ENO2

Summary

ENO2 (enolase 2, HGNC:3353) is a protein-coding gene on chromosome 12p13.31, encoding Gamma-enolase (P09104). Enolase that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in glycolysis and the reverse reaction in gluconeogenesis.

This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme, a homodimer, is found in mature neurons and cells of neuronal origin. A switch from alpha enolase to gamma enolase occurs in neural tissue during development in rats and primates.

Source: NCBI Gene 2026 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 54 total — 1 pathogenic
• MANE Select transcript: NM_001975

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3353
Approved symbol	ENO2
Name	enolase 2
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	NSE
Ensembl gene	ENSG00000111674
Ensembl biotype	protein_coding
OMIM	131360
Entrez	2026

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 16 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000229277, ENST00000441285, ENST00000534977, ENST00000535275, ENST00000535366, ENST00000536199, ENST00000537688, ENST00000537838, ENST00000538763, ENST00000539713, ENST00000541477, ENST00000542509, ENST00000543975, ENST00000545045, ENST00000879143, ENST00000879144, ENST00000879145, ENST00000934731, ENST00000934732, ENST00000967958, ENST00000967959, ENST00000967960, ENST00000967961

RefSeq mRNA: 1 — MANE Select: NM_001975 NM_001975

CCDS: CCDS8570

Canonical transcript exons

ENST00000229277 — 12 exons

Exon	Start	End
ENSE00001102855	6914580	6914659
ENSE00003478569	6922056	6922164
ENSE00003628411	6922344	6922402
ENSE00003699619	6916671	6916729
ENSE00003700162	6916417	6916512
ENSE00003845316	6922731	6923697
ENSE00003889063	6921581	6921782
ENSE00003889435	6917581	6917714
ENSE00003890449	6915821	6915917
ENSE00003892091	6919566	6919763
ENSE00003894695	6917038	6917107
ENSE00003894774	6917940	6918162

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.9387 / max 787.1093, expressed in 1696 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123798	27.5037	1631
123797	6.3688	1347
123796	3.2756	1153
123801	2.1406	359
123795	1.0976	451
123803	0.3333	152
123800	0.1293	53
123799	0.0583	26
123794	0.0315	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar cortex	UBERON:0002129	99.86	gold quality
cerebellar hemisphere	UBERON:0002245	99.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.86	gold quality
cerebellum	UBERON:0002037	99.82	gold quality
paraflocculus	UBERON:0005351	99.74	gold quality
cerebellar vermis	UBERON:0004720	99.65	gold quality
right frontal lobe	UBERON:0002810	99.59	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.59	gold quality
prefrontal cortex	UBERON:0000451	99.51	gold quality
frontal pole	UBERON:0002795	99.44	gold quality
frontal cortex	UBERON:0001870	99.42	gold quality
frontal lobe	UBERON:0016525	99.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.35	gold quality
cortical plate	UBERON:0005343	99.31	gold quality
neocortex	UBERON:0001950	99.29	gold quality
postcentral gyrus	UBERON:0002581	99.24	gold quality
cingulate cortex	UBERON:0003027	99.22	gold quality
anterior cingulate cortex	UBERON:0009835	99.21	gold quality
parietal lobe	UBERON:0001872	99.19	gold quality
superior frontal gyrus	UBERON:0002661	99.18	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.14	gold quality
nucleus accumbens	UBERON:0001882	99.08	gold quality
pons	UBERON:0000988	99.06	gold quality
cerebral cortex	UBERON:0000956	99.04	gold quality
orbitofrontal cortex	UBERON:0004167	99.02	gold quality
middle frontal gyrus	UBERON:0002702	98.93	gold quality
caudate nucleus	UBERON:0001873	98.92	gold quality
telencephalon	UBERON:0001893	98.91	gold quality
brain	UBERON:0000955	98.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	2438.88
E-MTAB-7316	yes	45.54
E-HCAD-35	yes	44.51
E-GEOD-93593	yes	18.28
E-MTAB-5061	yes	17.14
E-HCAD-25	yes	8.87
E-ENAD-17	no	1382.10
E-MTAB-9154	no	802.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ENO1, HIF1A, NOTO, STAT3

miRNA regulators (miRDB)

