Alternative titles; symbols
HGNC Approved Gene Symbol: NUP37
Cytogenetic location: 12q23.2 Genomic coordinates (GRCh38): 12:102,073,103-102,120,114 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 12q23.2 | ?Microcephaly 24, primary, autosomal recessive | 618179 | Autosomal recessive | 3 |
Bidirectional transport of macromolecules between the cytoplasm and nucleus occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope. NPCs are composed of subcomplexes, and NUP37 is part of one such subcomplex, NUP107 (607617)-NUP160 (607614) (Loiodice et al., 2004).
By proteomic analysis and mass spectrometry, Cronshaw et al. (2002) identified 94 proteins associated with NPCs purified from rat liver nuclei. Nup37 was relatively abundant, with 16 to 32 copies per NPC. By database analysis, Cronshaw et al. (2002) identified the deduced amino acid sequence of human NUP37, which contains WD repeats and has a calculated molecular mass of 37 kD. Transient transfection of NUP37 cDNA in HeLa cells resulted in punctate rim localization typical of nucleoporins.
Using antibodies directed against fluorescence-tagged NUP107, Loiodice et al. (2004) confirmed that NUP37 is part of the Nup107-160 complex. All constituents of this complex, including NUP37, were targeted to kinetochores from prophase to anaphase during mitosis.
Zuccolo et al. (2007) stated that the NUP107-NUP160 nucleoporin subcomplex contains NUP133 (607613), NUP96 (601021), NUP85 (170285), NUP43 (608141), NUP37, 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.
Hartz (2005) mapped the NUP37 gene to chromosome 12q23.2 based on an alignment of the NUP37 sequence (GenBank AF514994) with the genomic sequence.
In 3 brothers, born of consanguineous Pakistani parents (family PN-2), with autosomal recessive primary microcephaly-24 (MCPH24; 618179), Braun et al. (2018) identified a homozygous nonsense mutation in the NUP37 gene (R306X; 609264.0001). The mutation, which was found by high-throughput exon sequencing and confirmed by Sanger sequencing and homozygosity mapping, segregated with the disorder in the family.
In 3 brothers, born of consanguineous Pakistani parents (family PN-2), with autosomal recessive primary microcephaly-24 (MCPH24; 618179), Braun et al. (2018) identified a homozygous c.916C-T transition (c.916C-T, NM_024057.3) in exon 10 of the NUP37 gene, resulting in an arg306-to-ter (R306X) substitution. The mutation, which was found by high-throughput exon sequencing and confirmed by Sanger sequencing and homozygosity mapping, segregated with the disorder in the family. It was not found in the gnomAD database. Patient fibroblasts showed significant differences from controls, including a lower number of nuclear pores, altered chromatin organization and nucleolar morphology, and widened and irregular perinuclear spaces with bulbous invasions of the nuclear envelope. Additional in vitro studies showed that mutant fibroblasts had decreased cellular proliferation rates compared to controls.
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]
Cronshaw, J. M., Krutchinsky, A. N., Zhang, W., Chait, B. T., Matunis, M. J. Proteomic analysis of the mammalian nuclear pore complex. J. Cell Biol. 158: 915-927, 2002. [PubMed: 12196509] [Full Text: https://doi.org/10.1083/jcb.200206106]
Hartz, P. A. Personal Communication. Baltimore, Md. 3/16/2005.
Loiodice, I., Alves, A., Rabut, G., van Overbeek, M., Ellenberg, J., Sibarita, J.-B., Doye, V. The entire Nup107-160 complex, including three new members, is targeted as one entity to kinetochores in mitosis. Molec. Biol. Cell 15: 3333-3344, 2004. [PubMed: 15146057] [Full Text: https://doi.org/10.1091/mbc.e03-12-0878]
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]