Beta-2 microglobulin

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Available structures
PDBOrtholog search: PDBe RCSB
AliasesB2M, entrez:567, IMD43, beta-2-microglobulin, Β2 microglobulin
External IDsOMIM: 109700 MGI: 88127 HomoloGene: 2987 GeneCards: B2M
Gene location (Human)
Chromosome 15 (human)
Chr.Chromosome 15 (human)[1]
Chromosome 15 (human)
Genomic location for B2M
Genomic location for B2M
Band15q21.1Start44,711,487 bp[1]
End44,718,877 bp[1]
RNA expression pattern
PBB GE B2M 201891 s at fs.png

PBB GE B2M 216231 s at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 15: 44.71 – 44.72 MbChr 2: 122.15 – 122.15 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

β2 microglobulin also known as B2M is a component of MHC class I molecules, MHC class I molecules have α1, α2, and α3 proteins which are present on all nucleated cells (excludes red blood cells).[5][6] In humans, the β2 microglobulin protein[7] is encoded by the B2M gene.[6][8]

Structure and function[edit]

Schematic representation of MHC class I

β2 microglobulin lies beside the α3 chain on the cell surface. Unlike α3, β2 has no transmembrane region. Directly above β2 (that is, further away from the cell) lies the α1 chain, which itself is next to the α2.

β2 microglobulin associates not only with the alpha chain of MHC class I molecules, but also with class I-like molecules such as CD1 and Qa.

An additional function is association with the HFE protein, together regulating the expression of hepcidin in the liver which targets the iron transporter ferroportin on the basolateral membrane of enterocytes and cell membrane of macrophages for degradation resulting in decreased iron uptake from food and decreased iron release from recycled red blood cells in the MPS (mononuclear phagocyte system) respectively. Loss of this function causes iron excess and hemochromatosis.[9]

Mice models deficient for the β2 microglobulin gene have been engineered. These mice demonstrate that β2 microglobulin is necessary for cell surface expression of MHC class I and stability of the peptide binding groove. In fact, in the absence of β2 microglobulin, very limited amounts of MHC class I (classical and non-classical) molecules can be detected on the surface. In the absence of MHC class I, CD8 T cells cannot develop. (CD8 T cells are a subset of T cells involved in the development of acquired immunity.)[citation needed]

Clinical significance[edit]

In patients on long-term hemodialysis, it can aggregate into amyloid fibers that deposit in joint spaces, a disease, known as dialysis-related amyloidosis.

Low levels of β2 microglobulin can indicate non-progression of HIV.[citation needed]

Levels of β2 microglobulin can be elevated in multiple myeloma and lymphoma, though in these cases primary amyloidosis (amyloid light chain) and secondary amyloidosis (amyloid associated protein) are more common.[clarification needed] The normal value of β2 microglobulin is < 2 mg/L.[10] However, with respect to multiple myeloma, the levels of β2 microglobulin may also be at the other end of the spectrum.[clarification needed] Diagnostic testing for multiple myeloma includes obtaining the β2 microglobulin level, for this level is an important prognostic indicator. As of 2011, a patient with a level < 4 mg/L is expected to have a median survival of 43 months, while one with a level > 4 mg/L has a median survival of only 12 months.[11] β2 microglobulin levels cannot, however, distinguish between monoclonal gammopathy of undetermined significance (MGUS), which has a better prognosis, and smouldering (low grade) myeloma.[12][13]

Loss-of-function mutations in this gene have been reported in cancer patients unresponsive to immunotherapies.[citation needed]


  1. ^ a b c ENSG00000273686 GRCh38: Ensembl release 89: ENSG00000166710, ENSG00000273686 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000060802 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: Beta-2-microglobulin".
  6. ^ a b Güssow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, Ploegh HL (November 1987). "The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit". Journal of Immunology. 139 (9): 3132–8. PMID 3312414.
  7. ^ Cunningham BA, Wang JL, Berggård I, Peterson PA (November 1973). "The complete amino acid sequence of beta 2-microglobulin". Biochemistry. 12 (24): 4811–22. doi:10.1021/bi00748a001. PMID 4586824.
  8. ^ Suggs SV, Wallace RB, Hirose T, Kawashima EH, Itakura K (November 1981). "Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin". Proceedings of the National Academy of Sciences of the United States of America. 78 (11): 6613–7. Bibcode:1981PNAS...78.6613S. doi:10.1073/pnas.78.11.6613. PMC 349099. PMID 6171820.
  9. ^ Hundall SD (2011). "Chapter 3: Iron, Heme, and Hemoglobin". Hematology: A Pathophysiologic Approach (1st ed.). pp. 17–25. ISBN 978-0-323-04311-3.
  10. ^ Pignone M, Nicoll D; McPhee SJ (2004). Pocket guide to diagnostic tests (4th ed.). New York: McGraw-Hill. pp. 191. ISBN 0-07-141184-4.
  11. ^ Munshi NC, Longo DL, Anderson KC (2011). "Chapter 111: Plasma Cell Disorders". In Loscalzo J, Longo DL, Fauci AS, Dennis LK, Hauser SL (eds.). Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill Professional. pp. 936–44. ISBN 978-0-07-174889-6.
  12. ^ Rajkumar SV (2005). "MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management". Hematology. American Society of Hematology. Education Program. 2005: 340–5. doi:10.1182/asheducation-2005.1.340. PMID 16304401.
  13. ^ Bataille R, Klein B (November 1992). "Serum levels of beta 2 microglobulin and interleukin-6 to differentiate monoclonal gammopathy of undetermined significance". Blood. 80 (9): 2433–4. doi:10.1182/blood.V80.9.2433.2433. PMID 1421418.

Further reading[edit]

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