IGH (Immunoglobulin Heavy)

2000-07-01 Marie-Paule Lefranc Affiliation

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

Identity

HGNC

IGH

LOCATION

14q32.33

IMAGE

LEGEND

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

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

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

Article Bibliography

Pubmed ID	Last Year	Title	Authors
114999	1979	Chromosomal location of the genes for human immunoglobulin heavy chains.	Croce CM et al
1901541	1991	Sequence 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
1935893	1991	Physical 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
2571587	1989	A human immunoglobulin IGHG3 allele (Gmb0,b1,c3,c5,u) with an IGHG4 converted region and three hinge exons.	Huck S et al
3081877	1986	Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C gamma genes.	Huck S et al
3138112	1988	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.	Buluwela L et al
3243276	1988	Organization of human immunoglobulin heavy chain diversity gene loci.	Ichihara Y et al
3922054	1985	Human immunoglobulin D: genomic sequence of the delta heavy chain.	White MB et al
6101209	1981	Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes.	Ravetch JV et al
6287432	1982	The nucleotide sequence of a human immunoglobulin C gamma1 gene.	Ellison JW et al

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Other Information

Locus ID:

NCBI: 3492
MIM: 147070
HGNC: 5477

Variants:

dbSNP: 3492
ClinVar: 3492
COSMIC: IGH

References

Pubmed ID	Year	Title	Citations
34624089	2022	Oncogenic role of the SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2+ diffuse large B-cell lymphomas.	12
34840090	2022	Chronic 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
35614318	2022	Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: the 2022 update of the recommendations by ERIC, the European Research Initiative on CLL.	28
36113967	2023	IGH cytogenetic abnormalities can be detected in multiple myeloma by imaging flow cytometry.	0
36113967	2023	IGH cytogenetic abnormalities can be detected in multiple myeloma by imaging flow cytometry.	0
36798124	2023	Analysis of IGH allele content in a sample group of rheumatoid arthritis patients demonstrates unrevealed population heterogeneity.	1
36798124	2023	Analysis of IGH allele content in a sample group of rheumatoid arthritis patients demonstrates unrevealed population heterogeneity.	1
37085514	2023	Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells.	8
37085514	2023	Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells.	8
37143651	2023	Insights into IGH clonal evolution in BCP-ALL: frequency, mechanisms, associations, and diagnostic implications.	2

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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)