TP63

Summary

TP63 (tumor protein p63, HGNC:15979) is a protein-coding gene on chromosome 3q28, encoding Tumor protein 63 (Q9H3D4). Acts as a sequence specific DNA binding transcriptional activator or repressor.

This gene encodes a member of the p53 family of transcription factors. The functional domains of p53 family proteins include an N-terminal transactivation domain, a central DNA-binding domain and an oligomerization domain. Alternative splicing of this gene and the use of alternative promoters results in multiple transcript variants encoding different isoforms that vary in their functional properties. These isoforms function during skin development and maintenance, adult stem/progenitor cell regulation, heart development and premature aging. Some isoforms have been found to protect the germline by eliminating oocytes or testicular germ cells that have suffered DNA damage. Mutations in this gene are associated with ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3); split-hand/foot malformation 4 (SHFM4); ankyloblepharon-ectodermal defects-cleft lip/palate; ADULT syndrome (acro-dermato-ungual-lacrimal-tooth); limb-mammary syndrome; Rap-Hodgkin syndrome (RHS); and orofacial cleft 8.

Source: NCBI Gene 8626 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3 (Definitive, ClinGen) — +9 more curated relationships
• GWAS associations: 31
• Clinical variants (ClinVar): 824 total — 67 pathogenic, 52 likely-pathogenic
• Phenotypes (HPO): 254
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• Transcription factor: yes — 221 downstream targets (CollecTRI)
• MANE Select transcript: NM_003722

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15979
Approved symbol	TP63
Name	tumor protein p63
Location	3q28
Locus type	gene with protein product
Status	Approved
Aliases	p51, SHFM4, EEC3, p63, p73L, OFC8, KET, p73H, NBP, p53CP, p40
Ensembl gene	ENSG00000073282
Ensembl biotype	protein_coding
OMIM	603273
Entrez	8626

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 retained_intron

ENST00000264731, ENST00000320472, ENST00000354600, ENST00000392460, ENST00000392461, ENST00000392463, ENST00000418709, ENST00000434928, ENST00000437221, ENST00000440651, ENST00000449992, ENST00000456148, ENST00000460036, ENST00000486398

RefSeq mRNA: 13 — MANE Select: NM_003722 NM_001114978, NM_001114979, NM_001114980, NM_001114981, NM_001114982, NM_001329144, NM_001329145, NM_001329146, NM_001329148, NM_001329149, NM_001329150, NM_001329964, NM_003722

CCDS: CCDS3293, CCDS46976, CCDS46977, CCDS46978, CCDS46979, CCDS46980, CCDS82887, CCDS87179, CCDS87180, CCDS87181

Canonical transcript exons

ENST00000264731 — 14 exons

Exon	Start	End
ENSE00000781605	189889340	189889484
ENSE00000781606	189890789	189890882
ENSE00000871463	189872859	189872995
ENSE00001005407	189886394	189886551
ENSE00001184832	189738642	189738774
ENSE00001343828	189631389	189631577
ENSE00001608550	189894206	189897276
ENSE00003473100	189808272	189808526
ENSE00003476123	189866682	189866797
ENSE00003502961	189737740	189737868
ENSE00003525444	189868580	189868716
ENSE00003597426	189864232	189864418
ENSE00003641501	189867833	189867942
ENSE00003672778	189869324	189869406

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 98.64.

FANTOM5 (CAGE): breadth broad, TPM avg 7.2732 / max 468.1409, expressed in 313 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40527	3.8486	156
40524	2.4305	124
40521	0.3528	88
40528	0.2582	87
40529	0.1755	81
40523	0.1072	47
40532	0.0606	24
40522	0.0220	15
40531	0.0177	7

