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Gene Review

PTPN22  -  protein tyrosine phosphatase, non-receptor...

Homo sapiens

Synonyms: Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP, LYP, LYP1, LYP2, LyP, ...
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Disease relevance of PTPN22


High impact information on PTPN22


Chemical compound and disease context of PTPN22


Biological context of PTPN22


Anatomical context of PTPN22


Associations of PTPN22 with chemical compounds

  • It was reported that a missense single nucleotide polymorphism , R620W (rs2476601), 1858C->T encodes an amino-acid change in the P1 proline-rich motif of the gene PTPN22 and is associated with SLE in North American white individuals [19].
  • RESULTS: R620W was not associated in either case-control study, while significant association (corrected for multiple testing) with one haplotype (C-4) of the LD block encompassing PTPN22 as well with another haplotype (B-3) within an adjacent telomeric LD block was detected [20].
  • The IR and UV-vis spectra of the carbene were recorded and analyzed with the aid of density functional calculations (B3-LYP/6-31G) [21].
  • Recently, a single nucleotide polymorphism (SNP), encoding a functional arginine to tryptophan residue change at LYP codon 620 has been shown to be associated with type 1 diabetes and other autoimmune disorders [22].
  • In this B3 LYP model study, homoleptic nickel(0) ethyne complexes have been predicted as the catalyst resting state for the title reaction [23].

Physical interactions of PTPN22

  • Grb2 was co-immunoprecipitated with Lyp in 293T cells overexpressing both proteins [24].

Regulatory relationships of PTPN22

  • Additional analyses identified two SNPs on a single common haplotype that are associated with RA independent of R620W, suggesting that R620W and at least one additional variant in the PTPN22 gene region influence RA susceptibility [14].
  • The results indicate that the LYP missense R620W polymorphism may have an influence on the development of generalised vitiligo and provide further evidence for autoimmunity as an aetiological factor with respect to this disease [25].

