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Gene Review

IGKC  -  immunoglobulin kappa constant

Homo sapiens

Synonyms: HCAK1, IGKCD, Ig kappa chain C region, Km
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Disease relevance of IGKC

  • Immunoglobulin allotype markers on immunoglobulin G (Gm markers), immunoglobulin A (A2m markers), and kappa light chains (Km markers) were determined in 68 Crohn's disease patients, 39 ulcerative colitis patients, and 1027 healthy controls [1].
  • Further, there was no significant association between Km markers or A2m markers and inflammatory bowel disease [1].
  • In addition, Gm and Km phenotypes were unique risk factors (Gm 1,3,17 5,13,21 and Gm 1,17 23 21 and Km 3,3) or protective factors (Km 1,1) for the development of myositis and anti-Mi-2 autoantibodies (Gm 1,2,3,17 23 5,13,21) in adult Mestizos [2].
  • Furthermore, we have studied the expression of a construct consisting of the mutated c-myc allele, part of the bvr1 (Burkitt's variant rearranging region 1) locus, the human immunoglobulin kappa constant region, and the kappa intron enhancer after stable transfection into Burkitt's lymphoma cells [3].
  • The present study was performed to estimate the observed frequencies of the immunoglobulin heavy-chain (Gm) and light-chain (Km) allotypes among patients with early-onset periodontitis (EOP) and their effect on the IgG2 subclass responses against Actinobacillus actinomycetemcomitans Y4 and Porphyromonas gingivalis 381, respectively [4].

High impact information on IGKC

  • Analysis of the antibody-mediated VIP hydrolysis at varying concentrations of substrate suggested conformity with Michaelis-Menton kinetics (Km) [5].
  • MOPC167 catalysis displayed saturation kinetics with catalytic constant (kcat) = 0.4 min-1 and Michaelis constant (Km) = 208 microM, showed substrate specificity, and was inhibited by p-nitrophenylphosphorylcholine [6].
  • To determine whether th Km phenotype of an individual is related to his ability to make antibodies to polysaccharide antigens, we correlated the Km allotypes of 129 healthy caucasian adults with the concentrations of specific antibodies to three bacterial polysaccharide antigens after immunization [7].
  • Hypoxanthine phosphoribosyltransferase from this patient (E.S.) has been shown to be a Km mutant enzyme [8].
  • Using a combination of in vivo footprinting and site-directed mutagenesis, we have functionally characterized an enhancer located 12 kb downstream of the human immunoglobulin kappa constant-region gene [9].

Chemical compound and disease context of IGKC

  • We studied the effect a variety of hormones and chemical stimuli on the activity of low Km aldehyde dehydrogenase (ALDH) in rat H4IIEC3 hepatoma cells and ALDH activity in human HuH7 hepatoma cells [10].
  • Kinetic studies showed the presence of two isoforms of 5alpha-reductase in benign prostatic hyperplasia indicated by low and high Km isoforms for testosterone, while female breast skin tissue contained only one isoform [11].

Biological context of IGKC


Anatomical context of IGKC

  • Using pre-mortem bone marrow cells, we cloned and sequenced the cDNA for this AL protein (HCAK1) and, using DNA from post-mortem somatic tissue, we cloned and sequenced the patient's kappa germline O18-O8 donor and kappa constant region (Ckappa) gene segments [16].
  • The lymphocyte enzyme had an apparent Km congruent to 0.4 muM for cyclic AMP and Vmax congruent to 0.5 picomoles/min/10(6) cells [17].
  • Sedimentation velocity analyses indicated that the higher Km monocyte enzyme had a molecular weight near 45,000 and that the lower Km lymphocyte enzyme most likely had a molecular weight near 98,000 [17].
  • These results suggest that P450 1A2 is a low Km enzyme for 7-ethoxycoumarin O-deethylation in human liver microsome, although it has a low Vmax value than P450 2E1 [18].
  • Km mutant of acid alpha-glucosidase in a case of cardiomyopathy without signs of skeletal muscle involvement [19].

Associations of IGKC with chemical compounds

  • The apparent Km of the enzyme for uridine diphospho-GlcNAc was not significantly influenced by the nature of the glycoprotein acceptor, and it varied between 14 and 20 microM for the different glycoproteins [20].
  • Transferase I was assayed with Man alpha 1,6(Man alpha 1,3)Man alpha 1,6(Man alpha 1,3)Man beta 1,4GlcNAc beta 1, 4GlcNAc-Asn (Km 0.35 mM), and transferase II was assayed with Man alpha 1,6(GlcNAc beta 1,2Man alpha 1,3)Man beta 1,4GlcNAc beta 1,4-Glc-NAc-Asn (Km 1.0 mM), in which Asn is asparagine [20].
  • Values for Km and Vsat were determined for both viral and cellular dTK, using either deoxythymidine or IUdR as a substrate [21].
  • These isoenzymes had different Km values for UDP-galactose, N-acetylglucosamine, and Mn2+ [22].
  • MCT4 has been less well characterized but has a lower affinity for L-lactate (i.e. a higher Km of 20 mM) than does MCT1 (Km of 5 mM) [23].

