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IGH (Immunoglobulin Heavy)

Written2000-07Marie-Paule Lefranc
IMGT, LIGM, IGH, UPR CNRS 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesIGHDY1
IGH@
Other aliasIGH@ (Immunoglobulin Heavy)
HGNC (Hugo) IGH
LocusID (NCBI) 3492
Atlas_Id 40
Location 14q32.33  [Link to chromosome band 14q32]
Location_base_pair Starts at 105535746 and ends at 106879844 bp from pter
 
  for complete Figure, see: chromosome 14, IMGT (The International ImMunoGeneTics information system ®) © Copyright 1995-2017 IMGT, IMGT is a CNRS trademark
 
  IGH (Immunoglobulin Heavy) Hybridization with Vysis LSI IGH break apart rearrangement probe (Abbott Molecular, US) showing IGH on 14q32.33 (red-green or a fused yellow signal) - Courtesy Adriana Zamecnikova.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
Note The human IGH locus is located on the chromosome 14 at band 14q32.33, at the telomeric extremity of the long arm; the orientation of the locus has been determined by the analysis of translocations, involving the IGH locus, in leukemia and lymphoma

DNA/RNA

 
  IGH
V-GENE: Green box: Functional; Yellow box: Open reading frame; Red: Pseudogene; Grey triangle: Not sequenced, not found.
D-GENE: Blue: Functional; Blue open box: Open reading frame.
J-GENE: Grey: Functional .
C-GENE: Blue: Functional; Blue dashed box: Open reading frame; Blue open box: Pseudogene.
GENES NOT RELATED: Purple open box: Pseudogene.
for complete Figure, see: locus IGH, IMGT (The International ImMunoGeneTics information system ®) © Copyright 1995-2017 IMGT, IMGT is a CNRS trademark
Description
  • The human IGH locus at 14q32.33 spans 1250 kilobases (kb). It consists of 123 to 129 IGHV genes, depending from the haplotypes, 27 IGHD segments belonging to 7 subgroups, 9 IGHJ segments, and 11 IGHC genes.
  • Eighty-two to 88 IGHV genes belong to 7 subgroups, whereas 41 pseudogenes, which are too divergent to be assigned to subgroups, have been assigned to 4 clans. Seven non-mapped IGHV genes have been described as insertion/deletion polymorphism but have not yet been precisely located.
  • The most 5' IGHV genes occupy a position very close to the chromosome 14q telomere whereas the IGHC genes are in a more centromeric position.
  • The potentiel genomic IGH repertoire is more limited since it comprises 38-46 functional IGHV genes belonging to 6 or 7 subgroups depending from the haplotypes 23 IGHD, 6 IGHJ, and 9 IGHC genes.
  • Thirty-five IGH genes have been found outside the main locus in other chromosomal localizations. These genes designated as orphons cannot contribute to the synthesis of the immunoglobulin chains, even if they have an Open Reading Frame (ORF). 9 IGHV orphons and 10 IGHD orphons have been described on chromosome 15 (15q11.2), and 16 IGHV orphons on chromosome 16 (16p11.2). In addition, one IGHC processed gene, IGHEP2 is localised on chromosome 9 (9p24.2-p24.1)
  • This is so far the only processed Ig gene described. The total number of human IGH genes per haploid genome is 170 to 176 (206 to 212 genes, if the orphons and the processed gene are included) of which 77 to 84 genes are functional. List of the human IGH genes
  • Protein

    Description
  • 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 IMGT Repertoire 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 IMGT/V-QUEST tool
  • Mutations

    Note Mutations which correspond to allelic polymorphisms of the functional germline IGHV, IGHD, IGHJ and IGHC genes are described in the IMGT database: (IMGT Repertoire>Alignments of alleles)

    Implicated in

    Note
      
    Entity Translocations which frequently result from errors of the recombinase enzyme complexe (RAG1, RAG2, etc.), 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
     
    c-Immunoglobulin genes IgH at 14q32.33, in normal cells: PAC 998D24 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
      
