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The Immunoglobulin FactsBook



The human IGH locus is located on the chromosome 14 [1], at band 14q32.33, at the telomeric extremity of the long arm [2,3]. One processed gene has been localized on chromosome 9, and IGH orphons have been identified on chromosomes 15 and 16. The total number of IGH genes per haploid genome is 170 to 176 depending from the haplotypes (206 to 212, if the orphons and the processed gene are included) of which 77 to 84 genes are functional [4-6].

The list of human IGH genes is available at IMGT/GENE-DB.

Human IGH locus at 14q32.33

Orphons and processed gene

Thirty-five IGH genes have been found outside the main locus in other chromosomal localizations corresponding to 4 chromosomal orphon sets. These genes designated as orphons cannot contribute to the synthesis of the immunoglobulin chains, even if they have an Open Reading Frame (ORF). Nine IGHV orphons and 10 IGHD orphons have been described on chromosome 15 (15q11.2), and 16 IGHV orphons on chromosome 16 (16p11.2) [12,13]. In addition, one IGHC processed gene, IGHEP2 is localized on chromosome 9 (9p24.2-p24.1) [46]. This is so far the only processed Ig gene described.

Total number of human IGH genes

The total number of human IGH genes per haploid genome is 170 to 176 depending from the haplotypes (206 to 212, if the orphons and the processed gene are included) of which 76 to 84 genes are functional [47].

IG and TR number of genes: Human
Nomenclature and overview of the human immunoglobulin genes (IMGT Education)


IGHV gene nomenclature

IMGT and HUGO gene nomenclatures

Links between IMGT, HGNC and NCBI Gene

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 the and NCBI Gene accession ID. The table below reports entries which concern the IGH locus or groups and are found in the OMIM and NCBI Gene genome databases, and in HGNC:

IMGT name IMGT definition (a) OMIM NCBI Gene HGNC
IGH locus Immunoglobulin heavy locus - 3492 IGH
IGHC group Immunoglobulin heavy constant group (b) (b) (b)
IGHD group Immunoglobulin heavy diversity group 146910 50648 IGHD
IGHJ group Immunoglobulin heavy joining group 147010 3506 IGHJ
IGHV group Immunoglobulin heavy variable group 147070 3509 IGHV

(a) The locus definition is identical in IMGT, HGNC and NCBI Gene. The IMGT 'group' concept comprises genes of the major locus and of the chromosomal orphon sets, whereas the HGNC IG group symbols only refer to genes of the major locus.

(b) There is no entry for the IGHC group in the OMIM, NCBI Gene database and HGNC. The individual OMIM entries for the IGHC genes are the following: IGHA1: 146900, IGHA2: 147000, IGHD: 147170, IGHE: 147180, IGHG1: 147100, IGHG2: 147110, IGHG3: 147120, IGHG4: 147130, IGHM: 147020. Individual NCBI Gene entries are reported in the complete gene name list. HGNC symbols for the IGHC genes are identical to IMGT gene names.


Proteins encoded by the IGH locus are the immunoglobulin heavy chains. They result from the recombination (or rearrangement), at the DNA level, of three genes: IGHV, IGHD and IGHJ, with deletion of the intermediary DNA to create a rearranged IGHV-D-J gene. The rearranged IGHV-D-J gene is transcribed with the IGHM gene and translated into an immunoglobulin mu chain. The gamma, alpha or epsilon heavy chains, result from a new recombination (or switch), again at the DNA level, between sequences designated as "Switch" and localized upstream of the IGHM and of each of the functional IGHG, IGHA and IGHE constant genes. This recombination, accompanied by the deletion of the intermediary DNA, allows the IGHV-D-J initially transcribed with the IGHM, to be now transcribed with a IGHG, IGHA or IGHE gene, and translated into a gamma, alpha or epsilon chain. Translation of the variable germline genes involved in the IGHV-D-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.

Alleles and mutation

Mutations which correspond to allelic polymorphisms of the functional germline IGHV, IGHD, IGHJ and IGHC genes are described in Alignments of alleles [47] and Tables of alleles.


