ENO2

Chr 12

enolase 2

Also known as: HEL-S-279, NSE

NCBI Gene: 2026ENSG00000111674UniProt: P09104

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. [provided by RefSeq, Jul 2008]

100
ClinVar variants
46
Pathogenic / LP
0.38
pLI score
1
Active trials
Clinical Summary— ENO2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 51 VUS of 100 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.47LOEUF
pLI 0.384
Z-score 3.40
OE 0.22 (0.12–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.81Z-score
OE missense 0.69 (0.61–0.78)
180 obs / 262.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.12–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.61–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 5 / 22.3Missense obs/exp: 180 / 262.5Syn Z: 0.43

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic3
VUS51
Likely Benign2
Benign1
43
Pathogenic
3
Likely Pathogenic
51
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
3
0
3
VUS
1
38
12
0
51
Likely Benign
0
0
0
2
2
Benign
0
0
1
0
1
Total138592100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ENO2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ENOLASE 2; ENO2
MIM #131360 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects.
Isgrò MA et al.·Adv Exp Med Biol
2015Review
WDR45, one gene associated with multiple neurodevelopmental disorders.
Cong Y et al.·Autophagy
2021Review
METTL3-mediated m(6)A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance.
Wang Q et al.·Gut
2020
Tumor-derived Exosomal ENO2 Modulates Polarization of Tumor-associated Macrophages through Reprogramming Glycolysis to Promote Progression of Diffuse Large B-cell Lymphoma.
Shao R et al.·Int J Biol Sci
2024
Identification and analysis of oxidative stress-related genes in endometriosis.
Xie C et al.·Front Immunol
2025
HOXC6-mediated transcriptional activation of ENO2 promotes oral squamous cell carcinoma progression through the Warburg effect.
Feng J et al.·J Biochem Mol Toxicol
2024
ENO2 and BPTF axis drives tumor progression and macrophage polarization in T2DM-associated colorectal cancer.
Zhu Z et al.·Pathol Res Pract
2026
Genetic signatures of heroin addiction.
Chen SJ et al.·Medicine (Baltimore)
2016
ENO2 Promotes Cell Proliferation, Glycolysis, and Glucocorticoid-Resistance in Acute Lymphoblastic Leukemia.
Liu CC et al.·Cell Physiol Biochem
2018
ENO2 affects the EMT process of renal cell carcinoma and participates in the regulation of the immune microenvironment.
Chen WJ et al.·Oncol Rep
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
CNS Metastases

A Brain Metastases Research Platform to Tackle the Challenge of CNS Metastases in Solid Tumours

RECRUITING
NCT04109131Phase NAJules Bordet InstituteStarted 2020-07-01
Samples collection: PlasmaSamples collection: CSFSamples collection: Non-CNS Metastatic Tumour Tissue

External Resources

Links to major genomics databases and tools