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

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    69643961982A processed human immunoglobulin epsilon gene has moved to chromosome 9.Battey J et al
    19015411991Sequence of the CH1 and hinge-CH2 exons of the human immunoglobulin IGHA2 A2m(2) allele: comparison with the nonallelic and allelic IGHA genes.Bensmana M et al
    31381121988The 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.Buluwela L et al
    77792541995The human immunoglobulin VH repertoire.Cook GP et al
    92455891997Sequence 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.Corbett SJ et al
    1149991979Chromosomal location of the genes for human immunoglobulin heavy chains.Croce CM et al
    62996621981Nucleotide sequence of a human immunoglobulin C gamma 4 gene.Ellison J et al
    68049481982Linkage and sequence homology of two human immunoglobulin gamma heavy chain constant region genes.Ellison J et al
    62874321982The nucleotide sequence of a human immunoglobulin C gamma1 gene.Ellison JW et al
    68171411982Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing gamma, epsilon and alpha genes.Flanagan JG et al
    30818771986Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C gamma genes.Huck S et al
    25715871989A human immunoglobulin IGHG3 allele (Gmb0,b1,c3,c5,u) with an IGHG4 converted region and three hinge exons.Huck S et al
    32432761988Organization of human immunoglobulin heavy chain diversity gene loci.Ichihara Y et al
    68017641982Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes.Kirsch IR et al
    113402992001Nomenclature of the human immunoglobulin heavy (IGH) genes.Lefranc MP et al
    64384341983Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions.Lefranc MP et al
    98419281998The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus.Matsuda F et al
    62882681982Duplication and deletion in the human immunoglobulin epsilon genes.Max EE et al
    68195441982Localization of human variable and constant region immunoglobulin heavy chain genes on subtelomeric band q32 of chromosome 14.McBride OW et al
    100874051999The human immunoglobulin heavy variable genes.Pallarès N et al
    67955931981Human immunoglobulin heavy chain genes: evolutionary comparisons of C mu, C delta and C gamma genes and associated switch sequences.Rabbitts TH et al
    61012091981Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes.Ravetch JV et al
    103940551999The human immunoglobulin heavy diversity (IGHD) and joining (IGHJ) segments.Ruiz M et al
    105752771999Protein displays of the human immunoglobulin heavy, kappa and lambda variable and joining regions.Scaviner D et al
    19358931991Physical map of the 3' region of the human immunoglobulin heavy chain locus: clustering of autoantibody-related variable segments in one haplotype.Shin EK et al
    39220541985Human immunoglobulin D: genomic sequence of the delta heavy chain.White MB et al

    Other Information

    Locus ID:

    NCBI: 3492
    MIM: 147070
    HGNC: 5477

    Variants:

    dbSNP: 3492
    ClinVar: 3492
    COSMIC: IGH

    References

    Pubmed IDYearTitleCitations
    379857222024IGH repertoire analysis at scale: deciphering the complexity of B cell infiltration and migration in esophageal squamous cell carcinoma.0
    379857222024IGH repertoire analysis at scale: deciphering the complexity of B cell infiltration and migration in esophageal squamous cell carcinoma.0
    361139672023IGH cytogenetic abnormalities can be detected in multiple myeloma by imaging flow cytometry.0
    367981242023Analysis of IGH allele content in a sample group of rheumatoid arthritis patients demonstrates unrevealed population heterogeneity.1
    370855142023Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells.8
    371436512023Insights into IGH clonal evolution in BCP-ALL: frequency, mechanisms, associations, and diagnostic implications.2
    376787462023Unique repetitive nucleic acid structures mirror switch regions in the human IgH locus.0
    361139672023IGH cytogenetic abnormalities can be detected in multiple myeloma by imaging flow cytometry.0
    367981242023Analysis of IGH allele content in a sample group of rheumatoid arthritis patients demonstrates unrevealed population heterogeneity.1
    370855142023Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells.8
    371436512023Insights into IGH clonal evolution in BCP-ALL: frequency, mechanisms, associations, and diagnostic implications.2
    376787462023Unique repetitive nucleic acid structures mirror switch regions in the human IgH locus.0
    346240892022Oncogenic role of the SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2+ diffuse large B-cell lymphomas.12
    348400902022Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With Secondary Acquisition of t(11;14)(q13;q32)/CCND1-IGH: A Rare Variant Of Richter Transformation to Mantle Cell Lymphoma.1
    356143182022Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: the 2022 update of the recommendations by ERIC, the European Research Initiative on CLL.28

    Citation

    Marie-Paule Lefranc

    IGH (Immunoglobulin Heavy)

    Atlas Genet Cytogenet Oncol Haematol. 2000-07-01

    Online version: http://atlasgeneticsoncology.org/gene/40/igh-(immunoglobulin-heavy)