonic acid	1852635: Inhibition of ENO1 (unknown origin)	ic50	0.0063	uM
[(3S,5S)-1,5-dihydroxy-2-oxopyrrolidin-3-yl]phosphonic acid	1802194: Enolase Enzymatic Assays from Article 10.1038/nchembio.2195: “SF2312 is a natural phosphonate inhibitor of enolase.”	ic50	0.0379	uM
[2-(hydroxyamino)-2-oxoethyl]phosphonic acid	1852635: Inhibition of ENO1 (unknown origin)	ic50	0.0510	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148321: Binding affinity to human ENO1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0530	uM
2-bromo-N-[(2-bromoethylamino)-[(3-methyl-2-nitroimidazol-4-yl)methoxy]phosphoryl]ethanamine	1661328: Inhibition of ENO1 in overexpressed human D423 cells incubated for 5 days in presence of 1 % oxygen by crystal violet staining based spectrophotometry	ic50	0.3010	uM
N-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-2-[4-[[4-(cyclohexylmethylamino)-6-[(4-fluorophenyl)methylamino]-1,3,5-triazin-2-yl]amino]phenyl]acetamide	1167912: Inhibition of ENO1 (unknown origin)	ic50	0.5760	uM
[2,2-dimethylpropanoyloxymethoxy-(1-hydroxy-2-oxopiperidin-3-yl)phosphoryl]oxymethyl 2,2-dimethylpropanoate	1661322: Inhibition of ENO1 in overexpressed human D423 cells incubated for 5 days by crystal violet staining based spectrophotometry	ic50	0.6040	uM
(1-hydroxy-2-oxopyrrolidin-3-yl)phosphonic acid	1852635: Inhibition of ENO1 (unknown origin)	ic50	2.6910	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178762: Inhibition of ENO1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	3.4500	uM
[(benzylamino)-(1-hydroxy-2-oxopiperidin-3-yl)phosphoryl]oxymethyl 2,2-dimethylpropanoate	1661322: Inhibition of ENO1 in overexpressed human D423 cells incubated for 5 days by crystal violet staining based spectrophotometry	ic50	3.9450	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148321: Binding affinity to human ENO1 incubated for 45 mins by Kinobead based pull down assay	kd	4.3678	uM
[3-[(benzylamino)-[(5-nitrofuran-2-yl)methoxy]phosphoryl]-2-oxopiperidin-1-yl] acetate	1661328: Inhibition of ENO1 in overexpressed human D423 cells incubated for 5 days in presence of 1 % oxygen by crystal violet staining based spectrophotometry	ic50	5.7640	uM
(1-hydroxy-2-oxopiperidin-3-yl)phosphonic acid	1852635: Inhibition of ENO1 (unknown origin)	ic50	5.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases secretion, affects reaction, increases expression, decreases reaction (+2 more)	8
bisphenol A	decreases expression, increases expression, affects cotreatment, affects expression	5
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, affects cotreatment	5
Tretinoin	decreases expression, affects expression, increases expression, affects cotreatment	5
Valproic Acid	affects cotreatment, increases expression	5
trichostatin A	affects cotreatment, increases expression, affects expression	4
Oxygen	decreases reaction, increases expression	4
Cadmium Chloride	decreases expression, increases expression, increases secretion	4
arsenite	affects binding, increases reaction, increases expression, decreases activity, increases oxidation	3
cobaltous chloride	decreases expression, increases expression	3
Tobacco Smoke Pollution	increases expression, increases metabolic processing, affects expression	3
Cyclosporine	decreases expression, increases expression, increases secretion	3
cadmium acetate	decreases expression, 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
bisphenol S	increases expression	2
Amphotericin B	increases secretion, decreases reaction, increases expression	2
Arsenic	decreases expression, affects cotreatment, increases abundance, increases expression	2
Cadmium	decreases reaction, increases expression, increases secretion	2
Ibuprofen	affects expression, increases expression	2
Nickel	increases expression	2
Quercetin	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Dronabinol	decreases expression, increases expression	2
aristolochic acid I	decreases expression, increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
PF-06840003	decreases expression, decreases reaction	1
chloroacetaldehyde	increases expression	1
chlorophyllin	decreases expression	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3386525	Binding	Inhibition of ENO1 (unknown origin)	An update on therapeutic opportunities offered by cancer glycolytic metabolism. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00552045	Not specified	COMPLETED	Epilepsy Phenome/Genome Project
NCT04344626	Not specified	WITHDRAWN	Use of a Tonometer to Identify Epileptogenic Lesions During Pediatric Epilepsy Surgery