TNF, LEU29SER AND TNF receptor binding, altered

Clinical significance:Pathogenic (Last evaluated: Jan 21, 1993)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000013186.24

Allele description [Variation Report for TNF, LEU29SER]

TNF, LEU29SER

Gene:
TNF:tumor necrosis factor [Gene - OMIM - HGNC]
Variant type:
Variation
Cytogenetic location:
6p21.3
Preferred name:
TNF, LEU29SER
HGVS:
    Protein change:
    L29S; LEU29SER
    Links:
    OMIM: 191160.0001

    Condition(s)

    Name:
    TNF receptor binding, altered
    Identifiers:
    MedGen: C4016415

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    Assertion and evidence details

    Submission AccessionSubmitterReview Status
    (Assertion method)
    Clinical Significance
    (Last evaluated)
    OriginMethodCitations
    SCV000033433OMIMno assertion criteria providedPathogenic
    (Jan 21, 1993)
    germlineliterature only

    PubMed (1)
    [See all records that cite this PMID]

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

    Citations

    PubMed

    Human TNF mutants with selective activity on the p55 receptor.

    Van Ostade X, Vandenabeele P, Everaerdt B, Loetscher H, Gentz R, Brockhaus M, Lesslauer W, Tavernier J, Brouckaert P, Fiers W.

    Nature. 1993 Jan 21;361(6409):266-9.

    PubMed [citation]
    PMID:
    8380906

    Details of each submission

    From OMIM, SCV000033433.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedliterature only PubMed (1)

    Description

    Van Ostade et al. (1993) identified 2 cell lines with mutations in TNF that resulted in loss of almost all activity in the standard cytotoxic assay with the L929 murine fibrosarcoma cell line and were shown to have lost the binding affinity specifically for the TNF-R55 human receptor (191190). One of the mutants was found to carry a leu29-to-ser mutation and the other, an arg32-to-trp mutation (191160.0002). The remarkable ability of TNF, especially in combination with interferon, selectively to kill or inhibit malignant cell lines is unmatched by any other combination of cytokines. However, clinical trials have been disappointing, and it is estimated that a TNF dose would be effective only at 5 to 25 times the maximum tolerated dose. TNF binds to 2 types of receptors: the smaller, TNF-R55, is present on most cells and particularly on those susceptible to the cytotoxic action of TNF; the larger, TNF-R75 (191191), is also present on many cell types, especially those of myeloid origin, and is strongly expressed on stimulated T and B lymphocytes. The selective binding of the mutant TNF to TNF-R55 might make it useful in cancer therapy.

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

    Last Updated: Apr 7, 2017