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Gene Review

RAPGEF5  -  Rap guanine nucleotide exchange factor...

Homo sapiens

Synonyms: GFR, Guanine nucleotide exchange factor for Rap1, KIAA0277, M-Ras-regulated Rap GEF, MR-GEF, ...
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Disease relevance of RAPGEF5

  • These compensatory changes are adequate to maintain electrolyte and water homeostasis until severe renal failure ensures (GFR less than 20% of normal) [1].
  • Perhaps most importantly, the clinical impact of propranolol's effect on renal function is unclear, since the reductions in GFR have not been sufficient to produce azotemia [2].
  • We postulate that the increase in GFR which emerges as a consequence of increased plasma osmolality in diabetes mellitus delivers more albumin to the proximal tubule than can be reabsorbed [3].
  • METHODS: The expression of GDNF and GFR-alpha1 was investigated in experimental colitis of rats and in human inflammatory bowel disease (IBD) [4].
  • Baseline filtration rate (GFR) and effective renal plasma flow (ERPF) were significantly lower in patients with cirrhosis than in controls (GFR: mean 88 +/- SD 16 mL/min vs. 106 +/- 15 mL/min, P = .01, ERPF: 477 +/- 93 vs. 561 +/- 72 mL/min, P = .002) [5].

Psychiatry related information on RAPGEF5

  • ESRD risk reduction was predicted by basal proteinuria (P < 0.01) and GFR (P < 0.0001) and was strongly dependent on treatment duration (P < 0.0001) [6].
  • There was no correlation between cessation rate and urodynamic parameters, GFR, history of enuresis or previous urinary infections [7].
  • During the so-called latency period, which is clinically non-detectable, the predominant functional abnormalities (increase in GFR with sub-clinical glomerular proteinuria) can be corrected by strict control although there is no evidence for the regression of the associated anatomical changes such as the enlarged filtration area [8].

High impact information on RAPGEF5


Chemical compound and disease context of RAPGEF5

  • Baseline plasma ADMA concentrations in renal patients correlated significantly with serum creatinine (r = 0.595), GFR (r = -0.591), age (r = 0.281), and proteinuria (r = 0.184; all P < 0.01) [12].
  • During frusemide administration V/GFR was lower than in normal control subjects, indicating that proximal fractional reabsorption is enhanced in liver cirrhosis [13].
  • Other factors that were significantly associated with increased renal events after adjustment for baseline GFR, age, and gender, both with and without adjustment for baseline proteinuria, included serum creatinine, urea nitrogen, and phosphorus [14].
  • The decrease in GFR did not correlate wih sex, age at onset, duration of diabetes, arterial blood pressure, proteinuria, insulin requirement, postprandial blood glucose or the initial GFR in each individual was constant, but varied considerably between patients [15].
  • These changes include increased GFR and mean arterial pressure, but no differences in renal sodium and lithium handling in diabetics with a genetic predisposition to essential hypertension [16].

Biological context of RAPGEF5

  • C-terminally truncated MR-GEF, lacking the GEF catalytic domain, retained its ability to bind M-Ras-GTP, suggesting that the RA domain is important for this interaction [17].
  • In the normal subjects, maximum tubular reabsorptive capacity for phosphorus/glomerular filtration rate (TmP/GFR) rose progressively during phosphorus deprivation, and the rise from base line was more than two times greater than that seen in patients with FHR [18].
  • In both groups amino acid (aa) infusion increased GFR, ERPF, as well as cGMP and urinary NOx [5].
  • These methods were compared with renal clearance of 125I-iothalamate GFR (GFR1) in 193 hypertensive (diastolic blood pressure > or = 95 mm Hg) African-American screen (142 men, 51 women) [19].
  • In untreated dTGR, pressure-natriuresis relationships were maximally shifted rightward by approximately 70 to 80 mmHg, and both renal blood flow (RBF) and GFR were markedly decreased [20].

Anatomical context of RAPGEF5

  • In transfected HeLa cells, GFR has been found to be localized in the nuclei [21].
  • In contrast, GFR-alpha1 was constitutively expressed in rat and human colonic epithelium [4].
  • In rats, accordingly, mesangial cells play a role in the regulation of single-nephron GFR [22].
  • This study showed for the first time that measurement of SDMA can be a marker of estimated GFR and extent of coronary artery disease (CAD) [23].
  • These data suggest that the percentage of body fat remains the main determinant of serum leptin in CRF patients, but their levels increase with declining GFR, presumably by reduced renal clearance [24].

