TP53

tumor protein p53

Basic information

Region (hg38): 17:7661778-7687538

Links

ENSG00000141510 ∙ NCBI:7157 ∙ OMIM:191170 ∙ HGNC:11998 ∙ Uniprot:P04637 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sarcoma (Strong), mode of inheritance: AD
• Li-Fraumeni syndrome 1 (Strong), mode of inheritance: AD
• Li-Fraumeni syndrome (Strong), mode of inheritance: AD
• Li-Fraumeni syndrome (Supportive), mode of inheritance: AD
• choroid plexus carcinoma (Supportive), mode of inheritance: AD
• breast cancer (Definitive), mode of inheritance: AD
• Li-Fraumeni syndrome 1 (Definitive), mode of inheritance: AD
• adrenocortical carcinoma, hereditary (Strong), mode of inheritance: AD
• bone marrow failure syndrome 5 (Limited), mode of inheritance: AD
• Li-Fraumeni syndrome (Definitive), mode of inheritance: AD
• Li-Fraumeni syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Li-Fraumeni syndrome; Choroid plexus papilloma; Ependymoma, intracranial; Osteogenic sarcoma; Breast cancer, familial; Hepatoblastoma; Non-Hodgkin lymphoma; Adrenocortical carcinoma; Colorectal cancer; Bone marrow failure syndrome 5	AD	Oncologic	For individuals with cancer predisposition, though the optimal course is unclear, surveillance (including breast cancer and colorectal cancer screening starting no later than age 25) and awareness of the increased risk of malignancy could potentially be beneficial in order to allow early diagnosis and treatment; Mastectomy is preferred to lumpectomy in individuals with breast cancer, and may be a prophylactic option; Radiation therapy should be avoided due to the risk of radiation-induced malignancies; For Bone Marrow failure syndrome, individuals have been described as requiring interventions such as blood transfusions and IgG replacement, and awareness may allow prompt management	Allergy/Immunology/Infectious; Hematologic; Neurologic; Oncologic	6016796; 3409256; 1978757; 1679237; 1591732; 1349175; 1565144; 1565143; 8118819; 8718514; 7887414; 9242456; 10612830; 11332399; 11498785; 11600572; 11219776; 11481490; 12085209; 12610779; 12524418; 12619118; 14583457; 12619118; 15381368; 15695383; 15977174; 15741269; 18762572; 19171829; 19556618; 19652052; 20301488; 21056402; 21601526; 21837677; 21946351; 21990040; 22170717; 22551548; 22672556; 22878818; 22939227; 23015295; 23175693; 23355100; 23409989; 23667851; 23894400; 30146126
Variants may also be involved in susceptibility to a number of types of neoplasms (eg, Basal cell carcinoma, susceptibility to, Glioma, susceptibility to)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TP53 gene.