55 targeting ENO2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-892C-5P	99.16	70.56	2116

Literature-anchored findings (GeneRIF, showing 40)

• Serum level of enolase 2 heavily influences survival in neuroblastoma in children. (PMID:11881792)
• expressed in the placenta and umbilical cord (PMID:11919335)
• Serum time course of two brain-specific proteins, alpha(1) brain globulin and neuron-specific enolase, in tick-born encephalitis and Lyme disease. (PMID:11983209)
• neuron-specific enolase (NSE) may have a role in development of pyothorax-associated lymphoma (PAL) (PMID:11985791)
• the frequency of a high NSE serum value in acute and lymphoma type adult T-cell leukemia (ATL) suggests that ATL cells preferentially produce NSE compared with other NHL cells (PMID:12353304)
• Patients with viral meningitis showed high concentrations of inosine, guanosine, xanthine, urate and neuron-specific enolase. (PMID:12581805)
• Increased level of neuron-specific enolase is associated with small-cell lung cancer and non-small cell lung cancer patients (PMID:12636057)
• Decreasing levels of serum NSE but not S-100B over time may indicate selective attenuation of delayed neuronal death by therapeutic hypothermia in victims of cardiac arrest (PMID:14631087)
• enzyme has been purified, crystallized and its crystal structure determined. (PMID:15289101)
• NSE increases to similar degrees with and without traumatic brain injury (PMID:16044081)
• The crystal structure of the human neuronal enolase-Mg2F2P(i) complex determined at 1.36 A resolution shows that the combination of anions effectively mimics an intermediate state in catalysis (PMID:16411755)
• Serum neuron-specific enolase (NSE) measurement has prognostic value in predicting outcomes in patients recovering from cardiopulmonary resuscitation following in-hospital cardiac arrest. (PMID:16978415)
• MS patients had a greater prevalence of positive T-cell proliferative responses to neuron-specific enolase [NSE], retinal arrestin, and beta-arrestin than healthy controls (p<0.0001). (PMID:17436063)
• There is complementarity in the combined detection of the level of TPS, NSE, CEA and beta(2)-MG. Their levels have close correlation with lung cancer, histological grades and lymphoid nodule metastasis. (PMID:17618570)
• Neuron-specific enolase is a relevant marker in investigation of the patients with neurofibromatosis type 1 and associated tumors (PMID:18063947)
• Serum samples were investigated for carcinoembryonic antigen (CEA), CA125 and MUC1, alpha-foetoprotein, neuron-specific enolase and CA19.9. (PMID:18609108)
• serum levels of neuron-specific enolase were decreased slightly during and after migraine bouts. (PMID:18783450)
• Levels of plasma S-100 beta and NSE cannot predict encephalopathy after orthotopic liver transplantation. (PMID:19220958)
• Early upregulation of neuron-specific enolase in children with head injury, correlates significantly with the severity of the head injury. (PMID:19221293)
• There are no differences in S100B and NSE levels between patients with ischemic stroke or intracerebral hemorrhage. (PMID:19221847)
• The timing, intensity, and duration of serum NSE and S-100B biomarker concentration patterns are associated with neurologic and survival outcomes following pediatric cardiac arrest. (PMID:19307814)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• Data demonstrated the increasing expression of NSE and the decreasing expression of nestin, which revealed that hMSCs had neuronal characteristics. (PMID:19445653)
• Jugular venous neurone specific enolase (NSE) increases following carotid endarterectomy under general, but not local, anaesthesia. (PMID:19540138)
• serum levels of S100B may be a marker for brain functional condition and serum NSE levels may be a marker for morphological status in Alzheimer’s disease (PMID:20105309)
• This enzyme, synthesized by neurons and neuroendocrine cells, is a marker useful for the diagnosis and the monitoring of patients with neuroendocrine tumors. (PMID:20348052)
• This protein has been found differentially expressed in the anterior cingulate cortex in women patients with schizophrenia. (PMID:20381070)
• the concentration of neurospecific enolase was changed depending on the character of perinatal injury of central nervous system. (PMID:20495226)
• The serum level of NSE at relapse is a useful predictive marker for CR to salvage chemotherapy. (PMID:20537424)
• Study of development of secondary injuries following traumatic brain injury includes measurement of release of neuron-specific enolase (NSE) and S100B into the cerebrospinal fluid and blood. (PMID:20686797)
• In nonproliferative diabetic retinopathy, the concentration of NSE showed an 18-fold increase in the tear fluid and the content of its autoantibodies remained unchanged. (PMID:20873151)
• Autoantibodies targeting NSE were not observed in any healthy control subjects or patients with inflammatory eye disease. However, anti-NSE activity was found in 1 child with molecularly confirmed Leber congenital amaurosis. (PMID:21149784)
• Studies of pancreatic tissue specimens from adult patients with type 1 diabetes mellitus showed no immunopositive reaction to neuron-specific enolase in insulin-negative specimens (PMID:21165441)
• The findings of increased ictal serum S100B and NSE levels together with increased interictal levels of S100B suggested that migraine might be associated with glial and/or neuronal damage in the brain. (PMID:21293918)
• Brain-specific gamma1-syntrophin participates in gamma-enolase translocation towards the plasma membrane, a pre-requisite for its neurotrophic activity. (PMID:21358174)
• The relationship of clinical outcome with cerebrospinal fluid neuron-specific enolase (NSE), S100B and glial fibrillary acidic protein (GFAP) levels in patients with severe traumatic brain injury was investigated (PMID:21368691)
• The increased level of serum S100beta and NSE may be one of the mechanisms of brain damage and memory impairment in obstructive sleep apnea-hypopnea syndrome. (PMID:21553520)
• Neuron-specific enolase levels were not significantly different in off-pump coronary artery bypass patients with/without intracranial and cervical artery stenosis. (PMID:21587126)
• NSE correlates well with other markers of ischemic brain injury. (PMID:21775743)
• Serum NSE may be a novel marker of disease aggressiveness as well as a prognostic factor for DLBCL in the era of rituximab. (PMID:21815777)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eno2	ENSDARG00000014287
mus_musculus	Eno2	ENSMUSG00000004267
rattus_norvegicus	Eno2	ENSRNOG00000013141
drosophila_melanogaster	Eno	FBGN0000579
caenorhabditis_elegans		WBGENE00011884