Associations of RAPGEF5 with chemical compounds


Other interactions of RAPGEF5

  • By searching for in vitro interaction with Ras-GTP proteins, PDZ-GEF specifically bound to Rap1A- and Rap2B-GTP, whereas MR-GEF bound to M-Ras-GTP [17].

Analytical, diagnostic and therapeutic context of RAPGEF5

  • Co-immunoprecipitation studies confirmed the interaction of M-Ras-GTP with MR-GEF in vivo [17].
  • Northern blot analysis suggested that GFR mRNA is strongly expressed in the brain [21].
  • We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area [29].
  • Studies measuring GFR and using a concomitant control group are necessary to answer this question with certainty, however [30].
  • The baseline mean GFR at 6 mo after transplantation was 49.6 +/- 15.4 ml/min per 1.73 m(2) [31].


  1. Functional adaptation to reduction in renal mass. Hayslett, J.P. Physiol. Rev. (1979) [Pubmed]
  2. Antiadrenergic antihypertensive drugs: their effect on renal function. Bernstein, K.N., O'Connor, D.T. Annu. Rev. Pharmacol. Toxicol. (1984) [Pubmed]
  3. Suggested mechanism for the selective excretion of glucosylated albumin. The effects of diabetes mellitus and aging on this process and the origins of diabetic microalbuminuria. Kowluru, A., Kowluru, R., Bitensky, M.W., Corwin, E.J., Solomon, S.S., Johnson, J.D. J. Exp. Med. (1987) [Pubmed]
  4. Glial-derived neurotrophic factor regulates apoptosis in colonic epithelial cells. Steinkamp, M., Geerling, I., Seufferlein, T., von Boyen, G., Egger, B., Grossmann, J., Ludwig, L., Adler, G., Reinshagen, M. Gastroenterology (2003) [Pubmed]
  5. Renal functional reserve and nitric oxide in patients with compensated liver cirrhosis. Woitas, R.P., Heller, J., Stoffel-Wagner, B., Spengler, U., Sauerbruch, T. Hepatology (1997) [Pubmed]
  6. ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. Ramipril Efficacy in Nephropathy. Ruggenenti, P., Perna, A., Remuzzi, G. J. Am. Soc. Nephrol. (2001) [Pubmed]
  7. Vesico-ureteral reflux. II. The longterm outcome of kidney function in non-surgical treatment. Poulsen, E.U., Johannesen, N.L., Nielsen, J.B., Jørgensen, T.M., Andersen, A.J. Scandinavian journal of urology and nephrology. Supplementum. (1989) [Pubmed]
  8. The natural history of diabetic nephropathy in type I diabetes and the role of metabolic control in its prevention, reversibility and clinical course. Wajchenberg, B.L., Sabbaga, E., Fonseca, J.A. Acta diabetologica latina. (1983) [Pubmed]
  9. Mechanisms of filtration failure during postischemic injury of the human kidney. A study of the reperfused renal allograft. Alejandro, V., Scandling, J.D., Sibley, R.K., Dafoe, D., Alfrey, E., Deen, W., Myers, B.D. J. Clin. Invest. (1995) [Pubmed]
  10. Effects of recombinant human insulin-like growth factor I on glomerular dynamics in the rat. Hirschberg, R., Kopple, J.D., Blantz, R.C., Tucker, B.J. J. Clin. Invest. (1991) [Pubmed]
  11. Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset. Myers, B.D., Nelson, R.G., Williams, G.W., Bennett, P.H., Hardy, S.A., Berg, R.L., Loon, N., Knowler, W.C., Mitch, W.E. J. Clin. Invest. (1991) [Pubmed]
  12. Asymmetric dimethylarginine and progression of chronic kidney disease: the mild to moderate kidney disease study. Fliser, D., Kronenberg, F., Kielstein, J.T., Morath, C., Bode-Böger, S.M., Haller, H., Ritz, E. J. Am. Soc. Nephrol. (2005) [Pubmed]
  13. Reabsorption of sodium in the proximal renal tubule in cirrhosis of the liver. Chiandussi, L., Bartoli, E., Arras, S. Gut (1978) [Pubmed]
