Gene Detail

Gene Symbol MYD88
Synonyms MYD88D
Gene Description MYD88, myeloid differentiation primary response protein, is an adapter protein involved in Toll-like receptor and IL-1 signaling in the immune response, cytokine secretion, and inflammatory response (PMID: 19506249, PMID: 30086464). MYD88 mutations are frequently identified in hematological malignancies (PMID: 25132836, PMID: 29703722), including B-cell non-hodgkin lymphomas (PMID: 30203262).
Entrez Id 4615
Chromosome 3
Map Location 3p22.2
Canonical Transcript NM_002468

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
V217F missense gain of function - predicted MYD88 V217F lies within the TIR domain of the Myd88 protein (UniProt.org). V217F is predicted to confer a gain of function to the Myd88 protein, as indicated by increased NF-kappaB signaling in culture (PMID: 25359991).
N278Y missense loss of function - predicted MYD88 N278Y lies within the TIR domain of the Myd88 protein (UniProt.org). N278Y is predicted to confer a loss of function to the Myd88 protein as demonstrated by loss of binding to Mal in cell culture (PMID: 26876098).
P245S missense loss of function - predicted MYD88 P245S lies within the TIR domain of the Myd88 protein (UniProt.org). P245S is predicted to confer a loss of function to the Myd88 protein as demonstrated by loss of binding to Mal in cell culture (PMID: 26876098).
P279L missense loss of function - predicted MYD88 P279L lies within the TIR domain of the Myd88 protein (UniProt.org). P279L is predicted to confer a loss of function to the Myd88 protein as demonstrated by loss of binding to Mal in cell culture (PMID: 26876098).
F270S missense loss of function - predicted MYD88 F270S lies within the TIR domain of the Myd88 protein (UniProt.org). F270S is predicted to confer a loss of function to the Myd88 protein as demonstrated by loss of binding to Mal in cell culture (PMID: 26876098).
E104Q missense unknown MYD88 E104Q lies within the Death domain of the Myd88 protein (UniProt.org). E104Q has not been characterized in the scientific literature and therefore, its effect on Myd88 protein function is unknown (PubMed, Feb 2019).
over exp none no effect MYD88 over exp indicates an over expression of the Myd88 protein and/or mRNA. However, the mechanism causing the over expression is unspecified.
mutant unknown unknown MYD88 mutant indicates an unspecified mutation in the MYD88 gene.
wild-type none no effect Wild-type MYD88 indicates that no mutation has been detected within the MYD88 gene.
L229S missense unknown MYD88 L229S lies within the TIR domain of the Myd88 protein (UniProt.org). L229S is predicted to affect splicing by acting as a donor splice variant (PMID: 25886387), but has not been biochemically characterized and therefore, its effect on Myd88 protein function is unknown (PubMed, Feb 2019).
L289P missense unknown MYD88 L289P lies within the TIR domain of the Myd88 protein (UniProt.org). L289P has been identified in sequencing studies (PMID: 28292439), but has not been biochemically characterized and therefore, its effect on Myd88 protein function is unknown (PubMed, Feb 2019).
A24T missense unknown MYD88 A24T does not lie within any known functional domains of the Myd88 protein (UniProt.org). A24T has not been characterized in the scientific literature and therefore, its effect on Myd88 protein function is unknown (PubMed, Feb 2019).
L265P missense gain of function MYD88 L265P (corresponds to L252P in the canonical isoform in UniProt.org) lies within the TIR domain of the Myd88 protein (UniProt.org). L265P confers a gain of function to Myd88, resulting in increased NF-kappaB signaling, and promotes cell survival in culture (PMID: 23836557, PMID: 21179087).
S244A missense loss of function MYD88 S244A lies within the TIR domain of the Myd88 protein (UniProt.org). S244A confers a loss of function to the Myd88 protein as demonstrated by decreased NF-kappaB activity compared to wild-type, and disruption of both Myd88 homodimerization and recruitment of IL-1 receptor-associated kinases in culture (PMID: 24019529).
M232T missense gain of function - predicted MYD88 M232T lies within the TIR domain of the Myd88 protein (PMID: 27102345). M232T results in high activity of NF-kappaB compared to MYD88 wild-type in vitro and therefore, is predicted to result in a gain of function (PMID: 21179087).
S244D missense loss of function - predicted MYD88 S244D lies within the TIR domain of the Myd88 (UniProt.org). S244D is predicted to confer a loss of function to the Myd88 protein as demonstrated by loss of binding to Mal in cell culture (PMID: 26876098).
W205R missense unknown MYD88 W205R lies within the TIR domain of the Myd88 protein (UniProt.org). W205R has been identified in the scientific literature (PMID: 26876098), but has not been biochemically characterized and therefore, its effect on Myd88 protein function is unknown (PubMed, Feb 2019).
F174Y missense unknown MYD88 F174Y lies within the TIR domain of the Myd88 protein (UniProt.org). F174Y has not been characterized in the scientific literature and therefore, its effect on Myd88 protein function is unknown (PubMed, Feb 2019).
L211F missense loss of function - predicted MYD88 L211F lies within the TIR domain of the Myd88 protein (UniProt.org). L211F is predicted to confer a loss of function to the Myd88 protein as demonstrated by loss of binding to Mal in cell culture (PMID: 26876098).
act mut unknown gain of function MYD88 act mut indicates that this variant results in a gain of function in the Myd88 protein. However, the specific amino acid change has not been identified.