Paralogs (3): ENO1 (ENSG00000074800), ENO3 (ENSG00000108515), ENO4 (ENSG00000188316)

Protein

Protein identifiers

Gamma-enolase — P09104 (reviewed: P09104)

Alternative names: 2-phospho-D-glycerate hydro-lyase, Enolase 2, Neural enolase, Neuron-specific enolase

All UniProt accessions (6): P09104, F5H0C8, F5H1C3, Q6FHV6, U3KQP4, U3KQQ1

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. Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell survival.

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.

Subcellular location. Cytoplasm. Cell membrane.

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.

Cofactor. Mg(2+) is required for catalysis and for stabilizing the dimer.

Induction. Levels of ENO2 increase dramatically in cardiovascular accidents, cerebral trauma, brain tumors and Creutzfeldt-Jakob disease. (Microbial infection) Activated by human cytomegalovirus (HCMV) UL38 in order to provide the virus with glycosyl building blocks.

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

Similarity. Belongs to the enolase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P09104-1	1	yes
P09104-2	2

RefSeq proteins (1): NP_001966* (*=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 (92 total): modified residue 24, helix 22, strand 16, binding site 13, turn 5, sequence conflict 4, active site 2, sequence variant 2, initiator methionine 1, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
2AKZ	X-RAY DIFFRACTION	1.36
3UJR	X-RAY DIFFRACTION	1.4
3UCD	X-RAY DIFFRACTION	1.41
3UCC	X-RAY DIFFRACTION	1.5
3UJE	X-RAY DIFFRACTION	1.55
3UJS	X-RAY DIFFRACTION	1.65
1TE6	X-RAY DIFFRACTION	1.8
2AKM	X-RAY DIFFRACTION	1.92
4ZCW	X-RAY DIFFRACTION	1.99
5EU9	X-RAY DIFFRACTION	2.05
3UJF	X-RAY DIFFRACTION	2.1
7MBH	X-RAY DIFFRACTION	2.1
4ZA0	X-RAY DIFFRACTION	2.31
5TD9	X-RAY DIFFRACTION	2.32
5IDZ	X-RAY DIFFRACTION	2.63
5TIJ	X-RAY DIFFRACTION	2.63

