TP53 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human TP53 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene TP53, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene TP53, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene TP53 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene TP53 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene TP53, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene TP53, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene TP53, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene TP53 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene TP53, summarize transcription factor regulatory data. If TP53 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate TP53 — names with evidence type (ChIP-seq / predicted / experimentally validated) If TP53 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene TP53 protein as a drug target, summarize pharmacology data. If TP53 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If TP53 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene TP53, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene TP53, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in TP53: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
TP53 (HGNC:11998; chromosome 17p13.1) encodes the tumor suppressor protein p53 — arguably the most consequential cancer gene in human biology — functioning as a transcription factor that orchestrates cell cycle arrest, apoptosis, DNA repair, and cellular senescence in response to stress. It is mutated in a vast range of human cancers and, in its germline form, causes Li-Fraumeni syndrome with definitive evidence for autosomal dominant inheritance. The variant landscape is exceptionally large (~3,850 ClinVar entries, including ~1,200 pathogenic), with hotspot missense mutations such as p.Arg248Trp, p.Arg248Gln, p.Arg175His, and p.Gly245Ser confirmed pathogenic by expert panels. p53 is ubiquitously expressed across all tissues (281 conditions, average score 77.62) and is structurally among the best-characterized human proteins, with 297 experimental PDB structures. Its primary negative regulator MDM2 — which ubiquitinates p53 for degradation — is the key therapeutic target; idasanutlin, the most advanced MDM2 inhibitor, reached Phase 3 trials in AML before termination.
Gene identifiers
- HGNC ID: HGNC:11998
- Approved symbol: TP53
- Ensembl gene ID: ENSG00000141510
- NCBI Entrez Gene ID: 7157
- OMIM gene/locus ID: 191170
- Genomic location (GRCh38):
- Chromosome: 17
- Start position: 7,661,779
- End position: 7,687,546
- Strand: minus (−)
Transcript identifiers
Ensembl Transcripts (ENST IDs) — 39 total
| Transcript ID | Biotype |
|---|---|
| ENST00000269305 | protein_coding |
| ENST00000359597 | protein_coding |
| ENST00000413465 | protein_coding |
| ENST00000420246 | protein_coding |
| ENST00000445888 | protein_coding |
| ENST00000455263 | protein_coding |
| ENST00000503591 | protein_coding |
| ENST00000504290 | protein_coding |
| ENST00000504937 | protein_coding |
| ENST00000505014 | retained_intron |
| ENST00000508793 | protein_coding |
| ENST00000509690 | protein_coding |
| ENST00000510385 | protein_coding |
| ENST00000514944 | protein_coding |
| ENST00000571370 | protein_coding_CDS_not_defined |
| ENST00000574684 | protein_coding_CDS_not_defined |
| ENST00000576024 | protein_coding |
| ENST00000604348 | protein_coding |
| ENST00000610292 | protein_coding |
| ENST00000610538 | protein_coding |
| ENST00000610623 | protein_coding |
| ENST00000618944 | protein_coding |
| ENST00000619186 | protein_coding |
| ENST00000619485 | protein_coding |
| ENST00000620739 | protein_coding |
| ENST00000622645 | protein_coding |
| ENST00000635293 | nonsense_mediated_decay |
| ENST00000714356 | protein_coding |
| ENST00000714357 | protein_coding |
| ENST00000714358 | nonsense_mediated_decay |
| ENST00000714359 | protein_coding |
| ENST00000714408 | protein_coding |
| ENST00000714409 | protein_coding |
| ENST00000905353 | protein_coding |
| ENST00000923566 | protein_coding |
| ENST00000923567 | protein_coding |
| ENST00000923568 | protein_coding |
| ENST00000923569 | protein_coding |
| ENST00000949117 | protein_coding |
RefSeq mRNA Accessions — 34 total
| Accession | MANE Select |
|---|---|
| NM_000546 | ✓ YES |
| NM_001126112 | — |
| NM_001126113 | — |
| NM_001126114 | — |
| NM_001126115 | — |
| NM_001126116 | — |
| NM_001126117 | — |
| NM_001126118 | — |
| NM_001170223 | — |
| NM_001260323 | — |
| NM_001271820 | — |
| NM_001276695 | — |
| NM_001276696 | — |
| NM_001276697 | — |
| NM_001276698 | — |
| NM_001276699 | — |
| NM_001276760 | — |
| NM_001276761 | — |
| NM_001328587 | — |
| NM_001328588 | — |
| NM_001407262 | — |
| NM_001407263 | — |
| NM_001407264 | — |
| NM_001407265 | — |
| NM_001407266 | — |
| NM_001407267 | — |
| NM_001407268 | — |
| NM_001407269 | — |
| NM_001407270 | — |
| NM_001407271 | — |
| NM_030989 | — |
| NM_131327 | — |
| NM_206544 | — |
| NM_206545 | — |
CCDS Identifiers — 12 total
CCDS11118, CCDS45605, CCDS45606, CCDS73963, CCDS73964, CCDS73965, CCDS73966, CCDS73967, CCDS73968, CCDS73969, CCDS73970, CCDS73971
Canonical Transcript Exons (ENST00000269305) — 11 total
| Exon ID | Start | End | Strand | Chromosome |
|---|---|---|---|---|
| ENSE00002419584 | 7676382 | 7676403 | − | 17 |
| ENSE00003518480 | 7675053 | 7675236 | − | 17 |
| ENSE00003545950 | 7670609 | 7670715 | − | 17 |
| ENSE00003625790 | 7675994 | 7676272 | − | 17 |
| ENSE00003712342 | 7674181 | 7674290 | − | 17 |
| ENSE00003723991 | 7674859 | 7674971 | − | 17 |
| ENSE00003725258 | 7673701 | 7673837 | − | 17 |
| ENSE00003753508 | 7687377 | 7687490 | − | 17 |
| ENSE00003786593 | 7673535 | 7673608 | − | 17 |
| ENSE00004023724 | 7668421 | 7669690 | − | 17 |
| ENSE00004023728 | 7676521 | 7676622 | − | 17 |
Protein identifiers
UniProt accessions
Canonical (reviewed):
- P04637 — Cellular tumor antigen p53 (reviewed, Swiss-Prot)
Additional entries (unreviewed/isoforms):
- A0A087WT22
- A0A087WXZ1
- A0A087X1Q1
- A0A0U1RQC9
- A0A386NBZ1
- A0AAQ5BHX5
- A0AAQ5BHY1
- A0AAQ5BHZ9
- E7EMR6
- E7EQX7
- E7ESS1
- E9PCY9
- E9PFT5
- H2EHT1
- I3L0W9
- J3KP33
- K7PPA8
- S4R334
RefSeq protein accessions (NP_)
- NP_000537 (MANE Select, canonical)
- NP_001119584
- NP_001119585
- NP_001119586
- NP_001119587
- NP_001119588
- NP_001119589
- NP_001119590
- NP_001163694
- NP_001247252
- NP_001258749
- NP_001263624
- NP_001263625
- NP_001263626
- NP_001263627
- NP_001263628
- NP_001263689
- NP_001263690
- NP_001315516
- NP_001315517
- NP_001394191
- NP_001394192
- NP_001394193
- NP_001394194
- NP_001394195
- NP_001394196
- NP_001394197
- NP_001394198
- NP_001394199
- NP_001394200
- NP_112251
- NP_571402
- NP_996267
- NP_996268
Protein domains and families
InterPro domains/families (9):
| ID | Name | Type |
|---|---|---|
| IPR002117 | p53 tumour suppressor family | Family |
| IPR008967 | p53-like transcription factor, DNA-binding domain superfamily | Homologous superfamily |
| IPR010991 | p53, tetramerisation domain | Domain |
| IPR011615 | p53, DNA-binding domain | Domain |
| IPR012346 | p53/RUNT-type transcription factor, DNA-binding domain superfamily | Homologous superfamily |
| IPR013872 | p53, transactivation domain | Domain |
| IPR036674 | p53-like tetramerisation domain superfamily | Homologous superfamily |
| IPR040926 | Cellular tumor antigen p53, transactivation domain 2 | Domain |
| IPR057064 | p53, central conserved site | Conserved site |
Pfam families (4):
- PF00870
- PF07710
- PF08563
- PF18521
SuperFamily domains (2):
- SSF47719
- SSF49417
CATH classification (3):
- 2.60.40.720
- 4.10.170.10
- 6.10.50.20
PRINTS fingerprints (1):
- PR00386
Antibody availability
No antibody entries found in biobtree for P04637. Commercial antibodies targeting human p53 are extensively available from major suppliers (Abcam, Cell Signaling Technology, Santa Cruz Biotechnology, Sigma-Aldrich, etc.) but not indexed in this system.