Translocations in which the human IGH locus is implicated frequently result from errors of the recombinase enzyme complexe (RAG1, RAG2, ...), responsable of the Immunoglobulin and T cell receptor V-J and V-D-J rearrangements, or from errors of the switch enzyme. IGHV, IGHD or IGHJ recombination signals or isolated heptamer (first case) or switch sequences (second case) are observed at the breakpoints.


[1] Croce, C.M., Shander, M., Martinis, J., Cicurel, L., D'Ancona, G.G., Dolby, T.W. and Koprowski, H. "Chromosomal location of the genes for human immunoglobulin heavy chains" Proc. Natl. Acad. Sci. USA, 76, 3416-3419 (1979) PMID: 80034895
[2] Kirsch, I.R., Morton, C.C., Nakahara, K. and Leder, P. "Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes" Science, 216, 301-303 (1982) PMID: 82152814
[3] Mc Bride, O.W., Battey, J., Hollis, G.F., Swan, D.C., Siebenlist, U. and Leder, P. "Localization of human variable and constant region immunoglobulin heavy chain genes on subtelomeric band q32 of chromosome 14" Nucl. Acids Res., 10, 8155-8170 (1982) PMID: 83143283
[4] Lefranc, M.-P. "Locus maps and genomic repertoire of the human Ig genes" The Immunologist, 3, 80-87 (2000)
[5] Lefranc, M.-P. "Nomenclature of the human immunoglobulin genes" Curr. Prot. Immunol., A.1P.1-A.1P.37 (2000)
[6] Lefranc, M.-P. "IMGT Locus in Focus: Nomenclature of the human immunoglobulin heavy (IGH) genes" Exp. Clin. Immunogenet., 18, 100-116 (2001) PMID: 11340299 pdf
[7] Shin, E.K., Matsuda, F., Nagaoka, H., Fukita, Y., Imai, T., Kokoyama, K., Soeda, E., Honjo, T. "Physical map of the 3' region of the human immunoglobulin heavy chain locus: clustering of autoantibody-related variable segments in one haplotype" EMBO J., 10, 3641-3645 (1991) PMID: 92037524
[8] Matsuda, F., Shin, E.K., Nagaoka, H., Matsumura, R., Haino, M., Fukita, Y., Taka-ishi, S., Imai, T., Riley, J.H., Anand, R. et al. "Structure and physical map of 64 variable segments in the 3' 0.8-megabase region of the human immunoglobulin heavy-chain locus" Nature Genetics, 3, 88-94 (1993) PMID: 93258414
[9] Cook, G.P., Tomlinson, I.M., Walter, G., Riethman, H., Carter, N.P., Buluwela, L., Winter, G., Rabbitts, T.H. "A map of the human immunoglobulin VH locus completed by analysis of the telomeric region of chromosome 14q" Nature Genetics, 7, 162-168 (1994) PMID: 95004581
[10] Cook, G.P. and Tomlinson, I.M. "The human immunoglobulin VH repertoire" Immunology to-day, 16, 237-242 (1995) PMID: 95298183
[11] Matsuda, F., Ishii, K., Bourvagnet, P., Kuma, Ki, Hayashida, H., Miyata, T. and Honjo, T. "The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus" J. Exp. Med., 188, 2151-2162 (1998) PMID: 99059838
[12] Matsuda, F. and Honjo, T. "The human immunoglobulin VH locus" The Immunologist, 7, 171-176 (1999)
[13] Pallarès, N., Lefebvre, S., Contet, V., Matsuda, F. and Lefranc, M.-P. "IMGT Locus on Focus: The human immunoglobulin heavy variable (IGHV) genes" Exp. Clin. Immunogenet., 16, 36-60 (1999) PMID: 10087405 pdf
[14] 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 pdf
[15] Siebenlist, U., Ravetch, J.V., Korsmeyer, S., Waldmann, T. and Leder, P. "Human immunoglobulin D segments encoded in tandem multigenic families" Nature, 294, 631-635 (1981) PMID: 82080701
[16] Buluwela, L., Albertson, D.G., Sherrington, P., Rabbitts, P.H., Spurr, N. and Rabbitts, T.H. "The use of chromosomal translocations to study human immunoglobulin gene organization: mapping DH segments within 35 kb of the C mu gene and identification of a new DH locus" EMBO J., 7, 2003-2010 (1988) PMID: 88328988
