HGNC Approved Gene Symbol: NXF5Cytogenetic location: Xq22.1 Genomic coordinates (GRCh38): X:101,832,111-101,857,576 (from NCBI)▼ Cloning and ExpressionExport...
HGNC Approved Gene Symbol: NXF5
Cytogenetic location: Xq22.1 Genomic coordinates (GRCh38): X:101,832,111-101,857,576 (from NCBI)
▼ Cloning and Expression
Export of mRNAs from the nucleus involves a number of proteins, including nucleoporins, RNA-binding proteins, an RNA helicase (DDX19; 605812), and nuclear pore complex-associated proteins, such as NXF1 (602647). By searching EST databases for homologs of NXF1 and by RT-PCR analysis, Herold et al. (2000) obtained cDNAs encoding NXF2 (300315), NXF3 (300316), NXF4 (300318), and NXF5. The deduced 626-amino acid NXF5 protein has the conserved domain structure of NXF1, including a noncanonical RNP-type RNA-binding domain (RBD), 4 leucine-rich repeats (LRRs), a nuclear transport factor-2 (NTF2; 605813)-like domain that allows heterodimerization with NTF2-related export protein-1 (NXT1; 605811), and a ubiquitin-associated domain that mediates interactions with nucleoporins.
Using RT-PCR, Esposito et al. (2013) found variable expression of 3 NXF5 isoforms in multiple human tissues, including brain, pancreas, kidney, testis, ovary, and lung. There was low expression in heart and no expression in muscle. The mouse Nxf7 gene, the homolog of human NXF5, was found in several mouse tissues, including heart, kidney podocytes, cortex, white matter, and striatum.
▼ Gene Structure
Herold et al. (2000) determined that the NXF5 gene contains at least 21 exons.
Using genomic sequence analysis, Herold et al. (2000) mapped the NXF5 gene to the X chromosome.
▼ Molecular Genetics
See 300319.0001 for a possible association of focal segmental glomerulosclerosis (see 603278) with mutation in the NXF5 gene.
▼ ALLELIC VARIANTS ( 1 Selected Example):
.0001 VARIANT OF UNKNOWN SIGNIFICANCE
This variant is classified as a variant of unknown significance because its contribution to focal segmental glomerulosclerosis (FSGS; see 603278) has not been confirmed.
Esposito et al. (2013) reported a large 6-generation Australian family in which 12 males had focal segmental glomerulosclerosis resulting in progressive renal failure. The pattern was consistent with X-linked recessive inheritance, although some carrier females had proteinuria or preeclampsia. Six of the males with FSGS also had a progressive cardiac conduction disorder, necessitating a pacemaker in 5 patients. Linkage analysis for FSGS identified a 21.19-cM candidate disease interval on chromosome Xq21.33-q24 between DXS8077 and DXS8064 (lod score of 3.32 at DXS1106). Whole-exome sequencing of 2 affected males identified 2 variants in 2 different genes: a c.337C-T transition in exon 7 of the NXF5 gene, resulting in an arg113-to-trp (R113W) substitution at a conserved residue, and a variant in the ALG13 gene (300776.0003). The variants were not found in the 1000 Genomes Project database, in 6 in-house control exomes, or in 598 control chromosomes, and Sanger sequencing showed that both variants segregated with the disorder in the family. Both variants were on the same haplotype. The mutant NXF5 mRNA was detected in cells from both male and female mutation carriers. In vitro functional expression studies showed that the wildtype R113 protein localized in the nucleus and cytoplasm, including in cellular processes, and showed higher levels of expression compared to the W113 mutant protein. The mutant protein localized mainly to the nuclear membrane, suggesting that the mutation may affect stability and localization of the protein. Cells showed no differences in actin organization when transfected with the wildtype or mutant proteins.