Other interactions of PTPN22


Analytical, diagnostic and therapeutic context of PTPN22


  1. Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene. Michou, L., Lasbleiz, S., Rat, A.C., Migliorini, P., Balsa, A., Westhovens, R., Barrera, P., Alves, H., Pierlot, C., Glikmans, E., Garnier, S., Dausset, J., Vaz, C., Fernandes, M., Petit-Teixeira, E., Lemaire, I., Pascual-Salcedo, D., Bombardieri, S., Dequeker, J., Radstake, T.R., Van Riel, P., van de Putte, L., Lopes-Vaz, A., Prum, B., Bardin, T., Dieudé, P., Cornélis, F. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  2. Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene. Hinks, A., Barton, A., John, S., Bruce, I., Hawkins, C., Griffiths, C.E., Donn, R., Thomson, W., Silman, A., Worthington, J. Arthritis Rheum. (2005) [Pubmed]
  3. Association of the lymphoid tyrosine phosphatase R620W variant with rheumatoid arthritis, but not Crohn's disease, in Canadian populations. van Oene, M., Wintle, R.F., Liu, X., Yazdanpanah, M., Gu, X., Newman, B., Kwan, A., Johnson, B., Owen, J., Greer, W., Mosher, D., Maksymowych, W., Keystone, E., Rubin, L.A., Amos, C.I., Siminovitch, K.A. Arthritis Rheum. (2005) [Pubmed]
  4. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Vang, T., Congia, M., Macis, M.D., Musumeci, L., Orrú, V., Zavattari, P., Nika, K., Tautz, L., Taskén, K., Cucca, F., Mustelin, T., Bottini, N. Nat. Genet. (2005) [Pubmed]
  5. Association of PTPN22 haplotypes with Graves' disease. Heward, J.M., Brand, O.J., Barrett, J.C., Carr-Smith, J.D., Franklyn, J.A., Gough, S.C. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  6. The PTPN22 620W allele confers susceptibility to systemic sclerosis: findings of a large case-control study of European Caucasians and a meta-analysis. Dieudé, P., Guedj, M., Wipff, J., Avouac, J., Hachulla, E., Diot, E., Granel, B., Sibilia, J., Cabane, J., Meyer, O., Mouthon, L., Kahan, A., Boileau, C., Allanore, Y. Arthritis Rheum. (2008) [Pubmed]
  7. Gaining insight into PTPN22 and autoimmunity. Gregersen, P.K. Nat. Genet. (2005) [Pubmed]
  8. PTPN22 and autoimmune disease. Siminovitch, K.A. Nat. Genet. (2004) [Pubmed]
  9. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Bottini, N., Musumeci, L., Alonso, A., Rahmouni, S., Nika, K., Rostamkhani, M., MacMurray, J., Meloni, G.F., Lucarelli, P., Pellecchia, M., Eisenbarth, G.S., Comings, D., Mustelin, T. Nat. Genet. (2004) [Pubmed]
  10. Genetic susceptibility to type 1 diabetes. Maier, L.M., Wicker, L.S. Curr. Opin. Immunol. (2005) [Pubmed]
  11. A biosynthetic pathway for anandamide. Liu, J., Wang, L., Harvey-White, J., Osei-Hyiaman, D., Razdan, R., Gong, Q., Chan, A.C., Zhou, Z., Huang, B.X., Kim, H.Y., Kunos, G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  12. The codon 620 single nucleotide polymorphism of the protein tyrosine phosphatase-22 gene does not contribute to autoimmune thyroid disease susceptibility in the Japanese. Ban, Y., Tozaki, T., Taniyama, M., Tomita, M., Ban, Y. Thyroid (2005) [Pubmed]
  13. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Begovich, A.B., Carlton, V.E., Honigberg, L.A., Schrodi, S.J., Chokkalingam, A.P., Alexander, H.C., Ardlie, K.G., Huang, Q., Smith, A.M., Spoerke, J.M., Conn, M.T., Chang, M., Chang, S.Y., Saiki, R.K., Catanese, J.J., Leong, D.U., Garcia, V.E., McAllister, L.B., Jeffery, D.A., Lee, A.T., Batliwalla, F., Remmers, E., Criswell, L.A., Seldin, M.F., Kastner, D.L., Amos, C.I., Sninsky, J.J., Gregersen, P.K. Am. J. Hum. Genet. (2004) [Pubmed]
  14. PTPN22 genetic variation: evidence for multiple variants associated with rheumatoid arthritis. Carlton, V.E., Hu, X., Chokkalingam, A.P., Schrodi, S.J., Brandon, R., Alexander, H.C., Chang, M., Catanese, J.J., Leong, D.U., Ardlie, K.G., Kastner, D.L., Seldin, M.F., Criswell, L.A., Gregersen, P.K., Beasley, E., Thomson, G., Amos, C.I., Begovich, A.B. Am. J. Hum. Genet. (2005) [Pubmed]
  15. Pathways to gene identification in rheumatoid arthritis: PTPN22 and beyond. Gregersen, P.K. Immunol. Rev. (2005) [Pubmed]
  16. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Kyogoku, C., Langefeld, C.D., Ortmann, W.A., Lee, A., Selby, S., Carlton, V.E., Chang, M., Ramos, P., Baechler, E.C., Batliwalla, F.M., Novitzke, J., Williams, A.H., Gillett, C., Rodine, P., Graham, R.R., Ardlie, K.G., Gaffney, P.M., Moser, K.L., Petri, M., Begovich, A.B., Gregersen, P.K., Behrens, T.W. Am. J. Hum. Genet. (2004) [Pubmed]
