TP53 R175H gain-of-function hotspot
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-TP53-R175H |
|---|---|
| Type | Biomarker |
| Aliases | TP53 R175H gain-of-function hotspot mutationTP53 R175H — hotspot з підсиленою функцієюTP53 p.R175Hp53 R175Hstructural p53 mutant |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-NCCN-AML-2025 SRC-NCCN-BCELL-2025 SRC-NCCN-MM-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "5", "functional_impact": "loss_of_function tumor suppressor + gain-of-function (mutant p53 gains pro-oncogenic activities including chemoresistance, migration, metabolic reprogramming)", "gene": "TP53", "gene_hugo_id": "11998", "hgvs_coding": "c.524G>A", "hgvs_protein": "p.R175H", "variant_type": "missense"} |
| Measurement | MethodTumor-tissue NGS panel (TP53 hotspot or full-gene); FFPE acceptable; ctDNA NGS for liquid biopsy Unitscategorical (positive | negative); VAF % for clonality assessment |
| Related biomarkers | BIO-TP53-MUTATION BIO-TP53-R248Q BIO-TP53-R273H BIO-TP53-R282W |
Notes
R175H is the most common TP53 missense hotspot across all human cancers (~5-7% of TP53-mutant tumors per IARC TP53 Database). Structural class mutant — the R175 substitution to histidine disrupts the DNA-binding domain fold (zinc-coordination region). Beyond loss-of-function (LoF), R175H is a canonical example of mutant-p53 GAIN-OF-FUNCTION (GOF): the mutant protein acquires pro-oncogenic activities (chemoresistance via NF-kB, increased migration/invasion, metabolic reprogramming, chronic inflammation). Clinical implication: R175H+ tumors generally have worse chemo response than TP53-WT or even other TP53-mut tumors. In AML: TP53-mut (any) including R175H → very poor outcomes with intensive chemo, route to alloSCT or venetoclax-azacitidine + clinical trials. In MM: routes to quadruplet per high-risk cytogenetics composite. Emerging GOF-targeting strategies (eprenetapopt/APR-246, arsenic trioxide for structural mutants) are largely investigational; R175H specifically among the reactivatable structural mutants.
Used By
Biomarker
BIO-TP53-R248Q- TP53 R248Q DNA-contact hotspotBIO-TP53-R273H- TP53 R273H DNA-contact hotspotBIO-TP53-R282W- TP53 R282W partial loss-of-function hotspot