      
    Entity t(1;14)(p21;q32); involve IGH - BCL10 in 1p21
    Disease marginal zone B-cell lymphoma
      
      
    Entity t(3;14)(q27;q32); involve IGH -BCL6 in 3q27
    Disease B-cell non-Hodgkin lymphomas (NHL), mainly diffuse large cell lymphoma; adult aggressive lymphoma
    Prognosis controversial
      
      
    Entity t(4;14)(p16;q32); involve IGH - FGFR3 in 4p16
    Disease plasma cell leukaemia and multiple myeloma
    Prognosis yet poorly described
      
      
    Entity t(5;14)(q31;q32); involve IGH - IL3 in 5q31
    Disease B-cell acute lymphoblastic leukemia (ALL) with hypereosinophilia
    Prognosis prognosis appears to be poor
      
      
    Entity t(8;14)(q11;q32)
    Disease B-cell acute lymphoblastic leukemia (ALL); chronic myelogenous leukemia (CML)
    Prognosis still unknown
      
      
    Entity t(8;14)(q24;q32) ; involve IGH - C-MYC in 8q24
    Disease B-cell acute lymphoblastic leukemia (ALL3) and non-Hodgkin lymphomas (NHL), especially in the Burkitt lymphoma
    Prognosis the prognosis has evolved with new treatments
      
      
    Entity t(9;14)(p13;q32); involve IGH - PAX5 in 9p13
    Disease lymphoplasmatic lymphoma
      
      
    Entity t(10;14)(q24;q32); involve IGH - HOX 11 in 10q24
    Disease B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL)
    Prognosis not unfavourable
      
      
    Entity t(11;14)(q13;q32); involve IGH - BCL1 in 11q13
    Disease t(11;14) is mainly found in mantle cell lymphoma; B-prolymphocytic leukaemia, chronic lymphocytic leukaemia, splenic lymphoma with villous lymphocytes, and multiple myeloma other B-cell lymphoproliferations
      
      
    Entity t(14;18)(q32;q21); involve IGH - BCL2 in 18q21
    Disease follicle centre cell lymphoma mainly, and also diffuse large cell lyphoma; rarely in other B-cell lymphoproliferations
    Prognosis the t(14;18) may have little or no prognostic significance
      
      
    Entity t(14;19)(q32;q13.1); involve IGH - BCL3 in 19q13
    Disease chronic lymphocytic leukaemia (CLL) mainly, and other B-cell lymphoproliferations
    Prognosis t(14;19) is an adverse prognostic factor in CLL, compared to the usual prognosis in CLL
      

    Breakpoints

     

    Bibliography

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    PMID 6964396
     
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    Bensmana M, Chuchana P, Lefranc G, Lefranc MP
    Cytogenetics and cell genetics. 1991 ; 56 (2) : page 128.
    PMID 1901541
     
    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.
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    PMID 7779254
     
    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.
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    Journal of molecular biology. 1997 ; 270 (4) : 587-597.
    PMID 9245589
     
    Chromosomal location of the genes for human immunoglobulin heavy chains.
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    Proceedings of the National Academy of Sciences of the United States of America. 1979 ; 76 (7) : 3416-3419.
    PMID 114999
     
    Nucleotide sequence of a human immunoglobulin C gamma 4 gene.
    Ellison J, Buxbaum J, Hood L
    DNA (Mary Ann Liebert, Inc.). 1981 ; 1 (1) : 11-18.
    PMID 6299662
     
    Linkage and sequence homology of two human immunoglobulin gamma heavy chain constant region genes.
    Ellison J, Hood L
    Proceedings of the National Academy of Sciences of the United States of America. 1982 ; 79 (6) : 1984-1988.
    PMID 6804948
     
    The nucleotide sequence of a human immunoglobulin C gamma1 gene.
    Ellison JW, Berson BJ, Hood LE
    Nucleic acids research. 1982 ; 10 (13) : 4071-4079.
    PMID 6287432
     
    Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing gamma, epsilon and alpha genes.
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    Nature. 1982 ; 300 (5894) : 709-713.
    PMID 6817141
     
    Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C gamma genes.
    Huck S, Fort P, Crawford DH, Lefranc MP, Lefranc G
    Nucleic acids research. 1986 ; 14 (4) : 1779-1789.
    PMID 3081877
     
    A human immunoglobulin IGHG3 allele (Gmb0,b1,c3,c5,u) with an IGHG4 converted region and three hinge exons.
    Huck S, Lefranc G, Lefranc MP
    Immunogenetics. 1989 ; 30 (4) : 250-257.
    PMID 2571587
     
    Organization of human immunoglobulin heavy chain diversity gene loci.
    Ichihara Y, Matsuoka H, Kurosawa Y
    The EMBO journal. 1988 ; 7 (13) : 4141-4150.
    PMID 3243276
     
    Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes.
    Kirsch IR, Morton CC, Nakahara K, Leder P
    Science (New York, N.Y.). 1982 ; 216 (4543) : 301-303.
    PMID 6801764
     
    Nomenclature of the human immunoglobulin heavy (IGH) genes.
    Lefranc MP
    Experimental and clinical immunogenetics. 2001 ; 18 (2) : 100-116.
    PMID 11340299
     
    The Immunoglobulin FactsBook (Review)
    Lefranc MP and Lefranc G
    Academic Press, London, UK (458 pages), 2001. ISBN: 012441351X
     
    Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions.
    Lefranc MP, Lefranc G, de Lange G, Out TA, van den Broek PJ, van Nieuwkoop J, Radl J, Helal AN, Chaabani H, van Loghem E
    Molecular biology & medicine. 1983 ; 1 (2) : 207-217.
    PMID 6438434
     
    The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus.
    Matsuda F, Ishii K, Bourvagnet P, Kuma K, Hayashida H, Miyata T, Honjo T
    The Journal of experimental medicine. 1998 ; 188 (11) : 2151-2162.
    PMID 9841928
     
    Duplication and deletion in the human immunoglobulin epsilon genes.
    Max EE, Battey J, Ney R, Kirsch IR, Leder P
    Cell. 1982 ; 29 (2) : 691-699.
    PMID 6288268
     
    Localization of human variable and constant region immunoglobulin heavy chain genes on subtelomeric band q32 of chromosome 14.
    McBride OW, Battey J, Hollis GF, Swan DC, Siebenlist U, Leder P
    Nucleic acids research. 1982 ; 10 (24) : 8155-8170.
    PMID 6819544
     
    The human immunoglobulin heavy variable genes.
    Pallarès N, Lefebvre S, Contet V, Matsuda F, Lefranc MP
    Experimental and clinical immunogenetics. 1999 ; 16 (1) : 36-60.
    PMID 10087405
     
    Human immunoglobulin heavy chain genes: evolutionary comparisons of C mu, C delta and C gamma genes and associated switch sequences.
    Rabbitts TH, Forster A, Milstein CP
    Nucleic acids research. 1981 ; 9 (18) : 4509-4524.
    PMID 6795593
     
    Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes.
    Ravetch JV, Siebenlist U, Korsmeyer S, Waldmann T, Leder P
    Cell. 1981 ; 27 (3 Pt 2) : 583-591.
    PMID 6101209
     
    The human immunoglobulin heavy diversity (IGHD) and joining (IGHJ) segments.
    Ruiz M, Pallarès N, Contet V, Barbi V, Lefranc MP
    Experimental and clinical immunogenetics. 1999 ; 16 (3) : 173-184.
    PMID 10394055
     
    Protein displays of the human immunoglobulin heavy, kappa and lambda variable and joining regions.
    Scaviner D, Barbié V, Ruiz M, Lefranc MP
    Experimental and clinical immunogenetics. 1999 ; 16 (4) : 234-240.
    PMID 10575277
     