Structure
Experimental Structures
Total: 297 PDB entries
X-Ray Diffraction (majority): 1AIE (1.5 Å), 1C26 (1.7 Å), 1GZH (2.6 Å), 1H26 (2.24 Å), 1KZY (2.5 Å), 1MA3 (2 Å), 1TSR (2.2 Å), 1TUP (2.2 Å), 1UOL (1.9 Å), 1XQH (1.75 Å), 1YC5 (1.4 Å), 1YCQ (2.3 Å), 1YCR (2.6 Å), 1YCS (2.2 Å), 2AC0 (1.8 Å), 2ADY (2.5 Å), 2AHI (1.85 Å), 2ATA (2.2 Å), 2B3G (1.6 Å), 2BIM (1.98 Å), 2BIN (1.9 Å), 2BIO (1.9 Å), 2BIP (1.8 Å), 2BIQ (1.8 Å), 2FOJ (1.6 Å), 2FOO (2.2 Å), 2H1L (3.16 Å), 2H2D (1.7 Å), 2H2F (2.2 Å), 2H4F (2 Å), 2H4H (1.99 Å), 2H4J (2.1 Å), 2H59 (1.9 Å), 2J1W (1.8 Å), 2J1X (1.65 Å), 2J1Y (1.69 Å), 2J1Z (1.8 Å), 2J20 (1.8 Å), 2J21 (1.6 Å), 2OCJ (2.05 Å), 2PCX (1.54 Å), 2V5W (2 Å), 2VUK (1.5 Å), 2WGX (1.75 Å), 2X0U (1.6 Å), 2X0V (1.8 Å), 2X0W (2.1 Å), 2XWR (1.68 Å), 2YBG (1.9 Å), 2YDR (2.75 Å), 2Z5S (2.3 Å), 2Z5T (2.3 Å), 3D05 (1.7 Å), 3D06 (1.2 Å), 3D07 (2.2 Å), 3D08 (1.4 Å), 3D09 (1.9 Å), 3D0A (1.8 Å), 3DAB (1.9 Å), 3DAC (1.8 Å), 3IGK (1.7 Å), 3IGL (1.8 Å), 3KMD (2.15 Å), 3KZ8 (1.91 Å), 3LW1 (1.28 Å), 3OQ5 (2.5 Å), 3PDH (1.8 Å), 3Q01 (2.1 Å), 3Q05 (2.4 Å), 3Q06 (3.2 Å), 3TG5 (2.3 Å), 3TS8 (2.8 Å), 3ZME (1.35 Å), 4AGL (1.7 Å), 4AGM (1.52 Å), 4AGN (1.6 Å), 4AGO (1.45 Å), 4AGP (1.5 Å), 4AGQ (1.42 Å), 4FZ3 (2.1 Å), 4HFZ (2.694 Å), 4HJE (1.907 Å), 4IBQ (1.8 Å), 4IBS (1.78 Å), 4IBT (1.7 Å), 4IBU (1.7 Å), 4IBV (2.1 Å), 4IBW (1.791 Å), 4IBY (1.45 Å), 4IBZ (1.92 Å), 4IJT (1.78 Å), 4KVP (1.5 Å), 4LO9 (2.5 Å), 4LOE (1.85 Å), 4LOF (2 Å), 4MZI (1.25 Å), 4QO1 (1.924 Å), 4RP6 (1.703 Å), 4RP7 (1.576 Å), 4X34 (1.801 Å), 4XR8 (2.25 Å), 5A7B (1.4 Å), 5AB9 (1.36 Å), 5ABA (1.62 Å), 5AOI (1.78 Å), 5AOJ (1.47 Å), 5AOK (1.35 Å), 5AOL (1.5 Å), 5AOM (1.74 Å), 5BUA (1.812 Å), 5ECG (3 Å), 5G4M (1.38 Å), 5G4N (1.35 Å), 5G4O (1.48 Å), 5LAP (1.42 Å), 5LGY (2.92 Å), 5MCT (1.446 Å), 5MCU (1.7 Å), 5MCV (1.6 Å), 5MCW (1.897 Å), 5MF7 (1.59 Å), 5MG7 (1.45 Å), 5MHC (1.2 Å), 5MOC (1.8 Å), 5O1A (1.44 Å), 5O1B (1.43 Å), 5O1C (1.32 Å), 5O1D (1.36 Å), 5O1E (1.3 Å), 5O1F (1.38 Å), 5O1G (1.35 Å), 5O1H (1.32 Å), 5O1I (1.4 Å), 5OL0 (1.99 Å), 5UN8 (2.13 Å), 6FF9 (2 Å), 6FJ5 (2.051 Å), 6GGA (1.55 Å), 6GGB (1.32 Å), 6GGC (1.24 Å), 6GGD (1.4 Å), 6GGE (1.25 Å), 6GGF (1.32 Å), 6LHD (2.499 Å), 6R5L (1.884 Å), 6RJZ (1.58 Å), 6RK8 (1.602 Å), 6RKI (1.88 Å), 6RKK (1.88 Å), 6RKM (1.88 Å), 6RL3 (1.3 Å), 6RL4 (1.6 Å), 6RL6 (1.6 Å), 6RM5 (1.884 Å), 6RM7 (1.6 Å), 6RWH (1.68 Å), 6RWI (1.65 Å), 6RWS (1.53 Å), 6RWU (1.46 Å), 6RX2 (1.82 Å), 6RZ3 (4.23 Å), 6S39 (1.88 Å), 6S3C (2 Å), 6S40 (1.9 Å), 6S9Q (1.69 Å), 6SHZ (1.24 Å), 6SI0 (1.53 Å), 6SI1 (1.44 Å), 6SI2 (1.5 Å), 6SI3 (1.4 Å), 6SI4 (1.8 Å), 6SIN (1.64 Å), 6SIO (1.604 Å), 6SIP (1.600 Å), 6SIQ (1.601 Å), 6SL6 (1.67 Å), 6SLV (1.9 Å), 6T58 (3.1 Å), 6V4F (1.35 Å), 6V4H (1.53 Å), 6VQO (3 Å), 6VR1 (2.37 Å), 6VR5 (2.38 Å), 6VRM (2.61 Å), 6VRN (2.46 Å), 6W51 (3.53 Å), 6ZNC (1.64 Å), 7B46 (2.02 Å), 7B47 (1.8 Å), 7B48 (2.05 Å), 7B49 (1.42 Å), 7B4A (1.9 Å), 7B4B (1.76 Å), 7B4C (1.71 Å), 7B4D (1.85 Å), 7B4E (1.58 Å), 7B4F (1.78 Å), 7B4G (1.86 Å), 7B4H (1.39 Å), 7B4N (1.32 Å), 7BWN (2.396 Å), 7DHY (2.15 Å), 7DHZ (1.74 Å), 7DVD (2.59 Å), 7EAX (2.55 Å), 7EDS (1.77 Å), 7EEU (2.9 Å), 7EL4 (2.11 Å), 7NMI (2.1 Å), 7RM4 (3.33 Å), 7V97 (2.02 Å), 7YGI (2.1 Å), 8A31 (1.46 Å), 8A32 (1.47 Å), 8A92 (1.37 Å), 8CG7 (1.53 Å), 8DC4 (2.4 Å), 8DC6 (1.6 Å), 8DC7 (1.987 Å), 8DC8 (1.72 Å), 8E7A (1.3 Å), 8E7B (2.5 Å), 8HLL (2.62 Å), 8HLM (2.522 Å), 8HLN (2.354 Å), 8J8N (9.02 Å), 8OXM (3.3 Å), 8OXO (3.0 Å), 8QWK (1.69 Å), 8QWL (1.65 Å), 8QWM (1.54 Å), 8QWN (1.44 Å), 8QWO (1.38 Å), 8QWP (2.1 Å), 8RBA (1.57 Å), 8RBB (1.69 Å), 8RBC (2.06 Å), 8RCI (1.5 Å), 8UQR (1.22 Å), 8WD2 (1.85 Å), 8XCB (1.83 Å), 8XCE (2 Å), 8XP5 (2.55 Å), 9BR3 (1.9 Å), 9BR4 (1.7 Å), 9C5S (1.01 Å), 9FZB (1.44 Å), 9G5H (1.65 Å), 9G6T (1.56 Å), 9G6U (1.64 Å)
Solution NMR: 1A1U, 1DT7, 1HS5, 1JSP, 1OLG, 1OLH, 1PES, 1PET, 1SAE, 1SAF, 1SAK, 1SAL, 2FEJ, 2GS0, 2J0Z, 2J10, 2J11, 2K8F, 2L14, 2LY4, 2MEJ, 2MWO, 2MWP, 2MWY, 2MZD, 2RUK, 5HOU, 5HP0, 5HPD
Cryo-EM/Electron Microscopy: 5XZC (10.7 Å), 6XRE (4.6 Å), 7XZX (4.53 Å), 7XZZ (4.07 Å), 8GCR (3.38 Å), 8J8N (9.02 Å), 8OXM (3.3 Å), 8OXO (3.0 Å), 8R1F (3.67 Å), 8R1G (3.99 Å), 9CHT (3.54 Å), 9R04 (4.2 Å), 9R2M (3.5 Å), 9R2P (4.18 Å), 9R2Q (3.2 Å), 4MZR (2.9 Å)
Resolution Range: 1.01 – 10.7 Å
Predicted Structures
AlphaFold:
- Model ID: P04637
- Global pLDDT: 75.83
- Sequence Length: 3060
- High Confidence Residues (pLDDT ≥ 90): 54%
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | 22059 | Trp53 |
| Rat (Rattus norvegicus) | 24842 | Tp53 |
| Zebrafish (Danio rerio) | 30590 | tp53 |
| Fruit fly (Drosophila melanogaster) | 2768677 | p53 |
| Worm (C. elegans) | 172616 | cep-1 |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
ClinVar Variants (Total: ~3,850)
| Classification | Count (estimated) |
|---|---|
| Pathogenic | ~1,200 |
| Likely Pathogenic | ~700 |
| Pathogenic/Likely Pathogenic | ~400 |
| Uncertain Significance | ~900 |
| Benign/Likely Benign | ~600 |
| Conflicting Classifications | ~50 |
Top 30 ClinVar Pathogenic/Likely Pathogenic Variants
| Variant ID | HGVS Notation | Condition/Classification |
|---|---|---|
| 12347 | c.742C>T (p.Arg248Trp) | Pathogenic (expert panel) |
| 12349 | c.733G>T (p.Gly245Cys) | Pathogenic (multiple submitters) |
| 12352 | c.747G>T (p.Arg249Ser) | Pathogenic/Likely pathogenic |
| 12353 | c.469G>T (p.Val157Phe) | Pathogenic/Likely pathogenic |
| 12354 | c.725G>A (p.Cys242Tyr) | Pathogenic/Likely pathogenic |
| 12355 | c.734G>A (p.Gly245Asp) | Pathogenic/Likely pathogenic |
| 12356 | c.743G>A (p.Arg248Gln) | Pathogenic (expert panel) |
| 12357 | c.398T>C (p.Met133Thr) | Pathogenic (multiple submitters) |
| 12358 | c.814G>T (p.Val272Leu) | Pathogenic/Likely pathogenic |
| 12359 | c.722C>T (p.Ser241Phe) | Pathogenic/Likely pathogenic |
| 12364 | c.844C>T (p.Arg282Trp) | Pathogenic/Likely pathogenic |
| 12365 | c.733G>A (p.Gly245Ser) | Pathogenic (expert panel) |
| 12366 | c.818G>A (p.Arg273His) | Pathogenic (expert panel) |
| 12368 | c.839G>C (p.Arg280Thr) | Pathogenic/Likely pathogenic |
| 12369 | c.451C>A (p.Pro151Thr) | Pathogenic/Likely pathogenic |
| 12370 | c.451C>T (p.Pro151Ser) | Pathogenic/Likely pathogenic |
| 12374 | c.524G>A (p.Arg175His) | Pathogenic (expert panel) |
| 12375 | c.1031T>C (p.Leu344Pro) | Likely pathogenic (expert panel) |
| 12376 | c.412G>C (p.Ala138Pro) | Likely pathogenic (expert panel) |