Other interactions of IGKC

  • Loose linkage is possible between AKE and ACP1, IGKC, and Jk, but the estimated recombination fractions do not reach significant deviations from 0 [24].
  • Within the IGK region four probes (969D7, 316G9, 122B6 and 2575M21) have been identified covering the variable (IGKV) cluster, and one probe (1021F11) covering the IGK constant (IGKC) cluster [25].
  • Using these clones as a starting point, the expressed IGKV repertoire was sampled by anchored polymerase chain reaction using an IGKC-specific primer [26].

Analytical, diagnostic and therapeutic context of IGKC

  • The allotype of human immunoglobulin kappa light chain constant region gene (IGKC) has been identified by the serological assay or DNA typing method [27].
  • A human placental soluble "high Km" 5'-nucleotidase has been separated from "low Km" 5'-nucleotidase and nonspecific phosphatase by AMP-Sepharose affinity chromatography [14].
  • On comparing the HPLC patterns of these fragments derived from three major kappa marker (Km) types, two distinct peaks specific for the Km types were detected [28].
  • 2. Using gel filtration chromatography and 5'-AMP-Sepharose 4B affinity chromatography, it separated high Km 5'-nucleotidases from other two different soluble nucleoside 5'-phosphomonoesterase activities [29].
  • METHODS: Immunoglobulin heavy chains (Glm, G3m), Kappa light chains (Km) and allotype and phenotype frequencies were examined in 58 patients with gynecologic cancer (ovarian, cervical, endometrial, vulval, vaginal and uterine sarcoma) and a control group of 26 women [30].