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09104-F1	97.14	0.97

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 (13): 293; 293; 318; 318; 318; 370–373; 394; 40; 158; 167; 245; 245 …

Post-translational modifications (25): 2, 5, 26, 44, 60, 60, 64, 89, 89, 193, 197, 199, 202, 228, 228, 233, 233, 256, 263, 287 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-70171	Glycolysis
R-HSA-70263	Gluconeogenesis

MSigDB gene sets: 345 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, MODY_HIPPOCAMPUS_POSTNATAL, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_ESTRADIOL, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MENSE_HYPOXIA_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, MITSIADES_RESPONSE_TO_APLIDIN_DN

GO Biological Process (5): gluconeogenesis (GO:0006094), glycolytic process (GO:0006096), response to xenobiotic stimulus (GO:0009410), response to estradiol (GO:0032355), canonical glycolysis (GO:0061621)

GO Molecular Function (8): magnesium ion binding (GO:0000287), phosphopyruvate hydratase activity (GO:0004634), enzyme binding (GO:0019899), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (15): phosphopyruvate hydratase complex (GO:0000015), photoreceptor inner segment (GO:0001917), obsolete extracellular space (GO:0005615), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), cell surface (GO:0009986), membrane (GO:0016020), growth cone (GO:0030426), perikaryon (GO:0043204), membrane raft (GO:0045121), extracellular exosome (GO:0070062), synaptic membrane (GO:0097060), cytoplasm (GO:0005737), neuronal cell body (GO:0043025)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glucose metabolism	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	2
binding	2
cytoplasm	2
cell periphery	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
response to chemical	1
response to lipid	1
response to oxygen-containing compound	1
glucokinase activity	1
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity	1
glucose catabolic process	1
glycolytic process through glucose-6-phosphate	1
metal ion binding	1
hydro-lyase activity	1
catalytic activity	1
cation binding	1
cytosol	1
catalytic complex	1
membrane	1
site of polarized growth	1
distal axon	1
neuronal cell body	1
membrane microdomain	1
extracellular vesicle	1
synapse	1

Protein interactions and networks

STRING

5698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENO2	CHGA	P10645	939
ENO2	CEACAM5	P06731	919
ENO2	SYP	P08247	906
ENO2	S100B	P04271	881
ENO2	CD99	P14209	812
ENO2	UCHL1	P09936	801
ENO2	GRP	P07491	800
ENO2	PGK1	P00558	789
ENO2	NCAM1	P13591	773
ENO2	CD99L2	Q8TCZ2	773
ENO2	KRT19	P08727	771
ENO2	GFAP	P14136	728
ENO2	KRT20	P35900	727
ENO2	KRT7	P08729	722
ENO2	PGAM1	P18669	721

IntAct

72 interactions, top by confidence:

A	B	Type	Score
ENO2	ENO1	psi-mi:“MI:0914”(association)	0.710
ENO1	ENO2	psi-mi:“MI:0914”(association)	0.710
ENO2	ENO1	psi-mi:“MI:0915”(physical association)	0.710
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
ALX3	CRTAP	psi-mi:“MI:0914”(association)	0.530
TINF2	ENO2	psi-mi:“MI:0915”(physical association)	0.510
ENO2	TERF1	psi-mi:“MI:0915”(physical association)	0.370
ENO2	ACD	psi-mi:“MI:0915”(physical association)	0.370
ENO2	POT1	psi-mi:“MI:0915”(physical association)	0.370
ENO2	AKT1	psi-mi:“MI:0915”(physical association)	0.370
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
NEDD4	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
PIM1	A2ML1	psi-mi:“MI:0914”(association)	0.350
NTRK3	ERLIN1	psi-mi:“MI:0914”(association)	0.350
AURKC	CSTB	psi-mi:“MI:0914”(association)	0.350
MAP1LC3A		psi-mi:“MI:0914”(association)	0.350
GABARAPL2		psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (189): EXOC5 (Two-hybrid), ENO1 (Affinity Capture-MS), ENO3 (Affinity Capture-MS), ENO2 (Affinity Capture-MS), AKR1B1 (Co-fractionation), AKR1B15 (Co-fractionation), ARHGDIA (Co-fractionation), CALR (Co-fractionation), DUT (Co-fractionation), EEF1A1 (Co-fractionation), ENO2 (Co-fractionation), ENO2 (Co-fractionation), ENO2 (Co-fractionation), ENO2 (Co-fractionation), ENO2 (Co-fractionation)

ESM2 similar proteins: A5FRM5, A6L3M9, B0S8S8, B0SRL5, B1GYL7, B1JB38, B2KBA5, B5DGQ7, I0J1J1, O02654, O57391, P04764, P06733, P07323, P08734, P09104, P13929, P15429, P17182, P17183, P19140, P21550, P25704, P26300, P26301, P33676, P42894, P42896, P42897, P51913, P56252, Q1KYT0, Q27527, Q27655, Q27877, Q3Z8W4, Q3ZC09, Q3ZX11, Q43130, Q4R5L2

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

2 interactions.

A	Effect	B	Mechanism
ENO2	“up-regulates quantity”	phosphonatoenolpyruvate	“chemical modification”
ENO2	“down-regulates quantity”	2-phosphonato-D-glycerate(3-)	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
Macroautophagy	6	12.8×	5e-04
Cytokine Signaling in Immune system	8	6.0×	3e-03
Cellular responses to stress	8	5.5×	4e-03
Cellular responses to stimuli	8	4.7×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle organization	5	18.6×	1e-03
protein ubiquitination	9	5.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	40
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2445417	GRCh37/hg19 12p13.33-11.1(chr12:176047-34179852)x4	Pathogenic

SpliceAI

1927 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6915811:A:AG	acceptor_gain	1.0000
12:6915811:ACCC:A	acceptor_gain	1.0000
12:6915812:C:G	acceptor_gain	1.0000
12:6915814:C:CA	acceptor_gain	1.0000
12:6915817:G:A	acceptor_gain	1.0000
12:6915918:G:GA	donor_loss	1.0000
12:6916416:G:A	acceptor_loss	1.0000
12:6916416:GGTC:G	acceptor_gain	1.0000
12:6916510:AAGGT:A	donor_loss	1.0000
12:6916513:G:C	donor_loss	1.0000
12:6916513:G:GG	donor_gain	1.0000
12:6916725:GCTCA:G	donor_gain	1.0000
12:6916726:C:G	donor_gain	1.0000
12:6916730:G:GG	donor_gain	1.0000
12:6916804:G:T	donor_gain	1.0000
12:6917579:A:AG	acceptor_gain	1.0000
12:6917580:G:GG	acceptor_gain	1.0000
12:6917927:T:TA	acceptor_gain	1.0000
12:6917929:T:TA	acceptor_gain	1.0000
12:6917930:G:A	acceptor_gain	1.0000
12:6917936:CCAG:C	acceptor_loss	1.0000
12:6917937:CAG:C	acceptor_loss	1.0000
12:6917938:A:AG	acceptor_gain	1.0000
12:6917938:AG:A	acceptor_gain	1.0000
12:6917938:AGGC:A	acceptor_loss	1.0000
12:6917939:G:GA	acceptor_gain	1.0000
12:6917939:GG:G	acceptor_gain	1.0000
12:6917939:GGC:G	acceptor_gain	1.0000
12:6917939:GGCC:G	acceptor_gain	1.0000
12:6917939:GGCCT:G	acceptor_gain	1.0000

