TP73

tumor protein p73

Basic information

Region (hg38): 1:3652516-3736201

Links

ENSG00000078900 ∙ NCBI:7161 ∙ OMIM:601990 ∙ HGNC:12003 ∙ Uniprot:O15350 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ciliary dyskinesia, primary, 47, and lissencephaly (Strong), mode of inheritance: AR
• ciliary dyskinesia, primary, 47, and lissencephaly (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 47, and lissencephaly	AR	Allergy/Immunology/Infectious; Pulmonary	Among other features, the condition can include susceptibilty to respiratory infections and difficulties with mucociliary clearance, and awareness may allow preventative measures and early and aggressive treatment of infections	Allergy/Immunology/Infectious; Neurologic; Pulmonary	34077761

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TP73 gene.

• Respiratory failure (1 variants)
• Ciliary dyskinesia, primary, 47, and lissencephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TP73 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				1	7	8
missense			28	5	1	34
nonsense	1					1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding					3	3
Total	1	0	29	6	11

Variants in TP73

This is a list of pathogenic ClinVar variants found in the TP73 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-3682346-C-T		Ciliary dyskinesia, primary, 47, and lissencephaly	Benign (Apr 11, 2023)
1-3682369-G-T		Inborn genetic diseases	Likely benign (Sep 17, 2021)
1-3682397-G-T		Inborn genetic diseases	Uncertain significance (Jul 17, 2023)
1-3682439-G-A			Benign (Jan 12, 2018)
1-3683130-G-A		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
1-3683145-G-A		Inborn genetic diseases	Uncertain significance (May 01, 2024)
1-3683167-C-G		Inborn genetic diseases	Uncertain significance (Apr 04, 2023)
1-3683187-G-A			Benign (Feb 26, 2018)
1-3690918-G-A			Likely benign (May 01, 2023)
1-3707691-C-T		Inborn genetic diseases	Uncertain significance (May 27, 2022)
1-3707712-C-T		Inborn genetic diseases	Uncertain significance (Jun 01, 2023)
1-3707770-G-A			Benign (Apr 10, 2018)
1-3722094-C-A		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
1-3722110-C-T		Ciliary dyskinesia, primary, 47, and lissencephaly	Benign (Apr 11, 2023)
1-3722204-G-T		Ciliary dyskinesia, primary, 47, and lissencephaly • Respiratory failure	Pathogenic (Mar 25, 2024)
1-3723396-A-G		Inborn genetic diseases	Uncertain significance (Mar 04, 2024)
1-3727117-G-A			Benign (Dec 31, 2019)
1-3727123-G-A			Likely benign (Aug 16, 2018)
1-3727202-A-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
1-3727214-G-C		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
1-3727645-G-A		Ciliary dyskinesia, primary, 47, and lissencephaly	Uncertain significance (May 27, 2022)
1-3727647-C-T		Inborn genetic diseases	Uncertain significance (Apr 01, 2024)
1-3727686-G-A		Neurodevelopmental disorder	Uncertain significance (-)
1-3727704-G-GACC		Inborn genetic diseases	Uncertain significance (Sep 19, 2022)
1-3727743-G-A		Inborn genetic diseases	Uncertain significance (Jun 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TP73	protein_coding	protein_coding	ENST00000378295	13	83682

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00304	125688	0	8	125696	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.85	322	430	0.749	0.0000280	4147
Missense in Polyphen		93	167.17	0.55633		1520
Synonymous	-1.17	206	186	1.11	0.0000135	1246
Loss of Function	4.59	3	30.3	0.0991	0.00000156	313

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000299	0.0000299
Ashkenazi Jewish	0.000101	0.0000993
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000894	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein. {ECO:0000269|PubMed:10203277, ECO:0000269|PubMed:11753569, ECO:0000269|PubMed:18174154}.
• Pathway: Neurotrophin signaling pathway - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Measles - Homo sapiens (human);TP53 Network;ATM Signaling Pathway;Apoptosis;Apoptotic Signaling Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;DNA Damage Response (only ATM dependent);Gene expression (Transcription);Generic Transcription Pathway;Alpha6Beta4Integrin;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;Activation of PUMA and translocation to mitochondria;Activation of BH3-only proteins;Intrinsic Pathway for Apoptosis;Apoptosis;Programmed Cell Death;p73 transcription factor network;TP53 Regulates Transcription of Genes Involved in Cytochrome C Release;TP53 Regulates Transcription of Caspase Activators and Caspases;TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain;atm signaling pathway;TGF_beta_Receptor;Regulation of TP53 Activity through Association with Co-factors;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Direct p53 effectors;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Transcriptional regulation by RUNX1;E2F transcription factor network;TP53 Regulates Transcription of Death Receptors and Ligands (Consensus)

Recessive Scores

• pRec: 0.301

Intolerance Scores

• loftool: 0.0179
• rvis_EVS: -1.73
• rvis_percentile_EVS: 2.44

Haploinsufficiency Scores

• pHI: 0.444
• hipred: Y
• hipred_score: 0.851
• ghis: 0.642

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.909

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trp73
• Phenotype: skeleton phenotype; immune system phenotype; vision/eye 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; neoplasm; 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; 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: tp73
• Affected structure: ceratobranchial cartilage
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: activation of MAPK activity;kidney development;mismatch repair;cellular response to DNA damage stimulus;cell cycle arrest;regulation of mitotic cell cycle;intrinsic apoptotic signaling pathway in response to DNA damage;response to organonitrogen compound;regulation of gene expression;viral process;response to drug;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;regulation of apoptotic process;negative regulation of neuron differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of oligodendrocyte differentiation;protein tetramerization;negative regulation of cardiac muscle cell proliferation;positive regulation of cell cycle arrest;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway;regulation of signal transduction by p53 class mediator;regulation of hematopoietic stem cell differentiation
• Cellular component: chromatin;nucleus;nucleoplasm;mitochondrion;Golgi apparatus;cytosol;cell junction;intracellular membrane-bounded organelle
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;p53 binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;protein kinase binding;identical protein binding;transcription regulatory region DNA binding;metal ion binding;MDM2/MDM4 family protein binding