  1. Association between Crohn's disease and immunoglobulin heavy chain (Gm) allotypes. Kagnoff, M.F., Brown, R.J., Schanfield, M.S. Gastroenterology (1983) [Pubmed]
  2. Differences in idiopathic inflammatory myopathy phenotypes and genotypes between Mesoamerican Mestizos and North American Caucasians: ethnogeographic influences in the genetics and clinical expression of myositis. Shamim, E.A., Rider, L.G., Pandey, J.P., O'Hanlon, T.P., Jara, L.J., Samayoa, E.A., Burgos-Vargas, R., Vazquez-Mellado, J., Alcocer-Varela, J., Salazar-Paramo, M., Kutzbach, A.G., Malley, J.D., Targoff, I.N., Garcia-De la Torre, I., Miller, F.W. Arthritis Rheum. (2002) [Pubmed]
  3. The intron enhancer of the immunoglobulin kappa gene activates c-myc but does not induce the Burkitt-specific promoter shift. Polack, A., Strobl, L., Feederle, R., Schweizer, M., Koch, E., Eick, D., Wiegand, H., Bornkamm, G.W. Oncogene (1991) [Pubmed]
  4. Immunoglobulin allotypes and immunoglobulin G subclass responses to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in early-onset periodontitis. Choi, J.I., Ha, M.H., Kim, J.H., Kim, S.J. Infect. Immun. (1996) [Pubmed]
  5. Catalytic hydrolysis of vasoactive intestinal peptide by human autoantibody. Paul, S., Volle, D.J., Beach, C.M., Johnson, D.R., Powell, M.J., Massey, R.J. Science (1989) [Pubmed]
  6. Selective chemical catalysis by an antibody. Pollack, S.J., Jacobs, J.W., Schultz, P.G. Science (1986) [Pubmed]
  7. Correlation of the Km(1) immunoglobulin allotype with anti-polysaccharide antibodies in Caucasian adults. Ambrosino, D.M., Barrus, V.A., DeLange, G.G., Siber, G.R. J. Clin. Invest. (1986) [Pubmed]
  8. Radioimmune determination of hypoxanthine phosphoribosyltransferase crossreacting material in erythrocytes of Lesch-Nyhan patients. Ghangas, G.S., Milman, G. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  9. Characterization of the human immunoglobulin kappa gene 3' enhancer: functional importance of three motifs that demonstrate B-cell-specific in vivo footprints. Judde, J.G., Max, E.E. Mol. Cell. Biol. (1992) [Pubmed]
  10. Hormonal and chemical influences on the expression of class 2 aldehyde dehydrogenases in rat H4IIEC3 and human HuH7 hepatoma cells. Crabb, D.W., Stewart, M.J., Xiao, Q. Alcohol. Clin. Exp. Res. (1995) [Pubmed]
  11. Comparative study of human steroid 5alpha-reductase isoforms in prostate and female breast skin tissues: sensitivity to inhibition by finasteride and epristeride. Ranjan, M., Diffley, P., Stephen, G., Price, D., Walton, T.J., Newton, R.P. Life Sci. (2002) [Pubmed]
  12. Residual disease in B-cell chronic lymphocytic leukemia patients and prognostic value. Lenormand, B., Bizet, M., Fruchart, C., Tilly, H., Daliphard, S., Thouret, F., Canipel, C., Callat, M.P., Piguet, H., Lefranc, M.P. Leukemia (1994) [Pubmed]
  13. Six loci mapped on to human chromosome 2p are assigned to sheep chromosome 3p. Broad, T.E., Burkin, D.J., Cambridge, L.M., Jones, C., Lewis, P.E., Morse, H.G., Geyer, D., Pearce, P.D., Ansari, H.A., Maher, D.W. Anim. Genet. (1995) [Pubmed]
  14. High Km soluble 5'-nucleotidase from human placenta. Properties and allosteric regulation by IMP and ATP. Spychała, J., Madrid-Marina, V., Fox, I.H. J. Biol. Chem. (1988) [Pubmed]
  15. Association of immunoglobulin Km and Gm allotypes with specific antinuclear antibodies and disease susceptibility among connective tissue disease patients. Hoffman, R.W., Sharp, G.C., Irvin, W.S., Anderson, S.K., Hewett, J.E., Pandey, J.P. Arthritis Rheum. (1991) [Pubmed]
  16. Identification of a novel substitution in the constant region of a gene coding for an amyloidogenic kappa1 light chain. Wally, J., Kica, G., Zhang, Y., Ericsson, T., Connors, L.H., Benson, M.D., Liepnieks, J.J., Murray, J., Skinner, M., Comenzo, R.L. Biochim. Biophys. Acta (1999) [Pubmed]
  17. Cyclic adenosine 3':5'-monophosphate phosphodiesterase. Distinct forms in human lymphocytes and monocytes. Thompson, W.J., Ross, C.P., Pledger, W.J., Strada, S.J., Banner, R.L., Hersh, E.M. J. Biol. Chem. (1976) [Pubmed]
  18. 7-Ethoxycoumarin O-deethylation catalyzed by cytochromes P450 1A2 and 2E1 in human liver microsomes. Yamazaki, H., Inoue, K., Mimura, M., Oda, Y., Guengerich, F.P., Shimada, T. Biochem. Pharmacol. (1996) [Pubmed]
  19. Km mutant of acid alpha-glucosidase in a case of cardiomyopathy without signs of skeletal muscle involvement. Suzuki, Y., Tsuji, A., Omura, K., Nakamura, G., Awa, S., Kroos, M., Reuser, A.J. Clin. Genet. (1988) [Pubmed]
  20. Purification and properties of alpha-D-mannose:beta-1,2-N-acetylglucosaminyl-transferases and alpha-D-mannosidases from human adenocarcinoma. Chandrasekaran, E.V., Davila, M., Nixon, D., Mendicino, J. Cancer Res. (1984) [Pubmed]
  21. Optimized assay for thymidine kinase and its application to the detection of antibodies against herpes simplex virus type 1- and 2-induced thymidine kinase. Gronowitz, J.S., Källander, C.F. Infect. Immun. (1980) [Pubmed]
  22. Isolation and characterization of cancer-associated galactosyltransferase isoenzyme. Ram, B.P., Munjal, D.D. Clin. Chem. (1984) [Pubmed]
  23. Lactate transport in skeletal muscle - role and regulation of the monocarboxylate transporter. Juel, C., Halestrap, A.P. J. Physiol. (Lond.) (1999) [Pubmed]
  24. A linkage study of acrokeratoelastoidosis. Possible mapping to chromosome 2. Greiner, J., Krüger, J., Palden, L., Jung, E.G., Vogel, F. Hum. Genet. (1983) [Pubmed]
  25. Detection of illegitimate rearrangements within the immunoglobulin light chain loci in B cell malignancies using end sequenced probes. Poulsen, T.S., Silahtaroglu, A.N., Gisselø, C.G., Tommerup, N., Johnsen, H.E. Leukemia (2002) [Pubmed]
  26. Marsupial light chains: IGK with four V families in the opossum Monodelphis domestica. Miller, R.D., Bergemann, E.R., Rosenberg, G.H. Immunogenetics (1999) [Pubmed]
  27. Km genotyping using polymerase chain reaction-allele specific oligonucleotide in Koreans. Park, K.S., Nam, J.H., Kim, M.Y. Mol. Cells (1997) [Pubmed]
  28. Kappa marker typing with high-performance liquid chromatography: identification of kappa marker specific tryptic peptide from the kappa light chain of immunoglobulin G. Iida, R., Yasuda, T., Nadano, D., Takeshita, H., Kishi, K. J. Chromatogr. (1993) [Pubmed]
  29. Soluble "high Km" 5'-nucleotidase activity in human T- and B-lymphoblasts: isolation and some properties. Madrid-Marina, V. Int. J. Biochem. (1990) [Pubmed]
  30. Allotypes and gynecological cancer. Hitoglou-Hadji, S., Makedos, G., Papanicolaou, A., Dozi-Vasiliadou, I. Clinical and experimental obstetrics & gynecology. (1997) [Pubmed]
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