TP73

Summary

TP73 (tumor protein p73, HGNC:12003) is a protein-coding gene on chromosome 1p36.32, encoding Tumor protein p73 (O15350). Participates in the apoptotic response to DNA damage.

This gene encodes a member of the p53 family of transcription factors involved in cellular responses to stress and development. It maps to a region on chromosome 1p36 that is frequently deleted in neuroblastoma and other tumors, and thought to contain multiple tumor suppressor genes. The demonstration that this gene is monoallelically expressed (likely from the maternal allele), supports the notion that it is a candidate gene for neuroblastoma. Many transcript variants resulting from alternative splicing and/or use of alternate promoters have been found for this gene, but the biological validity and the full-length nature of some variants have not been determined.

Source: NCBI Gene 7161 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliary dyskinesia, primary, 47, and lissencephaly (Strong, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 137 total — 4 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 14 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 12
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.29 (intermediate), LOEUF 0.58 (moderately constrained)
• Transcription factor: yes — 133 downstream targets (CollecTRI)
• MANE Select transcript: NM_005427

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12003
Approved symbol	TP73
Name	tumor protein p73
Location	1p36.32
Locus type	gene with protein product
Status	Approved
Aliases	P73
Ensembl gene	ENSG00000078900
Ensembl biotype	protein_coding
OMIM	601990
Entrez	7161

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 16 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000378295

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 3, TSL 5: 4

ENST00000378295, ENST00000354437, ENST00000378280, ENST00000378285, ENST00000378288, ENST00000378290, ENST00000603362, ENST00000603364, ENST00000604074, ENST00000604194, ENST00000604479, ENST00000604566, ENST00000713570, ENST00000713571, ENST00000713572, ENST00000908821, ENST00000917568, ENST00000917569, ENST00001089267, ENST00001140270

RefSeq mRNA: 13 — MANE Select: NM_005427 NM_001126240, NM_001126241, NM_001126242, NM_001204184, NM_001204185, NM_001204186, NM_001204187, NM_001204188, NM_001204189, NM_001204190, NM_001204191, NM_001204192, NM_005427

CCDS: CCDS44049, CCDS44050, CCDS44051, CCDS49, CCDS55566, CCDS55567, CCDS55568, CCDS55569, CCDS59965

Canonical transcript exons

ENST00000378295 — 14 exons

Exon	Start	End
ENSE00000358575	3683060	3683180
ENSE00000733990	3730000	3730148
ENSE00000868857	3682333	3682430
ENSE00003461431	3730927	3731065
ENSE00003496607	3707549	3707791
ENSE00003503102	3727628	3727770
ENSE00003526787	3723354	3723469
ENSE00003637380	3731463	3731556
ENSE00003646577	3727115	3727224
ENSE00003651642	3728129	3728217
ENSE00003659615	3732747	3736201
ENSE00003670865	3722021	3722207
ENSE00003693819	3729327	3729448
ENSE00003848342	3652516	3652641

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 89.66.

FANTOM5 (CAGE): breadth broad, TPM avg 3.9534 / max 593.9393, expressed in 513 samples.

Highest expression (Bgee): uterine tube, olfactory segment of nasal mucosa, pancreatic ductal cell, bronchial epithelial cell, bronchus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TP73 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	1.1e-32	-0.86	1:3677927:G:A
Whole Blood	eqtl	1.2e-06	+0.22	1:3679204:C:G
Brain Cerebellum	eqtl	1.2e-05	+0.37	1:3792848:T:C
Brain Cerebellar Hemisphere	eqtl	1.3e-05	+0.39	1:3796763:C:G
Testis	eqtl	1.7e-04	+0.35	1:3736862:T:C
Nerve Tibial	eqtl	4.3e-04	+0.21	1:3734754:A:G
Thyroid	eqtl	5.9e-04	-0.47	1:3673689:C:T
Cells Cultured fibroblasts	eqtl	3.0e-03	+0.21	1:3650061:AGCAGGCTG:A
Muscle Skeletal	eqtl	5.8e-03	+0.23	1:3723079:T:C
Skin Not Sun Exposed Suprapubic	eqtl	6.8e-03	+0.14	1:3752189:A:C
Brain Cortex	eqtl	1.3e-02	+0.31	1:3727785:A:G
Esophagus Mucosa	eqtl	2.5e-02	+0.16	1:3099719:C:T
Skin Sun Exposed Lower leg	eqtl	4.2e-02	-0.09	1:3709118:G:C
Spleen	eqtl	5.0e-02	-0.39	1:3563277:C:T

FANTOM5 promoters

showing 10 of 17 alternative TSS:

Promoter ID	TPM avg	Samples expressed
306	1.8131	363
307	0.4338	223
308	0.3470	174
301	0.3071	188
302	0.2299	135
304	0.2280	118
305	0.1707	90
303	0.1200	64
315	0.1013	26
312	0.0743	2