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	98.64	gold quality
skin of hip	UBERON:0001554	98.26	gold quality
upper arm skin	UBERON:0004263	98.06	gold quality
penis	UBERON:0000989	98.00	gold quality
hair follicle	UBERON:0002073	97.57	gold quality
mammalian vulva	UBERON:0000997	97.53	gold quality
gingiva	UBERON:0001828	97.36	gold quality
nipple	UBERON:0002030	97.32	gold quality
tongue squamous epithelium	UBERON:0006919	97.08	gold quality
skin of abdomen	UBERON:0001416	97.00	gold quality
gingival epithelium	UBERON:0001949	96.98	gold quality
zone of skin	UBERON:0000014	96.53	gold quality
pharyngeal mucosa	UBERON:0000355	96.17	gold quality
skin of leg	UBERON:0001511	95.93	gold quality
oral cavity	UBERON:0000167	95.66	gold quality
cervix epithelium	UBERON:0004801	95.43	gold quality
esophagus mucosa	UBERON:0002469	94.71	gold quality
squamous epithelium	UBERON:0006914	94.57	gold quality
esophagus squamous epithelium	UBERON:0006920	93.81	gold quality
body of tongue	UBERON:0011876	93.78	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.65	gold quality
epithelium of esophagus	UBERON:0001976	92.89	gold quality
cervix squamous epithelium	UBERON:0006922	91.75	gold quality
deltoid	UBERON:0001476	91.51	gold quality
epithelium of nasopharynx	UBERON:0001951	91.45	gold quality
tibialis anterior	UBERON:0001385	91.21	gold quality
gluteal muscle	UBERON:0002000	91.21	gold quality
lower esophagus mucosa	UBERON:0035834	91.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.14	gold quality
tongue	UBERON:0001723	90.87	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-86618	yes	311.17
E-ENAD-21	yes	223.65
E-CURD-114	yes	172.52
E-ANND-3	yes	17.21

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

221 targets.

Target	Regulation
AACS
ABCB1
ACOT11
ACTB
ADA
ADAM2
AHCYL1
AHR
AKT1
ALDH2
ALOX12
APOD	Activation
AQP3	Activation
AR
ATM
AVP
AXL
B4GALT1
BAX	Activation
BBC3	Unknown
BCL2
BMAL1
BNC1
BRCA1	Unknown
CARM1
CASP1
CAT
CCDC28A
CCDC3	Activation
CCND3

JASPAR motifs

Motif	Name	Family
MA0525.1	TP63	p53-related factors
MA0525.2	TP63	p53-related factors

JASPAR matrix evidence (PMIDs): PMID:17188034

Upstream regulators (CollecTRI, top): AR, BHLHE40, BRCA1, CEBPA, CTNNB1, ESR2, HBP1, HDAC2, IRF3, JUN, LEF1, NFKB, NFKBIA, RELA, SATB2, SOX2, SSRP1, STAT3, TBP, TBPL1, TFAP2A, TP53, TP63, TP73, YBX1, ZEB1

miRNA regulators (miRDB)

137 targeting TP63, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-221-5P	99.86	65.45	1052

