Alternative titles; symbols
HGNC Approved Gene Symbol: NUP160
Cytogenetic location: 11p11.2 Genomic coordinates (GRCh38): 11:47,778,118-47,848,544 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 11p11.2 | ?Nephrotic syndrome, type 19 | 618178 | Autosomal recessive | 3 |
NUP160 is 1 of up to 60 proteins that make up the 120-MD nuclear pore complex (NPC), which mediates nucleoplasmic transport (Vasu et al., 2001). NUP160 encodes a direct interaction partner of NUP85 (170285) within the Y complex of the NPC, which is part of the outer ring scaffold (summary by Braun et al., 2018).
By sequencing clones obtained from a size-fractionated myeloid cell line cDNA library, Nagase et al. (1996) cloned NUP160, which they designated KIAA0197. The deduced 1,314-amino acid protein contains a histidine acid phosphatase motif. Northern blot analysis revealed moderate expression in all tissues examined.
Vasu et al. (2001) identified Nup160 as a protein in Xenopus egg extracts that interacts with the nuclear pore basket proteins Nup98 (601021) and Nup153 (603948). Peptide analysis revealed homology with KIAA0197. Antibody raised against the putative human protein detected endogenous NUP160 in puncta along the nuclear rim in HeLa cells, and differential permeabilization of HeLa cells indicated that NUP160 is localized to the basket side of the pore, facing the nucleoplasm.
Vasu et al. (2001) provided evidence that vertebrate Nup160 and Nup133 (607613) interact with Nup98 and Nup153 and mediate RNA export from the nucleus.
Using protein-binding assays and domain analyses, Mitchell et al. (2010) found that the N-terminal beta-propeller regions of human NUP155 (606694) and NUP160 interacted individually, but not simultaneously, with an N-terminal domain of the NPC pore membrane protein POM121 (615753), which lies close to the nuclear membrane. Mitchell et al. (2010) hypothesized that POM121 anchors the NPC core by positioning NUP155 and NUP160 and their binding partners in close proximity to the nuclear membrane.
Zuccolo et al. (2007) stated that the NUP107 (607617)-NUP160 nucleoporin subcomplex contains NUP133, NUP96 (601021), NUP85 (170285), NUP43 (608141), NUP37 (609264), SEC13 (SEC13L1; 600152), and SEH1 (SEH1L; 609263). The NUP107-NUP160 subcomplex stably associates on both faces of NPCs during interphase, and the entire subcomplex is recruited to chromatin during mitosis. A fraction of the subcomplex localizes at kinetochores during prophase, even before nuclear envelope breakdown. Zuccolo et al. (2007) found that recruitment of the NUP107-NUP160 complex to kinetochores depended mainly on the NDC80 complex (see 607272) and CENPF (600236). The SEH1 subunit of the NUP107-NUP160 complex was essential for targeting the complex to kinetochores. Codepletion of several NUP107-NUP160 subunits or of SEH1 alone resulted in kinetochores that failed to establish proper microtubule attachment, thus inducing a checkpoint-dependent mitotic delay. The mitotic Ran-GTP effector, CRM1 (XPO1; 602559), as well as its binding partner, the RANGAP1 (602362)-RANBP2 (601181) complex, were mislocalized upon depletion of NUP107-NUP160 complex from kinetochores.
Wang et al. (2018) found that knockdown of Nup160 via short hairpin RNA in conditionally immortalized mouse podocytes inhibited proliferation and promoted apoptosis, autophagy, and cell migration. Quantitative RT-PCR, Western blot, and immunofluorescence analyses showed that knockdown of Nup160 altered expression and subcellular localizations of podocyte-associated molecules, including nephrin (NPHS1; 602716), podocin (NPHS2; 604766), Cd2ap (604241), and alpha-actinin-4 (ACTN4; 604638).
By analysis of a panel of human-rodent hybrid cell lines, Nagase et al. (1996) mapped the NUP160 gene to chromosome 11.
