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Gene Review

RAPH1  -  Ras association (RalGDS/AF-6) and...

Homo sapiens

Synonyms: ALS2CR18, ALS2CR9, Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 18 protein, Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 9 protein, KIAA1681, ...
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Disease relevance of RAPH1

  • Altered expression and deletion of RMO1 in osteosarcoma [1].
  • Lpd is recruited to EPEC and Vaccinia, pathogens that exploit the actin cytoskeleton for their own motility [2].
  • Twelve cases of T gamma LPD (lymphoproliferative disorders of Fc gamma receptor-bearing T cells) involving an expansion of large granular lymphocyte/natural killer (LGL/NK) cells were investigated for the expression of LGL/NK-associated markers and for T beta gene rearrangement [3].
  • T-gamma lymphoproliferative disease (T-gamma LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena [4].
  • Maternal low protein diet (LPD) fed during only the preimplantation period of development (0-4.25 days after mating), before return to control diet for the remainder of gestation, induced programming of altered birthweight, postnatal growth rate, hypertension and organ/body-weight ratios in either male or female offspring at up to 12 weeks of age [5].

Psychiatry related information on RAPH1


High impact information on RAPH1

  • All the cases selected were classified as T gamma LPD on the basis of morphology, function, and phenotype of the circulating cells [3].
  • The LPD regimen significantly reduced insulin and essential amino acid levels, and increased glucose levels within maternal serum by day 4 of development [5].
  • MR-GEF and PDZ-GEF both contain a region immediately N-terminal to their catalytic domains that share sequence homology with Ras-associating or RalGDS/AF6 homology (RA) domains [8].
  • Predictive saccades were also strongly hypometric in both PD groups but especially in LPD (e.g. for rightwards saccades: controls = 19 degrees, SD = 1.6; LPD = 14 degrees, SD = 2.7; RPD = 15.7 degrees, SD = 2.3) [9].
  • Urinary urea appearance and plasma urea were significantly lower on LPD [10].

Chemical compound and disease context of RAPH1

  • To investigate the short-term renal effects of protein restriction and unchanged salt intake in chronic renal failure (CRF), patients with moderate CRF (creatinine clearance 41 +/- 5 ml/min) and healthy controls (CON) ate a normal protein diet (NPD) for four weeks, and thereafter a low protein diet (LPD, 0.4 g/kg body wt/day) for three weeks [11].
  • Low-protein diets (LPD) increase insulin-mediated glucose disposal in chronic renal failure (CRF), but the fate of the better utilized glucose and the effect on energy production rate are unknown [12].
  • On LPD, protein intake (0.64 +/- 0.05 vs 1.15 +/- 0.09 g kg-1 body weight (BW) per day, P less than 0.001), plasma urea (6.6 +/- 1.3 vs 11.0 +/- 2.0 mmol l-1, P less than 0.01) and urea appearance (0.06 +/- 0.01 vs 0.16 +/- 0.03 gN kg-1 body weight per day, P less than 0.001) were lower [13].
  • To test whether the combination of both may have an additive antiproteinuric effect, we studied the effects of single treatment with ACEi (10 mg enalapril o.d.), LPD (target, 50% reduction in protein intake), and the combination of both in 14 of such patients with stable proteinuria exceeding 3 g per day [14].
  • When UNEx, AUTO and LPD recurrent abortion subgroups were compared with each other (Student's t-test) total thiols and erythrocyte GSH of UNEx and AUTO subgroups were diminished in comparison with LPD [15].

Biological context of RAPH1


Anatomical context of RAPH1

  • Northern blot analysis indicated that RMO1 mRNA is ubiquitously expressed in tissues except for peripheral blood leukocytes [1].
  • Conversely, knockdown of Lpd expression impairs lamellipodia formation, reduces velocity of residual lamellipodial protrusion, and decreases F-actin content [2].
  • Lpd overexpression increases lamellipodial protrusion velocity, an effect observed when Ena/VASP proteins are overexpressed or artificially targeted to the plasma membrane [2].
  • Therefore, in an effort to characterize the usage of the TCR alpha- and beta-chain genes in patients with T-gamma LPD, we cloned and sequenced TCR alpha- and beta-chain mRNAs derived from the T-cell type LGL of five patients [4].
  • Highly significant changes in desmosome frequency, diameter and LPD were observed between epidermal strata and, in basal and upper horny cells, between different regions of the same cell surface [18].