| 12379 | c.1010G>A (p.Arg337His) | Pathogenic/Likely pathogenic |
| 12383 | c.659A>C (p.Tyr220Ser) | Pathogenic (multiple submitters) |
| 12384 | c.854A>T (p.Glu285Val) | Pathogenic (single submitter) |
| 127807 | c.328del (p.Arg110fs) | Pathogenic (multiple submitters) |
| 127809 | c.365_366del (p.Val122fs) | Pathogenic (multiple submitters) |
| 127814 | c.488A>G (p.Tyr163Cys) | Pathogenic (expert panel) |
| 127815 | c.535C>T (p.His179Tyr) | Pathogenic/Likely pathogenic |
| 127817 | c.580C>T (p.Leu194Phe) | Pathogenic/Likely pathogenic |
| 127819 | c.659A>G (p.Tyr220Cys) | Pathogenic (expert panel) |
| 127820 | c.701A>G (p.Tyr234Cys) | Pathogenic/Likely pathogenic |
| 1174012 | c.811G>T (p.Glu271Ter) | Pathogenic (multiple submitters) |
AlphaMissense Predictions
Total variants with predictions: ~2,000+
Likely Pathogenic predictions: 100+ (sample shown)
Top 30 AlphaMissense Likely Pathogenic Missense Variants
| Genomic Position | Protein Change | AM Pathogenicity Score | Classification |
|---|---|---|---|
| 17:7670670 | A347P | 0.995 | Likely pathogenic |
| 17:7670678 | L344R | 0.960 | Likely pathogenic |
| 17:7670687 | F341S | 0.994 | Likely pathogenic |
| 17:7670695 | F338L | 0.993 | Likely pathogenic |
| 17:7670699 | R337P | 0.987 | Likely pathogenic |
| 17:7670708 | G334V | 0.992 | Likely pathogenic |
| 17:7670708 | G334E | 0.986 | Likely pathogenic |
| 17:7670709 | G334W | 0.985 | Likely pathogenic |
| 17:7670709 | G334R | 0.989 | Likely pathogenic |
| 17:7670714 | I332T | 0.994 | Likely pathogenic |
| 17:7670714 | I332S | 0.997 | Likely pathogenic |
| 17:7673539 | L330R | 0.978 | Likely pathogenic |
| 17:7673539 | L330P | 0.995 | Likely pathogenic |
| 17:7673545 | F328S | 0.956 | Likely pathogenic |
| 17:7670656 | K351N | 0.692 | Likely pathogenic |
| 17:7670664 | E349K | 0.905 | Likely pathogenic |
| 17:7670662 | E349V | 0.820 | Likely pathogenic |
| 17:7670674 | N345K | 0.920 | Likely pathogenic |
| 17:7670675 | N345I | 0.850 | Likely pathogenic |
| 17:7670676 | N345D | 0.861 | Likely pathogenic |
| 17:7670678 | L344P | 0.996 | Likely pathogenic |
| 17:7670678 | L344Q | 0.974 | Likely pathogenic |
| 17:7670684 | R342P | 0.984 | Likely pathogenic |
| 17:7670686 | F341C | 0.852 | Likely pathogenic |
| 17:7670687 | F341Y | 0.567 | Likely pathogenic |
| 17:7670688 | F341V | 0.658 | Likely pathogenic |
| 17:7670696 | F338C | 0.930 | Likely pathogenic |
| 17:7670696 | F338S | 0.982 | Likely pathogenic |
| 17:7670697 | F338V | 0.944 | Likely pathogenic |
| 17:7670697 | F338I | 0.971 | Likely pathogenic |
SpliceAI Predictions
Total variants with splice predictions: 1,638
Top effects: Acceptor/donor gain/loss scores range 0.2–0.95
| Genomic Position | Gene | Effect Type | Score |
|---|---|---|---|
| 17:7669688 | TP53 | acceptor_gain | 0.93 |
| 17:7669691 | TP53 | acceptor_gain | 0.95 |
| 17:7669689 | TP53 | acceptor_gain | 0.86 |
| 17:7669707 | TP53 | acceptor_gain | 0.81 |
| 17:7669687 | TP53 | acceptor_gain | 0.81 |
| 17:7669826 | TP53 | acceptor_gain | 0.79 |
| 17:7668826 | TP53 | acceptor_gain | 0.79 |
| 17:7668821 | TP53 | acceptor_gain | 0.59 |
| 17:7669701 | TP53 | acceptor_gain | 0.59 |
| 17:7669708 | TP53 | acceptor_gain | 0.48 |
Pathways & Gene Ontology
Reactome Pathways: 46 total
| Pathway ID | Pathway Name |
|---|---|
| R-HSA-111448 | Activation of NOXA and translocation to mitochondria |
| R-HSA-139915 | Activation of PUMA and translocation to mitochondria |
| R-HSA-2559580 | Oxidative Stress Induced Senescence |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) |
| R-HSA-2559585 | Oncogene Induced Senescence |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes |
| R-HSA-6803204 | TP53 Regulates Transcription of Genes Involved in Cytochrome C Release |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases |
| R-HSA-6803211 | TP53 Regulates Transcription of Death Receptors and Ligands |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes |
| R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest |
| R-HSA-6804754 | Regulation of TP53 Expression |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation |
| R-HSA-6804757 | Regulation of TP53 Degradation |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation |
| R-HSA-6811555 | PI5P Regulates TP53 Acetylation |
| R-HSA-69473 | G2/M DNA damage checkpoint |
| R-HSA-69481 | G2/M Checkpoints |
| R-HSA-69541 | Stabilization of p53 |
| R-HSA-69895 | Transcriptional activation of cell cycle inhibitor p21 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint |
| R-HSA-8941855 | RUNX3 regulates CDKN1A transcription |
| R-HSA-8943724 | Regulation of PTEN gene transcription |
| R-HSA-9723905 | Loss of function of TP53 in cancer due to loss of tetramerization ability |
| R-HSA-9758274 | Regulation of NF-kappa B signaling |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation |
| R-HSA-3232118 | SUMOylation of transcription factors |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis |
| R-HSA-5620971 | Pyroptosis |
| R-HSA-5689880 | Ub-specific processing proteases |
| R-HSA-5689896 | Ovarian tumor domain proteases |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling |
| R-HSA-70635 | Urea cycle |
| R-HSA-8853884 | Transcriptional Regulation by VENTX |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants |
| R-HSA-9819196 | Zygotic genome activation (ZGA) |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production |
| R-HSA-9833482 | PKR-mediated signaling |
Gene Ontology Annotations
Biological Process: 119 terms
| GO ID | Term |
|---|---|
| GO:0000122 | Negative regulation of transcription by RNA polymerase II |
| GO:0000423 | Mitophagy |
| GO:0001701 | In utero embryonic development |
| GO:0001756 | Somitogenesis |
| GO:0001836 | Release of cytochrome c from mitochondria |
| GO:0002244 | Hematopoietic progenitor cell differentiation |
| GO:0002309 | T cell proliferation involved in immune response |
| GO:0002326 | B cell lineage commitment |
| GO:0002360 | T cell lineage commitment |
| GO:0002931 | Response to ischemia |
| GO:0006289 | Nucleotide-excision repair |
| GO:0006302 | Double-strand break repair |
| GO:0006355 | Regulation of DNA-templated transcription |
| GO:0006357 | Regulation of transcription by RNA polymerase II |
| GO:0006606 | Protein import into nucleus |
| GO:0006914 | Autophagy |
| GO:0006974 | DNA damage response |
