{"entity":{"id":"b2m","kind":"target","name":"B2M","aka":["beta-2-microglobulin","Beta-2-microglobulin"],"tldr":"B2M (Beta-2-microglobulin) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Colorectal cancer, Lung cancer and 5 more.","summary":"Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Exogenously applied M.tuberculosis EsxA or EsxA-EsxB (or EsxA expressed in host) binds B2M and decreases its export to the cell surface (total protein levels do not change), probably leading to defects in class I antigen presentation.\n\nCIViC holds 7 clinical evidence items and 0 assertions across 4 variants, naming Pembrolizumab, Nivolumab, Anti-PD-L1 Monoclonal Antibody and Immune Checkpoint Inhibitor and others. Open Targets scores its association with cancer at 0.69 (direct and indirect evidence; datatypes literature 0.98, affected pathway 0.61, genetic association 0.00, somatic mutation 0.88). IntOGen calls it a driver in 10 cohorts (4 activating, 6 loss-of-function), covering Cervical Squamous Cell Carcinoma, Diffuse Large B-Cell Lymphoma, NOS, Head and Neck Squamous Cell Carcinoma, Melanoma, Malignant Lymphoma, Non-Hodgkin Lymphoma and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:914","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:914"},{"label":"UniProt P61769","url":"https://www.uniprot.org/uniprotkb/P61769/entry"},{"label":"NCBI Gene 567","url":"https://www.ncbi.nlm.nih.gov/gene/567"},{"label":"Ensembl ENSG00000166710","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000166710"},{"label":"Sakata-Yanagimoto et al., Nat Genet 2014: somatic RHOA G17V in angioimmunoblastic T-cell lymphoma","url":"https://doi.org/10.1038/ng.2872"},{"label":"Palomero et al., Nat Genet 2014: recurrent mutations in epigenetic regulators, RHOA and FYN in peripheral T-cell lymphoma","url":"https://doi.org/10.1038/ng.2873"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["non-hodgkin-lymphoma","colorectal","lung-cancer","head-and-neck","cervical","dlbcl","melanoma","mantle-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["antigen-presentation-immunoediting","epigenetic-reprogramming","clonal-haematopoiesis"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-grasso-immune-evasion-colorectal-cancer-discov-2018"],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 5 therapies; IntOGen calls it an activating (Act) driver in 4 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 6 cohorts; CIViC holds 7 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Colorectal cancer: inactivating mutation in 3 to 7% overall but 31.0% of MSI-high against 1.5% of microsatellite-stable samples in crc_msk_2026, with biallelic B2M and HLA loss by copy-number change and copy-neutral loss of heterozygosity documented across 1,211 tumours (Grasso 2018). It is an immunoediting scar and the best available explanation for the mismatch repair deficient patients who do not respond to a checkpoint inhibitor.","Lymphoma, RHOA G17V and the epigenetic mutations of T-follicular-helper lymphoma: A single substitution, G17V, in the small GTPase RHOA produces a protein that does not bind GTP and that blocks the wild-type protein as well. It is specific to the tumour cell, whereas the TET2 mutations that accompany it are found in non-tumour haematopoietic cells too, which places the TET2 lesion earlier, in the stem cell, and makes this lymphoma a disease that grows out of clonal haematopoiesis. Frequency: RHOA G17V in 68% of angioimmunoblastic T-cell lymphoma samples, with every G17V case also carrying a TET2 mutation (Sakata-Yanagimoto 2014); independently, in 22 of 35 angioimmunoblastic cases, 67%, and 8 of 44 peripheral T-cell lymphoma not otherwise specified, 18%, alongside recurrent TET2, DNMT3A and IDH2 mutations and less frequent FYN, ATM, B2M and CD58 lesions (Palomero 2014). What it changes about treatment: Not through an approved test. The hypomethylating agents are used in this disease on the strength of the TET2 and DNMT3A biology rather than on a mutation result, and azacitidine-containing regimens have shown activity in T-follicular-helper histology specifically."