• Li-Fraumeni syndrome (2032 variants)
• Hereditary cancer-predisposing syndrome (1742 variants)
• Li-Fraumeni syndrome 1 (827 variants)
• not provided (572 variants)
• not specified (282 variants)
• Squamous cell carcinoma of the head and neck (207 variants)
• Lung adenocarcinoma (188 variants)
• Breast neoplasm (187 variants)
• Ovarian serous cystadenocarcinoma (176 variants)
• Neoplasm of ovary (168 variants)
• Pancreatic adenocarcinoma (167 variants)
• Carcinoma of esophagus (153 variants)
• Hepatocellular carcinoma (151 variants)
• Neoplasm of brain (151 variants)
• Neoplasm of the large intestine (150 variants)
• Gastric adenocarcinoma (149 variants)
• Squamous cell lung carcinoma (142 variants)
• Transitional cell carcinoma of the bladder (114 variants)
• Glioblastoma (114 variants)
• Adrenocortical carcinoma, hereditary (112 variants)
• Uterine carcinosarcoma (104 variants)
• Malignant neoplasm of body of uterus (101 variants)
• Malignant melanoma of skin (90 variants)
• Squamous cell carcinoma of the skin (73 variants)
• Prostate adenocarcinoma (72 variants)
• Small cell lung carcinoma (72 variants)
• Acute myeloid leukemia (68 variants)
• Multiple myeloma (60 variants)
• Papillary renal cell carcinoma type 1 (57 variants)
• B-cell chronic lymphocytic leukemia (54 variants)
• Hereditary breast ovarian cancer syndrome (51 variants)
• Breast and/or ovarian cancer (46 variants)
• Brainstem glioma (43 variants)
• Adrenal cortex carcinoma (38 variants)
• Malignant tumor of breast (30 variants)
• Familial cancer of breast (28 variants)
• TP53-related condition (22 variants)
• 12 conditions (22 variants)
• Medulloblastoma (20 variants)
• Lip and oral cavity carcinoma (18 variants)
• Neoplasm of uterine cervix (18 variants)
• Papillary renal cell carcinoma, sporadic (15 variants)
• Gallbladder carcinoma (14 variants)
• Non-Hodgkin lymphoma (14 variants)
• Gastric cancer (13 variants)
• Prostate cancer, hereditary, 1 (13 variants)
• Rhabdomyosarcoma (12 variants)
• Malignant tumor of urinary bladder (11 variants)
• Nasopharyngeal neoplasm (10 variants)
• Adenoid cystic carcinoma (9 variants)
• Colorectal cancer (8 variants)
• Neuroblastoma (7 variants)
• Sarcoma (6 variants)
• Gallbladder cancer (6 variants)
• Malignant tumor of prostate (6 variants)
• 11 conditions (6 variants)
• Neoplasm (6 variants)
• Breast carcinoma (5 variants)
• Myelodysplastic syndrome (5 variants)
• Li-fraumeni-like syndrome (5 variants)
• Malignant tumor of esophagus (5 variants)
• Carcinoma of colon (4 variants)
• 7 conditions (3 variants)
• Familial ovarian cancer (3 variants)
• Poly (ADP-Ribose) polymerase inhibitor response (3 variants)
• Glioma susceptibility 1 (3 variants)
• Squamous cell carcinoma (3 variants)
• Dyskeratosis Congenita, Recessive (3 variants)
• Bone marrow failure syndrome 5 (3 variants)
• Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (2 variants)
• Adrenocortical carcinoma, pediatric (2 variants)
• Diamond-Blackfan anemia (2 variants)
• Breast adenocarcinoma (2 variants)
• Choroid plexus carcinoma (2 variants)
• Familial colorectal cancer (2 variants)
• Bone osteosarcoma (2 variants)
• Adenocarcinoma (1 variants)
• Basal cell carcinoma, susceptibility to, 7 (1 variants)
• Colorectal polyposis;Colonic neoplasm (1 variants)
• Endometrial carcinoma (1 variants)
• Nasopharyngeal carcinoma (1 variants)
• Familial cancer of breast;Classic Hodgkin lymphoma;Thyroid cancer, nonmedullary, 1;Neoplasm of ovary (1 variants)
• Thyroid gland undifferentiated (anaplastic) carcinoma (1 variants)
• Carcinoma of pancreas (1 variants)
• Astrocytoma, anaplastic (1 variants)
• Astrocytoma, anaplastic;Pleomorphic xanthoastrocytoma (1 variants)
• Astrocytoma (1 variants)
• Ductal carcinoma in situ (1 variants)
• Colorectal cancer;Multiple myeloma (1 variants)
• CODON 72 POLYMORPHISM (1 variants)
• Vulvar adenocarcinoma of mammary gland type (1 variants)
• Congenital fibrosarcoma (1 variants)
• Neoplasm of stomach (1 variants)
• Atypical endometrial hyperplasia (1 variants)
• Head and neck neoplasm (1 variants)
• Breast-ovarian cancer, familial, susceptibility to, 1 (1 variants)
• Breast-ovarian cancer, familial, susceptibility to, 3 (1 variants)
• Mediastinal germ cell tumor;Acute megakaryoblastic leukemia (1 variants)
• Cervical cancer (1 variants)
• Malignant lymphoma, large B-cell, diffuse (1 variants)
• Metastatic pancreatic neuroendocrine tumours (1 variants)
• Hepatoblastoma (1 variants)
• Lymphoma (1 variants)
• Atypical teratoid rhabdoid tumor (1 variants)
• Colonic diverticula (1 variants)
• Lung sarcomatoid carcinoma (1 variants)
• Familial melanoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TP53 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	349	2	360
missense	76	109	629	120	7	941
nonsense	71	11	1	3		86
start loss	1	1	3	1		6
frameshift	298	20	14			332
inframe indel	16	11	79	1		107
splice donor/acceptor (+/-2bp)	32	53	5			90
splice region	4	4	66	55		129
non coding	8	6	80	293	39	426
Total	502	211	820	767	48