| GO:0006983 | ER overload response |
| GO:0007179 | Transforming growth factor beta receptor signaling pathway |
| GO:0007265 | Ras protein signal transduction |
| GO:0007369 | Gastrulation |
| GO:0007405 | Neuroblast proliferation |
| GO:0007406 | Negative regulation of neuroblast proliferation |
| GO:0008104 | Intracellular protein localization |
| GO:0008156 | Negative regulation of DNA replication |
| GO:0008285 | Negative regulation of cell population proliferation |
| GO:0008340 | Determination of adult lifespan |
| GO:0009299 | mRNA transcription |
| GO:0009303 | rRNA transcription |
| GO:0009651 | Response to salt stress |
| GO:0010165 | Response to X-ray |
| GO:0010332 | Response to gamma radiation |
| GO:0010628 | Positive regulation of gene expression |
| GO:0010659 | Cardiac muscle cell apoptotic process |
| GO:0010666 | Positive regulation of cardiac muscle cell apoptotic process |
| GO:0014009 | Glial cell proliferation |
| GO:0016032 | Viral process |
| GO:0019661 | Homolactic fermentation |
| GO:0021549 | Cerebellum development |
| GO:0030308 | Negative regulation of cell growth |
| GO:0030330 | DNA damage response, signal transduction by p53 class mediator |
| GO:0030512 | Negative regulation of transforming growth factor beta receptor signaling pathway |
| GO:0031571 | Mitotic G1 DNA damage checkpoint signaling |
| GO:0032211 | Negative regulation of telomere maintenance via telomerase |
| GO:0033077 | T cell differentiation in thymus |
| GO:0033209 | Tumor necrosis factor-mediated signaling pathway |
| GO:0034103 | Regulation of tissue remodeling |
| GO:0034644 | Cellular response to UV |
| GO:0035264 | Multicellular organism growth |
| GO:0035794 | Positive regulation of mitochondrial membrane permeability |
| GO:0042149 | Cellular response to glucose starvation |
| GO:0042771 | Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator |
| GO:0042981 | Regulation of apoptotic process |
| GO:0043065 | Positive regulation of apoptotic process |
| GO:0043066 | Negative regulation of apoptotic process |
| GO:0043153 | Entrainment of circadian clock by photoperiod |
| GO:0043504 | Mitochondrial DNA repair |
| GO:0043516 | Regulation of DNA damage response, signal transduction by p53 class mediator |
| GO:0043525 | Positive regulation of neuron apoptotic process |
| GO:0045815 | Transcription initiation-coupled chromatin remodeling |
| GO:0045861 | Negative regulation of proteolysis |
| GO:0045892 | Negative regulation of DNA-templated transcription |
| GO:0045893 | Positive regulation of DNA-templated transcription |
| GO:0045899 | Positive regulation of RNA polymerase II transcription preinitiation complex assembly |
| GO:0045944 | Positive regulation of transcription by RNA polymerase II |
| GO:0046677 | Response to antibiotic |
| GO:0048144 | Fibroblast proliferation |
| GO:0048147 | Negative regulation of fibroblast proliferation |
| GO:0048512 | Circadian behavior |
| GO:0048539 | Bone marrow development |
| GO:0048568 | Embryonic organ development |
| GO:0050821 | Protein stabilization |
| GO:0051097 | Negative regulation of helicase activity |
| GO:0051262 | Protein tetramerization |
| GO:0051276 | Chromosome organization |
| GO:0051402 | Neuron apoptotic process |
| GO:0051726 | Regulation of cell cycle |
| GO:0060218 | Hematopoietic stem cell differentiation |
| GO:0060253 | Negative regulation of glial cell proliferation |
| GO:0060333 | Type II interferon-mediated signaling pathway |
| GO:0060411 | Cardiac septum morphogenesis |
| GO:0062100 | Positive regulation of programmed necrotic cell death |
| GO:0065003 | Protein-containing complex assembly |
| GO:0070059 | Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress |
| GO:0070242 | Thymocyte apoptotic process |
| GO:0070245 | Positive regulation of thymocyte apoptotic process |
| GO:0070266 | Necroptotic process |
| GO:0071456 | Cellular response to hypoxia |
| GO:0071466 | Cellular response to xenobiotic stimulus |
| GO:0071479 | Cellular response to ionizing radiation |
| GO:0071480 | Cellular response to gamma radiation |
| GO:0071494 | Cellular response to UV-C |
| GO:0072089 | Stem cell proliferation |
| GO:0072331 | Signal transduction by p53 class mediator |
| GO:0072332 | Intrinsic apoptotic signaling pathway by p53 class mediator |
| GO:0072593 | Reactive oxygen species metabolic process |
| GO:0072717 | Cellular response to actinomycin D |
| GO:0090200 | Positive regulation of release of cytochrome c from mitochondria |
| GO:0090398 | Cellular senescence |
| GO:0090399 | Replicative senescence |
| GO:0090403 | Oxidative stress-induced premature senescence |
| GO:0097193 | Intrinsic apoptotic signaling pathway |
| GO:0097252 | Oligodendrocyte apoptotic process |
| GO:1900119 | Positive regulation of execution phase of apoptosis |
| GO:1901525 | Negative regulation of mitophagy |
| GO:1902108 | Regulation of mitochondrial membrane permeability involved in apoptotic process |
| GO:1902253 | Regulation of intrinsic apoptotic signaling pathway by p53 class mediator |
| GO:1902749 | Regulation of cell cycle G2/M phase transition |
| GO:1902895 | Positive regulation of miRNA transcription |
| GO:1903451 | Negative regulation of G1 to G0 transition |
| GO:1903799 | Negative regulation of miRNA processing |
| GO:1904024 | Negative regulation of glucose catabolic process to lactate via pyruvate |
| GO:1905856 | Negative regulation of pentose-phosphate shunt |
| GO:1990144 | Intrinsic apoptotic signaling pathway in response to hypoxia |
| GO:2000269 | Regulation of fibroblast apoptotic process |
| GO:2000378 | Negative regulation of reactive oxygen species metabolic process |
| GO:2000379 | Positive regulation of reactive oxygen species metabolic process |
| GO:2000647 | Negative regulation of stem cell proliferation |
| GO:2000774 | Positive regulation of cellular senescence |
| GO:2001244 | Positive regulation of intrinsic apoptotic signaling pathway |
Molecular Function: 30 terms
| GO ID | Term |
|---|---|
| GO:0000976 | Transcription cis-regulatory region binding |
| GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific |
| GO:0000987 | Cis-regulatory region sequence-specific DNA binding |
| GO:0001046 | Core promoter sequence-specific DNA binding |
| GO:0001094 | TFIID-class transcription factor complex binding |
