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Other entities represented in this entry:
HGNC Approved Gene Symbol: ERAL1
Cytogenetic location: 17q11.2 Genomic coordinates (GRCh38): 17:28,855,016-28,861,061 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17q11.2 | Perrault syndrome 6 | 617565 | Autosomal recessive | 3 |
Era is an essential GTPase that is required for proper cell cycle progression and cell division in E. coli. By EST database searching with the C terminus of E. coli Era as query, Britton et al. (2000) isolated several homologous human ESTs. By sequencing of the ESTs, they identified 2 splice variants of the human ERAL1 gene, which they designated ERAL1A and ERAL1B. ERAL1A encodes a deduced 443-amino acid protein with all of the domains of the bacterial Era protein: an N-terminal GTP-binding domain, a conserved BoxA sequence, and a C-terminal KH domain. ERAL1B contains an in-frame stop codon that removes the C terminus of the protein, including BoxA and the putative KH domain, and results in a shortened protein of 282 amino acids. Northern blot analysis detected ubiquitous expression of an approximately 2.2-kb transcript.
By somatic cell hybrid analysis and FISH, Britton et al. (2000) mapped the ERAL1 gene to chromosome 17q11.2. By interspecific backcross analysis, they mapped the mouse homolog to a region of conserved synteny on chromosome 11.
In 3 unrelated Dutch women from the same small village with Perrault syndrome (PRLTS6; 617565), Chatzispyrou et al. (2017) identified homozygosity for a missense mutation in the ERAL1 gene (N236I; 607435.0001).
In C. elegans, Chatzispyrou et al. (2017) knocked down expression of the nematode ERAL1 homolog, E02H1.2, and observed near-complete blockage of egg production, mimicking the compromised fertility in women with Perrault syndrome. In addition, the worms exhibited a significantly decreased oxygen consumption rate.
In 3 unrelated Dutch women from the same small village with Perrault syndrome (PRLTS6; 617565), Chatzispyrou et al. (2017) identified homozygosity for a c.707A-T transversion (c.707A-T, NM_005702.2) in the ERAL1 gene, resulting in an asn236-to-ile (N236I) substitution at a highly conserved residue. Sequencing of ERAL1 in 1 of the families revealed that the proband's healthy mother and 2 sisters were heterozygous for the mutation, whereas her father, who had sensorineural hearing loss since childhood but no fertility problems, was homozygous. The mutation was not found in any public variant databases, but was present in heterozygosity in 49 of 530 unaffected villagers (allele frequency, 4.6%). Western blot analysis of patient skin fibroblasts showed reduced levels of ERAL1 protein compared to controls. Complexome profiling revealed a 30 to 40% decrease in the overall abundance of proteins composing the small 28S mitochondrial ribosomal subunit in patients compared to controls, whereas the abundance of proteins composing the large 39S subunit was comparable between patients and controls, suggesting that the N236I variant perturbs proper assembly of the small 28S mitochondrial ribosomal subunit. Using qPCR, the authors found that the 12S/16S rRNA ratio was significantly reduced in patient fibroblasts compared to controls; overexpression of ERAL1 in patient fibroblasts rescued the 12S/16S ratio.
Britton, R. A., Chen, S.-M., Wallis, D., Koeuth, T., Powell, B. S., Shaffer, L. G., Largaespada, D., Jenkins, N. A., Copeland, N. G., Court, D. L., Lupski, J. R. Isolation and preliminary characterization of the human and mouse homologues of the bacterial cell cycle gene era. Genomics 67: 78-82, 2000. [PubMed: 10945472] [Full Text: https://doi.org/10.1006/geno.2000.6243]
Chatzispyrou, I. A., Alders, M., Guerrero-Castillo, S., Zapata Perez, R., Haagmans, M. A., Mouchiroud, L., Koster, J., Ofman, R., Baas, F., Waterham, H. R., Spelbrink, J. N., Auwerx, J., Mannens, M. M., Houtkooper, R. H., Plomp, A. S. A homozygous missense mutation in ERAL1, encoding a mitochondrial rRNA chaperone, causes Perrault syndrome. Hum. Molec. Genet. 26: 2541-2550, 2017. [PubMed: 28449065] [Full Text: https://doi.org/10.1093/hmg/ddx152]