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Free p63 core domain did not show specific binding to p53 DNA consensus sites. (PMID:11477076)
• Expression in the gastrointestinal tract and in esophageal metaplastic and neoplastic disorders (PMID:11727253)
• TP63 tumor protein 63 kDa with strong homology to p53 (PMID:11739646)
• Split-hand/split-foot malformation with paternal missense mutation in the p63 gene (PMID:11787035)
• p63 expression profiles in human normal and tumor tissues. (PMID:11839669)
• Review: Mutations in the p53 homolog p63: allele-specific developmental syndromes in humans (PMID:11879774)
• inhibition by p53 mutants (PMID:11893750)
• 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)
• The distribution of mutations over the various p63 protein domains and the structural and functional implications of these mutations establish a clear genotype-phenotype correlation. Review. (PMID:12037717)
• expressed in basal cell carcinoma (PMID:12102658)
• A common role is shown for p63 in classical EEC syndrome, both familial and sporadic, but not in other related or non-syndromic forms of orofacial clefts. (PMID:12161593)
• P63 gene mutations and developmental syndromes. Review. (PMID:12357472)
• loss of expression is associated with tumor progression in bladder cancer (PMID:12368193)
• SSRP1 stimulates p63 activity by associating with this activator at the promoter (PMID:12374749)
• prevalence and clinical implications of p63 immunoreactivity (IR) and mRNA expression in laryngeal squamous cell carcinomas (PMID:12379767)
• sequence deletion has a role in abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis (PMID:12379768)
• identified a novel domain within the C terminus that is necessary and sufficient for transcriptional inhibition and which acts by binding to a region in the N-terminal transactivation domain of p63 homologous to the MDM2 binding site in p53 (PMID:12446779)
• Data highlight the modularity of p63, identifying the SAM domain as a dominant transcriptional repression module and indicating that the AEC and EEC frameshift mutants are characterized by a subversion of the p63 transcriptional potential (PMID:12446784)
• Seven missense mutations involving codons for arginine residues have been detected in p63 in seven out of 10 non-syndromic split hand/foot malformation patients. (PMID:12525544)
• physical association of p63alpha and ABBP1 led to a specific shift of FGFR-2 alternative splicing toward the K-SAM isoform essential for epithelial differentiation (PMID:12692135)
• ZD1839 downregulates p63 expression at the messenger RNA level, suggesting that p63 is a downstream target of EGFR signaling. (PMID:12782800)
• study supports the hypothesis that in situations where p53 activation is desirable, as with DNA-damaging UVR, DeltaNp63alpha downregulation occurs and may possibly allow for better target gene transcription by p53 (PMID:12788532)
• The chemical shifts for backbone resonances of the p63 DNA-binding domain were determined and deposited in BMRB-5700. (PMID:12815266)
• Rapp-Hodgkin syndrome results from mutations of the TP63 gene. (PMID:12939657)
• DeltaNp63 transactivated the S100A2 promoter, and significantly more fold changes were seen in DeltaNp63-introduced cells than in p53-introduced cells, suggesting that DeltaNp63 may be a novel stimulator of the S100A2 promoter. (PMID:14519656)
• Treatment of keratinocytes with epidermal growth factor results in an increase in Delta Np63 alpha expression at the mRNA level, which is abrogated by inhibition of PI3K but not mitogen-activated protein kinase signaling. (PMID:14555649)
• The expression of p63 gene is associated with poor survival and locoregional failure in cervical squamous cell carcinoma. (PMID:14599865)
• Impaired expression associated with poor prognosis in invasive bladder carcinoma. (PMID:14654522)
• p63 plays critical roles in tumor progression and biochemical terminal differentiation of urothelial neoplasms. (PMID:14654529)
• patients with syndromic ectrodactyly had p63 heterozygous point mutations that affect the DNA binding domain of the protein (PMID:14656652)
• The level of p63 protein was almost the same as that of the control in all types of scars (PMID:14757278)
• This study demonstrated that sclerosing mucoepidermoid carcinomas with eosinophilia (SMECE) stain strongly positive for p63, which is a new marker for UBB/solid cell nests. (PMID:15001991)
• p63 has a role in breast myoepithelial cell differentiation (PMID:15024707)
• The complexity of these p63 expression patterns seen in primary squamous cell carcinoma of the head and neck indicates that p63 has multifaceted roles in tumour biology. (PMID:15201986)
• p63 and p53 play a major role in the carcinogenesis of human esophageal squamous cells and in the growth of the carcinoma (PMID:15254760)
• Emerging evidence in this review discusses a key survival/death checkpoint in both peripheral and central neurons that involves the p53 tumor suppressor and its newly discovered family members, p73 and p63. (PMID:15359011)
• findings suggest that analysis of p63 expression may help in the differential diagnosis of primary vs metastatic cutaneous adenocarcinomas. (PMID:15389254)
• RACK1 physically associated with the p63alpha C-terminal domain through its WD40 domain. However, stratifin binds with phosphorylated DeltaNp63alpha in response to cisplatin. (PMID:15467455)
• We propose the inclusion of p63 as part of the diagnostic workup of challenging spindle cell tumors of the breast as a highly specific marker for metaplastic carcinomas. (PMID:15489655)
• Immunohistochemical staining for p63 could be a useful means of distinguishing adenoid cystic carcinoma from basaloid squamous cell carcinoma. (PMID:15529180)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tp63	ENSDARG00000044356
mus_musculus	Trp63	ENSMUSG00000022510
rattus_norvegicus	Tp63	ENSRNOG00000001924
drosophila_melanogaster	p53	FBGN0039044