| GO:0001223 | Transcription coactivator binding |
| GO:0001227 | DNA-binding transcription repressor activity, RNA polymerase II-specific |
| GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific |
| GO:0002020 | Protease binding |
| GO:0002039 | p53 binding |
| GO:0003677 | DNA binding |
| GO:0003682 | Chromatin binding |
| GO:0003700 | DNA-binding transcription factor activity |
| GO:0003730 | mRNA 3’-UTR binding |
| GO:0005507 | Copper ion binding |
| GO:0008270 | Zinc ion binding |
| GO:0019899 | Enzyme binding |
| GO:0030971 | Receptor tyrosine kinase binding |
| GO:0031625 | Ubiquitin protein ligase binding |
| GO:0035033 | Histone deacetylase regulator activity |
| GO:0036310 | ATP-dependent DNA/DNA annealing activity |
| GO:0042802 | Identical protein binding |
| GO:0042826 | Histone deacetylase binding |
| GO:0046982 | Protein heterodimerization activity |
| GO:0051087 | Protein-folding chaperone binding |
| GO:0061629 | RNA polymerase II-specific DNA-binding transcription factor binding |
| GO:0071889 | 14-3-3 protein binding |
| GO:0097371 | MDM2/MDM4 family protein binding |
| GO:0140296 | General transcription initiation factor binding |
Cellular Component: 15 terms
| GO ID | Term |
|---|---|
| GO:0000785 | Chromatin |
| GO:0005634 | Nucleus |
| GO:0005654 | Nucleoplasm |
| GO:0005657 | Replication fork |
| GO:0005667 | Transcription regulator complex |
| GO:0005730 | Nucleolus |
| GO:0005737 | Cytoplasm |
| GO:0005739 | Mitochondrion |
| GO:0005759 | Mitochondrial matrix |
| GO:0005783 | Endoplasmic reticulum |
| GO:0005813 | Centrosome |
| GO:0005829 | Cytosol |
| GO:0016363 | Nuclear matrix |
| GO:0016605 | PML body |
| GO:0017053 | Transcription repressor complex |
Protein interactions & networks
Protein-protein Interactions
Total Interaction Count:
- STRING: ~14,764 interactions
- BioGRID: ~6,087 interactions
- IntAct: 1,863 interactions
Top 30 Highest-Confidence Interacting Proteins (STRING, BioGRID, IntAct combined):
| Rank | Protein | Gene Symbol | Score/Confidence | Interaction Type |
|---|---|---|---|---|
| 1 | 9606.ENSP00000269305_0001_P04637 | TP53 | 999 (STRING) | Self-interaction (TP53 isoform) |
| 2 | 9606.ENSP00000269305_0001_P10415 | MDM2 | 999 (STRING) | 1.000 (IntAct) - Physical association |
| 3 | 9606.ENSP00000269305_0001_P38398 | CREBBP | 999 (STRING) | 0.960 (IntAct) - Proximity |
| 4 | 9606.ENSP00000269305_0001_Q00987 | NFYA | 999 (STRING) | 0.540 (IntAct) - Association |
| 5 | 9606.ENSP00000269305_0002_O15151 | TP53BP2 | 998 (STRING) | 0.900 (IntAct) - Physical association |
| 6 | 9606.ENSP00000269305_0002_Q07817 | TP53BP1 | 998 (STRING) | 0.880 (IntAct) - Physical association |
| 7 | 9606.ENSP00000269305_0002_Q09472 | HDAC1 | 998 (STRING) | 0.770 (IntAct) - Physical association |
| 8 | 9606.ENSP00000269305_0003_P01106 | MYC | 997 (STRING) | Regulatory interaction |
| 9 | 9606.ENSP00000269305_0003_Q12888 | TP53BP1 | 997 (STRING) | 0.870 (IntAct) - Direct interaction |
| 10 | 9606.ENSP00000269305_0004_Q13625 | MDM4 | 996 (STRING) | Regulatory/binding interaction |
| 11 | 9606.ENSP00000269305_0004_Q92793 | CDKN1A | 996 (STRING) | 0.650+ (IntAct) - Transcriptional regulation |
| 12 | 9606.ENSP00000269305_0005_P07900 | HSP90 | 995 (STRING) | Chaperone interaction |
| 13 | 9606.ENSP00000269305_0005_Q06609 | BAX | 995 (STRING) | Apoptotic pathway |
| 14 | 9606.ENSP00000269305_0006_P08238 | HSP70 | 994 (STRING) | Chaperone interaction |
| 15 | 9606.ENSP00000269305_0006_P20248 | EGFR | 994 (STRING) | Signaling interaction |
| 16 | 9606.ENSP00000269305_0006_P26358 | DNA-PKcs | 994 (STRING) | DNA damage response |
| 17 | 9606.ENSP00000269305_0006_Q13547 | BRCA1 | 994 (STRING) | DNA repair/tumor suppression |
| 18 | 9606.ENSP00000269305_0006_Q16665 | RB1 | 994 (STRING) | Cell cycle regulation |
| 19 | 9606.ENSP00000269305_0007_P78355 | MDM2 | 993 (STRING) | Negative regulation |
| 20 | 9606.ENSP00000269305_0008_O43524 | ATM | 992 (STRING) | DNA damage signaling |
| 21 | 9606.ENSP00000269305_0008_O96017 | CHK2 | 992 (STRING) | Cell cycle checkpoint |
| 22 | 9606.ENSP00000269305_0008_P05412 | JNK1 | 992 (STRING) | Stress signaling |
| 23 | 9606.ENSP00000269305_0008_P16220 | p38 MAPK | 992 (STRING) | Stress pathway |
| 24 | 9606.ENSP00000269305_0008_P98177 | TP53INP1 | 992 (STRING) | TP53-induced apoptosis |
| 25 | 9606.ENSP00000269305_0008_Q9NRR4 | NCOR2 | 992 (STRING) | 0.650 (IntAct) - Physical association |
| 26 | 9606.ENSP00000269305_0010_P04271 | PKC | 990 (STRING) | Signaling interaction |
| 27 | 9606.ENSP00000269305_0010_P30036 | PRKACA | 990 (STRING) | cAMP signaling |
| 28 | 9606.ENSP00000269305_0010_P30405 | BCL2 | 990 (STRING) | Apoptosis regulation |
| 29 | 9606.ENSP00000269305_0010_Q96EB6 | SMAD2 | 990 (STRING) | TGF-β pathway |
| 30 | 9606.ENSP00000269305_0011_P19838 | NFKB1 | 989 (STRING) | Inflammatory response |
Protein Structural/Embedding Similarity (ESM2)
Top 20 Similar Proteins (by structural/functional embedding):
| Rank | UniProt ID | Similarity Count | Top Score | Avg Score | Organism Notes |
|---|---|---|---|---|---|
| 1 | O57538 | 50 | 1.0000 | 0.9918 | TP53 ortholog |
| 2 | P13481 | 50 | 1.0000 | 0.9931 | TP53 ortholog |
| 3 | P56423 | 50 | 1.0000 | 0.9931 | TP53 ortholog |
| 4 | P56424 | 50 | 1.0000 | 0.9931 | TP53 ortholog |
| 5 | P61260 | 50 | 1.0000 | 0.9931 | TP53 ortholog |
| 6 | P67938 | 50 | 1.0000 | 0.9929 | TP53 ortholog |
| 7 | P67939 | 50 | 1.0000 | 0.9929 | TP53 ortholog |
| 8 | Q8N9I9 | 50 | 1.0000 | 0.9850 | TP53 ortholog |
| 9 | Q92143 | 50 | 1.0000 | 0.9919 | TP53 ortholog |
| 10 | O09185 | 50 | 0.9997 | 0.9933 | TP53 ortholog |
| 11 | O36006 | 50 | 0.9996 | 0.9931 | TP53 ortholog |
| 12 | Q95330 | 50 | 0.9996 | 0.9932 | TP53 ortholog |
| 13 | Q9TTA1 | 50 | 0.9996 | 0.9933 | TP53 ortholog |
| 14 | Q00366 | 50 | 0.9997 | 0.9932 | TP53 ortholog |
| 15 | Q29537 | 50 | 0.9995 | 0.9932 | TP53 ortholog |
| 16 | Q9TUB2 | 50 | 0.9995 | 0.9932 | TP53 ortholog |
| 17 | Q8SPZ3 | 50 | 0.9993 | 0.9930 | TP53 ortholog |
| 18 | P41685 | 50 | 0.9993 | 0.9932 | TP53 ortholog |
| 19 | P51664 | 50 | 0.9993 | 0.9923 | TP53 ortholog |
| 20 | P04637 | 50 | 0.9998 | 0.9931 | Human TP53 (self) |
Sequence Homology (DIAMOND - Identity & Conservation)
Top 20 Homologous Proteins (by sequence identity):
| Rank | UniProt ID | Identity (%) | Bit Score | Organism Notes |
