Twenty-five IGKV orphons have been identified and sequenced corresponding to 5 chromosomal orphon sets: two on the short arm of chromosome 2 but outside of the main IGK locus, 12 on the long arm of chromosome 2, 5 on chromosome 22, one on chromosome 1, one on chromosome 15, and 4 outside of chromosome 2 .
If both the proximal and distal IGKV clusters are present, the total number of human IGK genes per haploid genome is 82 (107 genes, if the orphons are included) of which 37-42 are functional . If only the proximal IGKV cluster is present, the total number of genes per haploid genome is 46 (71 genes, if the orphons are included) of which 23-26 genes are functional.
The complete list of the human immunoglobulin and T cell receptor IMGT gene names (symbols) provides the IMGT definition (full name), the gene functionality, the IMGT accession number of the reference sequence, the number of alleles per gene, and Entrez Gene accession ID. The table below reports entries which concern the IGK locus or groups and are found in the OMIM and Entrez Gene genome databases, and in HUGO:
|IMGT name||IMGT definition (a)||OMIM||Entrez Gene||HUGO|
|IGK locus||Immunoglobulin kappa locus||-||-||IGK@|
|IGKJ group||Immunoglobulin kappa joining group||146970||7842||IGKJ@|
|IGKV group||Immunoglobulin kappa variable group||146980||3519||IGKV@|
(a) The locus definition is identical in IMGT, Entrez Gene and HUGO. The IMGT 'group' concept comprises genes of the major locus and of the chromosomal orphon sets, whereas the HUGO IG group symbols only refer to genes of the major locus.
Proteins encoded by the IGK locus are the immunoglobulin kappa chains. They result from the recombination (or rearrangement), at the DNA level, of two genes: IGKV and IGKJ, with deletion of the intermediary DNA to create a rearranged IGKV-J gene. The rearranged IGKV-J gene is transcribed with the IGKC gene and translated into an immunoglobulin kappa chain. Translation of the variable germline genes involved in the IGKV-J rearrangements are available at Protein displays. Compared to the germline genes, the rearranged variable genes will acquire somatic mutations during the B cell differentiation in the lymph nodes, which will considerably increase their diversity. These somatic mutations can be analysed using the IMGT/V-QUEST tool. The junctions can be analysed with IMGT/JunctionAnalysis.
Translocations in which the human IGK locus is implicated frequently result from errors of the recombinase enzyme complexe (RAG1, RAG2, ...), which is responsable of the Immunoglobulin and T cell receptor V-J and V-D-J rearrangements. IGKV or IGKJ recombination signals or isolated heptamer are observed at the breakpoints.
|||Malcolm, S., Barton, P., Murphy, C., Ferguson-Smith, M.A., Bentley, D.L. and Rabbitts, T.H. "Localization of human immunoglobulin kappa light chain variable region genes to the short arm of chromosome 2 by in situ hybridization" Proc. Natl. Acad. Sci. USA, 79, 4957-4961 (1982) PMID: 83015011|
|||Mc Bride, O.W., Hieter, P.A., Hollis, G.F., Swan, D., Otey, M.C. and Leder, P. "Chromosomal location of human kappa and lambda immunoglobulin light chain constant region genes" J. Exp. Med., 155, 1480-1490 (1982) PMID: 82169267|
|||Zachau, H.G. "The immunoglobulin kappa locus-or-what has been learned from looking closely at one-tenth of a percent of the human genome" Gene, 135, 167-173 (1993) PMID: 94102555|
|||Zachau, H.G., The Immunologist, 4, 49-54 (1996).|
|||Huber, C., Huber, E., Lautner-Rieske, A., Schable, K.F. and Zachau, H.G "The human immunoglobulin kappa locus. Characterization of the partially duplicated L regions" Eur. J. Immunol., 23, 2860-2867 (1993) PMID: 94039385|
|||Schable, K.F. and Zachau, H.G. "The variable genes of the human immunoglobulin kappa locus" Biol. Chem. Hoppe-Seyler, 374, 1001-1022 (1993) PMID: 94121783|
|||Cox, J.P., Tomlinson, I.M. and Winter, G. "A directory of human germ-line V kappa segments reveals a strong bias in their usage" Eur. J. Immunol., 24, 827-836 (1994) PMID: 94200218|
|||Schable, K.F., Thiebe, R., Flugel, A., Meindl, A. and Zachau, H.G. "The human immunoglobulin kappa locus: pseudogenes, unique and repetitive sequences" Biol. Chem. Hoppe-Seyler, 375, 189-199 (1994) PMID: 94280631|
|||Barbié, V. and Lefranc, M.-P. "IMGT Locus on Focus: The human immunoglobulin kappa variable (IGKV) genes and joining (IGKJ) segments" Exp. Clin. Immunogenet., 15, 171-183 (1998) PMID: 9813414|
|||Scaviner, D., Barbié, V., Ruiz, M. and Lefranc, M.-P. "IMGT Locus on Focus: Protein displays of the human immunoglobulin heavy, kappa and lambda variable and joining regions" Exp. Clin. Immunogenet., 16, 234-240 (1999) PMID: 10575277|
|||Hieter, P.A., Maizel, J.V. Jr. and Leder, P. "Evolution of human immunoglobulin kappa J region genes" J. Biol. Chem., 257, 1516-1522 (1982) PMID: 82120090|
|||Hieter, P.A., Max, E.E., Seidman, J.G., Maizel, J.V. Jr. and Leder, P. "Cloned human and mouse kappa immunoglobulin constant and J region genes conserve homology in functional segments" Cell, 22, 197-207 (1980) PMID: 81042304|
|||Lefranc, M.-P. "Locus maps and genomic repertoire of the human Ig genes" The Immunologist, 3, 80-87 (2000)|
|||Lefranc, M.-P. and Lefranc, G., "The immunoglobulin Factsbook" Academic Press, Hartcourt Publishers Limited, London, UK, 458 pages (2001) ISBN:012441351X|
|||Lefranc, M.-P. "Nomenclature of the human immunoglobulin genes" Curr. Prot. Immunol., A.1P.1-A.1P.37 (2000)|
|||Lefranc, M.-P. "IMGT Locus in Focus: Nomenclature of the human immunoglobulin kappa (IGK) genes", Exp. Clin. Immunogenet., 18, 161-174 (2001). PMID: 11549845|