Paralogs (2): TP73 (ENSG00000078900), TP53 (ENSG00000141510)

Protein

Protein identifiers

Tumor protein 63 — Q9H3D4 (reviewed: Q9H3D4)

Alternative names: Chronic ulcerative stomatitis protein, Keratinocyte transcription factor KET, Transformation-related protein 63, Tumor protein p73-like, p40, p51

All UniProt accessions (5): Q9H3D4, A0A0S2Z4N5, A0A0S2Z4N6, C9D7D0, C9JW72

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.

Subunit / interactions. Binds DNA as a homotetramer. Isoform composition of the tetramer may determine transactivation activity. Isoforms Alpha and Gamma interact with HIPK2. Interacts with SSRP1, leading to stimulate coactivator activity. Isoform 1 and isoform 2 interact with WWP1. Interacts with PDS5A. Isoform 5 (via activation domain) interacts with NOC2L.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed, notably in heart, kidney, placenta, prostate, skeletal muscle, testis and thymus, although the precise isoform varies according to tissue type. Progenitor cell layers of skin, breast, eye and prostate express high levels of DeltaN-type isoforms. Isoform 10 is predominantly expressed in skin squamous cell carcinomas, but not in normal skin tissues.

Post-translational modifications. May be sumoylated. Ubiquitinated. Polyubiquitination involves WWP1 and leads to proteasomal degradation of this protein.

Disease relevance. Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:103285] A form of ectodermal dysplasia. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia and loss of permanent teeth. ADULT syndrome differs significantly from EEC3 syndrome by the absence of facial clefting. Inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:106260] An autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate. The disease is caused by variants affecting the gene represented in this entry. Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3) [MIM:604292] A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting. The disease is caused by variants affecting the gene represented in this entry. Split-hand/foot malformation 4 (SHFM4) [MIM:605289] A limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have intellectual disability, ectodermal and craniofacial findings, and orofacial clefting. The disease is caused by variants affecting the gene represented in this entry. Limb-mammary syndrome (LMS) [MIM:603543] Characterized by ectrodactyly, cleft palate and mammary-gland abnormalities. The disease is caused by variants affecting the gene represented in this entry. Rapp-Hodgkin syndrome (RHS) [MIM:129400] A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate. RHS inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Orofacial cleft 8 (OFC8) [MIM:618149] A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. The disease is caused by variants affecting the gene represented in this entry. Premature ovarian failure 21 (POF21) [MIM:620311] A form of premature ovarian failure, an ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. POF21 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Gain-of-function variants located in the transactivation inhibition domain are responsible for premature ovarian failure by inducing accelerated oocyte loss, as shown in mutant mice carrying the pathogenic variant p.Arg647Cys.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The transactivation inhibitory domain (TID) can interact with, and inhibit the activity of the N-terminal transcriptional activation domain of TA*-type isoforms.

Miscellaneous. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative splicing of isoform 1. Produced by alternative splicing of isoform 2. Produced by alternative splicing of isoform 1. Produced by alternative splicing of isoform 2. Produced by alternative splicing of isoform 1. Produced by alternative splicing of isoform 2. Produced by alternative splicing of isoform 1. Produced by alternative splicing of isoform 2. Produced by alternative splicing of isoform 1. Produced by alternative splicing of isoform 2.

Similarity. Belongs to the p53 family.