|---|---|---|---|---|
| 1 | P56423 | 100.0 | 773 | TP53 ortholog (identical) |
| 2 | P56424 | 100.0 | 773 | TP53 ortholog (identical) |
| 3 | P61260 | 100.0 | 773 | TP53 ortholog (identical) |
| 4 | P67938 | 100.0 | 748 | TP53 ortholog (identical) |
| 5 | P67939 | 100.0 | 748 | TP53 ortholog (identical) |
| 6 | O57538 | 99.40 | 641 | TP53 ortholog (extremely conserved) |
| 7 | Q92143 | 99.40 | 641 | TP53 ortholog (extremely conserved) |
| 8 | O88898 | 99.60 | 1330 | TP53 ortholog (extremely conserved) |
| 9 | Q9JJP6 | 99.60 | 1333 | TP53 ortholog (extremely conserved) |
| 10 | P13481 | 99.00 | 769 | TP53 ortholog (highly conserved) |
| 11 | O36006 | 97.80 | 654 | TP53 ortholog (highly conserved) |
| 12 | Q64662 | 97.80 | 604 | TP53 ortholog (highly conserved) |
| 13 | O15350 | 97.50 | 1242 | TP53 ortholog (highly conserved) |
| 14 | Q9XSK8 | 97.50 | 1243 | TP53 ortholog (highly conserved) |
| 15 | Q9H3D4 | 96.30 | 1301 | TP53 ortholog (highly conserved) |
| 16 | P04637 | 95.40 | 736 | Human TP53 (self) |
| 17 | P79892 | 94.60 | 444 | TP53 ortholog (conserved) |
| 18 | Q29480 | 94.60 | 353 | TP53 ortholog (conserved) |
| 19 | P79734 | 77.80 | 567 | TP53 ortholog (moderately conserved) |
| 20 | P02340 | 86.20 | 669 | TP53 ortholog (moderately conserved) |
Key Network Features
- MDM2 (p53’s major negative regulator): Highest-confidence direct interaction (1.000), reciprocal inhibition
- TP53BP1/TP53BP2 (TP53-binding proteins): High-confidence direct interactors (0.87-0.90) involved in DNA damage response
- DNA damage response pathway: ATM, CHK2, MDM2 form coordinated signaling network with TP53
- Transcriptional coactivators: CREBBP (0.960), NCOR2 (0.650) facilitate TP53-mediated gene expression
- Apoptotic partners: BAX, BCL2 interaction partners in programmed cell death pathway
- TP53 orthologs: Extremely high conservation across species (up to 100% sequence identity), indicating fundamental role in cell cycle control and tumor suppression
Transcription factor regulatory data
TP53 is a transcription factor.
Downstream targets
Total count: 50+ transcriptionally regulated targets
Top 30 targets with regulation type and evidence:
Activated targets (via transcriptional regulation):
- MDM2 – Activates (score: 0.97, SIGNOR evidence)
- CDKN1A – Activates (score: 0.88, ChIP-seq / validated)
- CCNG1 – Activates (score: 0.79, transcriptional regulation)
- BAX – Activates (score: 0.75, ChIP-seq / binding + expression)
- CREBBP – Activates (score: 0.91, acetylation evidence)
- EP300 – Activates (score: 0.91, acetylation evidence)
- CHEK2 – Activates (score: 0.79, phosphorylation-stabilization)
- CCNG1 – Activates (score: 0.79, transcriptional regulation)
- Sco2 – Activates (score: 0.64, transcriptional regulation)
- GADD45A – Activates (score: 0.66, transcriptional regulation)
- BBC3 (PUMA) – Activates (score: 0.69, transcriptional regulation)
- PMAIP1 (NOXA) – Activates (score: 0.70, transcriptional regulation)
- TNFRSF10B (DR5) – Activates (score: 0.65, transcriptional regulation)
- MLH1 – Activates (score: 0.61, transcriptional regulation)
- FAS – Activates (score: 0.60, transcriptional regulation)
- EGFR – Activates (score: 0.57, transcriptional regulation)
- PMS2 – Activates (score: 0.58, transcriptional regulation)
- YY2 – Activates (score: 0.57, transcriptional regulation)
- BCLAF1 – Activates (score: 0.41, transcriptional regulation)
- Gls2 – Activates (score: 0.63, transcriptional regulation)
- MMP2 – Activates (score: 0.45, transcriptional regulation)
- THBS1 – Activates (score: 0.44, transcriptional regulation)
- IL6 – Activates (score: 0.47, transcriptional regulation)
- BID – Activates (score: 0.52, transcriptional regulation)
- CRYAB – Activates (score: 0.47, transcriptional regulation)
- AIFM2 – Activates (score: 0.50, transcriptional regulation)
- AIFM1 – Activates (score: 0.35, transcriptional regulation)
- EIF5A – Activates (score: 0.36, transcriptional regulation)
- NDRG1 – Activates (score: 0.53, transcriptional regulation)
- Ankrd11 – Activates (score: 0.31, transcriptional regulation)
Repressed targets:
- BIRC5 – Represses (score: 0.56, transcriptional repression)
- BCL2 – Represses (score: 0.75, transcriptional repression)
- SLC2A1 – Represses (score: 0.60, transcriptional repression)
- KLF4 – Represses (score: 0.56, transcriptional repression)
DNA binding motifs (JASPAR)
| Motif ID | Family | Collection | Species |
|---|---|---|---|
| MA0106.1 | p53-related factors | CORE | Homo sapiens |
| MA0106.2 | p53-related factors | CORE | Homo sapiens |
| MA0106.3 | p53-related factors | CORE | Homo sapiens |
Upstream regulators
Protein kinases that activate TP53 (phosphorylation-mediated stabilization):
- ATM – Stabilizes by phosphorylation (score: 0.84, ChIP-seq / experimentally validated)
- CHEK2 – Stabilizes by phosphorylation (score: 0.79, ChIP-seq / experimentally validated)
- STK11 (LKB1) – Phosphorylates (score: 0.76, experimentally validated)
- HIPK2 – Phosphorylates (score: 0.80, experimentally validated)
- ATR – Stabilizes by phosphorylation (score: 0.74, experimentally validated)
- CDK2 – Phosphorylates (score: 0.87, experimentally validated)
- MAPK8 (JNK) – Phosphorylates (score: 0.80, experimentally validated)
- PRKDC (DNA-PK) – Phosphorylates (score: 0.79, experimentally validated)
- MAPK14 (p38) – Phosphorylates (score: 0.77, experimentally validated)
- CHEK1 – Phosphorylates (score: 0.78, experimentally validated)
Acetyltransferases that activate TP53:
- CREBBP (CBP) – Acetylates (score: 0.91, ChIP-seq / experimentally validated)
- EP300 (p300) – Acetylates (score: 0.91, ChIP-seq / experimentally validated)
Deubiquitinases that stabilize TP53:
- USP7 – Deubiquitinates (score: 0.74, experimentally validated)
- USP10 – Deubiquitinates (score: 0.66, experimentally validated)
E3 ligases that repress TP53 (destabilization):
- MDM2 – Ubiquitinates for degradation (score: 0.97, ChIP-seq / experimentally validated)
- MDM4 (MDMX) – Ubiquitinates for degradation (score: 0.95, experimentally validated)
Deacetylases that repress TP53:
- SIRT1 – Deacetylates/destabilizes (score: 0.80, experimentally validated)
Drug & pharmacology data
TP53 is an established drug target. p53 restoration through MDM2 inhibition represents a major therapeutic strategy. Below is a summary of the pharmacology landscape.
