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Gene Review

SLC11A1  -  solute carrier family 11 (proton-coupled...

Homo sapiens

Synonyms: LSH, NRAMP, NRAMP 1, NRAMP1, Natural resistance-associated macrophage protein 1, ...
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Disease relevance of SLC11A1


Psychiatry related information on SLC11A1


High impact information on SLC11A1

  • This gene is the strongest candidate among the 42 genes in the Idd5.2 region; a naturally occurring mutation in the protective Idd5.2 haplotype results in loss of function of the Nramp1 protein [6].
  • In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to type 1 diabetes [6].
  • Slc11a1 encodes a phagosomal ion transporter, Nramp1, that affects resistance to intracellular pathogens and influences antigen presentation [6].
  • We typed polymorphisms in NRAMP1 in a case-control study of tuberculosis in the Gambia, West Africa. METHODS: Sequence-specific oligonucleotide hybridization and microsatellite analysis were used to type NRAMP1 polymorphisms in 410 adults (mean age, 34.7 years) with smear-positive pulmonary tuberculosis and 417 ethnically matched, healthy controls [7].
  • Subjects who were heterozygous for two NRAMP1 polymorphisms in intron 4 and the 3' untranslated region of the gene were particularly overrepresented among those with tuberculosis, as compared with those with the most common NRAMP1 genotype (odds ratio, 4.07; 95 percent confidence interval, 1.86 to 9.12; chi-square= 14.58; P<0.001) [7].

Chemical compound and disease context of SLC11A1


Biological context of SLC11A1


Anatomical context of SLC11A1


Associations of SLC11A1 with chemical compounds


Physical interactions of SLC11A1

  • Here we analyze the expression of SLC11A1 in human monocytes and HL-60 cells and then use HL-60 cells as a model to determine whether RNA-binding protein HuR is associated with the ARE and involved in SLC11A1 mRNA turnover [11].
  • The membrane topology and transport properties of Nramp1HA and Nramp2HA were indistinguishable, suggesting that Nramp1 divalent-metal transport at the phagosomal membrane is mechanistically similar to that of Nramp2 at the membrane of acidified endosomes [17].
  • SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1 [18].

Regulatory relationships of SLC11A1


Other interactions of SLC11A1

  • Thus, positive association with SLC11A1 should be interpreted cautiously, and IL8RB should also be considered as a potential candidate susceptibility gene unless proven otherwise [2].
  • Our results demonstrate a binding of HuR to the SLC11A1 ARE in phorbol myristate acetate (PMA)-differentiated cells dramatically increased compared to that in undifferentiated cells [11].
  • Stratification of the haplotype data suggested that susceptibility to JIA in the haplotype spanning the SLC11A1 locus is independent (P < 0.01) of an association with a DRB1 JIA shared epitope (DRB1*JIASE) that includes well-characterized strong susceptibility to DRB1*08 and *11 alleles [1].
  • SLC11A1 regulates macrophage functions that are of potential importance in the induction and/or maintenance of autoimmune diseases such as rheumatoid arthritis, type I diabetes and Crohn's disease [3].
  • We found no evidence of association between SLC11A1 polymorphisms and MS susceptibility in the Spanish population [3].

Analytical, diagnostic and therapeutic context of SLC11A1

  • Four SLC11A1 gene polymorphisms (5'GT repeat, D543N, 1729 + 55del4 and 1729 + 271del4) were analysed in a case-control study of 195 patients with MS and 125 control subjects [3].
  • Functional polymorphism in Z-DNA-forming motif of promoter of SLC11A1 gene and type 1 diabetes in Japanese subjects: association study and meta-analysis [22].
  • Stratification by BCG vaccination unmasked a potential genetic risk factor for atopy in the region of the SLC11A1 locus, and point to the importance of genotype by environment interactions in determining disease susceptibility [23].
  • Subcellular fractionation of granule populations together with immunoblotting studies with granule-specific markers indicate that NRAMP1 expression is primarily in tertiary granules [14].
  • Immunogold studies by cryoelectron microscopy with primary neutrophils confirm that a majority (75%) of NRAMP1-positive granules are also positive for gelatinase, but they also suggest further heterogeneity in this granule population [14].