Isoforms (12)

UniProt ID	Names	Canonical?
Q9H3D4-1	1, TA*-alpha, TAp63alpha, P51B	yes
Q9H3D4-2	2, DeltaN-alpha, DeltaNp63 alpha, P51delNalpha
Q9H3D4-3	3, TA*-beta, TAp63beta
Q9H3D4-4	4, DeltaN-beta, DeltaNp63 beta, P51delNbeta
Q9H3D4-5	5, TA*-gamma, TAp63gamma, P51A
Q9H3D4-6	6, DeltaN-gamma, DeltaNp63gamma, P51delNgamma
Q9H3D4-7	7, TA*-delta, TAp63delta, P51delta
Q9H3D4-8	8, DeltaN-delta
Q9H3D4-9	9, TA*-epsilon
Q9H3D4-10	10, DeltaN-epsilon, DeltaNp73L
Q9H3D4-11	11, P63 delta
Q9H3D4-12	12

RefSeq proteins (13): NP_001108450, NP_001108451, NP_001108452, NP_001108453, NP_001108454, NP_001316073, NP_001316074, NP_001316075, NP_001316077, NP_001316078, NP_001316079, NP_001316893, NP_003713* (*=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
IPR037611	Tumor-p63_SAM	Domain
IPR057064	P53_central_site	Conserved_site

Pfam: PF00870, PF07647, PF07710

UniProt features (134 total): sequence variant 52, strand 19, helix 16, mutagenesis site 8, region of interest 7, compositionally biased region 6, turn 6, splice variant 6, sequence conflict 6, binding site 4, chain 1, domain 1, DNA-binding region 1, cross-link 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
2Y9U	X-RAY DIFFRACTION	1.6
8P9C	X-RAY DIFFRACTION	1.76
7Z72	X-RAY DIFFRACTION	1.8
7Z7E	X-RAY DIFFRACTION	1.8
7Z71	X-RAY DIFFRACTION	1.85
3ZY0	X-RAY DIFFRACTION	1.9
6RU8	X-RAY DIFFRACTION	1.92
6RU6	X-RAY DIFFRACTION	2.05
6RU7	X-RAY DIFFRACTION	2.08
3ZY1	X-RAY DIFFRACTION	2.15
9N54	X-RAY DIFFRACTION	2.2
8P9E	X-RAY DIFFRACTION	2.25
7Z73	X-RAY DIFFRACTION	2.27
4A9Z	X-RAY DIFFRACTION	2.29
9GFO	X-RAY DIFFRACTION	2.4
3QYN	X-RAY DIFFRACTION	2.5
3US0	X-RAY DIFFRACTION	2.5
8P9D	X-RAY DIFFRACTION	2.7
3US1	X-RAY DIFFRACTION	2.8
3QYM	X-RAY DIFFRACTION	3.2
3US2	X-RAY DIFFRACTION	4.2
1RG6	SOLUTION NMR
2NB1	SOLUTION NMR
2RMN	SOLUTION NMR
2Y9T	SOLUTION NMR
6FGN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3D4-F1	63.70	0.35

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): 244; 247; 308; 312

Post-translational modifications (1): 676

Mutagenesis-validated functional residues (8):

Position	Phenotype
18	no effect on transcriptional activation in a luciferase reporter assay.
55	abrogates transcriptional activity and interaction with transactivation inhibition domain; when associated with a-59 and
59	abrogates transcriptional activity and interaction with transactivation inhibition domain; when associated with a-55 and
62	abrogates transcriptional activity and interaction with transactivation inhibition domain; when associated with a-55 and
97	no effect on transcriptional activation in a luciferase reporter assay.
543	abolishes ubiquitination.
643	increased transcriptional activation in a luciferase reporter assay.
647	increased transcriptional activation in a luciferase reporter assay.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-139915	Activation of PUMA and translocation to mitochondria
R-HSA-5620971	Pyroptosis
R-HSA-5628897	TP53 Regulates Metabolic 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 whose specific roles in p53-dependent apoptosis remain uncertain
R-HSA-6803207	TP53 Regulates Transcription of Caspase Activators and Caspases
R-HSA-6803211	TP53 Regulates Transcription of Death Receptors and Ligands
R-HSA-6804759	Regulation of TP53 Activity through Association with Co-factors
R-HSA-9725554	Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin
R-HSA-9927432	Developmental Lineage of Mammary Gland Myoepithelial Cells
R-HSA-9938206	Developmental Lineage of Mammary Stem Cells
R-HSA-9927418	Developmental Lineage of Mammary Gland Luminal Epithelial Cells

