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Gene Review

SUMO4  -  small ubiquitin-like modifier 4

Homo sapiens

Synonyms: IDDM5, SMT3H4, SUMO-4, Small ubiquitin-like protein 4, Small ubiquitin-related modifier 4, ...
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Disease relevance of SUMO4


High impact information on SUMO4

  • A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes [6].
  • Here, we report evidence for an association between T1D and multiple single-nucleotide polymorphisms in 197 kb of genomic DNA in the IDDM5 interval [6].
  • OBJECTIVE-SUMO4 mRNA was recently found to be mainly expressed in the kidney, and the methionine-to-valine substitution at codon 55 (M55V) variant of SUMO4 may induce higher nuclear factor-kappaB (NF-kappaB) activity [7].
  • We detected a significant linear trend for SUMO4 genotype between the macroalbuminuric and normoalbuminuric groups [7].
  • Multivariate logistic regression analysis showed the SUMO4 M55V variant to be independently associated with the severity of diabetic nephropathy [7].

Chemical compound and disease context of SUMO4


Biological context of SUMO4

  • CONTEXT: Recently, an association of a single nucleotide polymorphism, 163A>G encoding M55V, in the gene SUMO4, which has been shown to be a negative feedback regulator for nuclear factor kappaB, has been reported in type 1 diabetes [1].
  • Significant differences were found in the distribution of the SUMO4 genotypes and alleles among SLE patients with and without nephritis, but after multiple testing correction, the significance of the association was lost [2].
  • Genetic Heterogeneity in Association of the SUMO4 M55V Variant With Susceptibility to Type 1 Diabetes [8].
  • Alleles at markers in the TAB2/SUMO4 locus on chromosome 6q had been previously reported to be associated with T1D in two separate studies, but these studies disagreed on the identity of the risk allele [9].
  • The novel polymorphism M55V, causing an amino acid change in the evolutionarily conserved met55 residue has been shown to activate the nuclear factor kappaB (NF-kappaB), hence the suspected role of SUMO4 in the pathogenicity of T1DM [10].

Associations of SUMO4 with chemical compounds


Other interactions of SUMO4

  • SNP mapping in the RUNX1 gene associated with RA in a Japanese population and a SUMO4 polymorphism associated with T1D were also studied [11].
  • With regard to the RUNX1 and SUMO4 SNP, we did not observe statistically significant differences in the distribution of genotypes or alleles between patients with RA and healthy controls [11].
  • In contrast to SUMO-2, which is highly expressed in all of the tissues examined, SUMO-4 mRNA was detected mainly in the kidney [3].
  • An association of a methionine-to-valine polymorphism (rs237025, 163A --> G, M55V) in the SUMO4 gene within IDDM5 has recently been described in T1D [4].
  • No significant evidence of association with T1D was obtained for three SNP markers in the TAB2/SUMO4 region [9].

Analytical, diagnostic and therapeutic context of SUMO4

  • The M55V (rs237025, 163A-->G) polymorphism of SUMO4 was genotyped by real-time PCR, and urine albumin concentration was measured by radioimmunoassay [7].
  • Meta-analysis of published studies and the present data confirmed a highly significant association in Asian populations (summary OR 1.29, P = 7.0 x 10(-6)) but indicated heterogeneity in the genetic effect of the SUMO4/MAP3K7IP2 locus on type 1 diabetes among diverse ethnic groups [8].


  1. Evidence for the role of small ubiquitin-like modifier 4 as a general autoimmunity locus in the Japanese population. Tsurumaru, M., Kawasaki, E., Ida, H., Migita, K., Moriuchi, A., Fukushima, K., Fukushima, T., Abiru, N., Yamasaki, H., Noso, S., Ikegami, H., Awata, T., Sasaki, H., Eguchi, K. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  2. Study of the role of functional variants of SLC22A4, RUNX1 and SUMO4 in systemic lupus erythematosus. Orozco, G., Sánchez, E., Gómez, L.M., González-Gay, M.A., López-Nevot, M.A., Torres, B., Ortego-Centeno, N., Jiménez-Alonso, J., de Ramón, E., Sánchez Román, J., Anaya, J.M., Sturfelt, G., Gunnarsson, I., Svennungsson, E., Alarcón-Riquelme, M., González-Escribano, M.F., Martín, J. Ann. Rheum. Dis. (2006) [Pubmed]
  3. A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. Bohren, K.M., Nadkarni, V., Song, J.H., Gabbay, K.H., Owerbach, D. J. Biol. Chem. (2004) [Pubmed]
  4. The type 1 diabetes susceptibility gene SUMO4 at IDDM5 is not associated with susceptibility to rheumatoid arthritis or juvenile idiopathic arthritis. Gibbons, L.J., Thomson, W., Zeggini, E., Worthington, J., Barton, A., Eyre, S., Donn, R., Hinks, A. Rheumatology (Oxford, England) (2005) [Pubmed]
  5. No association of the codon 55 methionine to valine polymorphism in the SUMO4 gene with Graves' disease. Jennings, C.E., Owen, C.J., Wilson, V., Pearce, S.H. Clin. Endocrinol. (Oxf) (2005) [Pubmed]
  6. A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Guo, D., Li, M., Zhang, Y., Yang, P., Eckenrode, S., Hopkins, D., Zheng, W., Purohit, S., Podolsky, R.H., Muir, A., Wang, J., Dong, Z., Brusko, T., Atkinson, M., Pozzilli, P., Zeidler, A., Raffel, L.J., Jacob, C.O., Park, Y., Serrano-Rios, M., Larrad, M.T., Zhang, Z., Garchon, H.J., Bach, J.F., Rotter, J.I., She, J.X., Wang, C.Y. Nat. Genet. (2004) [Pubmed]
  7. SUMO4 M55V Variant Is Associated With Diabetic Nephropathy in Type 2 Diabetes. Lin, H.Y., Wang, C.L., Hsiao, P.J., Lu, Y.C., Chen, S.Y., Lin, K.D., Hsin, S.C., Hsieh, M.C., Shin, S.J. Diabetes (2007) [Pubmed]
  8. Genetic Heterogeneity in Association of the SUMO4 M55V Variant With Susceptibility to Type 1 Diabetes. Noso, S., Ikegami, H., Fujisawa, T., Kawabata, Y., Asano, K., Hiromine, Y., Tsurumaru, M., Sugihara, S., Lee, I., Kawasaki, E., Awata, T., Ogihara, T. Diabetes (2005) [Pubmed]
  9. Functional variants in SUMO4, TAB2, and NFkappaB and the risk of type 1 diabetes. Kosoy, R., Concannon, P. Genes Immun. (2005) [Pubmed]
  10. Association of SUMO4 M55V Polymorphism with Autoimmune Diabetes in Latvian Patients. Sedimbi, S.K., Shastry, A., Park, Y., Rumba, I., Sanjeevi, C.B. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  11. SLC22A4, RUNX1, and SUMO4 polymorphisms are not associated with rheumatoid arthritis: a case-control study in a Spanish population. Orozco, G., Sánchez, E., González-Gay, M.A., López-Nevot, M.A., Torres, B., Pascual-Salcedo, D., Balsa, A., Pablos, J.L., García, A., González-Escribano, M.F., Martín, J. J. Rheumatol. (2006) [Pubmed]
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