GeneBe

ENO3

protein-coding

enolase 3, the group of Enolases

Gene summary

This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme is found in skeletal muscle cells in the adult where it may play a role in muscle development and regeneration. A switch from alpha enolase to beta enolase occurs in muscle tissue during development in rodents. Mutations in this gene have be associated glycogen storage disease. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jul 2010]

MANE transcript

NM_053013.4

Inheritance

AR

ClinVar variants

P:9U:192B:94

Top phenotype

Glycogen storage disease XIII

gnomAD constraint

pLI —, LoF o/e 1.22

Max pathogenic AF

—

Genomic locus

chr17:4,948,092-4,957,131

External References & Databases

Ensembl (ENSG00000108515)NCBI Gene (2027)OMIM (131370)HGNC:3354GenCCUniProt (P13929)AlphaFoldClinVar (ENO3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~9.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

glycogen storage disease due to muscle beta-enolase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013046

Submitter: Genomics England PanelApp

glycogen storage disease due to muscle beta-enolase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013046

Submitter: Labcorp Genetics (formerly Invitae)

glycogen storage disease due to muscle beta-enolase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013046

Submitter: PanelApp Australia

glycogen storage disease due to muscle beta-enolase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013046

Submitter: Orphanet

Clinical Genomic Database (CGD)

Glycogen storage disease XIIIAR

Manifestation: Biochemical; Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: The reported individual had exercise intolerance and increased CK without myoglobinuria

Refs: 11506403Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ENO3 variants in ClinVar

5 Conditions Cataloged
Glycogen storage disease due to muscle beta-enolase deficiencyTotal: 327
Inborn genetic diseasesTotal: 75
not providedTotal: 54
not specifiedTotal: 33
ENO3-related disorderTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_053013.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
89
clinvar
2
clinvar
 94
missense
1
clinvar
1
clinvar
169
clinvar
1
clinvar
2
clinvar
 174
nonsense
1
clinvar
7
clinvar
 8
start loss
1
clinvar
 1
frameshift
1
clinvar
4
clinvar
6
clinvar
 11
splice donor/acceptor (+/-2bp)
1
clinvar
6
clinvar
 7
Total27192904295

Highest pathogenic variant AF is 0.0002410185

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 102 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_053013.4RefSeqNP_443739.311MANE Select
ENST00000519602.6EnsemblENSP00000430055.211MANE Select
NM_001193503.2RefSeqNP_001180432.19Standard
NM_001374523.1RefSeqNP_001361452.111Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Glycolysis / Gluconeogenesis - Homo sapiens (human)
  • HIF-1 signaling pathway - Homo sapiens (human)
  • RNA degradation - Homo sapiens (human)
  • Pathways in clear cell renal cell carcinoma
  • Glycolysis and Gluconeogenesis

Biological Process

  • gluconeogenesis
  • aging
  • response to drug
  • skeletal muscle tissue regeneration
  • canonical glycolysis

Molecular Function

  • magnesium ion binding
  • phosphopyruvate hydratase activity
  • protein homodimerization activity
  • protein heterodimerization activity

Cellular Component

  • phosphopyruvate hydratase complex
  • extracellular space
  • cytosol
  • plasma membrane
  • membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000323997
Coding exons
11
Length
9040
Individuals with no LoFs
125525
Homozygous LoFs
0
Heterozygous LoFs
223
Defined
125748
p
0.000887
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.9252922511.160.00001622836
Missense (PolyPhen)161141.821.13521582
Synonymous-0.5261111041.070.00000736867
Loss of Function-0.9552621.21.220.00000121242

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000930.00092rare
Latino/Admixed American0.00110.0011notable
Ashkenazi Jewish0.000710.00069rare
East Asian0.000440.00044rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.00100.0010notable
South Asian0.000980.00098rare
Other0.00130.0013notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Appears to have a function in striated muscle development and regeneration.;
Disease
DISEASE: Glycogen storage disease 13 (GSD13) [MIM:612932]: A metabolic disorder that results in exercise-induced myalgias, generalized muscle weakness and fatigability. It is characterized by increased serum creatine kinase and decreased enolase 3 activity. Dramatically reduced protein levels with focal sarcoplasmic accumulation of glycogen-beta particles are detected on ultrastructural analysis. {ECO:0000269|PubMed:11506403}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.377

Intolerance Scores

LoFtool
0.475
RVIS EVS
-0.49
RVIS percentile EVS
22.65

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.531

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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