Alternative titles; symbols
HGNC Approved Gene Symbol: ENO3
Cytogenetic location: 17p13.2 Genomic coordinates (GRCh38) : 17:4,948,710-4,957,129 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17p13.2 | Glycogen storage disease XIII | 612932 | Autosomal recessive | 3 |
Peshavaria and Day (1991) determined that the ENO3 gene encodes a deduced 433-amino acid protein.
Chen and Giblett (1976) and Pearce et al. (1976) presented evidence for 3 enolase loci. By in situ hybridization studies using a probe for ENO2 (131360), Craig et al. (1989) found small aggregates of grains at 1pter-p36, the site of ENO1 (172430), and some at 17pter-p12.
Feo et al. (1990) mapped the muscle-specific beta-enolase (ENO3) to chromosome 17pter-p11 by analysis of rodent-human somatic cell hybrids and transfectant cell lines carrying different portions of chromosome 17. This muscle-specific enzyme maps to the region encoding the gene cluster for the sarcomeric myosin heavy chains (MYH1; 160730).
Peshavaria and Day (1991) determined that the ENO3 gene contains 12 exons and spans approximately 6 kb.
In a man with glycogen storage disease XIII (GSD13; 612932), Comi et al. (2001) identified compound heterozygosity for 2 missense mutations in the ENO3 gene (G156D, 131370.0001; G374E, 131370.0002). Immunohistochemistry and immunoblotting detected dramatically reduced beta-enolase protein in this patient, while alpha-enolase was normally represented.
In 2 unrelated patients, born to consanguineous parents, with GSD13, Musumeci et al. (2014) identified homozygous missense mutations in the ENO3 gene (N151S, 131370.0003 and E187K, 131370.0004). The mutations were identified by Sanger sequencing of the ENO3 gene. Beta-enolase activity was reduced in muscle tissue of both patients.
In a 23-year-old patient with GSD13, Wigley et al. (2019) identified a homozygous missense mutation in the ENO3 gene (C357Y; 131370.0005). The mutation was identified by Sanger sequencing of the ENO3 gene. Beta-enolase activity was reduced in patient muscle tissue. Wigley et al. (2019) showed that the reduction in ENO3 activity resulted from decreased maximum velocity (slower rate of activity) of the enzyme.
In a 47-year-old man with adult onset of exercise-induced myalgias, generalized muscle weakness, and fatigability (GSD13; 612932), Comi et al. (2001) identified compound heterozygosity for 2 mutations in the ENO3 gene: a 467G-A transition resulting in a gly156-to-asp (G156D) substitution and a 1121G-A transition resulting in a gly374-to-glu (G374E; 131370.0002) substitution.
For discussion of the gly374-to-glu (G374E) mutation in the ENO3 gene that was found in compound heterozygous state in a patient with adult onset of exercise-induced myalgias, generalized muscle weakness, and fatigability (GSD13; 612932) by Comi et al. (2001), see 131370.0001.
In a 45-year-old Italian man, born to consanguineous parents, with glycogen storage disease type XIII (GSD13; 612932), Musumeci et al. (2014) identified homozygosity for a c.452A-G transition in exon 7 of the ENO3 gene, resulting in an asn151-to-ser (N151S) substitution at a conserved residue. The mutation, which was identified by Sanger sequencing, was present in heterozygous state in the patient's unaffected mother, sib, and daughter; the patient's father was deceased and no sample was available for testing. Beta-enolase activity was reduced in patient muscle tissue.
In a 28-year-old Turkish man, born to consanguineous parents, with glycogen storage disease type XIII (GSD13; 612932), Musumeci et al. (2014) identified homozygosity for a c.559G-A transition in exon 7 of the ENO3 gene, resulting in a glu187-to-lys (E187K) substitution at a highly conserved residue. The mutation, which was identified by Sanger sequencing, was present in heterozygous state in the patient's unaffected father and sib; the patient's mother was deceased and no sample was available for testing. Beta-enolase activity was reduced in patient muscle tissue. Wigley et al. (2019) also studied this patient and predicted that the mutation may disrupt hydrogen bonding involved in the protein dimer interface.
In a 23-year-old Asian man with glycogen storage disease XIII (GSD13; 612932), Wigley et al. (2019) identified homozygosity for a c.1070G-A transition in exon 10 of the ENO3 gene, resulting in a cys357-to-tyr (C357Y) substitution at a highly conserved residue. The mutation was identified by Sanger sequencing. Beta-enolase activity was reduced in patient muscle tissue. Wigley et al. (2019) showed that the reduction in ENO3 activity resulted from decreased maximum velocity (slower rate of activity) of the enzyme.
Chen, S.-H., Giblett, E. R. Enolase: human tissue distribution and evidence for three different loci. Ann. Hum. Genet. 39: 277-280, 1976. [PubMed: 1275442] [Full Text: https://doi.org/10.1111/j.1469-1809.1976.tb00131.x]
Comi, G. P., Fortunato, F., Lucchiari, S., Bordoni, A., Prelle, A., Jann, S., Keller, A., Ciscato, P., Galbiati, S., Chiveri, L., Torrente, Y., Scarlato, G., Bresolin, N. Beta-enolase deficiency, a new metabolic myopathy of distal glycolysis. Ann. Neurol. 50: 202-207, 2001. [PubMed: 11506403] [Full Text: https://doi.org/10.1002/ana.1095]
Craig, S. P., Day, I. N. M., Thompson, R. J., Craig, I. W. Localization of human neurone-specific enolase to chromosome 12p13. (Abstract) Cytogenet. Cell Genet. 51: 980 only, 1989.
Feo, S., Oliva, D., Barbieri, G., Xu, W., Fried, M., Giallongo, A. The gene for the muscle-specific enolase is on the short arm of human chromosome 17. Genomics 6: 192-194, 1990. [PubMed: 2303260] [Full Text: https://doi.org/10.1016/0888-7543(90)90467-9]
Musumeci, O., Brady, S., Rodolico, C., Ciranni, A., Montagnese, F., Aguennouz, M., Kirk, R., Allen E., Godfrey, R., Romeo, S., Murphy, E., Rahman, S., Quinlivan, R., Toscano, A. Recurrent rhabdomyolysis due to muscle beta-enolase deficiency: very rare or underestimated? J. Neurol. 261: 2424-2428, 2014. [PubMed: 25267339] [Full Text: https://doi.org/10.1007/s00415-014-7512-7]
Pearce, J. M., Edwards, Y. H., Harris, H. Human enolase isozymes: electrophoretic and biochemical evidence for three loci. Ann. Hum. Genet. 39: 263-276, 1976. [PubMed: 5939] [Full Text: https://doi.org/10.1111/j.1469-1809.1976.tb00130.x]
Peshavaria, M., Day, I. N. M. Molecular structure of the human muscle-specific enolase gene (ENO3). Biochem. J. 275: 427-433, 1991. [PubMed: 1840492] [Full Text: https://doi.org/10.1042/bj2750427]
Wigley, R., Scalco, R. S., Gardiner, A. R., Godfrey, R., Booth, S., Kirk, R., Hilton-Jones, D., Houlden, H., Heales, S., Quinlivan, R. The need for biochemical testing in beta-enolase deficiency in the genomic era. JIMD Rep. 50: 40-43, 2019. [PubMed: 31741825] [Full Text: https://doi.org/10.1002/jmd2.12070]