MSigDB gene sets: 841 (showing top): CREL_01, RRAGTTGT_UNKNOWN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, WANG_CLIM2_TARGETS_UP, GAANYNYGACNY_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_LIPID, JAEGER_METASTASIS_DN, TGCACTT_MIR519C_MIR519B_MIR519A, CMYB_01, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_ESTROGEN_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY

GO Biological Process (67): negative regulation of transcription by RNA polymerase II (GO:0000122), skeletal system development (GO:0001501), establishment of planar polarity (GO:0001736), epithelial cell development (GO:0002064), chromatin remodeling (GO:0006338), transcription by RNA polymerase II (GO:0006366), apoptotic process (GO:0006915), DNA damage response (GO:0006974), Notch signaling pathway (GO:0007219), spermatogenesis (GO:0007283), ectoderm and mesoderm interaction (GO:0007499), determination of adult lifespan (GO:0008340), proximal/distal pattern formation (GO:0009954), epidermal cell division (GO:0010481), regulation of epidermal cell division (GO:0010482), positive regulation of keratinocyte proliferation (GO:0010838), keratinocyte differentiation (GO:0030216), polarized epithelial cell differentiation (GO:0030859), hair follicle morphogenesis (GO:0031069), negative regulation of intracellular estrogen receptor signaling pathway (GO:0033147), embryonic forelimb morphogenesis (GO:0035115), embryonic hindlimb morphogenesis (GO:0035116), post-anal tail morphogenesis (GO:0036342), odontogenesis of dentin-containing tooth (GO:0042475), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), regulation of apoptotic process (GO:0042981), skin morphogenesis (GO:0043589), keratinocyte proliferation (GO:0043616), negative regulation of keratinocyte differentiation (GO:0045617), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of Notch signaling pathway (GO:0045747), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), sympathetic nervous system development (GO:0048485), female genitalia morphogenesis (GO:0048807), protein tetramerization (GO:0051262), neuron apoptotic process (GO:0051402), cloacal septation (GO:0060197), prostatic bud formation (GO:0060513)

GO Molecular Function (19): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), p53 binding (GO:0002039), DNA binding (GO:0003677), chromatin binding (GO:0003682), damaged DNA binding (GO:0003684), DNA-binding transcription factor activity (GO:0003700), identical protein binding (GO:0042802), metal ion binding (GO:0046872), WW domain binding (GO:0050699), MDM2/MDM4 family protein binding (GO:0097371), promoter-specific chromatin binding (GO:1990841), transcription cis-regulatory region binding (GO:0000976), double-stranded DNA binding (GO:0003690), protein binding (GO:0005515), protein domain specific binding (GO:0019904), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), dendrite (GO:0030425), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Death Genes	4
Developmental Lineages of the Mammary Gland	3
Activation of BH3-only proteins	1
Regulated Necrosis	1
Transcriptional Regulation by TP53	1
Regulation of TP53 Activity	1
Developmental Cell Lineages of the Integumentary System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
DNA binding	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
morphogenesis of a polarized epithelium	2
epithelial cell differentiation	2
transcription cis-regulatory region binding	2
binding	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
system development	1
establishment of tissue polarity	1
cell development	1
chromatin organization	1
DNA-templated transcription	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
cell surface receptor signaling pathway	1
developmental process involved in reproduction	1
male gamete generation	1
cell-cell signaling	1
mesoderm development	1
multicellular organismal process	1
regionalization	1
cell division	1
epidermal cell division	1
regulation of cell division	1
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
positive regulation of epithelial cell proliferation	1
epidermal cell differentiation	1
skin development	1
hair follicle development	1
anatomical structure morphogenesis	1
hair cycle process	1
epidermis morphogenesis	1
estrogen receptor signaling pathway	1