  1. Association of SLC11A1 (NRAMP1) with persistent oligoarticular and polyarticular rheumatoid factor-negative juvenile idiopathic arthritis in Finnish patients: haplotype analysis in Finnish families. Runstadler, J.A., Säilä, H., Savolainen, A., Leirisalo-Repo, M., Aho, K., Tuomilehto-Wolf, E., Tuomilehto, J., Seldin, M.F. Arthritis Rheum. (2005) [Pubmed]
  2. Extent and distribution of linkage disequilibrium around the SLC11A1 locus. Yip, S.P., Leung, K.H., Lin, C.K. Genes Immun. (2003) [Pubmed]
  3. Genetic analysis of SLC11A1 polymorphisms in multiple sclerosis patients. Comabella, M., Altet, L., Peris, F., Villoslada, P., Sánchez, A., Montalban, X. Mult. Scler. (2004) [Pubmed]
  4. Association of functional polymorphisms of SLC11A1 with risk of esophageal cancer in the South African Colored population. Zaahl, M.G., Warnich, L., Victor, T.C., Kotze, M.J. Cancer Genet. Cytogenet. (2005) [Pubmed]
  5. Candidate gene association study of solute carrier family 11a members 1 (SLC11A1) and 2 (SLC11A2) genes in Alzheimer's disease. Jamieson, S.E., White, J.K., Howson, J.M., Pask, R., Smith, A.N., Brayne, C., Evans, J.G., Xuereb, J., Cairns, N.J., Rubinsztein, D.C., Blackwell, J.M. Neurosci. Lett. (2005) [Pubmed]
  6. In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to type 1 diabetes. Kissler, S., Stern, P., Takahashi, K., Hunter, K., Peterson, L.B., Wicker, L.S. Nat. Genet. (2006) [Pubmed]
  7. Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. Bellamy, R., Ruwende, C., Corrah, T., McAdam, K.P., Whittle, H.C., Hill, A.V. N. Engl. J. Med. (1998) [Pubmed]
  8. The NRAMP proteins of Salmonella typhimurium and Escherichia coli are selective manganese transporters involved in the response to reactive oxygen. Kehres, D.G., Zaharik, M.L., Finlay, B.B., Maguire, M.E. Mol. Microbiol. (2000) [Pubmed]
  9. LSH hamster model of syphilitic infection. Schell, R.F., LeFrock, J.L., Chan, J.K., Bagasra, O. Infect. Immun. (1980) [Pubmed]
  10. HFIP-induced structures and assemblies of the peptides from the transmembrane domain 4 of membrane protein Nramp1. Xue, R., Wang, S., Wang, C., Zhu, T., Li, F., Sun, H. Biopolymers (2006) [Pubmed]
  11. RNA-binding protein HuR is required for stabilization of SLC11A1 mRNA and SLC11A1 protein expression. Xu, Y.Z., Di Marco, S., Gallouzi, I., Rola-Pleszczynski, M., Radzioch, D. Mol. Cell. Biol. (2005) [Pubmed]
  12. Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression. Cellier, M., Govoni, G., Vidal, S., Kwan, T., Groulx, N., Liu, J., Sanchez, F., Skamene, E., Schurr, E., Gros, P. J. Exp. Med. (1994) [Pubmed]
  13. Identification of polymorphisms and sequence variants in the human homologue of the mouse natural resistance-associated macrophage protein gene. Liu, J., Fujiwara, T.M., Buu, N.T., Sánchez, F.O., Cellier, M., Paradis, A.J., Frappier, D., Skamene, E., Gros, P., Morgan, K. Am. J. Hum. Genet. (1995) [Pubmed]
  14. Expression and subcellular localization of NRAMP1 in human neutrophil granules. Canonne-Hergaux, F., Calafat, J., Richer, E., Cellier, M., Grinstein, S., Borregaard, N., Gros, P. Blood (2002) [Pubmed]
  15. Identification of a Tyrosine-based Motif (YGSI) in the Amino Terminus of Nramp1 (Slc11a1) That Is Important for Lysosomal Targeting. Lam-Yuk-Tseung, S., Picard, V., Gros, P. J. Biol. Chem. (2006) [Pubmed]
  16. Identification of natural resistance-associated macrophage protein in peripheral blood lymphocytes. Kishi, F., Nobumoto, M. Immunol. Lett. (1995) [Pubmed]
  17. Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Forbes, J.R., Gros, P. Blood (2003) [Pubmed]
  18. SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1. Mackenzie, B., Hediger, M.A. Pflugers Arch. (2004) [Pubmed]
  19. Association of NRAMP1 promoter gene polymorphism with the susceptibility and radiological severity of rheumatoid arthritis. Rodríguez, M.R., González-Escribano, M.F., Aguilar, F., Valenzuela, A., García, A., Núñez-Roldán, A. Tissue Antigens (2002) [Pubmed]
  20. Interleukin-10, polymorphism in SLC11A1 (formerly NRAMP1), and susceptibility to tuberculosis. Awomoyi, A.A., Marchant, A., Howson, J.M., McAdam, K.P., Blackwell, J.M., Newport, M.J. J. Infect. Dis. (2002) [Pubmed]
  21. Normoxic stabilization of hypoxia-inducible factor-1alpha by modulation of the labile iron pool in differentiating U937 macrophages: effect of natural resistance-associated macrophage protein 1. Knowles, H.J., Mole, D.R., Ratcliffe, P.J., Harris, A.L. Cancer Res. (2006) [Pubmed]
  22. Functional polymorphism in Z-DNA-forming motif of promoter of SLC11A1 gene and type 1 diabetes in Japanese subjects: association study and meta-analysis. Nishino, M., Ikegami, H., Fujisawa, T., Kawaguchi, Y., Kawabata, Y., Shintani, M., Ono, M., Ogihara, T. Metab. Clin. Exp. (2005) [Pubmed]
  23. Atopy in children in relation to BCG vaccination and genetic polymorphisms at SLC11A1 (formerly NRAMP1) and D2S1471. Alm, J.S., Sanjeevi, C.B., Miller, E.N., Dabadghao, P., Lilja, G., Pershagen, G., Blackwell, J.M., Scheynius, A. Genes Immun. (2002) [Pubmed]
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