Highest pathogenic variant AF is 0.0000197

Variants in TP53

This is a list of pathogenic ClinVar variants found in the TP53 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-7666228-C-G		not specified	not provided (Sep 19, 2013)
17-7667874-G-C		Hereditary cancer-predisposing syndrome	Likely benign (Apr 26, 2016)
17-7667880-G-A		Hereditary cancer-predisposing syndrome	Likely benign (Jul 18, 2016)
17-7667888-G-A		Hereditary cancer-predisposing syndrome	Likely benign (Oct 09, 2019)
17-7667899-A-C		Hereditary cancer-predisposing syndrome	Likely benign (Feb 17, 2016)
17-7667901-C-T		Hereditary cancer-predisposing syndrome	Likely benign (Oct 26, 2018)
17-7667904-C-T		Hereditary cancer-predisposing syndrome	Likely benign (Mar 22, 2017)
17-7667906-C-A		Hereditary cancer-predisposing syndrome	Likely benign (Aug 31, 2016)
17-7667906-C-T		Hereditary cancer-predisposing syndrome	Likely benign (Apr 26, 2016)
17-7667908-C-A		Hereditary cancer-predisposing syndrome	Benign (Apr 15, 2015)
17-7667909-C-T		Hereditary cancer-predisposing syndrome	Likely benign (Nov 22, 2017)
17-7667910-C-A		Hereditary cancer-predisposing syndrome	Likely benign (Jul 26, 2021)
17-7667914-C-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Mar 18, 2019)
17-7667923-T-G		Hereditary cancer-predisposing syndrome	Uncertain significance (May 21, 2019)
17-7667926-C-T		Hereditary cancer-predisposing syndrome	Likely benign (Dec 06, 2018)
17-7667929-C-T		Hereditary cancer-predisposing syndrome	Likely benign (Oct 07, 2016)
17-7667933-C-T		Hereditary cancer-predisposing syndrome	Likely benign (Feb 21, 2017)
17-7668134-G-A			Benign (Jun 14, 2019)
17-7668169-A-AGCCGTG		Li-Fraumeni syndrome • Hereditary cancer-predisposing syndrome • Li-Fraumeni syndrome 1	Benign (Jan 22, 2024)
17-7668194-C-T		TP53-related disorder	Likely benign (Jun 19, 2020)
17-7668195-G-A		TP53-related disorder	Likely benign (May 09, 2022)
17-7668202-T-TC		Li-Fraumeni syndrome	Pathogenic (May 18, 2017)
17-7668388-C-G		Li-Fraumeni syndrome	Likely benign (Jul 26, 2019)
17-7668434-T-G		Basal cell carcinoma, susceptibility to, 7 • Li-Fraumeni syndrome 1 • Hereditary cancer-predisposing syndrome • TP53-related disorder	Conflicting classifications of pathogenicity (Nov 30, 2023)
17-7668440-T-C		TP53-related disorder	Likely benign (Oct 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TP53	protein_coding	protein_coding	ENST00000269305	10	25760

