ENO2

Chr 12

enolase 2

Also known as: HEL-S-279, NSE

NCBI Gene: 2026 ENSG00000111674 UniProt: P09104 OMIM: 131360

ENO2 encodes gamma-enolase, a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate and has neurotrophic properties in central nervous system neurons. Mutations cause autosomal recessive glycolytic enzymopathy with hemolytic anemia, characterized by exercise intolerance, muscle weakness, and chronic hemolysis. The gene is moderately constrained against loss-of-function variants (LOEUF 0.471), reflecting its essential role in neuronal glucose metabolism.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.81Z-score

OE missense 0.69 (0.61–0.78)

180 obs / 262.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.12–0.47)

0≤0.351.4

Missense OE?0.69 (0.61–0.78)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 5 / 22.3Missense obs/exp: 180 / 262.5Syn Z: 0.43

Background carrier burden — how many people carry a rare variant somewhere in ENO2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

449 rare PASS variants

Rare truncating (LoF)

1 in 4,500

49 rare PASS variants

Rare synonymous (reference)

1 in 320

206 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ENO2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 5,000
South Asian	~43k	1 in 200	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 150	1 in 2,700
European (Finnish)	~27k	1 in 860	1 in 1,200
Admixed American	~22k	1 in 200	≈ 1 in 11,000
African / African American	~21k	1 in 120	≈ 1 in 6,400
East Asian	~20k	1 in 220	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 770	1 in 1,300
Middle Eastern	~2,884	1 in 150	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