Associations of RAPH1 with chemical compounds

  • Lpd contains a PH domain that binds specifically to PI(3,4)P2, an asymmetrically localized signal in chemotactic cells [2].
  • RESULTS: As expected, maternal protein restriction led to reduced nephron endowment in LPD offspring [19].
  • This study examines the longitudinal changes in peritoneal macrophage (PMØ) function in patients dialyzed continuously with either lactate (LPD; 40 mM lactate, pH 5.2)-buffered or bicarbonate/lactate (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3)-buffered PDF [20].
  • RESULTS: UAER [median CD: 269.4 (range: 111-1128) microg/min; LPD: 229.3 (76.6-999.3) microg/min; UD: 312.8 (223.7-1223.7) microg/min; P < 0.01] and mean (+/-SD) non-HDL cholesterol (CD: 3.92 +/- 0.99 mmol/L; LPD: 3.92 +/- 0.93 mmol/L; UD: 4.23 +/- 1.06 mmol/L; P = 0.042) were lower after CD and LPD than after UD [21].
  • The blunted elevation in FSH during the luteal-follicular transition in exercising women with LPD may explain their lower follicular estradiol levels [16].

Other interactions of RAPH1

  • Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics [2].

Analytical, diagnostic and therapeutic context of RAPH1

  • None of the monkeys demonstrated significant adverse effects, and at 1 month the 2 LPD/pAAVaspa monkeys were positive for human ASPA transcript by reverse transcriptase polymerase chain reaction of brain tissue punches [22].
  • Podocyte density was lowest in the LPD diabetic animals (not significant), and the area covered by each podocyte was greater in the LPD diabetic group (2.40+/-0.693 x10(-3) mm(2)) than in the LPD control group (1.68+/-0.374 x10(-3) mm(2), p<0.001) and in the NPD diabetic animals (1.71+/-0.291 x10(-3) mm(2), p<0.05) [23].
  • Glomerular volume correlated inversely with glomerular number (r=-0.64, p=0.035), but total glomerular filtration surface area was reduced in the LPD animals (4,770+/-541 vs 5,779+/-1,302 mm(2), p=0.05) [23].
  • Sixteen CRF patients consuming an LPD were randomly assigned to receive a supplement of a highly fermentable fiber, gum arabic (50 g/d), or a placebo (1 g pectin/d) in a prospective, single-blind, crossover design [24].
  • Lipoproteins and lipoprotein-deficient plasma (LPDP) were purified and analyzed by Western blots [25].


