Alternative titles; symbols
HGNC Approved Gene Symbol: PEX19
Cytogenetic location: 1q23.2 Genomic coordinates (GRCh38) : 1:160,276,807-160,285,151 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q23.2 | Peroxisome biogenesis disorder 12A (Zellweger) | 614886 | Autosomal recessive | 3 |
The PEX19 gene encodes peroxisomal farnesylated protein, which plays a role in peroxisomal membrane synthesis (Gotte et al., 1998).
James et al. (1994) identified in hamster a farnesylated protein, called peroxisomal farnesylated protein or PxF, that localized to the outer surface of peroxisomes. Kammerer et al. (1997) found that the protein sequence of PxF is 93% identical to that of HK33, a human protein identified by Braun et al. (1994). Braun et al. (1994) reported that HK33 is a predicted 299-amino acid protein with a mass of 33 kD by SDS-PAGE. Northern blot analysis and RT-PCR revealed that HK33 is expressed ubiquitously as 2.2 to 2.5-kb and 4-kb mRNAs. The fact that the gene was transcribed in all cells and tissues tested indicated its status as a housekeeping gene. Braun et al. (1994) demonstrated that at least 2 different HK33 transcripts result from the use of alternative polyadenylation sites.
Kammerer et al. (1997) isolated 4 variant HK33, or PEX19, mRNAs produced by alternative splicing. They found that the proteins encoded by 2 of the splice variants were farnesylated in vitro. Using immunoelectron microscopy, Kammerer et al. (1997) showed that PEX19 is localized to the cytoplasmic surface of peroxisomes in liver cells.
Gotte et al. (1998) identified HK33 as the putative human ortholog of a S. cerevisiae gene, Pex19p. Pex19p encodes an oleic acid-inducible, farnesylated protein of 39.7 kD that is essential for peroxisome biogenesis. They showed that the essential C-terminal region of Pex19p could be replaced by the corresponding region of HK33. Kammerer et al. (1997) stated that the peroxisomal localization of PEX19 and its similarity to Pex19p suggest that PEX19 is involved in the process of peroxisomal biogenesis or assembly.
By functional complementation of peroxisome deficiency of a mutant hamster ovary cell line, ZP119, defective in import of both matrix and membrane proteins, Matsuzono et al. (1999) isolated a human PEX19 cDNA. A stable transformant of ZP119 with human PEX19 was morphologically and biochemically restored for peroxisome biogenesis.
Kammerer et al. (1997) determined that the PEX19 gene contains 8 exons and spans approximately 9 kb. The basal promoter is located within the first 239 bp upstream of the coding region.
By analysis of a somatic cell hybrid panel, Braun et al. (1994) mapped the PEX19 gene to chromosome 1. Using fluorescence in situ hybridization, Kammerer et al. (1997) refined the map position to chromosome 1q22.
Kinoshita et al. (1998) identified complementation group J (CGJ) from patients with a peroxisome biogenesis disorder (PBD), such as Zellweger syndrome (PBD12A; 614886). Two Chinese hamster ovary cell mutants were also found to belong to this group. In no CGJ mutant cell were peroxisomal ghosts found.
Matsuzono et al. (1999) found that human PEX19 expression restored peroxisomal protein import in fibroblasts from a patient with Zellweger syndrome of CGJ. This patient was found to be homozygous for an inactivating mutation, a 1-bp insertion (600279.0001). These results demonstrated that PEX19 is the causative gene for CGJ PBD and suggested that the C-terminal part of the PEX19 protein, including the CAAX homology box, is required for its biologic function. Moreover, the PEX19 protein is apparently involved in the initial stage of peroxisome membrane assembly, before the import of matrix protein.
Mohamed et al. (2010) identified a homozygous frameshift mutation in the PEX19 gene (600279.0002) in an infant girl, born of consanguineous Saudi parents, with Zellweger syndrome of complementation group J. She had neonatal hypotonia, global developmental delay, and multisystem involvement, resulting in death at age 16 months.
