Alternative titles; symbols
HGNC Approved Gene Symbol: MTX1
Cytogenetic location: 1q22 Genomic coordinates (GRCh38): 1:155,208,695-155,213,839 (from NCBI)
Bornstein et al. (1995) identified a mouse gene, which they termed metaxin, that spans the 6-kb interval separating the glucocerebrosidase gene (GBA; 606463) from the thrombospondin III gene (THBS3; 188062) on chromosome 3. The cDNA from metaxin encodes a 317-amino acid protein that lacks both a signal sequence and a consensus sequence for N-linked glycosylation. Metaxin protein is expressed ubiquitously in tissues of the young adult mouse. No close homologs were found in the DNA or protein databases.
Long et al. (1996) isolated human metaxin genomic clones and cDNA. The deduced 317-amino acid MTX protein is 91.5% identical to mouse metaxin.
Using a monoclonal antibody directed against the mitochondrial inner membrane protein mitofilin (IMMT; 600378), followed by SDS-PAGE and mass spectrometry, Xie et al. (2007) identified a protein complex in human heart mitochondria that, in addition to mitofilin, included SAMM50 (612058), MTX1, metaxin-2 (MTX2; 608555), CHCHD3 (613748), CHCHD6 (615634), and DNAJC11 (614827).
The mouse metaxin gene spans the 6-kb interval separating the glucocerebrosidase gene (Gba) from the thrombospondin III gene (Thbs3) on chromosome 3 (Bornstein et al., 1995). Metaxin (so named from a Greek word for 'in between') and Gba are transcribed convergently; their major polyadenylation sites are only 431 bp apart. On the other hand, metaxin and the Thbs3 gene are transcribed divergently and share a common promoter sequence.
Long et al. (1996) found that the human MTX gene contains 8 exons spanning 6 kb and is flanked by a pseudogene for GBA and thrombospondin-3, with which it shares a common promoter region. In the human genome the GBA-MTX region has been duplicated but mutations within one copy of each gene have resulted in their becoming pseudogenes. A comparison of psMTX and the functional MTX sequences, together with the presence of duplicated genes in the rhesus monkey, indicated to Long et al. (1996) that the duplication was a relatively recent evolutionary event in the primates.
Vos et al. (1995) identified a 70-kb region of human 1q21 that shows homology to a similar region on mouse chromosome 3. They identified 6 human genes in the following order from 1qter to 1cen (with the mouse loci in the opposite order, cen-to-tel): GBA, MTXN, THBS3, MUC1 (158340), GENEY (600986), and CD1 (188370).
Tayebi et al. (2000) described a novel recombinant allele consisting of duplication of the glucocerebrosidase pseudogene and a fusion between the metaxin gene and its pseudogene, resulting from a crossover between metaxin and pseudometaxin in the region downstream of the glucocerebrosidase gene. They also showed that some individuals have a metaxin-pseudometaxin fusion gene without a duplication, resulting from the same crossover. These alterations were more frequent in patients and controls of African American ancestry.
The MTX1 gene is a convergently transcribed gene contiguous to the 3-prime end of the GBA pseudogene. In patients with Gaucher disease (230800), LaMarca et al. (2004) identified a 628T-C transition in exon 7 of the MTX1 gene, resulting in a phe202-to-leu (F202L) change, in association with the common asn370-to-ser mutation in GBA (N370S; 606463.0003). The polymorphism was also present in 4.6% of 152 control alleles, but may have functional consequences that have a modifying role in Gaucher disease.
Bornstein et al. (1995) used homologous recombination in embryonic stem cells to introduce a targeted A-to-G mutation into exon 9 of the mouse Gba gene. In this way, they established a mouse model for a mild form of Gaucher disease. A phosphoglycerate kinase-neomycin gene cassette was also inserted into the 3-prime-flanking region of mouse Gba as a selectable marker; the site was later identified as the terminal exon of metaxin. Mice homozygous for the combined mutation died early in gestation. Since the same amino acid mutation in human GBA is associated with mild type I Gaucher disease, Bornstein et al. (1995) suggested that metaxin protein is likely to be essential for embryonic development in mice. Clearly, the contiguous gene organization of this locus limits targeting strategies for the production of mouse models of Gaucher disease. Mouse mucin-1 (158340), which encodes a polymorphic epithelial mucin, is located 2.3 kb 3-prime to the Thbs3 gene.
Bornstein, P., McKinney, C. E., LaMarca, M. E., Winfield, S., Shingu, T., Devarayalu, S., Vos, H. L., Ginns, E. I. Metaxin, a gene contiguous to both thrombospondin 3 and glucocerebrosidase, is required for embryonic development in the mouse: implications for Gaucher disease. Proc. Nat. Acad. Sci. 92: 4547-4551, 1995. [PubMed: 7753840] [Full Text: https://doi.org/10.1073/pnas.92.10.4547]
LaMarca, M. E., Goldstein, M., Tayebi, N., Arcos-Burgos, M., Martin, B. M., Sidransky, E. A novel alteration in metaxin 1, F202L, is associated with N370S in Gaucher disease. J. Hum. Genet. 49: 220-222, 2004. [PubMed: 15024629] [Full Text: https://doi.org/10.1007/s10038-004-0134-7]
Long, G. L., Winfield, S., Adolph, K. W., Ginns, E. I., Bornstein, P. Structure and organization of the human metaxin gene (MTX) and pseudogene. Genomics 33: 177-184, 1996. [PubMed: 8660965] [Full Text: https://doi.org/10.1006/geno.1996.0181]
Tayebi, N., Park, J., Madike, V., Sidransky, E. Gene rearrangement on 1q21 introducing a duplication of the glucocerebrosidase pseudogene and a metaxin fusion gene. Hum. Genet. 107: 400-403, 2000. [PubMed: 11129343] [Full Text: https://doi.org/10.1007/s004390000380]
Vos, H. L., Mockensturm-Wilson, M., Rood, P. M. L., Maas, A. M. C. E., Duhig, T., Gendler, S. J., Bornstein, P. A tightly organized, conserved gene cluster on mouse chromosome 3 (E3-F1). Mammalian Genome 6: 820-822, 1995. [PubMed: 8597643] [Full Text: https://doi.org/10.1007/BF00539013]
Xie, J., Marusich, M. F., Souda, P., Whitelegge, J., Capaldi, R. A. The mitochondrial inner membrane protein mitofilin exists as a complex with SAM50, metaxins 1 and 2, coiled-coil-helix coiled-coil-helix domain-containing protein 3 and 6 and DnaJC11. FEBS Lett. 581: 3545-3549, 2007. [PubMed: 17624330] [Full Text: https://doi.org/10.1016/j.febslet.2007.06.052]