  17. Association analysis of the R620W polymorphism of protein tyrosine phosphatase PTPN22 in systemic lupus erythematosus families: increased T allele frequency in systemic lupus erythematosus patients with autoimmune thyroid disease. Wu, H., Cantor, R.M., Graham, D.S., Lingren, C.M., Farwell, L., Jager, P.L., Bottini, N., Grossman, J.M., Wallace, D.J., Hahn, B.H., Julkunen, H., Hebert, L.A., Rovin, B.H., Birmingham, D.J., Rioux, J.D., Yu, C.Y., Kere, J., Vyse, T.J., Tsao, B.P. Arthritis Rheum. (2005) [Pubmed]
  18. Lack of association of a functional single nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with susceptibility to biopsy-proven giant cell arteritis. Gonzalez-Gay, M.A., Oliver, J., Orozco, G., Garcia-Porrua, C., Lopez-Nevot, M.A., Martin, J. J. Rheumatol. (2005) [Pubmed]
  19. The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1. Reddy, M.V., Johansson, M., Sturfelt, G., Jönsen, A., Gunnarsson, I., Svenungsson, E., Rantapää-Dahlqvist, S., Alarcón-Riquelme, M.E. Genes Immun. (2005) [Pubmed]
  20. Evidence for susceptibility determinant(s) to psoriasis vulgaris in or near PTPN22 in German patients. Hüffmeier, U., Steffens, M., Burkhardt, H., Lascorz, J., Schürmeier-Horst, F., Ständer, M., Kelsch, R., Baumann, C., Küster, W., Mössner, R., Reich, K., Wienker, T.F., Traupe, H., Reis, A. J. Med. Genet. (2006) [Pubmed]
  21. Carbomethoxychlorocarbene: spectroscopy, theory, chemistry and kinetics. Likhotvorik, I., Zhu, Z., Tae, E.L., Tippmann, E., Hill, B.T., Platz, M.S. J. Am. Chem. Soc. (2001) [Pubmed]
  22. The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves' disease. Velaga, M.R., Wilson, V., Jennings, C.E., Owen, C.J., Herington, S., Donaldson, P.T., Ball, S.G., James, R.A., Quinton, R., Perros, P., Pearce, S.H. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  23. Mechanism of Reppe's nickel-catalyzed ethyne tetramerization to cyclooctatetraene: a DFT study. Straub, B.F., Gollub, C. Chemistry (Weinheim an der Bergstrasse, Germany) (2004) [Pubmed]
  24. The lymphoid protein tyrosine phosphatase Lyp interacts with the adaptor molecule Grb2 and functions as a negative regulator of T-cell activation. Hill, R.J., Zozulya, S., Lu, Y.L., Ward, K., Gishizky, M., Jallal, B. Exp. Hematol. (2002) [Pubmed]
  25. A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosine phosphatase (PTPN22) confers susceptibility to generalised vitiligo. Cantón, I., Akhtar, S., Gavalas, N.G., Gawkrodger, D.J., Blomhoff, A., Watson, P.F., Weetman, A.P., Kemp, E.H. Genes Immun. (2005) [Pubmed]
  26. Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4. Plenge, R.M., Padyukov, L., Remmers, E.F., Purcell, S., Lee, A.T., Karlson, E.W., Wolfe, F., Kastner, D.L., Alfredsson, L., Altshuler, D., Gregersen, P.K., Klareskog, L., Rioux, J.D. Am. J. Hum. Genet. (2005) [Pubmed]
  27. Association of a functional single-nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus. Orozco, G., Sánchez, E., González-Gay, M.A., López-Nevot, M.A., Torres, B., Cáliz, R., Ortego-Centeno, N., Jiménez-Alonso, J., Pascual-Salcedo, D., Balsa, A., de Pablo, R., Nuñez-Roldan, A., González-Escribano, M.F., Martín, J. Arthritis Rheum. (2005) [Pubmed]
  28. Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp. Cohen, S., Dadi, H., Shaoul, E., Sharfe, N., Roifman, C.M. Blood (1999) [Pubmed]
  29. Type 1 diabetes: evidence for susceptibility loci from four genome-wide linkage scans in 1,435 multiplex families. Concannon, P., Erlich, H.A., Julier, C., Morahan, G., Nerup, J., Pociot, F., Todd, J.A., Rich, S.S. Diabetes (2005) [Pubmed]
  30. The 1858T PTPN22 gene variant contributes to a genetic risk of type 1 diabetes in a Ukrainian population. Fedetz, M., Matesanz, F., Caro-Maldonado, A., Smirnov, I.I., Chvorostinka, V.N., Moiseenko, T.A., Alcina, A. Tissue Antigens (2006) [Pubmed]
  31. Primary and secondary cutaneous CD30(+) lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment. Bekkenk, M.W., Geelen, F.A., van Voorst Vader, P.C., Heule, F., Geerts, M.L., van Vloten, W.A., Meijer, C.J., Willemze, R. Blood (2000) [Pubmed]
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