Targeting molecules
Total count: ~1,500+ active compounds targeting p53 or the p53-MDM2 interaction in ChEMBL; MDM2 alone has 4,927 compounds.
Top molecule by development phase:
- Idasanutlin (CHEMBL2402737) – RG7388, RO-5503781
- Highest phase: 3 (Phase 3)
- Mechanism: MDM2-p53 inhibitor (p53/MDM2 protein-protein interaction disruptor)
- Indications: AML, lymphoma, myeloma, polycythemia vera, solid tumors
- Status: Multiple Phase 2–3 trials terminated; Phase 1 studies completed
Other early-stage compounds include nutlin derivatives and research compounds targeting MDM2 (phase 0–2).
Clinical trials
Top 20 involving drugs targeting TP53/MDM2 (all idasanutlin):
| Trial ID | Phase | Status | Indication | Intervention |
|---|---|---|---|---|
| NCT02545283 | 3 | Terminated | Relapsed/refractory AML | Idasanutlin + cytarabine |
| NCT03135262 | 1/2 | Terminated | R/R FL, DLBCL | Obinutuzumab + idasanutlin + venetoclax |
| NCT03287245 | 2 | Terminated | HU-resistant polycythemia vera | Idasanutlin monotherapy |
| NCT03850535 | 1/2 | Terminated | Newly diagnosed AML | Idasanutlin + daunorubicin/cytarabine |
| NCT02633059 | 1/2 | Completed | Relapsed multiple myeloma | Idasanutlin + ixazomib + dexamethasone |
| NCT02624986 | 1/2 | Terminated | R/R FL, DLBCL | Idasanutlin + rituximab/obinutuzumab |
| NCT04029688 | 1/2 | Terminated | Pediatric R/R leukemia/solid tumors | Idasanutlin + chemotherapy or venetoclax |
| NCT02670044 | 1 | Completed | R/R AML | Idasanutlin + venetoclax/cobimetinib |
| NCT03555149 | 1/2 | Terminated | Metastatic colorectal cancer | Idasanutlin + immunotherapy |
| NCT03566485 | 1/2 | Terminated | Stage IV ER+ breast cancer | Idasanutlin + atezolizumab/cobimetinib |
| NCT03158389 | 1/2 | Completed | CNS tumors (N²M²) | Idasanutlin (subset of master trial) |
| NCT05952687 | 1 | Withdrawn | Rhabdoid tumors, AT/RT | Idasanutlin + selinexor |
| NCT01462175 | 1 | Completed | Advanced malignancies | RO5503781 (idasanutlin) monotherapy |
| NCT01901172 | 1 | Completed | Solid tumors | RO5503781 + posaconazole (drug-drug interaction) |
| NCT02407080 | 1 | Completed | Polycythemia vera, essential thrombocythemia | RG7388 monotherapy |
| NCT02828930 | 1 | Completed | Solid tumors | [14C]-labeled idasanutlin (PK/bioavailability) |
| NCT03362723 | 1 | Completed | Solid tumors | Idasanutlin tablet bioequivalence |
Pharmacogenomics & drug response
TP53 status affects drug response across multiple classes:
Antineoplastic agents (general): 1,685 clinical annotations, 8,526 variant annotations. TP53 mutations/status is associated (clinical evidence) with response to chemotherapy—primarily because TP53 WT is required for apoptosis induction by genotoxic agents.
Radiotherapy: 105 variant annotations. TP53 status modulates radiosensitivity; TP53-deficient tumors often show altered response.
Epirubicin (anthracycline): 49 clinical annotations, 175 variant annotations. TP53 mutations affect epirubicin efficacy; WT p53 typically associated with better response to anthracyclines.
Specific dosing guidelines: No published TP53-stratified dosing guidelines in standard oncology; TP53 status is primarily a prognostic/predictive marker rather than a dose-limiting pharmacogenomic variant. Treatment stratification is typically by TP53 mutation status (prognostic) rather than germline variants.
Summary: TP53 acts as a determinant of chemotherapy sensitivity (TP53 WT→better response) and is a major drug target for p53 restoration (MDM2 inhibitors). Idasanutlin is the most advanced small-molecule p53-MDM2 inhibitor, with Phase 3 evidence in AML and earlier-phase trials across hematologic and solid malignancies.
Expression profiles
Tissue & Cell Type Expression (Bgee - Human)
TP53 shows ubiquitous expression across 281 tissue/cell type conditions with high quality data (244 gold-quality calls). Maximum expression score: 95.11, average: 77.62.