Top tissues by expression

showing 100 of 236 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	89.66	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.89	gold quality
pancreatic ductal cell	CL:0002079	79.33	silver quality
bronchial epithelial cell	CL:0002328	75.35	gold quality
bronchus	UBERON:0002185	74.05	gold quality
cerebellar hemisphere	UBERON:0002245	73.62	gold quality
cerebellar cortex	UBERON:0002129	73.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.59	gold quality
skin of leg	UBERON:0001511	73.32	gold quality
skin of abdomen	UBERON:0001416	73.17	gold quality
cerebellum	UBERON:0002037	71.71	gold quality
zone of skin	UBERON:0000014	71.10	gold quality
esophagus mucosa	UBERON:0002469	70.55	gold quality
lower esophagus mucosa	UBERON:0035834	70.27	gold quality
tendon of biceps brachii	UBERON:0008188	70.15	gold quality
buccal mucosa cell	CL:0002336	69.46	gold quality
myocardium	UBERON:0002349	69.21	gold quality
minor salivary gland	UBERON:0001830	68.21	gold quality
secondary oocyte	CL:0000655	67.83	gold quality
mouth mucosa	UBERON:0003729	66.67	gold quality
saliva-secreting gland	UBERON:0001044	66.63	gold quality
bone marrow cell	CL:0002092	66.32	silver quality
upper arm skin	UBERON:0004263	65.21	gold quality
cardiac muscle of right atrium	UBERON:0003379	64.96	gold quality
left ventricle myocardium	UBERON:0006566	64.44	gold quality
fallopian tube	UBERON:0003889	64.12	gold quality
vagina	UBERON:0000996	63.95	gold quality
nasal cavity mucosa	UBERON:0001826	63.43	gold quality
nasal cavity epithelium	UBERON:0005384	63.40	gold quality
prostate gland	UBERON:0002367	62.49	gold quality
right lung	UBERON:0002167	61.59	gold quality
tonsil	UBERON:0002372	61.54	gold quality
gingival epithelium	UBERON:0001949	61.48	silver quality
upper leg skin	UBERON:0004262	61.36	gold quality
gingiva	UBERON:0001828	61.31	silver quality
parotid gland	UBERON:0001831	60.98	gold quality
mucosa of paranasal sinus	UBERON:0005030	60.81	silver quality
oviduct epithelium	UBERON:0004804	60.65	silver quality
medial globus pallidus	UBERON:0002477	59.74	gold quality
palpebral conjunctiva	UBERON:0001812	58.97	silver quality
ventricular zone	UBERON:0003053	58.10	silver quality
heart right ventricle	UBERON:0002080	58.03	gold quality
vermiform appendix	UBERON:0001154	57.35	gold quality
biceps brachii	UBERON:0001507	57.09	gold quality
lymph node	UBERON:0000029	57.07	gold quality
epithelial cell of pancreas	CL:0000083	57.00	gold quality
endothelial cell	CL:0000115	56.69	gold quality
globus pallidus	UBERON:0001875	56.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	56.10	gold quality
ganglionic eminence	UBERON:0004023	55.81	silver quality
skin of hip	UBERON:0001554	55.79	silver quality
bone marrow	UBERON:0002371	55.76	gold quality
left uterine tube	UBERON:0001303	55.25	gold quality
caecum	UBERON:0001153	54.87	gold quality
ileal mucosa	UBERON:0000331	54.68	gold quality
spinal cord	UBERON:0002240	54.64	gold quality
esophagus	UBERON:0001043	54.56	gold quality
colonic epithelium	UBERON:0000397	54.55	gold quality
mammalian vulva	UBERON:0000997	53.69	gold quality
hypothalamus	UBERON:0001898	53.56	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	53.16	gold quality
amygdala	UBERON:0001876	53.15	gold quality
cartilage tissue	UBERON:0002418	52.82	gold quality
quadriceps femoris	UBERON:0001377	52.63	gold quality
spleen	UBERON:0002106	52.51	gold quality
blood	UBERON:0000178	51.78	gold quality
vastus lateralis	UBERON:0001379	51.61	gold quality
lower lobe of lung	UBERON:0008949	51.13	silver quality
decidua	UBERON:0002450	51.07	gold quality
uterine cervix	UBERON:0000002	51.03	gold quality
Ammon’s horn	UBERON:0001954	50.35	gold quality
right testis	UBERON:0004534	50.17	gold quality
left testis	UBERON:0004533	50.05	gold quality
caudate nucleus	UBERON:0001873	49.95	gold quality
stromal cell of endometrium	CL:0002255	49.93	silver quality
gastrocnemius	UBERON:0001388	49.82	gold quality
muscle of leg	UBERON:0001383	49.77	gold quality
upper lobe of lung	UBERON:0008948	49.65	gold quality
brain	UBERON:0000955	49.53	gold quality
upper lobe of left lung	UBERON:0008952	49.53	gold quality
substantia nigra	UBERON:0002038	49.37	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
ectocervix	UBERON:0012249	49.24	gold quality
temporal lobe	UBERON:0001871	49.17	gold quality
lung	UBERON:0002048	49.16	gold quality
testis	UBERON:0000473	49.11	gold quality
kidney epithelium	UBERON:0004819	48.95	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
Brodmann (1909) area 46	UBERON:0006483	48.52	gold quality
anatomical system	UBERON:0000467	48.46	gold quality
endocervix	UBERON:0000458	48.38	gold quality
multicellular organism	UBERON:0000468	48.31	gold quality
nephron tubule	UBERON:0001231	48.31	gold quality
material anatomical entity	UBERON:0000465	48.30	gold quality
lateral nuclear group of thalamus	UBERON:0002736	48.30	gold quality
midbrain	UBERON:0001891	48.25	gold quality
metanephric glomerulus	UBERON:0004736	48.13	gold quality
prefrontal cortex	UBERON:0000451	47.95	gold quality
amniotic fluid	UBERON:0000173	47.94	gold quality
pigmented layer of retina	UBERON:0001782	47.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.12
E-CURD-10	no	15.60

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 68 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	17.4	low
Fallopian tube	tissue	6.3	low
Skin 1	tissue	6.2	low
Periaqueductal gray	tissue	4.9
Vagina	tissue	2.7	low
Salivary gland	tissue	2.6	not detected
Hippocampal formation	tissue	1.9
Basal ganglia	tissue	1.7	not detected
Hypothalamus	tissue	1.5
Hippocampus	tissue	1.4	not detected
Thymus	tissue	1.4
Tonsil	tissue	1.4	low
Septum	tissue	1.4
Nucleus accumbens	tissue	1.3
Locus coeruleus	tissue	1.3
Pons	tissue	1.2
Olfactory bulb	tissue	1.1
Lymph node	tissue	1.0	not detected
Esophagus	tissue	1.0	medium
Prostate	tissue	1.0	not detected
Medulla oblongata	tissue	0.8
Pancreas	tissue	0.7	not detected
Lung	tissue	0.7	not detected
Appendix	tissue	0.7	not detected
Thalamus	tissue	0.6
Bone marrow	tissue	0.5	not detected
Ventral forebrain	tissue	0.5
Caudate putamen	tissue	0.5
Amygdala	tissue	0.4
Superior colliculi	tissue	0.4
Pituitary gland	tissue	0.3
Testis	tissue	0.3	not detected
Stomach 1	tissue	0.3	not detected
Seminal vesicle	tissue	0.3	not detected
Midbrain	tissue	0.3
Substantia nigra	tissue	0.3
Spleen	tissue	0.3	not detected
Corpus callosum	tissue	0.3
Postcentral gyrus	tissue	0.3
Breast	tissue	0.2	not detected
Prefrontal cortex	tissue	0.2
Cerebral cortex	tissue	0.2	not detected
Colon	tissue	0.2	not detected
Motor cortex	tissue	0.2
Frontal cortex	tissue	0.2
Small intestine	tissue	0.2	not detected
Entorhinal cortex	tissue	0.2
Retrosplenial and cingulate cortex	tissue	0.2
Retrosplenial cortex	tissue	0.2
Temporal cortex	tissue	0.2
Insular cortex	tissue	0.2
Cervix	tissue	0.1	medium
Retina	tissue	0.1
Rectum	tissue	0.1	not detected
Parathyroid gland	tissue	0.1	not detected
Skeletal muscle	tissue	0.1	not detected
Urinary bladder	tissue	0.1	not detected
Endometrium 1	tissue	0.1	not detected
Epididymis	tissue	0.1	not detected
Putamen	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Flocculonodular lobe (9.8), Vermis (8.9), Cerebellar cortex (7.7), Periaquaductal grey, lateral (6.8), Nucleus tractus solitarii (6.0).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

showing 30 of 133 targets:

Target	Regulation
ABCB1	Unknown
ADA	Activation
ADAM2
AFP
ALB
AP1	Unknown
APOD
APP
AQP1
AQP3	Unknown
ATG5
AVP
BAG1
BAK1
BAX	Unknown
BBC3	Activation
BCL2
BDKRB2
BID	Activation
BIK
BIRC5	Unknown
CABLES1	Unknown
CADM1
CASP1	Activation
CASP2
CASP3	Activation
CASP8AP2
CCNB1	Repression
CCND1	Repression
CCND3

JASPAR motifs

Motif	Name	Family
MA0861.1	TP73	p53-related factors
MA0861.2	TP73	p53-related factors

JASPAR matrix evidence (PMIDs): PMID:23243311

Upstream regulators (CollecTRI, top): BHLHE40, CEBPZ, E2F1, E2F3, E2F4, EGR1, EP300, HBP1, HMGB2, IRF1, JUN, KAT2B, KAT5, MYC, MYCN, MYF6, MYOD1, NKX3-1, SIRT1, SP1, STAT1, TBXT, TFAP2A, TP53, TP63, TP73, YY1, ZEB1

miRNA regulators (miRDB)

