{"entity":{"id":"myd88","kind":"target","name":"MYD88","aka":["MYD88 innate immune signal transduction adaptor","Myeloid differentiation primary response protein MyD88"],"tldr":"MYD88 (Myeloid differentiation primary response protein MyD88) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Leukaemia, Breast cancer and 4 more.","summary":"Adapter protein involved in the Toll-like receptor and IL-1 receptor signalling pathway in the innate immune response. Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Increases IL-8 transcription.\n\nCIViC holds 5 clinical evidence items and 0 assertions across 2 variants, naming Paclitaxel, Ibrutinib, IRAK-1/4 Inhibitor and IMG-2005-5. Open Targets scores its association with cancer at 0.61 (direct and indirect evidence; datatypes literature 0.98, genetic association 0.00, somatic mutation 0.95). IntOGen calls it a driver in 10 cohorts (10 activating, 0 loss-of-function), covering Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma, Diffuse Large B-Cell Lymphoma, NOS, Malignant Lymphoma, Non-Hodgkin Lymphoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:7562","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7562"},{"label":"UniProt Q99836","url":"https://www.uniprot.org/uniprotkb/Q99836/entry"},{"label":"NCBI Gene 4615","url":"https://www.ncbi.nlm.nih.gov/gene/4615"},{"label":"Ensembl ENSG00000172936","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000172936"},{"label":"Ngo et al., Nature 2011: oncogenically active MYD88 mutations in human lymphoma","url":"https://doi.org/10.1038/nature09671"},{"label":"Treon et al., N Engl J Med 2012: MYD88 L265P somatic mutation in Waldenstrom macroglobulinaemia","url":"https://doi.org/10.1056/NEJMoa1200710"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["non-hodgkin-lymphoma","leukaemia","breast-cancer","dlbcl","all-leukemia","cll","waldenstrom"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["bcr-signalling","inflammation-nfkb"],"terms":[],"trials":["nct04274738"],"people":[],"bottlenecks":[],"keyPapers":[],"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 4 therapies; IntOGen calls it an activating (Act) driver in 10 cohorts; CIViC holds 5 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.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Lymphoplasmacytic Lymphoma.","Lymphoma, MYD88 L265P and the toll-like receptor arm of NF-kB: MYD88 is the adaptor of the toll-like and interleukin-1 receptors. A single substitution at an invariant residue in the hydrophobic core of its TIR domain, L265P, makes it assemble a signalling complex with IRAK1 and IRAK4 without a receptor signal, driving NF-kB and JAK kinase activity. Activated B-cell-like lymphoma cells carrying it die when MYD88, IRAK1 or IRAK4 are knocked down, and the wild-type protein cannot rescue them, so it is a gain-of-function driver rather than a passenger (Ngo 2011). Frequency: L265P in 29% of activated B-cell-like diffuse large B-cell lymphomas, rare or absent in other subtypes and in Burkitt lymphoma, and present in 9% of MALT lymphomas (Ngo 2011). In Waldenstrom macroglobulinaemia it is close to defining: Sanger sequencing found it in 49 of 54 patients, and in 91% of all lymphoplasmacytic lymphoma including the non-IgM form, while it was absent from paired normal tissue and from healthy donor B cells (Treon 2012). What it changes about treatment: In Waldenstrom macroglobulinaemia the MYD88 and CXCR4 genotype is now part of the first-line conversation, because BTK inhibitor response differs by it. In diffuse large B-cell lymphoma it marks the MCD subtype, which is the group in which BTK inhibition added to chemoimmunotherapy has shown activity in subgroup analyses, but no licensed regimen is selected on the mutation."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"MYD88","role":["drug-target","oncogene-driver","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:7562","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7562","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q99836","url":"https://www.uniprot.org/uniprotkb/Q99836/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene MYD88","url":"https://civicdb.org/features/3742","note":"5 evidence items, 0 assertions, 2 variants; diseases: Lymphoplasmacytic Lymphoma, Breast Cancer, Diffuse Large B-cell Lymphoma, Chronic Lymphocytic Leukaemia (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000172936","url":"https://platform.opentargets.org/target/ENSG00000172936/associations","note":"association with cancer (MONDO_0004992) 0.61; per-cancer scores at or above 0.5: acute lymphoblastic leukaemia 0.70, diffuse large B-cell lymphoma 0.72, B-cell chronic lymphocytic leukaemia 0.70, non-Hodgkin lymphoma 0.83, Waldenstrom macroglobulinemia 0.50, breast cancer 0.54 (GraphQL API, CC0)"},{"label":"IntOGen MYD88","url":"https://www.intogen.org/search?gene=MYD88","note":"driver in 10 cohorts (Act 10, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"few-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance); 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 MYD88: RNA low tissue specificity; high antibody staining in 32 normal tissues; highest cancer staining thyroid cancer (3 of 4 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Leukaemia, Breast cancer (all types)); Open Targets associates it with 3 specific cancer types at or above 0.5 (B-cell chronic lymphocytic leukemia, diffuse large B-cell lymphoma, lymphoid leukemia). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt Q99836","url":"https://www.uniprot.org/uniprotkb/Q99836/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene MYD88","url":"https://civicdb.org/features/3742","note":"5 evidence items, 0 assertions, 2 variants; diseases: Lymphoplasmacytic Lymphoma, Breast Cancer, Diffuse Large B-cell Lymphoma, Chronic Lymphocytic Leukaemia (GraphQL API, CC0)"},{"label":"IntOGen MYD88","url":"https://www.intogen.org/search?gene=MYD88","note":"driver in 10 cohorts (Act 10, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas MYD88 tissue","url":"https://www.proteinatlas.org/ENSG00000172936-MYD88/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000172936 associations","url":"https://platform.opentargets.org/target/ENSG00000172936/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7562","ensembl":"ENSG00000172936","uniprot":"Q99836","entrez":"4615","firstDescribed":1996,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Hardiman et al, Oncogene, 1996, \"Molecular characterization and modular analysis of human MyD88\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8957090/","biology":"Adapter protein involved in the Toll-like receptor and IL-1 receptor signalling pathway in the innate immune response. Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Increases IL-8 transcription. Involved in IL-18-mediated signalling pathway. Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. Upon TLR8 activation by GU-rich single-stranded RNA (GU-rich RNA) derived from viruses such as SARS-CoV-2, SARS-CoV and HIV-1, induces IL1B release through NLRP3 inflammasome activation. Location: Cytoplasm; Nucleus (UniProt). Locus 3p22.2 (HGNC).","whereFound":["Non-Hodgkin lymphoma: Open Targets association 0.83 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM, NHL)","Leukaemia: Open Targets association 0.74 with leukaemia (MONDO_0005059)","Breast cancer: Open Targets association 0.54 with breast cancer (MONDO_0007254); CIViC evidence names this disease","Diffuse large B-cell lymphoma: Open Targets association 0.72 with diffuse large B-cell lymphoma (MONDO_0018905); CIViC evidence names this disease","Acute lymphoblastic leukaemia: Open Targets association 0.70 with acute lymphoblastic leukaemia (MONDO_0004967)","Chronic lymphocytic leukaemia: Open Targets association 0.70 with B-cell chronic lymphocytic leukaemia (MONDO_0004948); CIViC evidence names this disease"],"targetClass":"oncogene","prevalence":[]},"route":"/targets/myd88/","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":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"malt-lymphoma","kind":"cancer","name":"Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)","route":"/cancers/malt-lymphoma/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-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/"},{"id":"waldenstrom","kind":"cancer","name":"Waldenström macroglobulinaemia","route":"/cancers/waldenstrom/"}],"pathway":[{"id":"bcr-signalling","kind":"pathway","name":"B-cell receptor / BTK signalling (to NF-κB)","route":"/pathways/bcr-signalling/"},{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","route":"/pathways/inflammation-nfkb/"}],"trial":[{"id":"nct04274738","kind":"trial","name":"A Study of Mavorixafor in Combination With Ibrutinib in Participants With Waldenstrom's Macroglobulinemia (WM) Whose Tumors Express Mutations in MYD88 and CXCR4","route":"/trials/nct04274738/"}],"term":[{"id":"cell-of-origin","kind":"term","name":"Cell of origin (GCB vs ABC)","route":"/terms/cell-of-origin/"},{"id":"lymphoma-bio-cell-of-origin-in-practice","kind":"term","name":"Cell of origin in practice: Hans against expression profiling, and what it changes","route":"/terms/lymphoma-bio-cell-of-origin-in-practice/"},{"id":"lymphoma-bio-lymphgen","kind":"term","name":"LymphGen and the genetic clusters of large B-cell lymphoma","route":"/terms/lymphoma-bio-lymphgen/"},{"id":"myd88-l265p","kind":"term","name":"MYD88 L265P and CXCR4 mutations","route":"/terms/myd88-l265p/"}],"biomarker":[{"id":"cd79b-itam-mutation","kind":"biomarker","name":"CD79B ITAM mutation","route":"/biomarkers/cd79b-itam-mutation/"}],"paper":[{"id":"paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020","kind":"paper","name":"A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications","route":"/key-papers/paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020/"},{"id":"paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018","kind":"paper","name":"Genetics and pathogenesis of diffuse large B-cell lymphoma","route":"/key-papers/paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018/"},{"id":"paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018","kind":"paper","name":"Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes","route":"/key-papers/paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}],"idea":[{"id":"lymphoma-ev-genetic-subtype-directed-first-line","kind":"idea","name":"Assign first-line treatment in diffuse large B-cell lymphoma by genetic subtype, not by a three-antibody stain","route":"/ideas/lymphoma-ev-genetic-subtype-directed-first-line/"}]}}