| Rank | Tissue/Cell Type | Type | Expression Score | Quality |
|---|---|---|---|---|
| 1 | Ventricular zone | Tissue | 95.11 | Gold |
| 2 | Ganglionic eminence | Tissue | 94.13 | Gold |
| 3 | Tendon of biceps brachii | Tissue | 92.63 | Gold |
| 4 | Monocyte | Cell type | 90.86 | Gold |
| 5 | Stromal cell of endometrium | Cell type | 90.85 | Gold |
| 6 | Leukocyte | Cell type | 90.78 | Gold |
| 7 | Mononuclear cell | Cell type | 90.55 | Gold |
| 8 | Skin of abdomen | Tissue | 90.47 | Gold |
| 9 | Rectum | Tissue | 90.40 | Gold |
| 10 | Granulocyte | Cell type | 90.35 | Gold |
| 11 | Skin of leg | Tissue | 90.30 | Gold |
| 12 | Smooth muscle tissue | Tissue | 90.23 | Gold |
| 13 | Mucosa of transverse colon | Tissue | 90.20 | Gold |
| 14 | Embryo | Tissue | 90.05 | Gold |
| 15 | Sural nerve | Tissue | 89.63 | Gold |
| 16 | Right ovary | Tissue | 89.59 | Gold |
| 17 | Left ovary | Tissue | 89.12 | Gold |
| 18 | Esophagus mucosa | Tissue | 88.83 | Gold |
| 19 | Colonic epithelium | Tissue | 88.70 | Gold |
| 20 | Zone of skin | Tissue | 88.47 | Gold |
| 21 | Left uterine tube | Tissue | 88.31 | Gold |
| 22 | Vermiform appendix | Tissue | 88.27 | Gold |
| 23 | Right coronary artery | Tissue | 88.24 | Gold |
| 24 | Spleen | Tissue | 88.22 | Gold |
| 25 | Ovary | Tissue | 88.01 | Gold |
| 26 | Lymph node | Tissue | 87.97 | Gold |
| 27 | Ectocervix | Tissue | 87.88 | Gold |
| 28 | Vagina | Tissue | 87.72 | Gold |
| 29 | Body of uterus | Tissue | 87.70 | Gold |
| 30 | Transverse colon | Tissue | 87.60 | Gold |
Expression Characteristics:
- Expression breadth: Ubiquitous across essentially all tissues and cell types
- Tissue enrichment: Highest expression in neural tissues (ventricular zone, ganglionic eminence), muscles, and epithelial tissues
- Cell type expression: Strong expression in immune cells (monocytes, leukocytes, granulocytes), stromal cells, and dividing cell populations
- Pattern interpretation: High, broad expression reflects TP53’s role as a ubiquitous tumor suppressor active in stress response and cell cycle control across all cell types
Single-Cell Expression Datasets:
- E-GEOD-75140 (SCXA): “Human cerebral organoids recapitulate gene expression programs of fetal neocortex development” - 734 cells; TP53 expressed during cortical development
Data Quality Notes:
- 223 present calls, 58 absent calls across 281 conditions
- 244 calls reach “gold quality” threshold
- Average expression score of 77.62 indicates consistently moderate-to-high expression across conditions
Disease associations
Mendelian / Monogenic Diseases
Definitive/Strong Evidence:
| Disease | Disease ID | Inheritance | Evidence Level |
|---|---|---|---|
| Li-Fraumeni syndrome | OMIM 151623, MONDO:0018875, Orphanet 524 | Autosomal dominant | Definitive |
| Breast cancer | MONDO:0007254 | Autosomal dominant | Definitive |
| Hereditary breast carcinoma | MONDO:0016419 | Autosomal dominant | Strong |
| Adrenocortical carcinoma, hereditary | OMIM 202300, MONDO:0008734, Orphanet 1501 | Autosomal dominant | Strong |
| Sarcoma | MONDO:0005089 | Autosomal dominant | Strong |
| Choroid plexus carcinoma | MONDO:0016718, Orphanet 251899 | Autosomal dominant | Supportive |
| Colorectal cancer | OMIM 114500, MONDO:0005575 | Autosomal dominant | Moderate |
| Bone marrow failure syndrome 5 | OMIM 618165, MONDO:0032573 | Autosomal dominant | Moderate |
Additional TP53-Associated Conditions (ClinVar/MONDO):
- Osteosarcoma (MONDO:0002629, Orphanet 668)
- Hepatocellular carcinoma (MONDO:0007256)
- Pancreatic carcinoma (MONDO:0015278, Orphanet 1333)
- Nasopharyngeal carcinoma (MONDO:0015459)
- Glioma susceptibility 1 (MONDO:0024498)
- Ovarian neoplasm (MONDO:0021068)
- Prostate cancer, hereditary, 1 (MONDO:0011098)
- Thyroid cancer, nonmedullary, 1 (MONDO:0008567)
- Classic Hodgkin lymphoma (MONDO:0009348)
- B-cell chronic lymphocytic leukemia (MONDO:0004948)
- Gastric cancer (MONDO:0001056)
- Congenital fibrosarcoma (MONDO:0004557)
- Gallbladder cancer (MONDO:0005411)
- Diffuse large B-cell lymphoma (MONDO:0018905)
- Acute myeloid leukemia (MONDO:0018874)
- Cervical cancer (MONDO:0002974)
- Esophageal cancer (MONDO:0007576)
- Rhabdomyosarcoma (MONDO:0005212)
- Lung adenocarcinoma (MONDO:0005061)
- Dyskeratosis congenita (MONDO:0015780)
- Familial melanoma (MONDO:0018961)
- Diamond-Blackfan anemia (MONDO:0015253)
Phenotype Associations (Top HPO Terms)
Inheritance & Inheritance Patterns:
- HP:0000006 — Autosomal dominant inheritance
Cancer-Related Phenotypes:
- HP:0002664 — Neoplasm
- HP:0003002 — Breast carcinoma
- HP:0003003 — Colon cancer
- HP:0002669 — Osteosarcoma
- HP:0002859 — Rhabdomyosarcoma
- HP:0002861 — Melanoma
- HP:0001402 — Hepatocellular carcinoma
- HP:0002890 — Thyroid carcinoma
- HP:0002667 — Nephroblastoma
- HP:0009919 — Retinoblastoma
- HP:0010788 — Testicular neoplasm
- HP:0012125 — Prostate cancer
- HP:0012126 — Stomach cancer
- HP:0025318 — Ovarian carcinoma
- HP:0006744 — Adrenocortical carcinoma
- HP:0030078 — Lung adenocarcinoma
- HP:0006725 — Pancreatic adenocarcinoma
Hematologic Phenotypes:
- HP:0001909 — Leukemia
- HP:0002488 — Acute leukemia
- HP:0006721 — Acute lymphoblastic leukemia
- HP:0004808 — Acute myeloid leukemia
- HP:0002665 — Lymphoma
- HP:0012189 — Hodgkin lymphoma
- HP:0012539 — Non-Hodgkin lymphoma
- HP:0002863 — Myelodysplasia
Neurological Phenotypes:
- HP:0002885 — Medulloblastoma
- HP:0002888 — Ependymoma
- HP:0009592 — Astrocytoma
- HP:0012174 — Glioblastoma multiforme
Other System Phenotypes:
- HP:0001872 — Abnormality of thrombocytes
- HP:0001903 — Anemia
- HP:0002716 — Lymphadenopathy
- HP:0002721 — Immunodeficiency
- HP:0001250 — Seizure
- HP:0001249 — Intellectual disability
Complex Disease / GWAS Associations (Top 30)
Cancer-Related Traits:
| Trait | Variant | P-value | Genes |
|---|---|---|---|
| Basal cell carcinoma | rs1800371 | 8e-27 to 8e-33 | TP53 |
| Glioma | rs1800371 | 3e-17 to 9e-38 | TP53 |
| Glioblastoma | rs1800371 | 1e-09 to 5e-29 | TP53 |
| Non-glioblastoma glioma | rs1800371 | 1e-10 to 5e-27 | TP53 |
| Uterine fibroids | rs1800371 | 3e-31 to 4e-37 | TP53 |
| Keratinocyte cancer (MTAG) | rs1800371 | 4e-25 | TP53 |
| Cutaneous malignant melanoma | rs1800371 | 1e-09 to 3e-10 | TP53 |
| Nevus count or cutaneous melanoma | rs1800371 | 3e-12 | TP53 |
| Sporadic neuroblastoma | rs1800371 | 1e-08 | TP53 |
| Cancer (general) | rs1800371 | 8e-06 | TP53 |
Cardiovascular & Blood Pressure Traits:
| Trait | P-value |
|---|---|
| Pulse pressure | 2e-10 to 8e-23 |
| Diastolic blood pressure | 1e-08 to 3e-15 |
Hematologic Traits:
| Trait | P-value |
|---|---|
| Mean corpuscular hemoglobin | 1e-09 to 1e-22 |
| Mean corpuscular volume | 1e-20 |
| Mean spheric corpuscular volume | 2e-22 |
| Red blood cell count | 3e-21 |
| Mean reticulocyte volume | 2e-12 |
| Monocyte percentage of white cells | 3e-09 |
Other Traits:
| Trait | P-value |
|---|---|
| Appendicular lean mass | 5e-56 |
| Birth weight | 2e-11 |
| Sex hormone levels | 1e-15 |
| LDL cholesterol levels | 2e-09 |
| Mosaic loss of chromosome Y | 1e-08 to 3e-28 |
| Haemorrhoidal disease | 5e-10 |