[17] Ichihara, Y., Matsuoka, H. and Kurosawa, Y. "Organization of human immunoglobulin heavy chain diversity gene loci" EMBO J., 7, 4141-4150 (1988) PMID: 89210798
[18] Corbett, S.J., Tomlinson, I.M., Sonnhammer, E.L.L., Buck, D. and Winter, G. "Sequence of the human immunoglobulin diversity (D) segment locus: a systematic analysis provides no evidence for the use of DIR segments, inverted D segments, "minor" D segments or D-D recombination" J. Mol. Biol., 270, 587-597 (1997) PMID: 97392804
[19] Ruiz, M., Pallarès, N., Contet, V., Barbiè, V. and Lefranc M.-P. "IMGT Locus on Focus: The human immunoglobulin heavy diversity (IGHD) and joining (IGHJ) segments" Exp. Clin. Immunogenet., 16, 173-184 (1999) PMID: 10394055 pdf
[20] Ravetch, J.V., Siebenlist, U., Korsmeyer, S., Waldmann, T. and Leder, P. "Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes" Cell, 27, 583-591 (1981) PMID: 93358331
[21] Flanagan, J.G. and Rabbitts, T.H. "Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing gamma, epsilon and alpha genes" Nature, 300, 709-713 (1982) PMID: 83088998
[22] Lefranc, M.-P., Lefranc, G. and Rabbitts, T.H. "Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals" Nature, 300, 760-762 (1982) PMID: 83089004
[23] Lefranc, M.-P., Lefranc, G., de Lange, G., Out, T.A., van der Broek, P.J., van Nieuwkoop, J., Radl, J., Helal, A.N., Chaabani, H., van Loghem, E. et al. "Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions" J. Mol. Biol. Med., 1, 207-217 (1983) PMID: 85060411
[24] Rabbitts, T.H., Forster, A. and Milstein, C.P. "Human immunoglobulin heavy chain genes: evolutionary comparisons of Cmu, Cdelta and Cgamma genes and associated switch sequences" Nucl. Acids Res., 9, 4509-4524 (1981) PMID: 82059479
[25] White, M.B., Shen, A.L., Word, C.J., Tucker, P.W. and Blattner, F.R. "Human immunoglobulin D: genomic sequence of the delta heavy chain" Science, 228, 733-737 (1985) PMID: 85192522
[26] Huck, S., Fort, P., Crawford, D.H., Lefranc, M.-P. and Lefranc, G. "Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C gamma genes" Nucl. Acids Res., 14, 1779-1789 (1986) PMID: 86148507
[27] Huck, S., Lefranc, G. and Lefranc, M.-P. "A human immunoglobulin IGHG3 allele (Gmb0,b1,c3,c5,u) with an IGHG4 converted region and three hinge exons" Immunogenetics, 30, 250-257 (1989) PMID: 90007613
[28] Ellison, J.W., Berson, B.J. and Hood, L.E. "The nucleotide sequence of a human immunoglobulin Cgamma1 gene" Nucl. Acids Res., 10, 4071-4079 (1982) PMID: 82274238
[29] Max, E.E., Battey, J., Ney, R., Kirsch, I.R. and Leder, P. "Duplication and deletion in the human immunoglobulin epsilon genes" Cell, 29, 691-699 (1982) PMID: 83001945
[30] Bensmana, M., Huck, S., Lefranc, G. and Lefranc, M.-P. "The human immunoglobulin pseudogamma IGHGP gene shows no major structural defect" Nucl. Acids Res., 16, 3108 (1988) PMID: 88217529
[31] Ellison, J.W. and Hood, L.E. "Linkage and sequence homology of two human immunoglobulin gamma heavy chain constant region genes" Proc. Natl. Acad. Sc. USA, 79, 1984-1988 (1982) PMID: 82197621
[32] Ellison, J.W., Buxbaum, J. and Hood, L. "Nucleotide sequence of a human immunoglobulin Cgamma4 gene" DNA, 1, 11-18 (1981) PMID: 83157104
[33] Flanagan, J.G. and Rabbitts, T.H. "The sequence of a human immunoglobulin epsilon heavy chain constant region gene, and evidence for three non-allelic genes" EMBO J., 1, 655-660 (1982) PMID: 84236029
[34] Flanagan, J.G., Lefranc, M.-P. and Rabbitts, T.H. "Mechanisms of divergence and convergence of the human immunoglobulin alpha 1 and alpha 2 constant region gene sequences" Cell, 36, 681-688 (1984) PMID: 84130179
[35] Bensmana, M., Chuchana, P., Lefranc, G. and Lefranc, M.-P. "Sequence of the CH1 and hinge-CH2 exons of the human immunoglobulin IGHA2 A2m(2) allele: comparison with the nonallelic and allelic IGHA genes" Cytogenet. Cell Genet., 56, 128 (1991) PMID: 91191891
[36] Lefranc, G., Chaabani, H., Van Loghem, E., Lefranc, M.-P., De Lange, G. and Helal, A.N. "Simultaneous absence of the human IgG1, IgG2, IgG4 and IgA1 subclasses: immunological and immunogenetical considerations" Eur. J. Immunol., 13, 240-244 (1983) PMID: 83157824
[37] Migone, N., Oliviero, S., de Lange, G., Delacroix, D.L., Boschis, D., Altruda, F., Silengo, L., DeMarchi, M. and Carbonara, A.O. "Multiple gene deletions within the human immunoglobulin heavy-chain cluster" Proc. Natl. Acad. Sci. USA, 81, 5811-5815 (1984) PMID: 85014857
[38] Lefranc, M.-P. and Lefranc, G. "Human immunoglobulin heavy-chain multigene deletions in healthy individuals" FEBS Letters, 213, 231-237 (1987) PMID: 87162487
[39] Lefranc, M.-P., Hammarstrom, L., Smith, C.I. and Lefranc, G. "Gene deletions in the human immunoglobulin heavy chain constant region locus: molecular and immunological analysis" Immunodeficiency Rev., 2, 265-281 (1991) PMID: 91283164
[40] Keyeux, G., Lefranc, G. and Lefranc, M.-P. "A multigene deletion in the human IGH constant region locus involves highly homologous hot spots of recombination" Genomics, 5, 431-441 (1989) PMID: 90129035
[41] Wiebe, V., Helal, A., Lefranc, M.-P. and Lefranc, G. "Molecular analysis of the T17 immunoglobulin CH multigene deletion (del A1-GP-G2-G4-E)" Hum. Genet., 93, 520-528 (1994) PMID: 94222416
[42] Bottaro, A., Cariota, U., DeMarchi, M. and Carbonara, A.O. "Pulsed-field electrophoresis screening for immunoglobulin heavy-chain constant-region (IGHC) multigene deletions and duplications" Am. J. Hum. Genet., 48, 745-756 (1991) PMID: 91196733
[43] Bottaro, A., Gallina, R., Brusco, A., Cariota, U., Boccazzi, C., Barilaro, M.R., Plebani, A., Ugazio, A.G., van Leeuwen A.M., DeLange, G.G. et al. "Familial clustering of IGHC deletions and duplications: functional and molecular analysis" Immunogenetics, 37, 356-363 (1993) PMID: 93154777
[44] Brusco, A., Cariota, U., Bottaro, A., Boccazzi, C., DeLange, G.G., van Leeuwen A.M., Galanello, R., Plebani, A., Ugazio, A.U., Guerra, M.G. et al. "Deletions, duplications and triplications of the IGHC region in different Italian populations" Immunodeficiency, 4, 243-244 (1993) PMID: 94221132
[45] Brusco, A., Cariota, U., Bottaro, A., Boccazzi, C., Plebani, A., Ugazio, A.G., Galanello, R., van Leeuwen A.M., DeLange, G.G., Depelchin, S. et al. "Structural and immunologic analysis of gene triplications in the Ig heavy chain constant region locus" J. Immunol., 152, 129-135 (1994) PMID: 94075815
[46] Battey, J., Max, E.E, Mc Bride, W.O., Swan, D.C. and Leder, P. "A processed human immunoglobulin epsilon gene has moved to chromosome 9" Proc. Natl. Acad. Sci. USA, 79, 5956-5960 (1982) PMID: 83299905
[47] Lefranc, M.-P. and Lefranc, G., "The immunoglobulin Factsbook" Academic Press, Hartcourt Publishers Limited, London, UK, 458 pages (2001) ISBN:012441351X
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Valérie Contet, Chantal Ginestoux