  14. Baseline predictors of renal disease progression in the african american study of hypertension and kidney disease. Norris, K.C., Greene, T., Kopple, J., Lea, J., Lewis, J., Lipkowitz, M., Miller, P., Richardson, A., Rostand, S., Wang, X., Appel, L.J. J. Am. Soc. Nephrol. (2006) [Pubmed]
  15. A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy. Parving, H.H., Smidt, U.M., Friisberg, B., Bonnevie-Nielsen, V., Andersen, A.R. Diabetologia (1981) [Pubmed]
  16. Predisposition to essential hypertension and renal hemodynamics in recent-onset insulin-dependent diabetic patients. Hannedouche, T.P., Marques, L.P., Guicheney, P., Lacour, B., Boitard, C., Grünfeld, J.P. J. Am. Soc. Nephrol. (1992) [Pubmed]
  17. Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. Rebhun, J.F., Castro, A.F., Quilliam, L.A. J. Biol. Chem. (2000) [Pubmed]
  18. Impaired phosphorus conservation and 1,25 dihydroxyvitamin D generation during phosphorus deprivation in familial hypophosphatemic rickets. Insogna, K.L., Broadus, A.E., Gertner, J.M. J. Clin. Invest. (1983) [Pubmed]
  19. Evaluation of serum creatinine for estimating glomerular filtration rate in African Americans with hypertensive nephrosclerosis: results from the African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study. Toto, R.D., Kirk, K.A., Coresh, J., Jones, C., Appel, L., Wright, J., Campese, V., Olutade, B., Agodoa, L. J. Am. Soc. Nephrol. (1997) [Pubmed]
  20. Angiotensin-converting enzyme inhibition and AT1 receptor blockade modify the pressure-natriuresis relationship by additive mechanisms in rats with human renin and angiotensinogen genes. Mervaala, E., Dehmel, B., Gross, V., Lippoldt, A., Bohlender, J., Milia, A.F., Ganten, D., Luft, F.C. J. Am. Soc. Nephrol. (1999) [Pubmed]
  21. Characterization of GFR, a novel guanine nucleotide exchange factor for Rap1. Ichiba, T., Hoshi, Y., Eto, Y., Tajima, N., Kuraishi, Y. FEBS Lett. (1999) [Pubmed]
  22. Species-specific properties of the glomerular mesangium. Sraer, J.D., Adida, C., Peraldi, M.N., Rondeau, E., Kanfer, A. J. Am. Soc. Nephrol. (1993) [Pubmed]
  23. Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary artery disease. Bode-Böger, S.M., Scalera, F., Kielstein, J.T., Martens-Lobenhoffer, J., Breithardt, G., Fobker, M., Reinecke, H. J. Am. Soc. Nephrol. (2006) [Pubmed]
  24. Inappropriate elevation of serum leptin levels in children with chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. Daschner, M., Tönshoff, B., Blum, W.F., Englaro, P., Wingen, A.M., Schaefer, F., Wühl, E., Rascher, W., Mehls, O. J. Am. Soc. Nephrol. (1998) [Pubmed]
  25. Creatinine clearance with cimetidine for measurement of GFR. Hilbrands, L.B., Wetzels, J.F., Koene, R.A. Lancet (1993) [Pubmed]
  26. Iohexol to monitor GFR. Kelly, I. Lancet (1992) [Pubmed]
  27. Creatinine clearance with cimetidine for measurement of GFR. van Acker, B.A., Koomen, G.C., Koopman, M.G., de Waart, D.R., Arisz, L. Lancet (1993) [Pubmed]
  28. Role of atrial natriuretic peptide in the pathogenesis of sodium retention in IDDM with and without glomerular hyperfiltration. Fioretto, P., Sambataro, M., Cipollina, M.R., Giorato, C., Carraro, A., Opocher, G., Sacerdoti, D., Brocco, E., Morocutti, A., Mantero, F. Diabetes (1992) [Pubmed]
  29. Outcome of the acute glomerular injury in proliferative lupus nephritis. Chagnac, A., Kiberd, B.A., Fariñas, M.C., Strober, S., Sibley, R.K., Hoppe, R., Myers, B.D. J. Clin. Invest. (1989) [Pubmed]
  30. Effects of protein intake on the progression of renal disease. Klahr, S. Annu. Rev. Nutr. (1989) [Pubmed]
  31. The change in allograft function among long-term kidney transplant recipients. Gill, J.S., Tonelli, M., Mix, C.H., Pereira, B.J. J. Am. Soc. Nephrol. (2003) [Pubmed]
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