    Physical map of the 3' region of the human immunoglobulin heavy chain locus: clustering of autoantibody-related variable segments in one haplotype.
    Shin EK, Matsuda F, Nagaoka H, Fukita Y, Imai T, Yokoyama K, Soeda E, Honjo T
    The EMBO journal. 1991 ; 10 (12) : 3641-3645.
    PMID 1935893
     
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    Citation

    This paper should be referenced as such :
    Lefranc, MP
    IGH (immunoglobulin heavy)
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):107-110.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/IgHID40.html


    Other Leukemias implicated (Data extracted from papers in the Atlas)

    Leukemias ALLHypereoID1184 LymphoidLeukDownSyndromeID1784 MantleCellID2062 MultipleMyelomaID1776 PlasmacytomaID1759
    t0114q21q32ID1319 t0114q21q32ID1341 t0114q21q32ID1375 t0114q21q32MUC1ID1342 t0114q25q32LHX4ID1352
    t0214p13q32ID1231 t0314p14q32ID1398 t04142059ID2059 t0614p21q32ID1306 t0614p22q32ID1480
    t0714q21q32ID1346 t0714q21q32ID1361 t0814ID1050 t0814ID1112 t0914p13q32ID2018
    t0914q33q32ID1659 t0X14p22q32IGHCRLF2ID1769 t1014q24q32NFKB2IGHID2019 t1114ID2021 t1114MMID2054
    t1114p13q32ID1609 t1114q11q32ID1806 t1114q24q32IGHMIR125B1ID1587 t114ID2044 t1214p13q32ID1368
    t1214p13q32ID1487 t1414q11q32CEBPEIGHID1438 t1415q32q12ID1349 t1416q32q23IGH-MAFID1308 t1417q32q21IGH-IGF2BP1ID1706
    t1418ID2006 t1418q32q21ID1350 t1419ID2050 t1419q32p13ID1681 t1419q32q13ALLID1335
    t1420q32q12IGHMAFBID1313 t1420q32q13CEBPBIGHID1439 t1422q32q11ID1076 t514ID1111 t614p25q32IRF4IGHID1175
    TL_del14q24q32ID3350 TL_inv14q11q32ID1372 TL_inv14q11q32ID2815 TL_t0114p13q32ID2785 TL_t0114p35q32ID1486
    TL_t0114q21q32ID2788 TL_t0214p24q32ID2805 TL_t0214q22q32ID2816 TL_t0314q27q32ID2787 TL_t0314q27q32ID3408
    TL_t0414q35q32ID2670 TL_t0414q35q32ID2796 TL_t0514p15q32ID2812 TL_t0514q22q32ID2794 TL_t0514q33q32ID2797
    TL_t0614p25q32ID2802 TL_t0714p11q32ID2798 TL_t0714p14q32ID3437 TL_t0714q21q32ID2799 TL_t0714q21q32ID3438
    TL_t0714q31q32ID2801 TL_t0X14p22q32ID3461 TL_t1014p12q32ID2789 TL_t1114q23q32ID1364 TL_t1114q23q32ID1365
    TL_t1114q23q32ID1366 TL_t1114q23q32ID2795 TL_t1114q23q32ID2809 TL_t1114q23q32ID3475 TL_t1214p12q32ID2810
    TL_t1214q23q32ID1692 TL_t1214q23q32ID2793 TL_t1414q11q32ID2791 TL_t1414q11q32ID2814 TL_t1414q11q32ID3487
    TL_t1415q32q25ID2786 TL_t1416q32q24ID1622 TL_t1416q32q24ID1669 TL_t1416q32q24ID2790 TL_t1416q32q24ID2803
    TL_t1417q32p13ID2813 TL_t1418q32q12ID1770 TL_t1418q32q12ID2807 TL_t1418q32q21ID1075 TL_t1419q32q13ID1462
    TL_t1419q32q13ID2792 TL_t1419q32q13ID2811 TL_t1419q32q13ID3489 tX14p11q32ID1637