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"B2M","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:914","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:914","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P61769","url":"https://www.uniprot.org/uniprotkb/P61769/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene B2M","url":"https://civicdb.org/features/537","note":"7 evidence items, 0 assertions, 4 variants; diseases: Colorectal Cancer, Melanoma, Lung Cancer, Mantle Cell Lymphoma, Diffuse Large B-cell Lymphoma and 1 more (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000166710","url":"https://platform.opentargets.org/target/ENSG00000166710/associations","note":"association with cancer (MONDO_0004992) 0.69; per-cancer scores at or above 0.5: colorectal cancer 0.56, melanoma 0.57, diffuse large B-cell lymphoma 0.67, non-Hodgkin lymphoma 0.72 (GraphQL API, CC0)"},{"label":"IntOGen B2M","url":"https://www.intogen.org/search?gene=B2M","note":"driver in 10 cohorts (Act 4, LoF 6); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA B2M: RNA low tissue specificity; high antibody staining in 7 normal tissues; highest cancer staining urothelial cancer (2 of 11 high). Distribution: 6 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Colorectal cancer, Lung cancer (all types), Head and neck squamous cell carcinoma, Cervical cancer, Skin cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (diffuse large B-cell lymphoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P61769","url":"https://www.uniprot.org/uniprotkb/P61769/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene B2M","url":"https://civicdb.org/features/537","note":"7 evidence items, 0 assertions, 4 variants; diseases: Colorectal Cancer, Melanoma, Lung Cancer, Mantle Cell Lymphoma, Diffuse Large B-cell Lymphoma and 1 more (GraphQL API, CC0)"},{"label":"IntOGen B2M","url":"https://www.intogen.org/search?gene=B2M","note":"driver in 10 cohorts (Act 4, LoF 6); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas B2M tissue","url":"https://www.proteinatlas.org/ENSG00000166710-B2M/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000166710 associations","url":"https://platform.opentargets.org/target/ENSG00000166710/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:914","ensembl":"ENSG00000166710","uniprot":"P61769","entrez":"567","firstDescribed":1973,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Cunningham B.A. et al, Biochemistry, 1973, \"The complete amino acid sequence of beta 2-microglobulin\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/4586824/","biology":"Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Exogenously applied M.tuberculosis EsxA or EsxA-EsxB (or EsxA expressed in host) binds B2M and decreases its export to the cell surface (total protein levels do not change), probably leading to defects in class I antigen presentation. Location: Secreted; Cell surface (UniProt). Locus 15q21.1 (HGNC).","whereFound":["Non-Hodgkin lymphoma: Open Targets association 0.72 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM, NHL)","Colorectal cancer: Open Targets association 0.56 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease","Lung cancer: CIViC evidence names this disease","Head and neck squamous cell carcinoma: IntOGen driver in 2 cohorts (HNSC)","Cervical cancer: IntOGen driver in 1 cohort (CESC)","Diffuse large B-cell lymphoma: Open Targets association 0.67 with diffuse large B-cell lymphoma (MONDO_0018905); CIViC evidence names this disease","Colorectal cancer: inactivating mutation or deletion (antigen presentation) 3-7%"],"targetClass":"tumor-suppressor","prevalence":[{"cancerId":"colorectal","pct":"3-7","measure":"Inactivating mutation or deletion (antigen presentation)","source":"https://www.cbioportal.org/study/summary?id=crc_msk_2026","note":"cBioPortal: 335 of 7,237, 4.6%, in crc_msk_2026; 39 of 1,134, 3.4%, in crc_msk_2017; 61 of 1,516, 4.0%, in crc_eo_2020; 24 of 534, 4.5%, plus 13 deep deletions of 592, in coadread_tcga_pan_can_atlas_2018; 44 of 619, 7.1%, in coadread_dfci_2016."}]},"route":"/targets/b2m/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"angioimmunoblastic-t-cell-lymphoma","kind":"cancer","name":"Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)","route":"/cancers/angioimmunoblastic-t-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"primary-cns-lymphoma","kind":"cancer","name":"Primary CNS lymphoma","route":"/cancers/primary-cns-lymphoma/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"},{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"}],"paper":[{"id":"paper-grasso-immune-evasion-colorectal-cancer-discov-2018","kind":"paper","name":"Genetic mechanisms of immune evasion in colorectal cancer","route":"/key-papers/paper-grasso-immune-evasion-colorectal-cancer-discov-2018/"},{"id":"paper-giannakis-genomic-correlates-immune-colorectal-cell-rep-2016","kind":"paper","name":"Genomic correlates of immune-cell infiltrates in colorectal carcinoma","route":"/key-papers/paper-giannakis-genomic-correlates-immune-colorectal-cell-rep-2016/"}]}}