HGNC Approved Gene Symbol: NXN
Cytogenetic location: 17p13.3 Genomic coordinates (GRCh38): 17:799,310-979,776 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17p13.3 | Robinow syndrome, autosomal recessive 2 | 618529 | Autosomal recessive | 3 |
Kurooka et al. (1997) cloned mouse nucleoredoxin from a neonatal skin cDNA library. The deduced 435-amino acid protein is rich in acidic amino acids, has an internal long direct repeat, and shares significant similarity with thioredoxin (TXN; 187700). Northern blot analysis detected several nucleoredoxin splice variants in adult mouse tissues, with highest expression in testis and skin and lowest expression in liver. In situ hybridization showed that expression of nucleoredoxin varied during mouse embryonic development. Expression was widespread in embryos at days 9.5 and 10.5, with expression in limb buds, somites, dorsal root ganglia, branchial bars, and parts of the brain, but expression was marginal at day 12.5. Epitope-tagged nucleoredoxin localized to nuclei of transfected COS-7 cells. Southern blot analysis detected nucleoredoxin orthologs in human, rat, and rabbit, but not in frog, fly, nematode, and yeast.
Hartz (2009) mapped the NXN gene to chromosome 17p13.3 based on an alignment of the NXN sequence (GenBank AF086523) with the genomic sequence (build 36.1).
Kurooka et al. (1997) mapped the mouse Nxn gene to chromosome 11.
Kurooka et al. (1997) showed that the recombinant C-terminal domain of mouse nucleoredoxin had oxidoreductase activity toward the disulfide bonds of insulin (INS; 176730), with kinetics similar to that of purified E. coli thioredoxin. Deletion of 55 N-terminal amino acids from the construct, including the putative redox active site, resulted in a protein that failed to reduce insulin.
In a Turkish girl and 2 sisters from an unrelated family with autosomal recessive Robinow syndrome (RRS2; 618529), White et al. (2018) identified homozygosity and compound heterozygosity, respectively, for mutations in the NXN gene (612895.0001-612895.0003).
In a 5-year-old Turkish girl (BAB8841) with autosomal recessive Robinow syndrome (RRS2; 618529), White et al. (2018) identified homozygosity for a c.625C-T transition (c.625C-T, NM_022463.4) in the NXN gene, resulting in an arg209-to-ter (R209X) substitution. Her unaffected consanguineous parents (family HOU3189) were heterozygous for the mutation.
In 2 sisters (BAB9844 and BAB9847) with autosomal recessive Robinow syndrome (RRS2; 618529), White et al. (2018) identified compound heterozygosity for an in-frame 3-bp deletion (c.1234_1236del, NM_022463.4) in the NXN gene, resulting in deletion of a single amino acid (Glu412del), and an intragenic 84-kb deletion (612895.0003) encompassing all of NXN exon 1 (chr17:805,043_889,090; GRCh37). Their unaffected consanguineous parents (family HOU3634) were each heterozygous for 1 of the mutations.
For discussion of the 84-kb deletion (chr17.805,043_889,090, NM_022463.4) encompassing all of exon 1 of the NXN gene that was found in compound heterozygous state in 2 sisters with autosomal recessive Robinow syndrome (RRS2; 618529) by White et al. (2018), see 612895.0002.
Hartz, P. A. Personal Communication. Baltimore, Md. 6/30/2009.
Kurooka, H., Kato, K., Minoguchi, S., Takahashi, Y., Ikeda, J., Habu, S., Osawa, N., Buchberg, A. M., Moriwaki, K., Shisa, H., Honjo, T. Cloning and characterization of the nucleoredoxin gene that encodes a novel nuclear protein related to thioredoxin. Genomics 39: 331-339, 1997. [PubMed: 9119370] [Full Text: https://doi.org/10.1006/geno.1996.4493]
White, J. J., Mazzeu, J. F., Coban-Akdemir, Z., Bayram, Y., Bahrambeigi, V., Hoischen, A., van Bon, B. W. M., Gezdirici, A., Gulec, E. Y., Ramond, F., Touraine, R., Thevenon, J., and 24 others. WNT signaling perturbations underlie the genetic heterogeneity of Robinow syndrome. Am. J. Hum. Genet. 102: 27-43, 2018. [PubMed: 29276006] [Full Text: https://doi.org/10.1016/j.ajhg.2017.10.002]