In a patient with Zellweger syndrome of complementation group J (PBD12A; 614886), Matsuzono et al. (1999) identified homozygosity for a 1-bp insertion (764insA) in the codon for met255 of the PEX19 gene. The mutation resulted in a frameshift, inducing a 24-amino acid sequence entirely distinct from that of normal protein.
In an infant girl, born of consanguineous Saudi parents, with Zellweger syndrome of complementation group J (PBD12A; 614886), Mohamed et al. (2010) identified a homozygous 1-bp deletion (320delA) in the PEX19 gene, resulting in a frameshift. The patient had neonatal hypotonia, poor growth, and subtle dysmorphic features, including cranial asymmetry, triangular face, low hairline, open fontanels, and broad nasal bridge. Laboratory studies showed elevated liver enzymes, hyperbilirubinemia, and a very long chain fatty acid (VLCFA) profile consistent with a PBD. Brain imaging showed cerebral atrophy, cortical changes, and diffuse demyelination. There was a complete absence of peroxisomes in patient fibroblasts. The patient had a severe clinical course, complicated by global developmental delay, refractory seizures, renal tubular defect, multiple gallstones, and recurrent hospitalizations. She died of sepsis at age 16 months.
Braun, A., Kammerer, S., Weissenhorn, W., Weiss, E. H., Cleve, H. Sequence of a putative human housekeeping gene (HK33) localized on chromosome 1. Gene 146: 291-295, 1994. [PubMed: 8076834] [Full Text: https://doi.org/10.1016/0378-1119(94)90308-5]
Gotte, K., Girzalsky, W., Linkert, M., Baumgart, E., Kammerer, S., Kunau, W.-H., Erdmann, R. Pex19p, a farnesylated protein essential for peroxisome biogenesis. Molec. Cell. Biol. 18: 616-628, 1998. [PubMed: 9418908] [Full Text: https://doi.org/10.1128/MCB.18.1.616]
James, G. L., Goldstein, J. L., Pathak, R. K., Anderson, R. G. W., Brown, M. S. PxF, a prenylated protein of peroxisomes J. Biol. Chem. 269: 14182-14190, 1994. [PubMed: 8188701]
Kammerer, S., Arnold, N., Gutensohn, W., Mewes, H.-W., Kunau, W.-H., Hofler, G., Roscher, A. A., Braun, A. Genomic organization and molecular characterization of a gene encoding HsPXF, a human peroxisomal farnesylated protein. Genomics 45: 200-210, 1997. [PubMed: 9339377] [Full Text: https://doi.org/10.1006/geno.1997.4914]
Kinoshita, N., Ghaedi, K., Shimozawa, N., Wanders, R. J. A., Matsuzono, Y., Imanaka, T., Okumoto, K., Suzuki, Y., Kondo, N., Fujiki, Y. Newly identified Chinese hamster ovary cell mutants are defective in biogenesis of peroxisomal membrane vesicles (peroxisomal ghosts), representing a novel complementation group in mammals J. Biol. Chem. 273: 24122-24130, 1998. [PubMed: 9727033] [Full Text: https://doi.org/10.1074/jbc.273.37.24122]
Matsuzono, Y., Kinoshita, N., Tamura, S., Shimozawa, N., Hamasaki, M., Ghaedi, K., Wanders, R. J. A., Suzuki, Y., Kondo, N., Fujiki, Y. Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly. Proc. Nat. Acad. Sci. 96: 2116-2121, 1999. [PubMed: 10051604] [Full Text: https://doi.org/10.1073/pnas.96.5.2116]
Mohamed, S., El-Meleagy, E., Nasr, A., Ebberink, M. S., Wanders, R. J. A., Waterham, H. R. A mutation in PEX19 causes a severe clinical phenotype in a patient with peroxisomal biogenesis disorder. Am. J. Med. Genet. 152A: 2318-2321, 2010. [PubMed: 20683989] [Full Text: https://doi.org/10.1002/ajmg.a.33560]