HGNC Approved Gene Symbol: EMP2
Cytogenetic location: 16p13.13 Genomic coordinates (GRCh38): 16:10,528,422-10,580,598 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 16p13.13 | Nephrotic syndrome, type 10 | 615861 | Autosomal recessive | 3 |
By homology screening of databases, Ben-Porath and Benvenisty (1996) and Taylor and Suter (1996) independently identified a cDNA encoding epithelial membrane protein-2 (EMP2). The predicted 167-amino acid EMP2 protein contains 4 membrane-spanning domains and 3 N-linked glycosylation motifs in the first extracellular loop. Taylor and Suter (1996) showed that the EMP2 cDNA generates an 18-kD protein in vitro. The EMP2 protein shares 43% amino acid identity with peripheral myelin protein-22 (PMP22; 601097); they are particularly homologous in their transmembrane domains. Due to the high amino acid sequence homology among PMP22, EMP1 (602334), EMP2, and EMP3 (602335), Ben-Porath and Benvenisty (1996) stated that these proteins belong to a novel family. Based on the suggested functions of PMP22, Ben-Porath and Benvenisty (1996) and Taylor and Suter (1996) proposed that EMP2 is involved in cell proliferation and cell-cell interactions. Using Northern blot analysis, Taylor and Suter (1996) found prominent EMP2 expression in adult ovary, heart, lung, and intestine and lower expression in most other tissues, including the liver. In the fetus, they found high EMP2 mRNA levels in the lung and kidney and lower levels in the liver and brain.
In zebrafish embryos, Gee et al. (2014) found expression of the emp2 gene in the arches, orbits, pectoral fins, vessels, pronephric renal tubules, and glomeruli. Emp2 was highly enriched in the glomeruli of adult rat kidney, where it localized to the cytoplasm and foot processes of podocytes. Emp2 was also detected in the nucleus of endothelial cells.
By somatic cell hybridization, radiation hybrid analysis, and YAC library screening, Liehr et al. (1999) mapped the EMP2 gene to chromosome 16p13.2. Ben Porath et al. (1998) mapped the homologous gene in the mouse to chromosome 16.
In 4 patients from 3 unrelated families with nephrotic syndrome, type 10 (NPHS10; 615861), Gee et al. (2014) identified homozygous or compound heterozygous mutations in the EMP2 gene (602334.0001-602334.0003). The mutations in the first family were found by a combination of homozygosity mapping and whole-exome sequencing of 67 families with the disorder. The mutations in the other 2 families were found by sequencing the EMP2 gene in over 1,600 individuals with nephrotic syndrome. Expression of the mutations failed to rescue the nephrotic syndrome phenotype of pericardial effusion in emp2-null zebrafish, consistent with a loss of function. The findings suggested that EMP2 is necessary for renal integrity. In vitro knockdown of EMP2 in human podocytes and endothelial cells resulted in an increased amount of caveolin-1 (CAV1; 601047) and decreased cell proliferation.
Gee et al. (2014) found that knockdown of the emp2 gene in zebrafish embryos resulted in pericardial effusion, indicative of defective glomerular filtration.
In 2 Turkish sibs, born of consanguineous parents, with nephrotic syndrome-10 (NPHS10; 615861), Gee et al. (2014) identified a homozygous c.184C-T transition in the EMP2 gene, resulting in a gln62-to-ter (Q62X) substitution. The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder and was not found in 86 Turkish controls. Another affected individual of Turkish descent was found to be compound heterozygous for Q62X and a c.21C-G transversion, resulting in a phe7-to-leu (F7L; 602334.0002) substitution at a highly conserved residue. The mutations segregated with the disorder in the families and were not found in the Exome Variant Server database or in over 190 control individuals.
For discussion of the phe7-to-leu (F7L) mutation in the EMP2 gene that was found in compound heterozygous state in a patient with nephrotic syndrome-10 (NPHS10; 615861) by Gee et al. (2014), see 602334.0001.
In an African American patient with nephrotic syndrome-10 (NPHS10; 615861), Gee et al. (2014) identified a homozygous c.28G-A transition in the EMP2 gene, resulting in an ala10-to-thr (A10T) substitution at a highly conserved residue. The mutation was not found in the Exome Variant Server database or in over 190 control individuals. The patient's mother was heterozygous for the mutation; paternal DNA was not available.
Ben-Porath, I., Benvenisty, N. Characterization of a tumor-associated gene, a member of a novel family of genes encoding membrane glycoproteins. Gene 183: 69-75, 1996. [PubMed: 8996089] [Full Text: https://doi.org/10.1016/s0378-1119(96)00475-1]
Ben Porath, I., Kozak, C. A., Benvenisty, N. Chromosomal mapping of Tmp (Emp1), Xmp (Emp2), and Ymp (Emp3), genes encoding membrane proteins related to Pmp22. Genomics 49: 443-447, 1998. [PubMed: 9615230] [Full Text: https://doi.org/10.1006/geno.1998.5238]
Gee, H. Y., Ashraf, S., Wan, X., Vega-Warner, V., Esteve-Rudd, J., Lovric, S., Fang, H., Hurd, T. W., Sadowski, C. E., Allen, S. J., Otto, E. A., Korkmaz, E., Washburn, J., Levy, S., Williams, D. S., Bakkaloglu, S. A., Zolotnitskaya, A., Ozaltin, F., Zhou, W., Hildebrandt, F. Mutations in EMP2 cause childhood-onset nephrotic syndrome. Am. J. Hum. Genet. 94: 884-890, 2014. [PubMed: 24814193] [Full Text: https://doi.org/10.1016/j.ajhg.2014.04.010]
Liehr, T., Kuhlenbaumer, G., Wulf, P., Taylor, V., Suter, U., Van Broeckhoven, C., Lupski, J. R., Claussen, U., Rautenstrauss, B. Regional localization of the human epithelial membrane protein genes 1, 2, and 3 (EMP1, EMP2, EMP3) to 12p12.3, 16p13.2, and 19q13.3. Genomics 58: 106-108, 1999. [PubMed: 10331954] [Full Text: https://doi.org/10.1006/geno.1999.5803]
Taylor, V., Suter, U. Epithelial membrane protein-2 and epithelial membrane protein-3: two novel members of the peripheral myelin protein 22 gene family. Gene 175: 115-120, 1996. [PubMed: 8917086] [Full Text: https://doi.org/10.1016/0378-1119(96)00134-5]