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.532	0.468	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.983	192	234	0.819	0.0000153	2531
Missense in Polyphen		72	95.319	0.75536		1053
Synonymous	-0.544	96	89.5	1.07	0.00000581	780
Loss of Function	3.26	4	19.5	0.205	0.00000111	220

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA- Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1- mediated transcriptional activation of PER2 (PubMed:24051492). {ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17317671, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24051492, ECO:0000269|PubMed:9840937}.
• Disease: DISEASE: Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma.; DISEASE: Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Li-Fraumeni syndrome (LFS) [MIM:151623]: An autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers. {ECO:0000269|PubMed:10484981, ECO:0000269|PubMed:1565144, ECO:0000269|PubMed:1737852, ECO:0000269|PubMed:1933902, ECO:0000269|PubMed:1978757, ECO:0000269|PubMed:2259385, ECO:0000269|PubMed:7887414, ECO:0000269|PubMed:8825920, ECO:0000269|PubMed:9452042}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Papilloma of choroid plexus (CPP) [MIM:260500]: A benign tumor of neuroectodermal origin that generally occurs in childhood, but has also been reported in adults. Although generally found within the ventricular system, choroid plexus papillomas can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. Patients present with signs and symptoms of increased intracranial pressure including headache, hydrocephalus, papilledema, nausea, vomiting, cranial nerve deficits, gait impairment, and seizures. {ECO:0000269|PubMed:12085209}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Adrenocortical carcinoma (ADCC) [MIM:202300]: A malignant neoplasm of the adrenal cortex and a rare childhood tumor. It occurs with increased frequency in patients with Beckwith- Wiedemann syndrome and Li-Fraumeni syndrome. {ECO:0000269|PubMed:11481490}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Basal cell carcinoma 7 (BCC7) [MIM:614740]: A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter. {ECO:0000269|PubMed:21946351}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Fluoropyrimidine Pathway, Pharmacodynamics;PI3K-Akt signaling pathway - Homo sapiens (human);Non-small cell lung cancer - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Melanoma - Homo sapiens (human);Doxorubicin Pathway (Cancer Cell), Pharmacodynamics;Bladder cancer - Homo sapiens (human);Cell cycle - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Breast cancer - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Vincristine Action Pathway;Vinblastine Action Pathway;Vinorelbine Action Pathway;Vindesine Action Pathway;Cell Cycle;AMP-activated Protein Kinase (AMPK) Signaling;miRNA Regulation of DNA Damage Response;miRNAs involved in DNA damage response;Fluoropyrimidine Activity;TP53 Network;Folate Metabolism;Apoptosis Modulation and Signaling;Alzheimers Disease;Metastatic brain tumor;Signaling Pathways in Glioblastoma;Gastric Cancer Network 2;Oncostatin M Signaling Pathway;Spinal Cord Injury;Retinoblastoma (RB) in Cancer;Amyotrophic lateral sclerosis (ALS);ATM Signaling Pathway;Apoptosis;Mammary gland development pathway - Involution (Stage 4 of 4);Bladder Cancer;Copper homeostasis;Rac1-Pak1-p38-MMP-2 pathway;Photodynamic therapy-induced AP-1 survival signaling.;Photodynamic therapy-induced HIF-1 survival signaling;Apoptotic Signaling Pathway;Hepatitis C and Hepatocellular Carcinoma;Pathways Affected in Adenoid Cystic Carcinoma;TGF-beta Signaling Pathway;LncRNA-mediated mechanisms of therapeutic resistance;Regulation of TP53 Expression and Degradation;MAPK Signaling Pathway;miRNA regulation of prostate cancer signaling pathways;miRNA regulation of p53 pathway in prostate cancer;Wnt Signaling Pathway and Pluripotency;Interleukin-4 and 13 signaling;apoptotic signaling in response to dna damage;Endometrial cancer;PI3K-Akt Signaling Pathway;Caloric restriction and aging;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Chromosomal and microsatellite