Alternative titles; symbols
HGNC Approved Gene Symbol: TMEM240
SNOMEDCT: 718774001;
Cytogenetic location: 1p36.33 Genomic coordinates (GRCh38): 1:1,534,778-1,540,624 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1p36.33 | Spinocerebellar ataxia 21 | 607454 | Autosomal dominant | 3 |
TMEM240 is a small, highly conserved transmembrane protein expressed in brain (Delplanque et al., 2014).
By mass spectrometric and database analyses, Trinidad et al. (2012) identified mouse Tmem240, which they called EG381582, as a phosphoprotein expressed in adult brain synaptic membranes.
Delplanque et al. (2014) reported that the deduced 173-amino acid human TMEM240 protein has a short N-terminal tail, followed by 2 transmembrane domains and a long C-terminal domain. It has 2 putative phosphorylation sites in the loop between the transmembrane domains, and 1 putative phosphorylation site in the C-terminal domain. Database analysis revealed orthologs in several vertebrates.
Delplanque et al. (2014) determined that the TMEM240 gene has 4 coding exons and spans 5.6 kb.
Delplanque et al. (2014) stated that the TMEM240 gene maps to chromosome 1p36.33.
In affected members of 8 unrelated French families with spinocerebellar ataxia-21 (SCA21; 607454), Delplanque et al. (2014) identified 6 different heterozygous mutations in the TMEM240 gene (see, e.g., 616101.0001-616101.0005). There were 5 missense mutations and 1 truncating mutation. The mutation in the first family was found by linkage analysis combined with whole-exome sequencing. Mutations in the 7 additional families were found by direct sequencing of the TMEM240 gene in 368 French pedigrees with autosomal dominant SCA. All the mutations affected highly conserved residues, but functional studies of the variants were not performed.
In affected members of a large French family with spinocerebellar ataxia-21 (SCA21; 607454), originally reported by Devos et al. (2001), Delplanque et al. (2014) identified a heterozygous c.509C-T transition in exon 4 of the TMEM240 gene, resulting in a pro170-to-leu (P170L) substitution at a highly conserved residue at the C terminus. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 934 French controls. The same mutation was subsequently identified in affected members of 2 of 368 French families with a similar disorder, but haplotype analysis did not suggest a founder effect among these families. Functional studies of the variant were not performed.
In affected members of a French family with spinocerebellar ataxia-21 (SCA21; 607454), Delplanque et al. (2014) identified a heterozygous c.489C-G transversion in exon 4 of the TMEM240 gene, resulting in a tyr163-to-ter (Y163X) substitution near the C terminus. The mutation was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 396 French controls. Functional studies of the variant were not performed. (There is a discrepancy in the nucleotide change for this allelic variant in the article by Delplanque et al. (2014): it is stated as c.489C-G in the abstract, but as c.489C-T in the text. Sablonniere (2014) confirmed that c.489C-G is correct.)
In a French man with spinocerebellar ataxia-21 (SCA21; 607454), Delplanque et al. (2014) identified a heterozygous c.346C-T transition in exon 3 of the TMEM240 gene, resulting in an arg116-to-cys (R116C) substitution at a highly conserved residue. The mutation, which was not found in 5 unaffected family members, was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 396 French controls. Functional studies of the variant were not performed.
In a French man with spinocerebellar ataxia-21 (SCA21; 607454), Delplanque et al. (2014) identified a heterozygous c.239C-T transition in exon 3 of the TMEM240 gene, resulting in a thr80-to-met (T80M) substitution at a highly conserved residue between the 2 transmembrane alpha helices. The mutation, which was not found in 2 unaffected family members, was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 396 French controls. Functional studies of the variant were not performed. Unlike SCA21 patients with other TMEM240 mutations, the patient with the T80M mutation did not have cognitive impairment.
In a French woman with spinocerebellar ataxia-21 (SCA21; 607454), Delplanque et al. (2014) identified a heterozygous c.511C-T transition in exon 4 of the TMEM240 gene, resulting in an arg171-to-trp (R171W) substitution at a highly conserved residue in the C terminus. The mutation, which was not found in an unaffected family member, was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 396 French controls. Functional studies of the variant were not performed. The patient had late onset of gait ataxia in her sixties.
Delplanque, J., Devos, D., Huin, V., Genet, A., Sand, O., Moreau, C., Goizet, C., Charles, P., Anheim, M., Monin, M. L., Buee, L., Destee, A., and 9 others. TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment. Brain 137: 2657-2663, 2014. [PubMed: 25070513] [Full Text: https://doi.org/10.1093/brain/awu202]
Devos, D., Schraen-Maschke, S., Vuillaume, I., Dujardin, K., Naze, P., Willoteaux, C., Destee, A., Sablonniere, B. Clinical features and genetic analysis of a new form of spinocerebellar ataxia. Neurology 56: 234-238, 2001. [PubMed: 11160961] [Full Text: https://doi.org/10.1212/wnl.56.2.234]
Sablonniere, B. Personal Communication. Lille, France 12/2/2014.
Trinidad, J. C., Barkan, D. T., Gulledge, B. F., Thalmhammer, A., Sali, A., Schoepfer, R., Burlingame, A. L. Global identification and characterization of both O-GlcNAcylation and phosphorylation at the murine synapse. Molec. Cell. Proteomics 11: 215-229, 2012. [PubMed: 22645316] [Full Text: https://doi.org/10.1074/mcp.O112.018366]