Annotation Detail
Information
- Associated Genes
- TP53
- Associated Variants
-
TP53 p.Arg248Gln (p.R248Q)
(
ENST00000604348.6,
ENST00000504937.5,
ENST00000269305.9,
ENST00000576024.2,
ENST00000420246.6,
ENST00000510385.5,
ENST00000504290.5,
ENST00000610538.4,
ENST00000445888.6,
ENST00000455263.6,
ENST00000359597.8,
ENST00000413465.6,
ENST00000610292.4,
ENST00000610623.4,
ENST00000618944.4,
ENST00000619186.4,
ENST00000619485.4,
ENST00000620739.4,
ENST00000622645.4,
ENST00000714356.1,
ENST00000714357.1,
ENST00000714359.1,
ENST00000714408.1,
ENST00000714409.1 )
TP53 p.Arg248Gln (p.R248Q) ( ENST00000269305.9, ENST00000359597.8, ENST00000413465.6, ENST00000420246.6, ENST00000445888.6, ENST00000455263.6, ENST00000504290.5, ENST00000504937.5, ENST00000510385.5, ENST00000576024.2, ENST00000604348.6, ENST00000610292.4, ENST00000610538.4, ENST00000610623.4, ENST00000618944.4, ENST00000619186.4, ENST00000619485.4, ENST00000620739.4, ENST00000622645.4, ENST00000714356.1, ENST00000714357.1, ENST00000714359.1, ENST00000714408.1, ENST00000714409.1 ) - Associated Disease
- acute myeloid leukemia
- Source Database
- CIViC Evidence
- Description
- R248Q mutation was used to create five isogenic MOLM13-TP53 AML cell lines: p53+/+, p53+/-, p53-/-, R248Q/+, and R248Q/-. cells were treated with and without DNA damaging agent and p53 inducing agent Daunorubicin and western blot used to assess p21 induction. p21 was induced in +/+ and +/-, but not -/-, R248Q/+, and R248Q/- cells. Daunorubicin treatment caused less cell death in +/- than in +/+ cells, but induced significantly less death in -/-, R248Q/+, and R248Q/-, where these three conditions were not statistically different. A similar result was seen with p53 activating agent Nutlin-3a, where p53-/-, R248Q/+, and R248Q/- cells grouped together with equivalent resistance to the agent in comparison to +/+ and +/- cells. The grouping in results of -/-, R248Q/+, and R248Q/- suggest that R248Q inactivates the wt p53 copy, which does not occur in the +/- condition.
- Variant Origin
- Unknown
- Variant Origin
- Unknown
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7525
- Gene URL
- https://civic.genome.wustl.edu/links/genes/45
- Variant URL
- https://civic.genome.wustl.edu/links/variants/117
- Rating
- 4
- Evidence Type
- Functional
- Disease
- Acute Myeloid Leukemia
- Evidence Direction
- Supports
- Evidence Level
- D
- Clinical Significance
- Dominant Negative
- Pubmed
- 31395785
Drugs