Alternative titles; symbols
HGNC Approved Gene Symbol: TECR
Cytogenetic location: 19p13.12 Genomic coordinates (GRCh38): 19:14,527,726-14,565,980 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 19p13.12 | Intellectual developmental disorder, autosomal recessive 14 | 614020 | Autosomal recessive | 3 |
Microsomal long and very long chain fatty acid elongation uses malonyl-CoA as the 2-carbon donor and consists of 4 sequential reactions. TECR catalyzes the final step, reducing trans-2,3-enoyl-CoA to saturated acyl-CoA (Moon and Horton, 2003).
By sequencing cDNAs obtained from umbilical cord blood CD34 (142230)-positive hematopoietic stem/progenitor cells, Mao et al. (1998) identified TECR, which they called GPSN2.
By searching databases for homologs of yeast Tsc13, followed by PCR of a human adipose tissue cDNA library, Moon and Horton (2003) cloned TECR, which they called TER. The deduced 308-amino acid protein contains 5 transmembrane domains. It shares 95% amino acid identity with mouse Tecr and 34% identity with yeast Tsc13. Northern blot analysis detected a 1.2-kb transcript in all human and mouse tissues examined. Epitope-tagged TECR colocalized predominantly with long chain fatty acid elongase (ELOVL6; 611546) in the endoplasmic reticulum of transfected Chinese hamster ovary cells. A small amount colocalized with GM130 (GOLGA2; 602580) in the Golgi.
Abe et al. (2013) stated that, based on the structures of yeast and Arabidopsis homologs, TECR is likely to be an integral endoplasmic reticulum (ER) membrane protein with 6 membrane-spanning domains, 3 luminal loops, and cytosolic N and C termini.
Caliskan et al. (2011) determined that the TECR gene contains 13 exons.
Caliskan et al. (2011) stated that the TECR gene maps to chromosome 19p13.
Hartz (2015) mapped the TECR gene to chromosome 19q13.12 based on an alignment of the TECR sequence (GenBank AF038958) with the genomic sequence (GRCh38).
Moon and Horton (2003) found that cotransfection of TECR with ELOVL6 in human embryonic kidney cells resulted in the disappearance of trans-2,3-stearoyl-CoA, indicating that TECR is a trans-2,3-enoyl-CoA reductase. They confirmed this finding by RNA interference experiments in human hepatoma cells.
In all affected members of a large Hutterite family in which autosomal recessive intellectual developmental disorder (MRT14) was mapped by Nolan et al. (2008) to chromosome 19p13, Caliskan et al. (2011) detected a homozygous pro182-to-leu mutation in the TECR gene (610057.0001).
In 5 sibs with intellectual developmental disorder-14 (MRT14; 614020) from a large Hutterite family originally reported by Ober et al. (2001), Caliskan et al. (2011) detected homozygosity for a C-to-T transition in exon 8 of the TECR gene that resulted in a pro182-to-leu (P182L) substitution in trans-2,3-enoyl-CoA reductase. None of the 8 unaffected sibs in the family was homozygous for the missense mutation, which altered a highly conserved residue.
Among 1,496 Schmiedeleut (S-leut) Hutterites from the United States, Chong et al. (2012) found 103 heterozygotes and 5 homozygotes for the P182L mutation in the TECR gene, for a frequency of 0.069, or 1 in 14.5. This is a private mutation in the Hutterite population.
By assaying yeast and human cell lines expressing wildtype TECR or TECR with the P182L mutation, Abe et al. (2013) found that the mutation reduced the activity and stability of TECR but did not interfere with its localization at the ER. Analysis of fatty acid elongation in membrane fractions of B-lymphoblastoid cell lines (BLCLs) derived from MRT14 patients, asymptomatic P182L carriers, and controls confirmed reduced TECR activity in patient BLCLs. Patient BLCLs also showed an indirect effect on the third reaction in fatty acid elongation, resulting in reduced formation of the TECR substrate trans-2-enoyl-CoA. Impairment of very long chain fatty acid synthesis in P182L mutant BLCLs in turn altered the sphingolipid profile, with reduced content of C24 sphingomyelin and C24 ceramide and concomitant increases in C16:0 sphingomyelin and C16:0 ceramide. P182 is positioned in the second of 3 luminal loops in TECR and is predicted to confer a local rigid turn in the protein backbone. Abe et al. (2013) hypothesized that substitution of proline with leucine at this position may impair the turn in the enzyme backbone and dislocate the secondary structure, reducing enzyme activity and stability.
Abe, K., Ohno, Y., Sassa, T., Taguchi, R., Caliskan, M., Ober, C., Kihara, A. Mutation for nonsyndromic mental retardation in the trans-2-enoyl-CoA reductase TER gene involved in fatty acid elongation impairs the enzyme activity and stability, leading to change in sphingolipid profile. J. Biol. Chem. 288: 36741-36749, 2013. [PubMed: 24220030] [Full Text: https://doi.org/10.1074/jbc.M113.493221]
Caliskan, M., Chong, J. X., Uricchio, L., Anderson, R., Chen, P., Sougnez, C., Garimella, K., Gabriel, S. B., DePristo, M. A., Shakir, K., Matern, D., Das, S., Waggoner, D., Nicolae, D. L., Ober, C. Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13. Hum. Molec. Genet. 20: 1285-1289, 2011. [PubMed: 21212097] [Full Text: https://doi.org/10.1093/hmg/ddq569]
Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C. A population-based study of autosomal-recessive disease-causing mutations in a founder population. Am. J. Hum. Genet. 91: 608-620, 2012. [PubMed: 22981120] [Full Text: https://doi.org/10.1016/j.ajhg.2012.08.007]
Hartz, P. A. Personal Communication. Baltimore, Md. 2/2/2015.
Mao, M., Fu, G., Wu, J.-S., Zhang, Q.-H., Zhou, J., Kan, L.-X., Huang, Q.-H., He, K.-L., Gu, B.-W., Han, Z.-G., Shen, Y., Gu, J., Yu, Y.-P., Xu, S.-H., Wang, Y.-X., Chen, S.-J., Chen, Z. Identification of genes expressed in human CD34+ hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning. Proc. Nat. Acad. Sci. 95: 8175-8180, 1998. [PubMed: 9653160] [Full Text: https://doi.org/10.1073/pnas.95.14.8175]
Moon, Y.-A., Horton, J. D. Identification of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade. J. Biol. Chem. 278: 7335-7343, 2003. [PubMed: 12482854] [Full Text: https://doi.org/10.1074/jbc.M211684200]
Nolan, D. K., Chen, P., Das, S., Ober, C., Waggoner, D. Fine mapping of a locus for nonsyndromic mental retardation on chromosome 19p13. Am. J. Med. Genet. 146A: 1414-1422, 2008. [PubMed: 18446860] [Full Text: https://doi.org/10.1002/ajmg.a.32307]
Ober, C., Abney, M., McPeek, M. S. The genetic dissection of complex traits in a founder population. Am. J. Hum. Genet. 69: 1068-1079, 2001. Note: Erratum: Am. J. Hum. Genet. 70: 284 only, 2002. [PubMed: 11590547] [Full Text: https://doi.org/10.1086/324025]