Alternative titles; symbols
HGNC Approved Gene Symbol: ELOVL5
SNOMEDCT: 734021001;
Cytogenetic location: 6p12.1 Genomic coordinates (GRCh38) : 6:53,267,404-53,348,950 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6p12.1 | Spinocerebellar ataxia 38 | 615957 | Autosomal dominant | 3 |
ELOVL5 plays a role in elongation of long-chain polyunsaturated fatty acids (Leonard et al., 2000).
By database analysis using Saccharomyces cerevisiae Elo2 sequence as query, followed by PCR of a human liver cDNA library, Leonard et al. (2000) cloned ELOVL5, which they called HELO1. The deduced 299-amino acid protein contains 6 transmembrane regions and a histidine box, characteristic of membrane-bound enzymes. Quantitative RT-PCR analysis of human tissues detected highest expression in testis and adrenal gland with lower expression in brain, lung, prostate, mammary gland, thymus, and fetal liver.
Di Gregorio et al. (2014) found expression of the ELOVL5 gene in human and mouse cerebellum. In Purkinje cells, the protein localized to the soma and proximal portion of the dendritic tree.
Leonard et al. (2000) showed that ELOVL5 expressed in yeast catalyzed the elongation of the polyunsaturated fatty acid substrate gamma-linolenic acid (GLA) and several other long-chain polyunsaturated fatty acids.
By genomic sequence analysis, Leonard et al. (2000) mapped the ELOVL5 gene to chromosome 6p12.
In affected members of a large Italian family with autosomal dominant spinocerebellar ataxia-38 (SCA38; 615957), Di Gregorio et al. (2014) identified a heterozygous missense mutation in the ELOVL5 gene (G230V; 611805.0001). The mutation was found by linkage analysis and candidate gene sequencing. Screening of the ELOVL5 gene in 456 European probands with SCA identified heterozygous mutations in 3 additional families (611805.0001 and 611805.0002). Affected individuals had adult onset of a pure phenotype with slowly progressive gait ataxia and nystagmus; several patients had evidence of an axonal neuropathy. Transfection of the mutations into several cell lines showed that the mutant proteins had a less diffuse endoplasmic reticulum signal compared to wildtype, and tended to accumulate in the Golgi apparatus. Transfected cells showed increased levels of CHOP (126337), suggesting activation of the unfolded protein response that could lead to apoptosis.
In 20 affected members from 3 large unrelated families of Italian origin with spinocerebellar ataxia-38 (SCA38; 615957), Di Gregorio et al. (2014) identified a heterozygous c.689G-T transversion in exon 7 of the ELOVL5 gene, resulting in a gly230-to-val (G230V) substitution at a highly conserved residue. The mutation, which was found in the first family by linkage analysis and targeted resequencing of genes within the candidate region, was confirmed by Sanger sequencing. The mutation segregated with the disorder in all families and was not present in 800 control chromosomes or in the dbSNP (build 137), 1000 Genomes Project, or Exome Variant Server databases. Haplotype analysis indicated a founder effect for the 3 families. Arachidonic acid and docosahexaenoic acid, 2 final products of the enzyme, were reduced in the serum of affected individuals. Patient cells showed increased ELOVL5 mRNA and protein, suggesting a compensatory effect.
In a French man with spinocerebellar ataxia-38 (SCA38; 615957), Di Gregorio et al. (2014) identified a heterozygous c.214C-G transversion in exon 3 of the ELOVL5 gene, resulting in a leu72-to-val (L72V) substitution at a highly conserved residue. The mutation was not present in the dbSNP (build 137), 1000 Genomes Project, or Exome Variant Server databases, or in 800 control chromosomes. The patient's sister and mother were affected, but their DNA was not available for segregation analysis.
Di Gregorio, E., Borroni, B., Giorgio, E., Lacerenza, D., Ferrero, M., Lo Buono, N., Ragusa, N., Mancini, C., Gaussen, M., Calcia, A., Mitro, N., Hoxha, E., and 23 others. ELOVL5 mutations cause spinocerebellar ataxia 38. Am. J. Hum. Genet. 95: 209-217, 2014. [PubMed: 25065913] [Full Text: https://doi.org/10.1016/j.ajhg.2014.07.001]
Leonard, A. E., Bobik, E. G., Dorado, J., Kroeger, P. E., Chuang, L.-T., Thurmond, J. M., Parker-Barnes, J. M., Das, T., Huang, Y.-S., Mukerji, P. Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids. Biochem. J. 350: 765-770, 2000. [PubMed: 10970790]