Alternative titles; symbols
HGNC Approved Gene Symbol: PEX11B
Cytogenetic location: 1q21.1 Genomic coordinates (GRCh38) : 1:145,911,348-145,918,717 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q21.1 | Peroxisome biogenesis disorder 14B | 614920 | Autosomal recessive | 3 |
Mammalian cells contain hundreds of peroxisomes under normal growth conditions, suggesting that there are constitutive mechanisms for raising peroxisome abundance above 1 per cell. By searching an EST database with the amino acid sequence of S. cerevisiae Pex11, Schrader et al. (1998) identified cDNAs derived from a human homolog of Pex11. The closest relative of the encoded human protein was the product of a second human gene; the authors designated the 2 human genes PEX11-alpha (603866) and PEX11-beta. The deduced 259-amino acid PEX11-beta protein shares approximately 20% amino acid identity with yeast Pex11. PEX11-beta has 2 predicted membrane-spanning domains, 1 at its C terminus and a second located approximately 100 amino acids from its N terminus. The termini of PEX11-beta are predicted to extend into the cytoplasm. Localization studies indicated that PEX11-beta is a peroxisomal protein. Northern blot analysis of rat tissues showed that Pex11-beta mRNA levels were similar in all tissues examined and were unaffected by peroxisome-proliferating agents.
Abe and Fujiki (1998) cloned human PEX11-beta cDNAs. The deduced PEX11-alpha and PEX11-beta proteins are approximately 40% identical. Northern blot analysis detected a 2-kb PEX11-beta transcript.
Schrader et al. (1998) found that overexpression of PEX11-beta in human cells was sufficient to induce peroxisome proliferation, demonstrating that proliferation can occur in the absence of extracellular stimuli and may be mediated by a single gene. Time course studies indicated that PEX11-beta induced peroxisome proliferation through a multistep process involving peroxisome elongation and segregation of PEX11-beta from other peroxisomal membrane proteins, followed by peroxisome division. Schrader et al. (1998) suggested that PEX11-beta may control constitutive peroxisome abundance.
Li and Gould (2003) showed that dynamin-like protein-1 (DLP1, or DNM1L; 603850) was essential for peroxisome division induced by overexpression of PEX11-beta in human fibroblasts. The 710-amino acid DLP1 isoform, DLP1a, associated with peroxisomes, and PEX11-beta overexpression recruited DLP1a to peroxisome membranes. DLP1a and PEX11 proteins did not appear to interact directly.
Ebberink et al. (2012) identified a 26-year-old Dutch man with homozygosity for a nonsense mutation in the PEX11-beta gene (Q22R; 603867.0001). He had a defect in peroxisome division causing a phenotype consistent with a peroxisome biogenesis disorder (PEX14B; 614920).
In a brother and sister with PEX14B, Tian et al. (2020) identified a homozygous nonsense mutation (R93X; 603867.0002) in the PEX11B gene. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. No functional studies were reported.
Using gene targeting, Li et al. (2002) generated mice lacking Pex11b. They observed neonatal lethality, intrauterine growth retardation, and hypotonia. Using histologic analysis, they determined that the Pex11b-deficient mice exhibited neuronal migration defects and a developmental delay characteristic of Zellweger syndrome (ZS; see 214100) and ZS mouse models generated by disruption of Pex5 (600414) or Pex2 (170993). Using ultrastructural analysis, Li et al. (2002) showed that, unlike ZS, Pex11b-deficiency did not result in defects in peroxisomal protein import or mitochondrial structure. Pex11b-deficient mice also had normal levels of brain very long chain fatty acids (VLCFAs), unlike the elevated levels seen in ZS. Li et al. (2002) concluded that Pex11b deficiency represents a novel peroxisomal disorder that mimics major neurologic and developmental pathologic features of ZS but lacks many of its cellular and biochemical features.
In a 26-year-old Dutch man with mild intellectual disability, congenital cataracts, progressive hearing loss, sensory nerve involvement, gastrointestinal problems, and recurrent migraine-like episodes (PBD14B; 614920), Ebberink et al. (2012) identified a C-to-T transition at nucleotide 64 of the PEX11B gene, resulting in a glutamine-to-termination substitution at codon 22 (Q22X) in PEX11-beta. Both parents were heterozygous for this mutation. Immunoblot analysis of protein homogenates of the patient's fibroblasts detected no PEX11-beta protein.
In a 9-year-old Chinese proband and her younger brother with peroxisome biogenesis disorder-14B (PBD14B; 614920), Tian et al. (2020) identified a homozygous c.277C-T transition (c.277C-T, NM_003846.2) in exon 3 of the PEX11B gene, resulting in an arg93-to-ter (R93X) substitution at a conserved site. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. The variant was not present in the Shenzhou Genome, 1000 Genome Project, ExAC, or gnomAD databases. No functional studies were reported.
Abe, I., Fujiki, Y. cDNA cloning and characterization of a constitutively expressed isoform of the human peroxin Pex11p. Biochem. Biophys. Res. Commun. 252: 529-533, 1998. [PubMed: 9826565] [Full Text: https://doi.org/10.1006/bbrc.1998.9684]
Ebberink, M. S., Koster, J., Visser, G., van Spronsen, F., Stolte-Dijkstra, I., Smit, G. P. A., Fock, J. M., Kemp, S., Wanders, R. J. A., Waterham, H. R. A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11-beta gene. J. Med. Genet. 49: 307-313, 2012. [PubMed: 22581968] [Full Text: https://doi.org/10.1136/jmedgenet-2012-100778]
Li, X., Baumgart, E., Morrell, J. C., Jimenez-Sanchez, G., Valle, D., Gould, S. J. PEX11-beta deficiency is lethal and impairs neuronal migration but does not abrogate peroxisome function. Molec. Cell. Biol. 22: 4358-4365, 2002. [PubMed: 12024045] [Full Text: https://doi.org/10.1128/MCB.22.12.4358-4365.2002]
Li, X., Gould, S. J. The dynamin-like GTPase DLP1 is essential for peroxisome division and is recruited to peroxisomes in part by PEX11. J. Biol. Chem. 278: 17012-17020, 2003. [PubMed: 12618434] [Full Text: https://doi.org/10.1074/jbc.M212031200]
Schrader, M., Reuber, B. E., Morrell, J. C., Jimenez-Sanchez, G., Obie, C., Stroh, T. A., Valle, D., Schroer, T. A., Gould, S. J. Expression of PEX11-beta mediates peroxisome proliferation in the absence of extracellular stimuli. J. Biol. Chem. 273: 29607-29614, 1998. [PubMed: 9792670] [Full Text: https://doi.org/10.1074/jbc.273.45.29607]
Tian, Y., Zhang, L., Li, Y., Gao, J., Yu, H., Guo, Y., Jia, L. Variant analysis of PEX11B gene from a family with peroxisome biogenesis disorder 14B by whole exome sequencing. Molec. Genet. Genomic Med. 8: e1042, 2020. Note: Electronic Article. [PubMed: 31724321] [Full Text: https://doi.org/10.1002/mgg3.1042]