instability in colorectal cancer;EMT transition in Colorectal Cancer;G1 to S cell cycle control;Senescence and Autophagy in Cancer;ErbB Signaling Pathway;DNA Damage Response;DNA Damage Response (only ATM dependent);double stranded rna induced gene expression;DNA Repair;RUNX3 regulates CDKN1A transcription;Signal Transduction;Gene expression (Transcription);DNA Double-Strand Break Repair;Transcriptional regulation by RUNX3;hypoxia and p53 in the cardiovascular system;btg family proteins and cell cycle regulation;role of brca1 brca2 and atr in cancer susceptibility;telomeres telomerase cellular aging and immortality;chaperones modulate interferon signaling pathway;tumor suppressor arf inhibits ribosomal biogenesis;estrogen responsive protein efp controls cell cycle and breast tumors growth;cell cycle: g1/s check point;overview of telomerase protein component gene htert transcriptional regulation;regulation of cell cycle progression by plk3;Generic Transcription Pathway;Oncogene Induced Senescence;Oxidative Stress Induced Senescence;Formation of Senescence-Associated Heterochromatin Foci (SAHF);DNA Damage/Telomere Stress Induced Senescence;Cellular Senescence;SUMOylation of transcription factors;Factors involved in megakaryocyte development and platelet production;Cellular responses to stress;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;PI5P Regulates TP53 Acetylation;Autodegradation of the E3 ubiquitin ligase COP1;Stabilization of p53;Transcriptional activation of cell cycle inhibitor p21 ;Transcriptional activation of p53 responsive genes ;p53-Dependent G1 DNA Damage Response;p53-Dependent G1/S DNA damage checkpoint;G1/S DNA Damage Checkpoints;G2/M DNA damage checkpoint;Activation of NOXA and translocation to mitochondria;Activation of PUMA and translocation to mitochondria;Activation of BH3-only proteins;G2/M Checkpoints;Chaperonin-mediated protein folding;Intrinsic Pathway for Apoptosis;Cell Cycle Checkpoints;Oncostatin_M;Association of TriC/CCT with target proteins during biosynthesis;Apoptosis;Programmed Cell Death;Hypoxic and oxygen homeostasis regulation of HIF-1-alpha;Pre-NOTCH Transcription and Translation;Pre-NOTCH Expression and Processing;Signaling by NOTCH;TP53 Regulates Metabolic Genes;Aurora A signaling;SUMOylation;TP53 Regulates Transcription of Genes Involved in Cytochrome C Release;cell cycle: g2/m checkpoint;regulation of transcriptional activity by pml;TP53 Regulates Transcription of Caspase Activators and Caspases;Cellular responses to external stimuli;TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain;TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest;p53 signaling pathway;TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest;atm signaling pathway;TGF_beta_Receptor;TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain;TP53 Regulates Transcription of Cell Cycle Genes;EGFR1;TP53 Regulates Transcription of DNA Repair Genes;Regulation of TP53 Expression;Glucocorticoid receptor regulatory network;Regulation of PTEN gene transcription;The role of GTSE1 in G2/M progression after G2 checkpoint;Hemostasis;Ub-specific processing proteases;rb tumor suppressor/checkpoint signaling in response to dna damage;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;G2/M Transition;Mitotic G2-G2/M phases;PTEN Regulation;PIP3 activates AKT signaling;Ovarian tumor domain proteases;Protein folding;Deubiquitination;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity through Association with Co-factors;Regulation of TP53 Activity through Methylation;Regulation of TP53 Activity through Acetylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Direct p53 effectors;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Cell Cycle, Mitotic;Intracellular signaling by second messengers;Signaling mediated by p38-alpha and p38-beta;PLK3 signaling events;Validated targets of C-MYC transcriptional activation;AP-1 transcription factor network;BARD1 signaling events;p75(NTR)-mediated signaling;Signaling events mediated by HDAC Class III;p53 pathway;LKB1 signaling events;TP53 Regulates Transcription of Death Receptors and Ligands (Consensus)