AlphaMissense

2831 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6916444:G:A	G38E	1.000
12:6917957:T:A	N154K	1.000
12:6917957:T:G	N154K	1.000
12:6917959:G:A	G155D	1.000
12:6917967:C:G	H158D	1.000
12:6917969:T:A	H158Q	1.000
12:6917969:T:G	H158Q	1.000
12:6917993:G:C	Q166H	1.000
12:6917993:G:T	Q166H	1.000
12:6917995:A:T	E167V	1.000
12:6918118:G:A	G208E	1.000
12:6918124:A:T	E210V	1.000
12:6918126:G:C	G211R	1.000
12:6919631:G:C	D245H	1.000
12:6919632:A:T	D245V	1.000
12:6919633:T:A	D245E	1.000
12:6919633:T:G	D245E	1.000
12:6921667:G:C	D318H	1.000
12:6921668:A:C	D318A	1.000
12:6921668:A:T	D318V	1.000
12:6921669:T:A	D318E	1.000
12:6921669:T:G	D318E	1.000
12:6921671:A:T	D319V	1.000
12:6921744:G:C	K343N	1.000
12:6921744:G:T	K343N	1.000
12:6921753:G:C	Q346H	1.000
12:6921753:G:T	Q346H	1.000
12:6922096:A:C	S370R	1.000
12:6922098:T:A	S370R	1.000
12:6922098:T:G	S370R	1.000

dbSNP variants (sampled 300 via entrez): RS1000634103 (12:6916457 C>T), RS1001276024 (12:6923220 C>T), RS1001391324 (12:6916164 A>C), RS1002345369 (12:6923375 T>C), RS1002861692 (12:6919881 G>A), RS1003304976 (12:6920223 G>T), RS1003605491 (12:6918452 G>A), RS1004373106 (12:6920315 T>C), RS1004384686 (12:6920556 T>C,G), RS1004633835 (12:6914331 T>C), RS1004706512 (12:6918753 G>A), RS1005232906 (12:6915608 C>G,T), RS1005359464 (12:6921597 C>A,T), RS1005611430 (12:6915320 G>C), RS1007183735 (12:6920987 A>C,G)

Disease associations

OMIM: gene MIM:131360 | disease phenotypes: MIM:601803

GenCC curated gene-disease

Mondo (2): tetrasomy 12p (MONDO:0011146), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (2): Pallister-Killian syndrome (Orphanet:884), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
C538105	Pallister Killian syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PubChem BioAssay actives

2 with measured affinity, of 2 total; 2 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
[(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	0.0425	uM
[2-(hydroxyamino)-2-oxoethyl]phosphonic acid	1802194: Enolase Enzymatic Assays from Article 10.1038/nchembio.2195: “SF2312 is a natural phosphonate inhibitor of enolase.”	ic50	0.0623	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	7
Oxygen	decreases reaction, increases expression	5
trichostatin A	affects cotreatment, decreases expression, affects expression	4
cobaltous chloride	increases expression, decreases reaction	4
Cisplatin	affects expression, increases expression	4
bisphenol A	decreases expression, increases expression	3
bisphenol S	decreases expression, increases expression, affects cotreatment	3
Benzo(a)pyrene	increases expression, increases methylation	3
Cyclosporine	decreases expression, increases expression	3
Cadmium Chloride	increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases expression	2
nickel chloride	increases expression	2
deguelin	decreases expression, decreases secretion	2
Decitabine	affects expression, affects cotreatment	2
Vorinostat	affects cotreatment, affects expression, decreases expression	2
Ethanol	decreases expression	2
Cocaine	decreases expression, increases expression	2
Doxorubicin	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	increases expression	2
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	2
aristolochic acid I	decreases expression, increases expression	1
abemaciclib	increases expression	1
1-cyclopropyl-4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl)pyridin-2-yl)piperazine	decreases reaction, increases expression	1
GSK-J4	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
aminomethylphosphonic acid (AMPA)	increases expression	1
tungsten carbide	affects binding, increases expression	1
chloroacetaldehyde	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1G6	Abcam Jurkat ENO2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome