ENO3

enolase 3, the group of Enolases

Basic information

Region (hg38): 17:4948092-4957131

Links

ENSG00000108515 ∙ NCBI:2027 ∙ OMIM:131370 ∙ HGNC:3354 ∙ Uniprot:P13929 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease due to muscle beta-enolase deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to muscle beta-enolase deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to muscle beta-enolase deficiency (Supportive), mode of inheritance: AR
• glycogen storage disease due to muscle beta-enolase deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease XIII	AR	General	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	Biochemical; Musculoskeletal	11506403
The reported individual had exercise intolerance and increased CK without myoglobinuria

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ENO3 gene.

• Glycogen storage disease due to muscle beta-enolase deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ENO3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	65	2	68
missense			123	2	3	128
nonsense			7			7
start loss			1			1
frameshift	1	1	7			9
inframe indel				2		2
splice donor/acceptor (+/-2bp)		1	3			4
splice region			9	14	2	25
non coding				50	17	67
Total	1	2	142	119	22

Highest pathogenic variant AF is 0.0000131

Variants in ENO3

This is a list of pathogenic ClinVar variants found in the ENO3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-4948130-C-G			Benign (Sep 29, 2018)
17-4948243-C-A			Likely benign (Mar 23, 2023)
17-4948251-G-T			Likely benign (Sep 23, 2022)
17-4948258-A-T			Uncertain significance (Feb 25, 2023)
17-4948259-G-A			Uncertain significance (Nov 23, 2022)
17-4948272-G-A			Likely benign (Nov 23, 2022)
17-4948281-T-C			Likely benign (Nov 26, 2017)
17-4948290-G-A			Likely benign (Jan 19, 2024)
17-4948298-C-T		PFN1-related disorder	Uncertain significance (Jul 26, 2024)
17-4948305-G-A			Likely benign (Feb 28, 2022)
17-4948309-G-A		Amyotrophic lateral sclerosis	Uncertain significance (Feb 08, 2022)
17-4948321-TA-AG			Uncertain significance (May 10, 2021)
17-4948327-A-C			Uncertain significance (May 10, 2021)
17-4948350-C-G			Likely benign (Nov 05, 2023)
17-4948352-C-T			Uncertain significance (Oct 29, 2023)
17-4948357-G-A			Uncertain significance (Mar 12, 2023)
17-4948358-C-T		Amyotrophic lateral sclerosis	Uncertain significance (Mar 31, 2020)
17-4948360-A-G		Inborn genetic diseases	Uncertain significance (Jan 26, 2023)
17-4948364-G-A			Uncertain significance (Oct 24, 2023)
17-4948371-G-A			Likely benign (Sep 01, 2023)
17-4948452-G-C			Likely benign (Dec 24, 2018)
17-4948472-G-A			Benign (Oct 17, 2018)
17-4948480-C-T			Likely benign (Oct 24, 2018)
17-4948526-G-A			Likely benign (Dec 31, 2018)
17-4948563-TC-T			Benign (Jul 03, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ENO3	protein_coding	protein_coding	ENST00000323997	11	9040

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.57e-19	0.000415	125525	0	223	125748	0.000887

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.925	292	251	1.16	0.0000162	2836
Missense in Polyphen		161	141.82	1.1352		1582
Synonymous	-0.526	111	104	1.07	0.00000736	867
Loss of Function	-0.955	26	21.2	1.22	0.00000121	242

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00200	0.00200
Ashkenazi Jewish	0.000713	0.000695
East Asian	0.000436	0.000435
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00103	0.00103
Middle Eastern	0.000436	0.000435
South Asian	0.000981	0.000980
Other	0.00130	0.00130

dbNSFP

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.
• Pathway: 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;Metabolism of carbohydrates;Citrate cycle;Glycolysis Gluconeogenesis;Glycolysis and Gluconeogenesis;Metabolism;Glycolysis;gluconeogenesis;glycolysis;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Gluconeogenesis;Glucose metabolism (Consensus)

Recessive Scores

• pRec: 0.377

Intolerance Scores

• loftool: 0.475
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.65

Haploinsufficiency Scores

• pHI: 0.889
• hipred: Y
• hipred_score: 0.605
• ghis: 0.582

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.531

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Eno3

Gene ontology

• Biological process: gluconeogenesis;aging;response to drug;skeletal muscle tissue regeneration;canonical glycolysis
• Cellular component: phosphopyruvate hydratase complex;extracellular space;cytosol;plasma membrane;membrane;extracellular exosome
• Molecular function: magnesium ion binding;phosphopyruvate hydratase activity;protein homodimerization activity;protein heterodimerization activity