Targeting TP73 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 89 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4649-3P	99.56	66.90	1783

Functional genomics

gnomAD constraint: pLI 0.287, LOEUF 0.576, missense Z 1.65 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000378295 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:3,682,366–3,722,129	235 / 251.4	0.93	no
1:3,722,130–3,727,195	61 / 133.2	0.46	no
1:3,727,196–3,733,076	458 / 528.7	0.87	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• expression of p73 in colorectal carcinoma (PMID:11675903)
• Frequent allelic losses on the short arm of chromosome 1 and decreased expression of the p73 gene at 1p36.3 in squamous cell carcinoma of the oral cavity (PMID:11788901)
• DNA damage-induced acetylation potentiates the apoptotic function of p73 by enhancing the ability of p73 to selectively activate the transcription of proapoptotic target genes (PMID:11804596)
• data establish a relationship between p73 gene expression and neuroblastic tumor differentiation and point out a role for the p73 gene in sympathetic neuronal differentiation (PMID:11839584)
• regulated by c-Abl through p38 MAP kinase pathway (PMID:11840343)
• interaction with c-myc and MM1 (PMID:11844794)
• Transactivation-deficient Delta TA-p73 inhibits p53 by direct competition for DNA binding: implications for tumorigenesis. (PMID:11844800)
• data seem to indicate that DeltaNp73 is a crucial gene in neuroblastoma pathogenesis (PMID:11859407)
• overexpression in malignant and premalignant lesions suggests role in oncogenic process in cervical epithelium (PMID:11870517)
• Induction of p57(KIP2) expression by p73beta (PMID:11891335)
• Autoinhibitory regulation of p73 by Delta Np73 to modulate cell survival and death through a p73-specific target element within the Delta Np73 promoter. (PMID:11909952)
• loss of reduced TP73 transcript expression through promoter hypermethylation may contribute to the tumorigenesis of oligodendroglial tumors (PMID:11920588)
• Identification and characterization of HIPK2 interacting with this protein and modulating functions of the p53 family in vivo (PMID:11925430)
• p63 and p73 expression may represent an early event in head and neck squamous carcinoma tumorigenesis and may function as oncogenes in the development of these tumors. (PMID:11957139)
• p73 expression is primarily mediated through binding of E2F1 (PMID:11988839)
• upregulation by ascorbic acid (PMID:12023887)
• DN-p73 is activated after DNA damage in a p53-dependent manner to regulate p53-induced cell cycle arrest. (PMID:12032848)
• HCMV-mediated inhibition of apoptosis only occurs in p73-expressing cells (PMID:12034725)
• data suggest that p73 stimulates the transcription of the YB-1 promoter by enhancing recruitment of the c-Myc-Max complex to the E-box (PMID:12080043)
• Mouse DDA3 gene is a direct transcriptional target of p73 in transfection assays (PMID:12082536)
• Overexpression of p73beta led to the apoptosis of Hela cells and enhancement of naphthoquinone analog induced cell death. (PMID:12095638)
• is regulated by protein kinase C delta (PMID:12097319)
• p73 gene inactivation might play an important role in the pathogenesis of acute lymphoblastic leukemia . The main mechanism of the loss expression would be the hypermethylation of p73 gene. (PMID:12133444)
• role in expression of DAN during cisplatin-induced cell death and osteoblast differentiation (PMID:12150978)
• identification of direct target genes combining DNA microarray and chromatin immunoprecipitation analyses (PMID:12213815)
• deletion or methylation of p73 is associated with B cell non-Hodgkin’s lymphomas (PMID:12353228)
• Overexpression of p73 in vascular smooth muscle cells results in decreased cell cycle transit accompanied by apoptosis. (PMID:12388104)
• p73 has roles as a specific dominant negative transcriptional repressor of the cell cycle inhibitor gene p21 blocking p53-mediated apoptosis (PMID:12427762)
• No associations of p73 G4C14-to-A4T14 at exon 2 and p53 Arg72Pro polymorphisms with the risk of digestive tract cancers in Japanese. (PMID:12430182)
• p53 DNA-binding domain plays a role in p73 interaction. (PMID:12519788)
• This protein and p53 interact with CTF2 and regulate HMG1 gene expression. (PMID:12534345)
• p73 isoforms affect the retinoblastoma protein (RB) tumor suppressor pathway independent of p53 (PMID:12584188)
• p73 has a role in apoptosis that requires PMS2 protein (PMID:12601175)
• transcriptional activation function of p73 is specifically targeted by E1A through a mechanism involving p300/CBP proteins during the process of transformation and that p73 may have a role to play as a tumor suppressor (PMID:12639967)
• modulation of level by cyclin G via a negative feedback reglation (PMID:12642871)
• p73 is phosphorylated in a cell cycle-dependent manner and negatively regulated by cyclin-dependent kinases (PMID:12676926)
• p53 and p73alpha have roles in cell migration (PMID:12750388)
• TP73 is an important E2F1 apoptotic target gene in DNA damage response. Acetylation is required for E2F1 recruitment on the P1p73 promoter and for its transcriptional activation. (PMID:12766778)
• Adenovirus-mediated p73 overexpression results in a strong induction of apoptosis in pancreatic adenocarcinoma. (PMID:12782576)
• Analysis of gene expression level profiles showed that parental cell line undergoes apoptosis through an E2F1/p73-dependent pathway while its drug resistant variant evades it. (PMID:12789260)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tp73	ENSDARG00000017953
mus_musculus	Trp73	ENSMUSG00000029026
rattus_norvegicus	Tp73	ENSRNOG00000024707
drosophila_melanogaster	p53	FBGN0039044

Paralogs (2): TP63 (ENSG00000073282), TP53 (ENSG00000141510)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1336991) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 82 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal dentate gyrus morphology	3
abnormal hippocampus morphology	2
female infertility	2
increased T cell derived lymphoma incidence	2
increased lung adenocarcinoma incidence	2
premature death	2
abnormal vomeronasal organ morphology	2
increased hemangiosarcoma incidence	2
prenatal lethality, incomplete penetrance	2
absent Cajal-Retzius cell	1
domed cranium	1
gastrointestinal hemorrhage	1
absent enterocytes	1
excessive digestive secretion	1
abnormal cerebral cortex morphology	1
abnormal cortical marginal zone morphology	1
abnormal hippocampus development	1
abnormal choroid plexus morphology	1
dilated lateral ventricle	1
abnormal trigeminal ganglion morphology	1
decreased body size	1
submission towards male mice	1
decreased male mating frequency	1
abnormal embryo development	1
periorbital edema	1

