IGH (Immunoglobulin Heavy)

2000-07-01   Marie-Paule Lefranc 

IMGT, LIGM, IGH, UPR CNRS 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France

Identity

HGNC
IGH
LOCATION
14q32.33
IMAGE
Atlas Image
LEGEND
for complete Figure, see: chromosome 14, IMGT (The International ImMunoGeneTics information system ®) © Copyright 1995-2017 IMGT, IMGT is a CNRS trademark
IMAGE
Atlas Image
LEGEND
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.
LOCUSID
3492
ALIAS
IGD1,IGH.1@,IGH@,IGHD@,IGHDY1,IGHJ,IGHJ@,IGHV,IGHV@

DNA/RNA

Atlas Image
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

    • 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

    Entity name
    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
    Atlas Image
    c-Immunoglobulin genes IgH at 14q32.33, in normal cells: PAC 998D24 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
    Entity name
    t(1;14)(p21;q32); involve IGH - BCL10 in 1p21
    Disease
    marginal zone B-cell lymphoma
    Entity name
    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 name
    t(4;14)(p16;q32); involve IGH - FGFR3 in 4p16
    Disease
    plasma cell leukaemia and multiple myeloma
    Prognosis
    yet poorly described
    Entity name
    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 name
    t(8;14)(q11;q32)
    Disease
    B-cell acute lymphoblastic leukemia (ALL); chronic myelogenous leukemia (CML)
    Prognosis
    still unknown
    Entity name
    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 name
    t(9;14)(p13;q32); involve IGH - PAX5 in 9p13
    Disease
    lymphoplasmatic lymphoma
    Entity name
    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 name
    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 name
    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 name
    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

    Atlas Image

    Bibliography

    Pubmed IDLast YearTitleAuthors

    Other Information

    Locus ID:

    NCBI: 3492
    MIM: 147070
    HGNC: 5477

    Variants:

    dbSNP: 3492
    ClinVar: 3492
    COSMIC: IGH

    References

    Pubmed IDYearTitleCitations
    157037842005T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma.65
    229157602012Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features.54
    214871092011Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults.45
    204710302010Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkers candidates for schizophrenia.42
    205116622010Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation.38
    121145432002Internal IgH class switch region deletions are position-independent and enhanced by AID expression.35
    233036722013High-affinity IgG antibodies develop naturally in Ig-knockout rats carrying germline human IgH/Igκ/Igλ loci bearing the rat CH region.28
    215493112011Direct interactions of OCA-B and TFII-I regulate immunoglobulin heavy-chain gene transcription by facilitating enhancer-promoter communication.26
    247115572014IGH@ translocations are prevalent in teenagers and young adults with acute lymphoblastic leukemia and are associated with a poor outcome.23
    123704272002The origin of a developmentally regulated Igh replicon is located near the border of regulatory domains for Igh replication and expression.22

    Citation

    Marie-Paule Lefranc

    IGH (Immunoglobulin Heavy)

    Atlas Genet Cytogenet Oncol Haematol. 2000-07-01

    Online version: http://atlasgeneticsoncology.org/gene/40/img/logo-atlas-4.svg