Recessive Scores

• pRec: 1.00

Intolerance Scores

• loftool: 0.000965
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 1.00
• hipred: Y
• hipred_score: 0.831
• ghis: 0.599

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trp53
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; neoplasm; pigmentation phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: tp53
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: immature

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;DNA strand renaturation;base-excision repair;nucleotide-excision repair;regulation of transcription, DNA-templated;autophagy;cellular response to DNA damage stimulus;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator;ER overload response;cell cycle arrest;Ras protein signal transduction;multicellular organism development;cell aging;protein localization;cell population proliferation;negative regulation of cell population proliferation;determination of adult lifespan;mRNA transcription;response to gamma radiation;positive regulation of gene expression;viral process;protein deubiquitination;cytokine-mediated signaling pathway;cell differentiation;negative regulation of cell growth;DNA damage response, signal transduction by p53 class mediator;chromatin assembly;mitotic G1 DNA damage checkpoint;positive regulation of protein oligomerization;cellular response to UV;cellular response to drug;cellular response to glucose starvation;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;regulation of apoptotic process;positive regulation of apoptotic process;negative regulation of apoptotic process;entrainment of circadian clock by photoperiod;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;positive regulation of transcription by RNA polymerase II;response to antibiotic;positive regulation of protein export from nucleus;regulation of mitochondrial membrane permeability;negative regulation of fibroblast proliferation;circadian behavior;positive regulation of peptidyl-tyrosine phosphorylation;negative regulation of helicase activity;RNA polymerase II preinitiation complex assembly;protein tetramerization;protein homotetramerization;negative regulation of telomerase activity;protein-containing complex assembly;positive regulation of thymocyte apoptotic process;positive regulation of cell cycle arrest;cellular response to hypoxia;cellular response to ionizing radiation;cellular response to gamma radiation;signal transduction by p53 class mediator;intrinsic apoptotic signaling pathway by p53 class mediator;cellular response to actinomycin D;positive regulation of release of cytochrome c from mitochondria;replicative senescence;oxidative stress-induced premature senescence;intrinsic apoptotic signaling pathway;oligodendrocyte apoptotic process;positive regulation of execution phase of apoptosis;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway;regulation of signal transduction by p53 class mediator;regulation of cell cycle G2/M phase transition;positive regulation of pri-miRNA transcription by RNA polymerase II;positive regulation of production of miRNAs involved in gene silencing by miRNA;positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress;positive regulation of reactive oxygen species metabolic process;positive regulation of intrinsic apoptotic signaling pathway
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;transcription factor complex;transcription factor TFIID complex;nucleolus;cytoplasm;mitochondrion;mitochondrial matrix;endoplasmic reticulum;cytosol;nuclear matrix;nuclear body;PML body;protein-containing complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;core promoter sequence-specific DNA binding;RNA polymerase II transcription factor binding;TFIID-class transcription factor complex binding;DNA-binding transcription activator activity, RNA polymerase II-specific;protease binding;p53 binding;DNA binding;chromatin binding;DNA-binding transcription factor activity;mRNA 3'-UTR binding;copper ion binding;protein binding;ATP binding;transcription factor binding;zinc ion binding;enzyme binding;protein kinase binding;protein phosphatase binding;receptor tyrosine kinase binding;ubiquitin protein ligase binding;histone acetyltransferase binding;identical protein binding;histone deacetylase binding;protein self-association;transcription regulatory region DNA binding;protein heterodimerization activity;protein N-terminus binding;chaperone binding;protein phosphatase 2A binding;disordered domain specific binding;promoter-specific chromatin binding