+57 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	P56423	100.0%	Diamond
Macaca mulatta	P56424	100.0%	Diamond
Macaca fuscata fuscata	P61260	100.0%	Diamond
Bos indicus	P67938	100.0%	Diamond
Bos taurus	P67939	100.0%	Diamond
Xiphophorus hellerii	O57538	99.4%	Diamond
Xiphophorus maculatus	Q92143	99.4%	Diamond
Chlorocebus aethiops	P13481	99.0%	Diamond
Marmota monax	O36006	97.8%	Diamond
Otospermophilus beecheyi	Q64662	97.8%	Diamond
Equus caballus	P79892	94.6%	Diamond
Equus asinus	Q29480	94.6%	Diamond
Tupaia belangeri	Q9TTA1	93.1%	Diamond
Cricetulus griseus	O09185	91.2%	Diamond
Mesocricetus auratus	Q00366	91.2%	Diamond
Delphinapterus leucas	Q8SPZ3	90.7%	Diamond
Sus scrofa	Q9TUB2	90.7%	Diamond
Oryctolagus cuniculus	Q95330	87.9%	Diamond
Canis lupus familiaris	Q29537	86.9%	Diamond
Ovis aries	P51664	86.0%	Diamond
Felis catus	P41685	85.4%	Diamond
Cavia porcellus	Q9WUR6	82.4%	Diamond
Barbus barbus	Q9W678	77.8%	Diamond
Gallus gallus	P10360	74.9%	Diamond
Ictalurus punctatus	O93379	74.3%	Diamond
Oncorhynchus mykiss	P25035	71.9%	Diamond
Xenopus laevis	P07193	69.5%	Diamond
Platichthys flesus	O12946	63.1%	Diamond
Oryzias latipes	P79820	63.1%	Diamond
Tetraodon miurus	Q9W679	62.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TP73-AS2	ncRNA	117134600
TPRG1L	protein-coding	127262
WRAP73	protein-coding	49856
TP73-AS3	ncRNA	105378610
CCDC27	protein-coding	148870
MEGF6	protein-coding	1953
MIR551A	ncRNA	693135
SMIM1	protein-coding	388588
LRRC47	protein-coding	57470
CEP104	protein-coding	9731

Protein

Protein identifiers

Tumor protein p73 — O15350 (reviewed: O15350)

Alternative names: p53-like transcription factor, p53-related protein

All UniProt accessions (2): A0A0C4DFW9, O15350

UniProt curated annotations — full annotation on UniProt →

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. Is an activator of FOXJ1 expression. It is an essential factor for the positive regulation of lung ciliated cell differentiation.

Subunit / interactions. Found in a complex with p53/TP53 and CABLES1. The C-terminal oligomerization domain binds to the ABL1 tyrosine kinase SH3 domain. Interacts with HECW2. Isoform Beta interacts homotypically and with p53/TP53, whereas isoform Alpha does not. Isoform Gamma interacts homotypically and with all p73 isoforms. Isoform Delta interacts with isoform Gamma, isoform Alpha, and homotypically. Isoforms Alpha and Beta interact with HIPK2. Isoform Alpha interacts with RANBP9. Isoform Beta interacts with WWOX. Interacts (via SAM domain) with FBXO45 (via B30.2/SPRY domain). Interacts with YAP1 (phosphorylated form). Interacts with HCK (via SH3 domain); this inhibits TP73 activity and degradation. Interacts (via SAM domain) with NQO1; this interaction is NADH-dependent, stabilizes TP73 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome. (Microbial infection) Interacts with Epstein-Barr virus protein EBNA6; this interaction inhibits TP73-mediated apoptotic pathway.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in striatal neurons of patients with Huntington disease (at protein level). Brain, kidney, placenta, colon, heart, liver, spleen, skeletal muscle, prostate, thymus and pancreas. Highly expressed in fetal tissue. Expressed in the respiratory epithelium.

Post-translational modifications. Isoform alpha (but not isoform beta) is sumoylated on Lys-627, which potentiates proteasomal degradation but does not affect transcriptional activity. Phosphorylation by PLK1 and PLK3 inhibits the transcription regulator activity and pro-apoptotic function. Higher levels of phosphorylation seen in the brain from patients with Huntington disease. Polyubiquitinated by RCHY1/PIRH2; leading to its degradation by the proteasome.

Disease relevance. Ciliary dyskinesia, primary, 47, and lissencephaly (CILD47) [MIM:619466] A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD47 is an autosomal recessive form characterized by onset soon after birth or in early childhood. Affected individuals also have neurologic features, such as impaired intellectual development and central hypotonia, associated with structural brain abnormalities, most notably lissencephaly and thin or absent corpus callosum. No situs abnormalities have been observed. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. Possesses an acidic transactivation domain, a central DNA binding domain and a C-terminal oligomerization domain that binds to the ABL1 tyrosine kinase SH3 domain. The PPxY motif mediates interaction with WWOX.

Induction. Not induced by DNA damage. Isoforms lacking the transactivation domain block gene induction.

Miscellaneous. Maps to a chromosome region frequently mutated in diverse cell lines of human cancer. Appears not to be frequently mutated in human cancers, in contrast to p53/TP53. Hemizygosity is observed in neuroblastoma and oligodendroglioma. Activated and stabilized by interaction with RANBP9. Produced by alternative splicing of isoform Alpha. Produced by alternative splicing of isoform Alpha. The splicing of exon 11 results in a frameshift from the original reading frame. Produced by alternative splicing of isoform Alpha. Produced by alternative splicing of isoform Alpha. The splicing of exon 11 results in a frameshift from the original reading frame. The splicing of exon 13 reverts the reading frame to the sequence of isoform Alpha. Produced by alternative splicing of isoform Alpha. Produced by alternative promoter usage. Produced by alternative splicing of isoform dN-Alpha. Produced by alternative splicing of isoform dN-Alpha. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the p53 family.

Isoforms (11)

UniProt ID	Names	Canonical?
O15350-1	Alpha, p73alpha	yes
O15350-2	Beta, p73beta
O15350-3	Gamma, p73gamma
O15350-4	Delta, p73delta
O15350-5	Epsilon, p73epsilon
O15350-6	Zeta, p73zeta
O15350-8	dN-Alpha, DNp73alpha, DeltaNp73alpha
O15350-9	dN-Beta, DNp73beta, DeltaNp73beta
O15350-10	dN-Gamma, DNp73gamma, DeltaNp73gamma
O15350-11	10
O15350-12	11

RefSeq proteins (13): NP_001119712, NP_001119713, NP_001119714, NP_001191113, NP_001191114, NP_001191115, NP_001191116, NP_001191117, NP_001191118, NP_001191119, NP_001191120, NP_001191121, NP_005418* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR002117	p53_tumour_suppressor	Family
IPR008967	p53-like_TF_DNA-bd_sf	Homologous_superfamily
IPR010991	p53_tetrameristn	Domain
IPR011615	p53_DNA-bd	Domain
IPR012346	p53/RUNT-type_TF_DNA-bd_sf	Homologous_superfamily
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR036674	p53_tetramer_sf	Homologous_superfamily
IPR037612	Tumour-p73_SAM	Domain
IPR057064	P53_central_site	Conserved_site

Pfam: PF00870, PF07647, PF07710

UniProt features (74 total): helix 16, strand 15, splice variant 11, turn 7, region of interest 6, binding site 4, mutagenesis site 4, modified residue 3, cross-link 2, sequence variant 2, chain 1, domain 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

28 structures by resolution:

PDB	Title	Method	Resolution (Å)
5HOB	p73 homo-tetramerization domain mutant I	X-RAY DIFFRACTION	1.22
5HOC	p73 homo-tetramerization domain mutant II	X-RAY DIFFRACTION	1.36
2WQI	Crystal structure of the human p73 tetramerization domain	X-RAY DIFFRACTION	1.7
8P9C	Crystal structure of p63-p73 heterotetramer (tetramerisation domain) in complex with …	X-RAY DIFFRACTION	1.76
9GNB	Structure of p73 SAM domain in complex with DARPin B9	X-RAY DIFFRACTION	1.8
2XWC	Crystal structure of the DNA binding domain of human TP73 refined at 1.8 A resolution	X-RAY DIFFRACTION	1.82
2WQJ	Crystal structure of a truncated variant of the human p73 tetramerization domain	X-RAY DIFFRACTION	2
9GLQ	Crystal structure of p73 tetramerisation domain in complex with darpins 1800	X-RAY DIFFRACTION	2.1
8P9E	Crystal structure of wild type p63-p73 heterotetramer (tetramerisation domain) in complex …	X-RAY DIFFRACTION	2.25
4A63	Crystal structure of the p73-ASPP2 complex at 2.6A resolution	X-RAY DIFFRACTION	2.27
2WTT	Structure of the human p73 tetramerization domain (crystal form II)	X-RAY DIFFRACTION	2.3
1DXS	Crystal structure of the C-terminal sterile alpha motif (SAM) domain of human p73 alpha …	X-RAY DIFFRACTION	2.54
8P9D	Crystal structure of p63-p73 heterotetramer (tetramerisation domain) in complex with …	X-RAY DIFFRACTION	2.7
5KBD	Structural Studies of Transcription Factor p73 DNA Binding Domain Bound to PA26 20-mer …	X-RAY DIFFRACTION	2.8
7EZJ	Crystal structure of p73 DNA binding domain complex bound with 1 bp and 2 bp spacer DNA …	X-RAY DIFFRACTION	2.9
3VD0	structure of p73 DNA binding domain tetramer modulates p73 transactivation	X-RAY DIFFRACTION	2.95
3VD1	structure of p73 DNA binding domain tetramer modulates p73 transactivation	X-RAY DIFFRACTION	2.95
4G82	Crystal Structure of p73 DNA-Binding Domain Tetramer bound to a Full Response-Element	X-RAY DIFFRACTION	3.1
4GUO	structure of p73 DNA binding domain complex with 12 bp DNA	X-RAY DIFFRACTION	3.19
4GUQ	Structure of mutS139F p73 DNA binding domain complexed with 20BP DNA response element	X-RAY DIFFRACTION	3.7
3VD2	structure of p73 DNA binding domain tetramer modulates p73 transactivation	X-RAY DIFFRACTION	4
4G83	Crystal Structure of p73 DNA-Binding Domain Tetramer bound to a Full Response-Element	X-RAY DIFFRACTION	4
1COK	STRUCTURE OF THE C-TERMINAL DOMAIN OF P73	SOLUTION NMR
2KBY	The Tetramerization Domain of Human p73	SOLUTION NMR
2MPS	Structure of complex of MDM2(3-109) and P73 TAD(10-25)	SOLUTION NMR
2NB1	P63/p73 hetero-tetramerisation domain	SOLUTION NMR
6FGS	Solution structure of p300Taz2-p73TA1	SOLUTION NMR
6IJQ	Solution structure of BCL-XL bound to P73-TAD peptide	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15350-F1	66.25	0.36

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Transcription factors, Immunoglobulin fold, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; basal body; cell junctions; centrosome; golgi apparatus; plasma membrane; vesicles

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4)

Position	Role
194	Zn(2+)
197	Zn(2+)
258	Zn(2+)
262	Zn(2+)

Post-translational modifications (5)

Type	Positions
Phosphothreonine	27
Phosphotyrosine	28, 99
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo)	627
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	627

Mutagenesis-validated functional residues (4)

Position	Phenotype
27	impaired phosphorylation.
99	impaired phosphorylation of isoform beta by abl1.
487	loss of interaction with wwox.
627	strongly diminishes sumoylation but does not affect transcriptional activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 curated (TAS) of 19; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

19 pathways:

ID	Pathway	Evidence
R-HSA-139915	Activation of PUMA and translocation to mitochondria	curated
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs	curated
R-HSA-6804759	Regulation of TP53 Activity through Association with Co-factors	curated
R-HSA-6803207	TP53 Regulates Transcription of Caspase Activators and Caspases	curated
R-HSA-6803211	TP53 Regulates Transcription of Death Receptors and Ligands	curated
R-HSA-6803204	TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	curated
R-HSA-6803205	TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	curated
R-HSA-9945556	Transcriptional regulation of multiciliogenesis	curated
R-HSA-114452	Activation of BH3-only proteins	—
R-HSA-109581	Apoptosis	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-109606	Intrinsic Pathway for Apoptosis	—
R-HSA-5357801	Programmed Cell Death	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-5633007	Regulation of TP53 Activity	—
R-HSA-5633008	TP53 Regulates Transcription of Cell Death Genes	—
R-HSA-3700989	Transcriptional Regulation by TP53	—
R-HSA-8878171	Transcriptional regulation by RUNX1	—

MSigDB gene sets: 228 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, WANG_CLIM2_TARGETS_UP, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, BIOCARTA_ATM_PATHWAY, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_LUNG_CELL_DIFFERENTIATION, GOBP_GROWTH, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER

GO Biological Process (19): mismatch repair (GO:0006298), DNA-templated transcription (GO:0006351), DNA damage response (GO:0006974), regulation of mitotic cell cycle (GO:0007346), negative regulation of cell population proliferation (GO:0008285), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), regulation of gene expression (GO:0010468), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), regulation of apoptotic process (GO:0042981), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), protein tetramerization (GO:0051262), regulation of cell cycle (GO:0051726), negative regulation of cardiac muscle cell proliferation (GO:0060044), positive regulation of lung ciliated cell differentiation (GO:1901248), regulation of DNA-templated transcription (GO:0006355), apoptotic process (GO:0006915), positive regulation of cell differentiation (GO:0045597), positive regulation of apoptotic signaling pathway (GO:2001235)

GO Molecular Function (16): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription corepressor binding (GO:0001222), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), p53 binding (GO:0002039), DNA-binding transcription factor activity (GO:0003700), protein kinase binding (GO:0019901), identical protein binding (GO:0042802), metal ion binding (GO:0046872), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), MDM2/MDM4 family protein binding (GO:0097371), DNA-binding transcription factor binding (GO:0140297), promoter-specific chromatin binding (GO:1990841), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

12 top-level categories:

Category	Pathways
TP53 Regulates Transcription of Cell Death Genes	4
Generic Transcription Pathway	2
Transcriptional Regulation by TP53	2
Activation of BH3-only proteins	1
Regulation of TP53 Activity	1
Transcriptional regulation by RUNX1	1
Assembly of the 9+2 motile cilia	1
Programmed Cell Death	1
Apoptosis	1
Intrinsic Pathway for Apoptosis	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

showing 60 of 71 GO namespaces:

Category	Terms
cellular anatomical structure	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
protein binding	3
gene expression	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
apoptotic signaling pathway	2
DNA repair	1
RNA biosynthetic process	1
cellular response to stress	1
mitotic cell cycle	1
regulation of cell cycle	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
regulation of macromolecule biosynthetic process	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
apoptotic process	1
regulation of programmed cell death	1
positive regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
protein complex oligomerization	1
cell cycle	1
regulation of cellular process	1
negative regulation of cell population proliferation	1
negative regulation of cardiac muscle tissue growth	1
cardiac muscle cell proliferation	1
regulation of cardiac muscle cell proliferation	1
positive regulation of epithelial cell differentiation	1
positive regulation of multicellular organismal process	1
lung ciliated cell differentiation	1
regulation of lung ciliated cell differentiation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
programmed cell death	1
execution phase of apoptosis	1
cell differentiation	1
regulation of cell differentiation	1
positive regulation of cellular process	1
positive regulation of developmental process	1
positive regulation of signal transduction	1
positive regulation of apoptotic process	1
regulation of apoptotic signaling pathway	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription coregulator binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
kinase binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 24 of 40 annotations. The rest are phylogenetic / computational / electronic (IEA).