Hartz (2014) mapped the NUP160 gene to chromosome 11p11.2 based on an alignment of the NUP160 sequence (GenBank D83781) with the genomic sequence (GRCh37).
In 2 Chinese sibs (family 17F00494) with nephrotic syndrome type 19 (NPHS19; 618178), Braun et al. (2018) identified compound heterozygous mutations in the NUP160 gene (E803K, 607614.0001 and R910X, 607614.0002). The mutations, which were found by targeted exome sequencing of candidate genes and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed, but both variants were predicted to result in a loss of function.
In 2 Chinese sibs (family 17F00494) with nephrotic syndrome type 19, (NPHS19; 618178), Braun et al. (2018) identified compound heterozygous mutations in the NUP160 gene: a c.2407G-A transition (c.2407G-A, NM_015231.1) in exon 19, resulting in a glu803-to-lys (E803K) substitution at a conserved residue, and a c.2728C-T transition in exon 22, resulting in an arg910-to-ter (R910X; 607614.0002) substitution. The mutations, which were found by targeted exome sequencing of candidate genes and confirmed by Sanger sequencing, segregated with the disorder in the family. Both variants were found in heterozygous state at low frequencies in the gnomAD database (4 of 246,020 alleles for E803K, and 2 of 245,806 alleles for R910X). Functional studies of the variants and studies of patient cells were not performed, but both variants were predicted to result in a loss of function.
For discussion of the c.2728C-T transition (c.2728C-T, NM_015231.1) in exon 22 of the NUP160 gene, resulting in an arg910-to-ter (R910X) substitution, that was found in compound heterozygous state in 2 sibs with nephrotic syndrome type 19 (NPHS19; 618178) by Braun et al. (2018), see 607614.0001.
Braun, D. A., Lovric, S., Schapiro, D., Schneider, R., Marquez, J., Asif, M., Hussain, M. S., Daga, A., Widneier, E., Rao, J., Ashraf, S., Tan, W., and 46 others. Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome. J. Clin. Invest. 128: 4313-4328, 2018. [PubMed: 30179222] [Full Text: https://doi.org/10.1172/JCI98688]
Hartz, P. A. Personal Communication. Baltimore, Md. 4/23/2014.
Mitchell, J. M., Mansfeld, J., Capitanio, J., Kutay, U., Wozniak, R. W. Pom121 links two essential subcomplexes of the nuclear pore complex core to the membrane. J. Cell Biol. 191: 505-521, 2010. [PubMed: 20974814] [Full Text: https://doi.org/10.1083/jcb.201007098]
Nagase, T., Seki, N., Ishikawa, K., Tanaka, A., Nomura, N. Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 3: 17-24, 1996. [PubMed: 8724849] [Full Text: https://doi.org/10.1093/dnares/3.1.17]
Vasu, S., Shah, S., Orjalo, A., Park, M., Fischer, W. H., Forbes, D. J. Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export. J. Cell. Biol. 155: 339-353, 2001. [PubMed: 11684705] [Full Text: https://doi.org/10.1083/jcb.200108007]
Wang, P., Zhao, F., Nie, X., Liu, J., Yu, Z. Knockdown of NUP160 inhibits cell proliferation, induces apoptosis, autophagy and cell migration, and alters the expression and localization of podocyte associated molecules in mouse podocytes. Gene 664: 12-21, 2018. [PubMed: 29704630] [Full Text: https://doi.org/10.1016/j.gene.2018.04.067]
Zuccolo, M., Alves, A., Galy, V., Bolhy, S., Formstecher, E., Racine, V., Sibarita, J.-B., Fukagawa, T., Shiekhattar, R., Yen, T., Doye, V. The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions. EMBO J. 26: 1853-1864, 2007. [PubMed: 17363900] [Full Text: https://doi.org/10.1038/sj.emboj.7601642]