    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 18 ]

    Solid Tumors TT_t0114p21q32ID104179 TT_t0114p22q32ID104180 TT_t0114p22q32ID104181 TT_t0314q27q32ID105643 TT_t0614p21q32ID106925
    TT_t0914p24q32ID108315 TT_t0914p24q32ID108316 TT_t0X14p11q32ID108634 TT_t1418q32q21ID101877 TT_t1418q32q21ID101878
    TT_t1418q32q21ID101879 TT_t1418q32q21ID101880 TT_t1418q32q21ID101881 TT_t1418q32q21ID101882 TT_t1418q32q21ID101883
    TT_t1418q32q21ID101884 TT_t1418q32q21ID101885 TT_t1418q32q21ID101886


    External links

    Nomenclature
    HGNC (Hugo)IGH   5477
    Cards
    AtlasIgHID40
    Entrez_Gene (NCBI)IGH  3492  immunoglobulin heavy locus
    AliasesIGD1; IGH.1@; IGH@; IGHD@; 
    IGHDY1; IGHJ; IGHJ@; IGHV; IGHV@
    GeneCards (Weizmann)IGH
    Ensembl hg19 (Hinxton) [Gene_View]
    Ensembl hg38 (Hinxton) [Gene_View]   [Sequence]  chr14:105535746-106879844 [Contig_View]  IGH [Vega]
    TCGA cBioPortalIGH
    AceView (NCBI)IGH
    Genatlas (Paris)IGH
    WikiGenes3492
    SOURCE (Princeton)IGH
    Genetics Home Reference (NIH)IGH
    Genomic and cartography
    GoldenPath hg38 (UCSC)IGH  -     chr14:105535746-106879844 14q32.33  hg19-Feb_2009   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)IGH  -     hg19-Feb_2009   [Description]    (hg19-Feb_2009)
    GoldenPathIGH - hg19-Feb_2009 [CytoView hg19]  IGH - hg19-Feb_2009 [CytoView hg38]
    Mapping of homologs : NCBIIGH [Mapview hg19]  IGH [Mapview hg38]
    OMIM146910   147010   147070   
    Gene and transcription
    Genbank (Entrez)AK123975 AK125079 AK126352 BC066594 BX538066
    RefSeq transcript (Entrez)
    RefSeq genomic (Entrez)NC_000014 NG_001019 NT_187600
    Consensus coding sequences : CCDS (NCBI)IGH
    Cluster EST : UnigeneHs.699841 [ NCBI ]
    CGAP (NCI)Hs.699841
    Gene ExpressionIGH [ NCBI-GEO ]   IGH [ EBI - ARRAY_EXPRESS ]   IGH [ SEEK ]   IGH [ MEM ]
    Gene Expression Viewer (FireBrowse)IGH [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    BioGPS (Tissue expression)3492
    GTEX Portal (Tissue expression)IGH
    Protein : pattern, domain, 3D structure
    Domain families : Pfam (Sanger)
    Domain families : Pfam (NCBI)
    Conserved Domain (NCBI)IGH
    DMDM Disease mutations3492
    Blocks (Seattle)IGH
    IPIIPI00382678   IPI00382682   IPI00936563   
    Protein Interaction databases
    BioGRIDIGH
    STRING (EMBL)IGH
    ZODIACIGH
    Ontologies - Pathways
    Huge Navigator IGH [HugePedia]
    snp3D : Map Gene to Disease3492
    BioCentury BCIQIGH
    ClinGenIGH
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD3492
    Chemical/Pharm GKB GenePA35106
    Clinical trialIGH
    Miscellaneous
    canSAR (ICR)IGH (select the gene name)
    DataMed IndexIGH
    Other databaseIGH@ - IMGT
    Probes
    Litterature
    PubMed126 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineIGH
    EVEXIGH
    GoPubMedIGH
    iHOPIGH
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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