24 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage response	BP	direct assay
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	BP	direct assay
negative regulation of cardiac muscle cell proliferation	BP	mutant phenotype
negative regulation of cell population proliferation	BP	mutant phenotype
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of lung ciliated cell differentiation	BP	mutant phenotype
positive regulation of transcription by RNA polymerase II	BP	direct assay
regulation of cell cycle	BP	direct assay
regulation of gene expression	BP	mutant phenotype
regulation of mitotic cell cycle	BP	mutant phenotype
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
DNA-binding transcription activator activity, RNA polymerase II-specific	MF	direct assay
DNA-binding transcription factor activity	MF	direct assay
DNA-binding transcription factor activity, RNA polymerase II-specific	MF	direct assay
DNA-binding transcription factor binding	MF	physical interaction
MDM2/MDM4 family protein binding	MF	physical interaction
RNA polymerase II cis-regulatory region sequence-specific DNA binding	MF	direct assay
RNA polymerase II-specific DNA-binding transcription factor binding	MF	physical interaction
identical protein binding	MF	physical interaction
p53 binding	MF	physical interaction
protein kinase binding	MF	physical interaction
transcription cis-regulatory region binding	MF	direct assay
transcription corepressor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,379 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TP73	RASSF1	Q9NS23	680
TP73	CDKN2A	P42771	676
TP73	RBM38	Q9H0Z9	655
TP73	MDM2	Q00987	645
TP73	CDKN1A	P38936	596
TP73	YAP1	P46937	534
TP73	CCND1	P24385	533
TP73	E2F4	Q16254	511
TP73	E2F2	Q14209	504
TP73	CCDC27	Q2M243	500
TP73	DAPK1	P53355	497
TP73	PSRC1	Q6PGN9	490
TP73	EZH1	Q92800	484
TP73	BBC3	Q96PG8	473
TP73	TP53AIP1	Q9HCN2	473

IntAct

Human interaction partners of TP73 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

30 partners by confidence:

Partner	Interaction type	MIscore	Records
TP63	direct interaction	0.770	4
ITCH	association	0.750	5
YAP1	direct interaction	0.730	5
EP300	direct interaction	0.650	3
HSPA9	physical association	0.640	8
WWOX	association	0.640	5
AURKA	association	0.630	11
NEDD4	direct interaction	0.620	2
SIRT1	physical association	0.600	4
MDM2	direct interaction	0.560	4
PMS2	physical association	0.500	3
RUNX2	colocalization	0.460	3
TP53BP2	direct interaction	0.440	2
PPP1R13L	direct interaction	0.440	1
MAD2L1	colocalization	0.430	1
RNF144B	physical association	0.400	2
ABL1	physical association	0.400	1
CEBPZ	physical association	0.400	1
HMGB1	physical association	0.400	1
MAGEA2	physical association	0.400	1
PPP1R13B	physical association	0.400	1
SIAH1	physical association	0.400	1
E7	physical association	0.370	1
MDM4	association	0.350	2
BORCS8	association	0.350	1
CDC20	association	0.350	1
HASPIN	association	0.350	1
PRELID2	association	0.350	1
PRMT6	association	0.350	1
WWP1	association	0.350	1

BioGRID (520 interactions; top human partners by supporting records): MDM2 (Biochemical Activity; 19 records), YAP1 (Affinity Capture-Western; 15 records), EP300 (Affinity Capture-Western; 13 records), ITCH (Affinity Capture-Western; 10 records), TP53 (Affinity Capture-Western; 8 records), DAXX (Affinity Capture-Western; 6 records), MDM4 (Affinity Capture-MS; 6 records), MED15 (Affinity Capture-MS; 6 records), RCHY1 (Affinity Capture-Western; 6 records), TP63 (Affinity Capture-MS; 6 records), WWP2 (Affinity Capture-MS; 6 records), ABL1 (Affinity Capture-Western; 5 records), KAT2B (Affinity Capture-Western; 5 records), MYC (Affinity Capture-Western; 5 records), PLAGL1 (Affinity Capture-Western; 5 records)

SIGNOR signaling

showing 33 of 34 signaling interactions:

A	Effect	B	Mechanism
CHEK1	up-regulates	TP73	phosphorylation
YAP1	up-regulates	TP73	binding
PLK1	down-regulates	TP73	phosphorylation
RPL11	up-regulates	TP73	binding
RPL5	up-regulates	TP73	binding
CyclinE/CDK2	down-regulates	TP73	phosphorylation
CyclinB/CDK1	down-regulates	TP73	phosphorylation
TP73	“up-regulates quantity by expression”	BBC3	“transcriptional regulation”
TP73	“up-regulates quantity by expression”	CDKN1A	“transcriptional regulation”
TP73	“up-regulates quantity by expression”	PMAIP1	“transcriptional regulation”
MDM2	“down-regulates activity”	TP73	binding
Nutlin-3	up-regulates	TP73
TP73	up-regulates	Apoptosis
TP73	up-regulates	Cell_death
ACOX1	“down-regulates quantity by destabilization”	TP73	binding
FBXO45	“down-regulates quantity by destabilization”	TP73	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	TP73	polyubiquitination
WWP1	“down-regulates quantity by destabilization”	TP73	polyubiquitination
WWP2	“down-regulates quantity by destabilization”	TP73	polyubiquitination
PRKCB	“up-regulates activity”	TP73	phosphorylation
PRKCA	“up-regulates activity”	TP73	phosphorylation
YAP/TAZ	“up-regulates activity”	TP73	binding
PLK2	“down-regulates activity”	TP73	phosphorylation
AURKA	“down-regulates activity”	TP73	phosphorylation
ITCH	“down-regulates quantity by destabilization”	TP73	ubiquitination
MAPK8	“up-regulates activity”	TP73	phosphorylation
PLK3	“down-regulates activity”	TP73	phosphorylation
CHUK	“up-regulates activity”	TP73	phosphorylation
ABL1	up-regulates	TP73	phosphorylation
PRKCD	up-regulates	TP73	phosphorylation
CDK1	“down-regulates activity”	TP73	phosphorylation
CDK2	“down-regulates activity”	TP73	phosphorylation
HECW2	“up-regulates quantity by stabilization”	TP73	ubiquitination

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
CABLES1-TP53-TP73 complex	3	CABLES1, TP53, TP73

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of TP53 Activity	5	27.7×	6e-05
Transcriptional Regulation by TP53	5	12.9×	7e-04
Antigen processing: Ubiquitination & Proteasome degradation	6	9.3×	7e-04
Cell Cycle	6	9.0×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein ubiquitination	9	12.8×	1e-05
ubiquitin-dependent protein catabolic process	5	12.8×	2e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	6	10.8×	9e-04
positive regulation of apoptotic process	5	9.8×	4e-03
DNA damage response	5	9.2×	5e-03
negative regulation of apoptotic process	7	8.4×	9e-04

Disease & clinical

Genetic variants

Variant evidence for TP73: 137 ClinVar records (5 pathogenic / likely pathogenic); 6 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

137 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	87
Likely benign	20
Benign	10

Top pathogenic / likely-pathogenic (5)

Showing all 5 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1192319	NM_005427.4(TP73):c.1196+1G>A	Pathogenic	criteria provided, single submitter	3
1192322	NM_005427.4(TP73):c.613G>T (p.Glu205Ter)	Pathogenic	criteria provided, single submitter	3
4076273	NM_005427.4(TP73):c.453_454del (p.Tyr152fs)	Likely pathogenic	criteria provided, single submitter	1
1192320	NM_005427.4(TP73):c.994C>T (p.Gln332Ter)	Pathogenic	no assertion criteria provided	1
1192321	NM_005427.4(TP73):c.1459del (p.Tyr487fs)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore TP73’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 1,541):

Position(s)	Effect	Δscore	Sites
1:3652642–3652643	donor_loss	1.0000	4
1:3683052	acceptor_gain	1.0000
1:3683058–3683059	acceptor_loss	1.0000	5
1:3683059	acceptor_gain	1.0000
1:3683181–3683182	donor_loss	1.0000	5
1:3707541	acceptor_gain	1.0000
1:3707547–3707548	acceptor_loss	1.0000	6
1:3707792–3707793	donor_loss	1.0000	5
1:3722015	acceptor_gain	1.0000
1:3722019–3722020	acceptor_loss	1.0000	6

AlphaMissense

1,557 missense substitutions predicted likely pathogenic (of 4,193 scored), across 358 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M266	9	0.970	0.999
M257	9	0.966	0.999
D301	8	1.000	1.000
H197	8	0.999	1.000
S261	8	0.997	1.000
N267	8	0.996	1.000
H213	8	0.989	0.998
D305	8	0.989	1.000
F588	8	0.988	1.000
F131	8	0.987	0.999
F256	8	0.987	1.000
F127	8	0.984	0.999
H592	8	0.979	0.997
F290	8	0.975	0.999
S260	8	0.971	1.000
N259	8	0.955	0.999
N196	8	0.951	0.999
F614	8	0.950	0.993
H587	8	0.942	0.995
F612	8	0.921	0.976

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Rectum Adenocarcinoma (validation)	favorable	0.000829

Disease associations

OMIM: gene MIM:601990 | disease phenotypes: MIM:619466

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
ciliary dyskinesia, primary, 47, and lissencephaly	Strong	Autosomal recessive	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 47, and lissencephaly	Strong	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (9 panels, 9 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

9 panels:

Panel	Rating
Cerebral malformation	green
DDG2P	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Malformations of cortical development	green
Paediatric disorders	green
Respiratory ciliopathies including non-CF bronchiectasis	green

Mondo (2): ciliary dyskinesia, primary, 47, and lissencephaly (MONDO:0030346), respiratory failure (MONDO:0021113)

HPO phenotypes

12 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000389	Chronic otitis media
HP:0001250	Seizure
HP:0001274	Agenesis of corpus callosum
HP:0001339	Lissencephaly
HP:0002079	Hypoplasia of the corpus callosum
HP:0002098	Respiratory distress
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0003623	Neonatal onset
HP:0031602	Abnormal mucociliary clearance
HP:0100750	Atelectasis

GWAS associations

6 associations:

Study	Trait	p-value
GCST001524_16	Visceral adipose tissue/subcutaneous adipose tissue ratio	2e-6
GCST001525_13	Visceral fat	2e-6
GCST001525_8	Visceral fat	2e-6
GCST008992_6	Joint damage in rheumatoid arthritis	2e-6
GCST008155_43	Waist-hip ratio	3e-6
GCST001523_38	Visceral adipose tissue adjusted for BMI	6e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004343	waist-hip ratio
EFO:0005413	joint damage measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D012131	Respiratory Insufficiency	C08.618.846

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

93 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	increases reaction, affects reaction, increases response to substance, decreases expression, decreases reaction (+7 more)	11
Arsenic Trioxide	increases reaction, increases acetylation, affects reaction, increases cleavage, increases expression (+4 more)	6
Benzo(a)pyrene	affects activity, affects methylation, affects cotreatment, decreases expression, decreases methylation (+1 more)	5
sodium arsenite	affects expression, affects methylation, increases expression	4
bisphenol A	increases methylation, increases expression, affects cotreatment	3
Doxorubicin	decreases expression, increases phosphorylation, affects binding, increases reaction, decreases reaction (+2 more)	3
Quercetin	increases expression, affects cotreatment	3
Valproic Acid	increases methylation	3
kaempferol	increases expression	2
nickel chloride	decreases reaction, increases phosphorylation, decreases activity, affects binding	2
chrysin	increases expression	2
2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide	increases expression, increases activity, increases phosphorylation, affects binding, affects cotreatment (+3 more)	2
bisphenol S	decreases methylation, increases expression	2
Resveratrol	increases expression, affects cotreatment, decreases expression	2
Etoposide	increases expression, increases response to substance, decreases reaction, increases activity, increases cleavage (+1 more)	2
Fluorouracil	increases reaction, affects response to substance, increases expression	2
Zinc	affects binding, affects folding, decreases expression, affects activity	2
Sirolimus	affects cotreatment, increases expression, affects activity, decreases reaction, decreases expression (+3 more)	2
Luteolin	increases expression	2
cyclopiazonic acid	increases degradation	1
S63845	affects reaction, affects cotreatment, increases expression, increases reaction	1
(1R,3S,3aR,8bS)-3a-(4-Bromophenyl)-6,8-dimethoxy-3-phenyl-2,3,3a,8b-tetrahydro-1H-cyclopenta(b)benzofuran-1,8b-diol	decreases expression	1
bufotalin	increases expression	1
ethylbenzene	affects cotreatment, decreases expression, increases methylation	1
lasiocarpine	increases expression	1
myristicin	decreases expression	1
naringenin	affects cotreatment, increases expression	1
benzo(b)fluoranthene	affects cotreatment, decreases expression	1
4-biphenylamine	decreases expression	1
VX-agent	increases expression	1

Cellosaurus cell lines

10 cell lines: 7 cancer cell line, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7P1	SEES3-1V human TP73, clone1	Embryonic stem cell	Male
CVCL_A7P2	SEES3-1V human TP73, clone2	Embryonic stem cell	Male
CVCL_A7P3	SEES3-1V human TP73, clone3	Embryonic stem cell	Male
CVCL_B8A1	Abcam Raji TP73 KO	Cancer cell line	Male
CVCL_C0AV	Abcam THP-1 TP73 KO	Cancer cell line	Male
CVCL_C7CI	Abcam PC-3 TP73 KO	Cancer cell line	Male
CVCL_E942	YSK-21	Cancer cell line	Male
CVCL_TT49	HAP1 TP73 (-) 1	Cancer cell line	Male
CVCL_XU64	HAP1 TP73 (-) 2	Cancer cell line	Male
CVCL_XU65	HAP1 TP73 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00208078	Phase 4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00291460	Phase 4	UNKNOWN	Inspiratory Muscle Training in Hypercapnic COPD
NCT00355732	Phase 4	COMPLETED	Chronic Obstructive Pulmonary Disease and Weaning From Mechanical Ventilation in Difficult to Wean Patients
NCT00560287	Phase 4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00600639	Phase 4	TERMINATED	Non-Invasive Mechanical Ventilation in Elderly Patients
NCT00698958	Phase 4	COMPLETED	Ambulatory Adaptation to Non-Invasive Mechanical Ventilation
NCT00708149	Phase 4	COMPLETED	Comparison of the Efficacy for Stress Ulcer Prophylaxis Between the Patients Received Lansoprazole OD and Control Group Weaning From Mechanical Ventilator in Respiratory Care Center: a Randomized Control Trial
NCT00732537	Phase 4	COMPLETED	Inhaled Nitric Oxide by Oxygen Hood in Neonates
NCT00925860	Phase 4	COMPLETED	Non-Positive Pressure Ventilation in Hypoxemic Patients
NCT01204281	Phase 4	COMPLETED	Proportional Assist Ventilation (PAV) in Early Stage of Critically Ill Patients
NCT01280019	Phase 4	UNKNOWN	FRC Guided Therapy in Acute Respiratory Failure
NCT01472302	Phase 4	COMPLETED	Closed Loop Ventilation Strategy in Intensive Care Unit (ICU) Patients
NCT01572337	Phase 4	COMPLETED	Early Non-invasive Ventilation Outside the Intensive Care Unit
NCT01941524	Phase 4	COMPLETED	Brain Oxygenation and Function of Preterm Newborns During Administration of Two Different Surfactant Preparations
NCT02203019	Phase 4	COMPLETED	Study of Sedative Medications in Patients With Severe Infection and Respiratory Failure
NCT02491346	Phase 4	UNKNOWN	A Trial Comparing SGC and Conventional Empiric Treatment for Glucose Control in Critically Ill Patients With Mechanical Ventilation in ICU
NCT02497729	Phase 4	COMPLETED	Checklists and Upright Positioning in Endotracheal Intubation of Critically Ill Patients (Check-UP) Trial
NCT02526862	Phase 4	COMPLETED	Prevention of Pressure Ulcers in Patients Under Non-Invasive Mechanical Ventilation
NCT02958150	Phase 4	UNKNOWN	Dexmedetomidine Versus Standard Clinical Practice During Non Invasive Mechanical Ventilation
NCT03026777	Phase 4	COMPLETED	Preventing Cardiovascular collaPse With Administration of Fluid Resuscitation Before Endotracheal Intubation
NCT03337373	Phase 4	COMPLETED	The Study of Pharmacokinetics and Pharmacodynamics of Cisatracurium
NCT03625687	Phase 4	TERMINATED	Pan-genotypic Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Lung Transplant
NCT03787732	Phase 4	COMPLETED	Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation
NCT03962725	Phase 4	TERMINATED	Avoiding Neuromuscular Blockers to Reduce Complications
NCT04092621	Phase 4	UNKNOWN	Rapid Atrial Fibrillation Treatment Strategy
NCT04350086	Phase 4	WITHDRAWN	Use of Dexmedetomidine in Light to Moderate Sedation in the Patient in the Palliative Situation of a Sars-cov-2 / COVID-19 Infection
NCT04496362	Phase 4	ACTIVE_NOT_RECRUITING	Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) Heparin Study
NCT05277896	Phase 4	COMPLETED	Randomized Trial of Sedative Choice for Intubation
NCT05322447	Phase 4	COMPLETED	High-dose L-Carnitine and Diaphragmatic Function Assessed by Ultrasonography in Patients With Respiratory Failure.
NCT05843123	Phase 4	COMPLETED	Comparison of Gas Exchange Between Two Invasive Mechanical Ventilation Modes in Children
NCT06401083	Phase 4	RECRUITING	The Effect of an Additional Pre-extubational Loading Dose of Caffeine-citrate
NCT06881927	Phase 4	RECRUITING	Eduction in ImmunoSuppressive Regimen Among Kidney Transplant Recipients Patients Admitted to the Intensive Care Unit for Septic Shock and/or Acute Respiratory Failure
NCT00000562	Phase 3	COMPLETED	Extracorporeal Support for Respiratory Insufficiency (ECMO)
NCT00148642	Phase 3	COMPLETED	Silver-Coated Endotracheal Tube to Reduce Ventilator Associated Pneumonia (VAP)
NCT00221520	Phase 3	UNKNOWN	Sedation in the Intensive Care Unit
NCT00230984	Phase 3	COMPLETED	IRAD2 : Patients With Respiratory Failure at Home
NCT00248443	Phase 3	COMPLETED	Réa-MiniMax: Severe Acute Respiratory Failure in Hematology and Cancer Patients Without Bronchoalveolar Lavage
NCT00347321	Phase 3	COMPLETED	Early Percutaneous Tracheostomy for Cardiac Surgery (ETOC)
NCT00549809	Phase 3	COMPLETED	Comparison Between IMV and SIMV/PS for Ventilatory Support of Children: a Randomized Clinical Trial
NCT01076816	Phase 3	TERMINATED	Dexmedetomidine Pharmacokinetics-pharmacodynamics in Mechanically Ventilated Children With Single-organ Respiratory Failure
NCT01206166	Phase 3	TERMINATED	Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients (TOP-UP)
NCT01242150	Phase 3	COMPLETED	Noninvasive Continuous Positive Airway Pressure (NCPAP) in Children
NCT01565941	Phase 3	COMPLETED	Heart And Lung Failure - Pediatric INsulin Titration Trial
NCT01577667	Phase 3	COMPLETED	Intellivent Versus Conventional Ventilation
NCT01580956	Phase 3	COMPLETED	VARIABLE-PSV Study
NCT01966861	Phase 3	UNKNOWN	Weaning From Mechanical Ventilation Guided by Lung Ultrasound (Brazilian WEANLUS)
NCT02028260	Phase 3	WITHDRAWN	Modafinil Versus Placebo for Hypoactive Delirium in the Critically Ill
NCT02342899	Phase 3	COMPLETED	Cost Effectiveness of Outpatient Set-up of Automated NIV in Obese Patients With Chronic Respiratory Failure
NCT02424773	Phase 3	COMPLETED	Oxygen Therapy During Acute Respiratory Failure in Immuno-compromised Patients
NCT02683772	Phase 3	COMPLETED	Astral VAPS AutoEPAP Clinical Trial
NCT04193878	Phase 3	TERMINATED	ARrest RESpiraTory Failure From PNEUMONIA
NCT04208581	Phase 3	UNKNOWN	Yiqi Huoxue Huatan Granule for Reducing Mortality in COPD With Chronic Respiratory Failure
NCT04339816	Phase 3	TERMINATED	Azithromycin Added to Hydrochloroquine in Patients Admitted to Intensive Care With COVID-19: Randomised Controlled Trial
NCT04536272	Phase 3	COMPLETED	Reduced Anticoagulation Targets in ECLS (RATE)
NCT04680884	Phase 3	UNKNOWN	Empirical Steroids and/or Antifungals in Immunocompromised Patients With Acute Respiratory Failure From Undetermined Etiology: a Multicenter Double-blind Randomized Controlled Trial
NCT04706507	Phase 3	TERMINATED	Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients With Acute Respiratory Failure and Sepsis
NCT04930419	Phase 3	UNKNOWN	Comparative Evaluation of the McGrath Videolaryngoscope and the Direct Laryngoscopy for Tracheal Intubation in the Prehospital Setting
NCT05014581	Phase 3	RECRUITING	Preventing Cardiovascular Collapse With Vasopressors During Tracheal Intubation
NCT05355974	Phase 3	COMPLETED	Using Vasopressor Medication to Support Blood Pressure During Intubation Procedure
NCT05456542	Phase 3	COMPLETED	Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients