ENO1

Chr 1

enolase 1

Also known as: ENO1-IT1, ENO1L1, HEL-S-17, MPB1, NNE, PPH

NCBI Gene: 2023 ENSG00000074800 UniProt: P06733 OMIM: 172430

Alpha-enolase catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in glycolysis and serves as a structural lens protein (tau-crystallin) in its monomeric form. Mutations cause ENO1 deficiency, an autosomal recessive disorder presenting with hemolytic anemia and intellectual disability. The gene shows minimal constraint to loss-of-function variants, consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Jan 2011]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.86

Clinical Summary— ENO1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

50 VUS of 86 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.000

Z-score 2.03

OE 0.52 (0.33–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.84Z-score

OE missense 0.85 (0.76–0.95)

219 obs / 256.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.33–0.86)

0≤0.351.4

Missense OE?0.85 (0.76–0.95)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 11 / 21.1Missense obs/exp: 219 / 256.8Syn Z: -0.23

This gene — mechanism propensity

0.7228th %ile

GOF

0.6149th %ile

LOF

0.2680th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

VUS50

Likely Benign2

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	50	0	0	50
Likely Benign	0	1	1	2
Benign	0	0	2	2
Total	50	1	3	54

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 49) ClinVar copy-number / structural variants overlap ENO1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →