Browse All / Genes / TP53

TP53

tumor protein p53
100 disorders 64 untyped 19 somatic driver 6 no genetic record 3 cooperating 2 unknown 2 causative 2 modifier 1 biomarker 1 risk factor 1 susceptibility 17p13.1 gene with protein product
HGNC:11998MonarchNCBI Gene 7157ENSG00000141510UniProt P04637OMIM 191170

Aliases: p53, LFS1.

Normal function · from ai-gene-review (P04637, commit 79fe13b38970) · AI-generated, not KB evidence

Tumor suppressor p53 is a multifunctional transcription factor that acts as a guardian of the genome, coordinating cellular responses to diverse stress signals including DNA damage, oxidative stress, hypoxia, and metabolic stress. It regulates cell fate decisions through transcriptional control of genes involved in cell cycle arrest, apoptosis, senescence, DNA repair, and metabolism. TP53 is the most frequently mutated gene in human cancers (~50%), underlining its critical role in preventing malignant transformation. Beyond its canonical tumor suppressive functions, p53 also regulates ferroptosis, autophagy, immune responses, and stemness.

p53 functions as a sequence-specific DNA-binding transcription factor that binds p53 response elements to regulate transcription of target genes involved in cell cycle arrest, apoptosis, DNA repair, and metabolism
molecular function: transcription cis-regulatory region binding · directly involved in: DNA damage response, signal transduction by p53 class mediator; negative regulation of mitotic cell cycle; intrinsic apoptotic signaling pathway by p53 class mediator · locations: nucleus
p53 localizes to nuclear bodies and regulates both activation and repression of transcription, including senescence programs
molecular function: transcription cis-regulatory region binding · directly involved in: positive regulation of transcription by RNA polymerase II; negative regulation of transcription by RNA polymerase II; regulation of cellular senescence · locations: nuclear body
In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