A6fs frameshift loss of function - predicted MYD88 A6fs results in a change in the amino acid sequence of the Myd88 protein beginning at aa 6 of 296, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), A6fs is predicted to lead to a loss of function.
T272H missense loss of function - predicted MYD88 T272H lies within the TIR domain of the Myd88 protein (UniProt.org). T272H is predicted to confer a loss of function to the Myd88 protein as demonstrated by loss of binding to Mal in cell culture (PMID: 26876098).
Molecular Profile Protein Effect Treatment Approaches
MYD88 V217F gain of function - predicted
MYD88 N278Y loss of function - predicted
MYD88 P245S loss of function - predicted
MYD88 P279L loss of function - predicted
MYD88 F270S loss of function - predicted
MYD88 E104Q unknown
MYD88 over exp no effect
MYD88 mutant unknown
MYD88 wild-type no effect
MYD88 L229S unknown
MYD88 L289P unknown
MYD88 A24T unknown
MYD88 L265P gain of function Ibrutinib IMO-8400
MYD88 S244A loss of function
MYD88 M232T gain of function - predicted
MYD88 S244D loss of function - predicted
MYD88 W205R unknown
MYD88 F174Y unknown
MYD88 L211F loss of function - predicted
MYD88 act mut gain of function
MYD88 A6fs loss of function - predicted
MYD88 T272H loss of function - predicted
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MYD88 mutant marginal zone B-cell lymphoma not applicable N/A Guideline Diagnostic MYD88 mutations are used to differentiate Waldenstroem's macroglobulinemia from marginal zone B-cell lymphoma in the presence of plasmacytic differentiation (NCCN.org). detail...
MYD88 mutant Waldenstroem's macroglobulinemia not applicable N/A Guideline Diagnostic MYD88 mutations are used to differentiate Waldenstroem's macroglobulinemia from marginal zone B-cell lymphoma in the presence of plasmacytic differentiation (NCCN.org). detail...
MYD88 mutant lymphoplasmacytic lymphoma not applicable N/A Clinical Study Diagnostic MYD88 mutations are used in the diagnosis of lymphoplasmacytic lymphoma (Guidelines, PMID: 22944768). detail... 26230596 22944768
MYD88 wild-type diffuse large B-cell lymphoma predicted - sensitive ST2825 Preclinical Actionable In a preclinical study, STS2825 demonstrated effective inhibition of MYD88 homodimerization and signalling in cultured cells and is currently being evaluated in preclinical studies of B cell lymphoma (Blood Lymph Canc 2013; 3: 53-61). detail...
MYD88 L265P central nervous system lymphoma sensitive Ibrutinib Phase I Actionable In a Phase I trial, two patients with primary central nervous system lymphoma each harboring MYD88 L265P demonstrated a complete response when treated with Imbruvica (ibrutinib) (PMID: 28619981). 28619981
MYD88 L265P diffuse large B-cell lymphoma not applicable N/A Clinical Study Prognostic In multiple clinical studies, MYD88 L265P was associated with a worse overall survival in patients with diffuse large B-cell lymphoma when compared to MYD88 wild-type (PMID: 24903481, PMID: 25055137, PMID: 26792260). 26792260 24903481 25055137
MYD88 L265P diffuse large B-cell lymphoma resistant Ibrutinib Phase II Actionable In a Phase II trial, all of diffuse large B-cell lymphoma patients harboring MYD88 L265P (n=4) did not respond to Imbruvica (ibrutinib) treatment (Blood 2012, 120 (21): 686). detail...
MYD88 L265P non-Hodgkin lymphoma no benefit Ibrutinib Preclinical - Pdx Actionable In a preclinical study, a non-Hodgkin lymphoma (NHL) patient derived xenograft (PDX) model harboring both CD79B Y197N and MYD88 L265P demonstrated sensitivity to Ibruvica (ibrutinib) while an NHL patient derived xenograft (PDX) model harboring only MYD88 L265P did not respond to Ibruvica (ibrutinib) (ASH 57th Annual Meeting, 2015, abstract #2759). detail...
MYD88 L265P diffuse large B-cell lymphoma sensitive Vorinostat Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line harboring MYD88 L256P demonstrated sensitivity to Zolinza (vorinostat) in culture, resulting in increased apoptosis (PMID: 27733371). 27733371
MYD88 L265P B-cell lymphoma sensitive IMO-8400 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with IMO-8400 resulted in decreased survival of B-cell lymphoma cell lines harboring MYD88 L265P in culture, and decreased tumor growth in a MYD88 L265P-positive B-cell lymphoma cell line xenograft models (Cancer Res October 1, 2014 74:2570). detail...
MYD88 L265P Waldenstroem's macroglobulinemia not applicable N/A Guideline Diagnostic MYD88 L265P is diagnostic and aids distinguishing Waldenstroem's macroglobulinemia from non-IgM lymphoplasmacytic lymphoma, B-cell lymphomas, and plasma cell myeloma (NCCN.org). detail...
MYD88 act mut diffuse large B-cell lymphoma predicted - sensitive eFT508 Preclinical - Cell line xenograft Actionable In a preclinical study, eFT508 demonstrated anti-tumor activity in two diffuse large B-cell lymphoma cell line xenograft models, both harboring MYD88 activating mutations (Blood Dec 2015, 126 (23) 1554). detail...