Alternative titles; symbols
HGNC Approved Gene Symbol: ARHGAP4
Cytogenetic location: Xq28 Genomic coordinates (GRCh38): X:153,907,378-153,926,264 (from NCBI)
By constructing a detailed transcription map of the region of 2 Mb in distal Xq28, Tribioli et al. (1996) identified a large number of novel genes, including ARHGAP4, which they designated RGC1. RGC1 encodes a cytoplasmic protein of 115 kD preferentially expressed in hematopoietic cells and containing SH3 and GAP homologous regions. It appears to be a member of the group of signaling proteins involved in regulation of the small GTP-binding proteins of the RAS superfamily. Its localization in a narrow cytoplasmic region just below the plasma membrane (as indicated by immunocytochemistry on human cell lines using a polyclonal antibody) and its inhibitory effect on stress fiber organization indicated to the authors that the protein may downregulate RHO-like GTPase in hematopoietic cells. The gene is approximately 20 kb long and encodes an mRNA of 3.5 kb. The protein contains 946 amino acids.
Schoneberg et al. (1999) described a 16-year-old male with nephrogenic diabetes insipidus (NDI; 304800) diagnosed at 8 months of age who had a 21.5-kb deletion encompassing the entire AVPR2 gene (300538) and most of the RGC1 gene. Besides the symptoms of NDI, the patient had no major morphologic abnormalities as determined by physical examination, radiography, ultrasound, and CT scan. Blood chemical, enzyme, and hormone values over a period of 16 years showed no deviations from normal ranges. Close attention was paid to hematopoietic and immunologic abnormalities because of the predominant expression pattern of the RGC1 gene in hematopoietic cells, but no abnormalities were observed. Schoneberg et al. (1999) postulated that the loss of RGC1 function is most likely compensated for by other members of the GAP family.
Demura et al. (2002) reported 2 novel types of contiguous gene deletion of both the AVPR2 gene and the ARHGAP4 gene in unrelated Japanese kindreds with NDI. They discussed the mechanism of each of the deletions, which were 21.3 and 26.3 kb, respectively. Both patients, despite lacking ARHGAP4, had no morphologic, clinical, or laboratory abnormalities except for those usually found in patients with NDI.
Huang et al. (2012) reported 2 male dizygotic twins with a 17.9-kb deletion of Xq28 encompassing the entire AVPR2 gene and extending into intron 7 of the ARHGAP4 gene. The mother was a carrier of the deletion. The boys showed significant failure to thrive in infancy and were diagnosed with nephrogenic diabetes insipidus at 27 months of age. Both showed delayed psychomotor development. At age 11 years, they had intellectual impairment (IQ in the fifties), short stature, and some mild but inconsistent dysmorphic features, such as pes planus, cupped ears, and undescended testes. Neither patient had signs of an immunodeficiency. Huang et al. (2012) hypothesized that the ARHGAP4 gene plays a role in brain function.
Demura, M., Takeda, Y., Yoneda, T., Furukawa, K., Usukura, M., Itoh, Y., Mabuchi, H. Two novel types of contiguous gene deletion of the AVPR2 and ARHGAP4 genes in unrelated Japanese kindreds with nephrogenic diabetes insipidus. Hum. Mutat. 19: 23-29, 2002. [PubMed: 11754100] [Full Text: https://doi.org/10.1002/humu.10011]
Huang, L., Poke, G., Gecz, J., Gibson, K. A novel contiguous gene deletion of AVPR2 and ARHGAP4 genes in male dizygotic twins with nephrogenic diabetes insipidus and intellectual disability. Am. J. Med. Genet. 158A: 2511-2518, 2012. [PubMed: 22965914] [Full Text: https://doi.org/10.1002/ajmg.a.35591]
Schoneberg, T., Pasel, K., von Baehr, V., Schulz, A., Volk, H.-D., Gudermann, T., Filler, G. Compound deletion of the rhoGAP C1 and V2 vasopressin receptor genes in a patient with nephrogenic diabetes insipidus. Hum. Mutat. 14: 163-174, 1999. [PubMed: 10425039] [Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)14:2<163::AID-HUMU8>3.0.CO;2-B]
Tribioli, C., Droetto, S., Bione, S., Cesareni, G., Torrisi, M. R., Lotti, L. V., Lanfrancone, L., Toniolo, D., Pelicci, P. An X chromosome-linked gene encoding a protein with characteristics of a rhoGAP predominantly expressed in hematopoietic cells. Proc. Nat. Acad. Sci. 93: 695-699, 1996. [PubMed: 8570618] [Full Text: https://doi.org/10.1073/pnas.93.2.695]