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Gene Review

CAPN10  -  calpain 10

Homo sapiens

Synonyms: CANP 10, CANP10, Calcium-activated neutral proteinase 10, Calpain-10, KIAA1845, ...
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Disease relevance of CAPN10


High impact information on CAPN10


Chemical compound and disease context of CAPN10

  • No significant associations between CAPN10 SNP-43 and obesity were seen, neither in the case control study nor in the transmission disequilibrium test, but obese subjects homozygous for the SNP-43 G allele had significantly elevated triglyceride levels compared with subjects carrying the A allele [1.7 (1.1-2.4) vs. 1.4 (1.0-2.0); P = 0.03] [2].

Biological context of CAPN10


Anatomical context of CAPN10

  • CAPN10 mRNA expression was studied in adipose tissue biopsies from 33 of the obese subjects participating in the case control study [2].
  • The CAPN10 mRNA expression in sc fat was significantly reduced in subjects with the SNP-43 G/G genotype compared with carriers of SNP-43 G/A (G/G, 0.33 +/- 0.02, vs. G/A, 0.51 +/- 0.09; P = 0.048), and a similar trend was observed in visceral fat (G/G, 0.52 +/- 0.06, vs. G/A, 0.65 +/- 0.10; P = 0.22) [2].
  • Many investigators, but not all, have subsequently found associations between CAPN10 polymorphism and type 2 diabetes (T2D) as well as insulin action, insulin secretion, aspects of adipocyte biology and microvascular function [8].
  • Therefore, we investigated the effects of four polymorphisms in CAPN10 (single nucleotide polymorphism [SNP]-43, SNP-44, Insertion/Deletion [Indel]-19 and SNP-63) on insulin secretion, insulin action and abdominal fat distribution in offspring of patients with type 2 diabetes [9].
  • RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets [10].

Associations of CAPN10 with chemical compounds

  • No significant difference in insulin sensitivity of lipolysis was found between Gly/Gly compared with X/Arg ( IRS-1) and G/G compared with G/A + A/A ( CAPN10) (all p values > 0.15) [11].
  • The calpain-10 gene (CAPN10) has been implicated in type 2 diabetes (T2DM) susceptibility by both linkage and association in a Hispanic population from Starr County Texas. Common intronic variants seem to alter CAPN10 mRNA levels and were associated with insulin resistance but not diabetes in Pima Indians [6].
  • Variation in CAPN10, the gene encoding the ubiquitously expressed cysteine protease calpain-10, has been associated with type 2 diabetes in Mexican Americans and in two northern-European populations, from Finland and Germany. We have studied CAPN10 in white subjects of British/Irish ancestry, using both family-based and case-control studies [12].
  • MAIN OUTCOME MEASURE(S): Genotyping of the UCSNP43, UCSNP44, and UCSNP45 polymorphisms in CAPN10 and serum androgen levels [13].
  • After the elevation of intracellular calcium levels with ionomycin, calpain 10 protein levels in the nucleus of alphaTN4-1 cells increased markedly, whereas those in the cytoplasm decreased [14].

Regulatory relationships of CAPN10

  • Specific inhibition of calpain 10 by antisense expression reduced insulin-stimulated GLUT4 translocation and actin reorganization [15].

Other interactions of CAPN10


Analytical, diagnostic and therapeutic context of CAPN10

  • (1) CAPN10 is a susceptibility gene only in particular ethnic groups; (2) our study lacks power to detect the effects of CAPN10 polymorphisms (but our sample size is comparable to that of earlier reports); or (3) the underlying biological mechanism is too complex and requires further research [19].
  • The CAPN10 single-nucleotide polymorphism (SNP)-43 was genotyped using PCR followed by NdeI digestion or by allelic discrimination [2].
  • We have examined the effect of variation in CAPN10 on plasma glucose and insulin levels in a group of 285 nondiabetic British subjects after a 75-g OGTT [20].
  • Calpain 10 protein was found to be present in all tissues examined by Western blotting including the lens, retina, brain, heart, and skeletal muscle [14].
  • In the lens, immunohistochemistry revealed that calpain 10 was predominately located in the cytoplasm of epithelial and newly differentiating lens fibers at the transition zone [14].


  1. A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance. Baier, L.J., Permana, P.A., Yang, X., Pratley, R.E., Hanson, R.L., Shen, G.Q., Mott, D., Knowler, W.C., Cox, N.J., Horikawa, Y., Oda, N., Bell, G.I., Bogardus, C. J. Clin. Invest. (2000) [Pubmed]
  2. Variation in the calpain-10 gene is associated with elevated triglyceride levels and reduced adipose tissue messenger ribonucleic acid expression in obese Swedish subjects. Carlsson, E., Fredriksson, J., Groop, L., Ridderstråle, M. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  3. Specific CAPN10 gene haplotypes influence the clinical profile of polycystic ovary patients. Gonzalez, A., Abril, E., Roca, A., Aragón, M.J., Figueroa, M.J., Velarde, P., Ruiz, R., Fayez, O., Galán, J.J., Herreros, J.A., Real, L.M., Ruiz, A. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  4. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Horikawa, Y., Oda, N., Cox, N.J., Li, X., Orho-Melander, M., Hara, M., Hinokio, Y., Lindner, T.H., Mashima, H., Schwarz, P.E., del Bosque-Plata, L., Horikawa, Y., Oda, Y., Yoshiuchi, I., Colilla, S., Polonsky, K.S., Wei, S., Concannon, P., Iwasaki, N., Schulze, J., Baier, L.J., Bogardus, C., Groop, L., Boerwinkle, E., Hanis, C.L., Bell, G.I. Nat. Genet. (2000) [Pubmed]
  5. Population genetics of CAPN10 and GPR35: implications for the evolution of type 2 diabetes variants. Vander Molen, J., Frisse, L.M., Fullerton, S.M., Qian, Y., Del Bosque-Plata, L., Hudson, R.R., Di Rienzo, A. Am. J. Hum. Genet. (2005) [Pubmed]
  6. Role of calpain-10 gene variants in familial type 2 diabetes in Caucasians. Elbein, S.C., Chu, W., Ren, Q., Hemphill, C., Schay, J., Cox, N.J., Hanis, C.L., Hasstedt, S.J. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  7. Genetic and nongenetic regulation of CAPN10 mRNA expression in skeletal muscle. Carlsson, E., Poulsen, P., Storgaard, H., Almgren, P., Ling, C., Jensen, C.B., Madsbad, S., Groop, L., Vaag, A., Ridderstråle, M. Diabetes (2005) [Pubmed]
  8. Calpain-10: from genome search to function. Turner, M.D., Cassell, P.G., Hitman, G.A. Diabetes Metab. Res. Rev. (2005) [Pubmed]
  9. Common polymorphisms of calpain-10 are associated with abdominal obesity in subjects at high risk of type 2 diabetes. Pihlajamäki, J., Salmenniemi, U., Vänttinen, M., Ruotsalainen, E., Kuusisto, J., Vauhkonen, I., Kainulainen, S., Ng, M.C., Cox, N.J., Bell, G.I., Laakso, M. Diabetologia (2006) [Pubmed]
  10. RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets. Johnson, J.D., Han, Z., Otani, K., Ye, H., Zhang, Y., Wu, H., Horikawa, Y., Misler, S., Bell, G.I., Polonsky, K.S. J. Biol. Chem. (2004) [Pubmed]
  11. Insulin sensitivity of glucose disposal and lipolysis: no influence of common genetic variants in IRS-1 and CAPN10. Stumvoll, M., Wahl, H.G., Machicao, F., Häring, H. Diabetologia (2002) [Pubmed]
  12. Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom. Evans, J.C., Frayling, T.M., Cassell, P.G., Saker, P.J., Hitman, G.A., Walker, M., Levy, J.C., O'Rahilly, S., Rao, P.V., Bennett, A.J., Jones, E.C., Menzel, S., Prestwich, P., Simecek, N., Wishart, M., Dhillon, R., Fletcher, C., Millward, A., Demaine, A., Wilkin, T., Horikawa, Y., Cox, N.J., Bell, G.I., Ellard, S., McCarthy, M.I., Hattersley, A.T. Am. J. Hum. Genet. (2001) [Pubmed]
  13. Common single nucleotide polymorphisms in intron 3 of the calpain-10 gene influence hirsutism. Escobar-Morreale, H.F., Peral, B., Villuendas, G., Calvo, R.M., Sancho, J., San Millán, J.L. Fertil. Steril. (2002) [Pubmed]
  14. Characterization and expression of calpain 10. A novel ubiquitous calpain with nuclear localization. Ma, H., Fukiage, C., Kim, Y.H., Duncan, M.K., Reed, N.A., Shih, M., Azuma, M., Shearer, T.R. J. Biol. Chem. (2001) [Pubmed]
  15. Calpain facilitates GLUT4 vesicle translocation during insulin-stimulated glucose uptake in adipocytes. Paul, D.S., Harmon, A.W., Winston, C.P., Patel, Y.M. Biochem. J. (2003) [Pubmed]
  16. Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels. Sáez, M.E., Martínez-Larrad, M.T., Ramírez-Lorca, R., González-Sánchez, J.L., Zabena, C., Martinez-Calatrava, M.J., González, A., Morón, F.J., Ruiz, A., Serrano-Ríos, M. BMC Med. Genet. (2007) [Pubmed]
  17. Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population. Malecki, M.T., Moczulski, D.K., Klupa, T., Wanic, K., Cyganek, K., Frey, J., Sieradzki, J. Eur. J. Endocrinol. (2002) [Pubmed]
  18. Comment: CAPN10 alleles are associated with polycystic ovary syndrome. Gonzalez, A., Abril, E., Roca, A., Aragón, M.J., Figueroa, M.J., Velarde, P., Royo, J.L., Real, L.M., Ruiz, A. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  19. Type 2 diabetes and three calpain-10 gene polymorphisms in Samoans: no evidence of association. Tsai, H.J., Sun, G., Weeks, D.E., Kaushal, R., Wolujewicz, M., McGarvey, S.T., Tufa, J., Viali, S., Deka, R. Am. J. Hum. Genet. (2001) [Pubmed]
  20. Variation in the calpain-10 gene affects blood glucose levels in the British population. Lynn, S., Evans, J.C., White, C., Frayling, T.M., Hattersley, A.T., Turnbull, D.M., Horikawa, Y., Cox, N.J., Bell, G.I., Walker, M. Diabetes (2002) [Pubmed]
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