  1. Altered expression and deletion of RMO1 in osteosarcoma. Eppert, K., Wunder, J.S., Aneliunas, V., Tsui, L.C., Scherer, S.W., Andrulis, I.L. Int. J. Cancer (2005) [Pubmed]
  2. Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics. Krause, M., Leslie, J.D., Stewart, M., Lafuente, E.M., Valderrama, F., Jagannathan, R., Strasser, G.A., Rubinson, D.A., Liu, H., Way, M., Yaffe, M.B., Boussiotis, V.A., Gertler, F.B. Dev. Cell (2004) [Pubmed]
  3. T cell receptor beta chain gene rearrangements in lymphoproliferative disorders of large granular lymphocytes/natural killer cells. Rambaldi, A., Pelicci, P.G., Allavena, P., Knowles, D.M., Rossini, S., Bassan, R., Barbui, T., Dalla-Favera, R., Mantovani, A. J. Exp. Med. (1985) [Pubmed]
  4. T-cell receptor gene rearrangement in T-cell large granular leukocyte leukemia: preferential V alpha but diverse J alpha usage in one of five patients. Kasten-Sportès, C., Zaknoen, S., Steis, R.G., Chan, W.C., Winton, E.F., Waldmann, T.A. Blood (1994) [Pubmed]
  5. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Kwong, W.Y., Wild, A.E., Roberts, P., Willis, A.C., Fleming, T.P. Development (2000) [Pubmed]
  6. Assessment of depression by questionnaire compared to DSM-III diagnosis. Carr, V., Smith, J. Journal of affective disorders. (1985) [Pubmed]
  7. Association of socio-psychological factors with the effects of low protein diet for the prevention of the progression of chronic renal failure. Kanazawa, Y., Nakao, T., Ohya, Y., Shimomitsu, T. Intern. Med. (2006) [Pubmed]
  8. 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]
  9. Abnormalities of predictive saccades in hemi-Parkinson's disease. Ventre, J., Zee, D.S., Papageorgiou, H., Reich, S. Brain (1992) [Pubmed]
  10. Renal response to restricted protein intake in diabetic nephropathy. Bending, J.J., Dodds, R.A., Keen, H., Viberti, G.C. Diabetes (1988) [Pubmed]
  11. Short-term effects of low protein-normal sodium diet on renal function in chronic renal failure. Cianciaruso, B., Bellizzi, V., Capuano, A., Bovi, G., Nastasi, A., Conte, G., De Nicola, L. Kidney Int. (1994) [Pubmed]
  12. Low protein diet in uremia: effects on glucose metabolism and energy production rate. Rigalleau, V., Combe, C., Blanchetier, V., Aubertin, J., Aparicio, M., Gin, H. Kidney Int. (1997) [Pubmed]
  13. Effect of low protein diet on the renal response to meat ingestion in diabetic nephropathy. Pinto, J.R., Bending, J.J., Dodds, R.A., Viberti, G.C. Eur. J. Clin. Invest. (1991) [Pubmed]
  14. Additive antiproteinuric effect of ACE inhibition and a low-protein diet in human renal disease. Gansevoort, R.T., de Zeeuw, D., de Jong, P.E. Nephrol. Dial. Transplant. (1995) [Pubmed]
  15. Antioxidant defence in recurrent abortion. Vural, P., Akgül, C., Yildirim, A., Canbaz, M. Clin. Chim. Acta (2000) [Pubmed]
  16. High frequency of luteal phase deficiency and anovulation in recreational women runners: blunted elevation in follicle-stimulating hormone observed during luteal-follicular transition. De Souza, M.J., Miller, B.E., Loucks, A.B., Luciano, A.A., Pescatello, L.S., Campbell, C.G., Lasley, B.L. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  17. Chicken and fish diet reduces glomerular hyperfiltration in IDDM patients. Pecis, M., de Azevedo, M.J., Gross, J.L. Diabetes Care (1994) [Pubmed]
  18. Changes to desmosomal antigens and lectin-binding sites during differentiation in normal human epidermis: a quantitative ultrastructural study. Skerrow, C.J., Clelland, D.G., Skerrow, D. J. Cell. Sci. (1989) [Pubmed]
  19. A developmental nephron deficit in rats is associated with increased susceptibility to a secondary renal injury due to advanced glycation end-products. Zimanyi, M.A., Denton, K.M., Forbes, J.M., Thallas-Bonke, V., Thomas, M.C., Poon, F., Black, M.J. Diabetologia (2006) [Pubmed]
  20. Continuous dialysis with bicarbonate/lactate-buffered peritoneal dialysis fluids results in a long-term improvement in ex vivo peritoneal macrophage function. Jones, S., Holmes, C.J., Mackenzie, R.K., Stead, R., Coles, G.A., Williams, J.D., Faict, D., Topley, N. J. Am. Soc. Nephrol. (2002) [Pubmed]
  21. Withdrawal of red meat from the usual diet reduces albuminuria and improves serum fatty acid profile in type 2 diabetes patients with macroalbuminuria. de Mello, V.D., Zelmanovitz, T., Perassolo, M.S., Azevedo, M.J., Gross, J.L. Am. J. Clin. Nutr. (2006) [Pubmed]
  22. Aspartoacylase gene transfer to the mammalian central nervous system with therapeutic implications for Canavan disease. Leone, P., Janson, C.G., Bilaniuk, L., Wang, Z., Sorgi, F., Huang, L., Matalon, R., Kaul, R., Zeng, Z., Freese, A., McPhee, S.W., Mee, E., During, M.J., Bilianuk, L. Ann. Neurol. (2000) [Pubmed]
  23. The effect of intrauterine environment and low glomerular number on the histological changes in diabetic glomerulosclerosis. Jones, S.E., White, K.E., Flyvbjerg, A., Marshall, S.M. Diabetologia (2006) [Pubmed]
  24. Supplementation with gum arabic fiber increases fecal nitrogen excretion and lowers serum urea nitrogen concentration in chronic renal failure patients consuming a low-protein diet. Bliss, D.Z., Stein, T.P., Schleifer, C.R., Settle, R.G. Am. J. Clin. Nutr. (1996) [Pubmed]
  25. Transfer of dehydroepiandrosterone- and pregnenolone-fatty acid esters between human lipoproteins. Provost, P.R., Lavallée, B., Bélanger, A. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
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