DisorderRelationshipWhere the gene appears
Acute Erythroid Leukemia somatic driver somatic
mechanism: Biallelic TP53 Inactivation
Acute Megakaryoblastic Leukemia biomarker somatic
mechanism: Adult Adverse Genomic Landscape and Therapy Resistance
scoped to subtype: Adult AMKL
Adult T-Cell Leukemia/Lymphoma somatic driver somatic
mechanism: TP53-Mutant Senescence Escape
Aflatoxin-Related Hepatocellular Carcinoma somatic driver somatic
mechanism: TP53 R249S Hotspot Mutation
Aggressive NK-cell Leukemia unknown unknown
mechanism: TP53 Checkpoint and DNA-Repair Impairment
Anaplastic Thyroid Carcinoma somatic driver somatic
mechanism: TP53 Loss and p53-Mediated DNA Damage Response Failure
Angiosarcoma unknown somatic
Appendiceal Neoplasm somatic driver somatic
Bile Duct Cyst somatic driver somatic
Bone Giant Cell Tumor somatic driver somatic
Bone Marrow Failure Syndrome 5 causative germline gain of function
mechanism: TP53 C-Terminal Domain Truncation
variant: TP53 c.1077delA p.(Ser362AlafsTer8)
Bone Marrow Failure Syndrome 6 cooperating somatic loss of function
mechanism: Somatic TP53 Loss-of-Function as Maladaptive Clonal Rescue
Burkitt Lymphoma cooperating
mechanism: Apoptosis Resistance
Chondrosarcoma somatic driver somatic
mechanism: TP53 Dysfunction
subtype: Conventional; Dedifferentiated
Choroid Plexus Neoplasm causativesomatic driver germlinesomatic
mechanism: TP53 Pathway Inactivation
subtype: CPC
animal model: Mus musculus
scoped to subtype: CPC
Chromophobe Renal Cell Carcinoma somatic driver somatic
Embryonal Carcinoma modifier somatic
mechanism: Acquired Cisplatin Resistance; Intact Apoptotic Apparatus with Limited DNA Repair Capacity
Embryonal Rhabdomyosarcoma risk factor germline
subtype: Anaplastic Embryonal Rhabdomyosarcoma
scoped to subtype: Anaplastic Embryonal Rhabdomyosarcoma
Gastric Adenocarcinoma somatic driver somatic
mechanism: Chromosomal Instability and Aneuploidy
subtype: CIN
scoped to subtype: CIN
Kidney Sarcoma somatic driver
scoped to subtype: Renal LMS
Large Cell Neuroendocrine Carcinoma somatic driver somatic
mechanism: TP53 Inactivation
Liposarcoma cooperating somatic
scoped to subtype: PLPS
Myelodysplastic Syndrome somatic driver somatic
Oligoastrocytoma somatic driver somatic
Pancytopenia-Developmental Delay Syndrome somatic driver somatic
mechanism: Somatic TP53 Clonal Rescue
Postcricoid Region Cancer susceptibility
Pseudomyxoma Peritonei somatic driver somatic
Splenic Marginal Zone Lymphoma modifier somatic
Triple-Negative Breast Cancer somatic driver somatic
Wilms Tumor somatic driver
mechanism: TP53-Deficient Anaplastic Progression
scoped to subtype: Anaplastic
Anal Canal Carcinoma untyped
Inactivated by E6 Oncoprotein
Arsenic-Related Cancers untyped
Somatic loss of function
Basal Cell Carcinoma untyped
Somatic Mutations
Bladder Urothelial Carcinoma untyped
Somatic Inactivation
Breast Carcinoma untyped
Somatic loss of function
somatic
mechanism: TP53 Loss of Function
Cervical Adenocarcinoma untyped
Somatic Mutation
Cervical Cancer untyped
Inactivated by E6 Oncoprotein
mechanism: miR-4327-Mediated TP53 Repression
Choroid Plexus Carcinoma untyped
Germline and Somatic Tumor Suppressor Loss
Classic Familial Adenomatous Polyposis untyped
Somatic progression-associated alterations
Cutaneous Squamous Cell Carcinoma untyped
Somatic Mutation
Diffuse Astrocytoma untyped
Somatic Mutation
Diffuse Midline Glioma, H3 K27-Altered untyped
Somatic Mutation
Endometrial Carcinoma untyped
Somatic mutation
somatic
mechanism: TP53 Mutation and Copy-Number High State
Endometrial Endometrioid Adenocarcinoma untyped
Somatic p53-abnormal high-risk alteration
somatic
Esophageal Adenocarcinoma untyped
Somatic Loss-of-Function Mutation
Esophageal Carcinoma untyped
Somatic Loss-of-Function Mutation
Esophageal Squamous Cell Carcinoma untyped
Somatic Driver Mutation
mechanism: TP53 Dysfunction
Ethmoid Sinus Adenocarcinoma untyped
Somatic mutation associated with wood-dust exposure
mechanism: Inflammation-Associated TP53 Mutagenesis
Ewing Sarcoma untyped
Somatic Tumor Suppressor Mutation
somatic
Fallopian Tube Cancer untyped
Somatic Loss-of-Function Mutations
Gallbladder Cancer untyped
Somatic Loss-of-Function Mutation
Gastric Cancer H. pylori Associated untyped
Somatic Mutations
Glioblastoma, IDH-Wildtype untyped
Somatic Mutation
Hepatocellular Carcinoma untyped
Somatic Loss of Function
HER2-Positive Gastric Cancer untyped
Co-occurring Mutations
HPV-Negative Head and Neck Cancer untyped
Somatic Mutations
somatic
mechanism: TP53 Mutation and Inactivation
HPV-Positive Head and Neck Cancer untyped
Wild-type (rarely mutated)
IDH-Mutant Astrocytoma untyped
Somatic Mutation
Laryngeal Squamous Cell Carcinoma untyped
Somatic mutation
mechanism: TP53 Dysfunction
Leiomyosarcoma untyped
Somatic mutation or deletion
Li-Fraumeni Syndrome untyped
Germline Loss-of-Function Mutations
mechanism: Germline TP53 Heterozygosity
Malignant Peripheral Nerve Sheath Tumor untyped
Somatic loss of function
mechanism: TP53 Pathway Loss
Mantle Cell Lymphoma untyped
Adverse Prognostic Marker
Medulloblastoma, SHH-Activated untyped
Somatic/Germline Mutation
Medulloblastoma, WNT-Activated untyped
Somatic Mutation
Melanoma_in_Congenital_Melanocytic_Nevus untyped
Mutations
Merkel Cell Carcinoma untyped
Somatic Mutations (in MCPyV-negative MCC)
Mixed Germ Cell Tumor untyped
Wild-type in most germ cell tumors; the most recurrently mutated driver in TGCT
Mucoepidermoid Carcinoma untyped somatic
mechanism: p16-CDK4/6-RB Pathway Deregulation and High-Grade Progression
Multiple Myeloma untyped
Somatic
Nasopharyngeal Carcinoma untyped
Occasionally Mutated
Non-Small Cell Lung Cancer untyped
Loss-of-function Mutations
Oral Cavity Squamous Cell Carcinoma untyped
Somatic Mutations
somatic
mechanism: TP53 Mutation and Inactivation
scoped to subtype: HPV-Independent
Osteosarcoma untyped
Somatic mutation / germline predisposition
Ovarian High-Grade Serous Carcinoma untyped
Near-universal somatic mutation
Ovarian Mucinous Carcinoma untyped
Mutation enriched in invasive/high-grade carcinoma and associated with progression
Pancreatic Ductal Adenocarcinoma untyped
Somatic Loss-of-Function Mutation
Pancreatic Mucinous Cystadenoma untyped
PREDISPOSING
Paranasal Sinus Squamous Cell Carcinoma untyped
Somatic mutation
mechanism: TP53 Dysfunction
Penile Cancer untyped
Somatic Driver Mutation
somatic
mechanism: HPV-Independent Somatic Tumor Suppressor Loss
Pleuropulmonary Blastoma untyped
Frequent Somatic Biallelic Loss
mechanism: TP53 Loss
Prostate Adenocarcinoma untyped
Somatic loss of function
Sarcoma Of Cervix Uteri untyped
Somatic mutation
Sezary Syndrome untyped
Tumor Suppressor Loss
Shwachman-Diamond syndrome untyped
Somatic driver of malignant progression
Sinonasal Undifferentiated Carcinoma untyped
Co-occurring somatic mutation
Small Cell Lung Cancer untyped
Somatic Inactivating Mutation
Squamous Cell Carcinoma of Penis untyped
Somatic Driver Mutation
somatic
mechanism: Somatic Cell-Cycle Driver Alteration
Testicular Germ Cell Tumor untyped
Wild-type in most TGCTs; mutations in ~10-17% of refractory cases
Thymic Carcinoma untyped
Recurrent somatic tumor suppressor mutation
Transitional Cell Carcinoma untyped somatic
Urinary Bladder Small Cell Neuroendocrine Carcinoma untyped
Somatic Mutations
mechanism: Recurrent TP53 and RB1 Tumor-Suppressor Alterations
Vulvar Carcinoma untyped
Somatic Mutation
somatic
mechanism: HPV E6-Mediated p53 Degradation; HPV-Independent Somatic Driver Accumulation
Yolk Sac Tumor untyped
Infrequently mutated in the studied ovarian YST cohort; not a universal absence
somatic
scoped to subtype: Ovarian YST
Amatoxin Poisoning no genetic record
mechanism: p53- and Caspase-Dependent Hepatocyte Apoptosis
Balkan Endemic Nephropathy no genetic record
mechanism: A:T to T:A Transversion Mutational Signature
BRAF V600 Mutant Melanoma no genetic record
animal model: Danio rerio
BRAF V600E-Mutant Non-Small Cell Lung Cancer no genetic record
mechanism: Cooperating Tumor-Suppressor and Lineage-State Alterations
animal model: Mus musculus
Gestational Trophoblastic Neoplasm no genetic record
mechanism: Tumor Suppressor and Apoptosis Dysregulation
Small Intestine Cancer no genetic record
mechanism: Adenoma-Carcinoma Sequence and Wnt-APC Activation
subtype: Adenocarcinoma
ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen diseaseMOIClassificationdismech entry
Li-Fraumeni syndrome MONDO:0018875 AD Definitive
2024-03-22
Mechanism modules · computed from kb/

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.