Protein interactions and networks

STRING

2404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TP63	SOX2	P48431	918
TP63	TP73	O15350	779
TP63	WNT10B	O00744	760
TP63	DLX6	P56179	723
TP63	PERP	Q96FX8	716
TP63	KRT14	P02533	704
TP63	PIK3CA	P42336	674
TP63	MYC	P01106	673
TP63	KRT5	P13647	653
TP63	DLX5	P56178	649
TP63	SPATS2	Q86XZ4	649
TP63	CDKN2A	P42771	648
TP63	DUSP22	Q9NRW4	616
TP63	MDM2	Q00987	599
TP63	KMT2D	O14686	594

IntAct

88 interactions, top by confidence:

A	B	Type	Score
TP63	TP63	psi-mi:“MI:0407”(direct interaction)	0.770
TP63	TP73	psi-mi:“MI:0407”(direct interaction)	0.770
TP63	TP73	psi-mi:“MI:0915”(physical association)	0.770
TP63	TP73	psi-mi:“MI:0914”(association)	0.770
SMAD2	TP53	psi-mi:“MI:0915”(physical association)	0.670
TP53	SMAD2	psi-mi:“MI:0915”(physical association)	0.670
YAP1	TP63	psi-mi:“MI:0407”(direct interaction)	0.610
TP63	YAP1	psi-mi:“MI:0915”(physical association)	0.610
	TP63	psi-mi:“MI:0915”(physical association)	0.590
TP53	TP63	psi-mi:“MI:0915”(physical association)	0.590
SMAD2	TP63	psi-mi:“MI:0915”(physical association)	0.590
TP63	TP53	psi-mi:“MI:0915”(physical association)	0.590
TP63	SMAD2	psi-mi:“MI:0915”(physical association)	0.590
HNRNPAB	TP63	psi-mi:“MI:0915”(physical association)	0.570
TP63	HNRNPAB	psi-mi:“MI:0915”(physical association)	0.570
TP63	PELI2	psi-mi:“MI:0915”(physical association)	0.560
MCRS1	TP63	psi-mi:“MI:0915”(physical association)	0.560
PELI1	TP63	psi-mi:“MI:0915”(physical association)	0.560
PIN1	TP63	psi-mi:“MI:0915”(physical association)	0.560
UBASH3A	TP63	psi-mi:“MI:0915”(physical association)	0.560
PPP1R13B	TP63	psi-mi:“MI:0407”(direct interaction)	0.540
TP63	PPP1R13B	psi-mi:“MI:0915”(physical association)	0.540

BioGRID (401): TP63 (Affinity Capture-Western), TP63 (Affinity Capture-Western), EP300 (Affinity Capture-Western), TP63 (Biochemical Activity), TP63 (Biochemical Activity), EP300 (Reconstituted Complex), TP63 (Reconstituted Complex), TP63 (Affinity Capture-Western), EP300 (Affinity Capture-Western), BRCA1 (Co-localization), TP63 (Biochemical Activity), TP63 (Affinity Capture-Western), TP53 (Affinity Capture-Western), TP63 (Proximity Label-MS), ITCH (Reconstituted Complex)

ESM2 similar proteins: A0A3Q0KHE7, A3KPF2, B0W3L6, B4JXV2, B4KA23, B4LVS8, D9PTN5, G5EFI7, H2KYJ8, M9PD06, O45666, O88898, P10383, P49881, P51592, P79926, Q08639, Q09441, Q14149, Q14186, Q17370, Q174R2, Q18192, Q21006, Q23985, Q24143, Q28CK1, Q3SA46, Q66J63, Q6E3C9, Q6E3D0, Q6GN21, Q7Q2B7, Q84W92, Q86NH1, Q8AXW8, Q8UW76, Q91766, Q94527, Q95YE2

Diamond homologs: O09185, O12946, O15350, O36006, O57538, O88898, O93379, P02340, P04637, P07193, P10360, P10361, P13481, P25035, P41685, P51664, P56423, P56424, P61260, P67938, P67939, P79734, P79820, P79892, Q00366, Q29480, Q29537, Q64662, Q8SPZ3, Q92143, Q95330, Q9H3D4, Q9JJP2, Q9JJP6, Q9TTA1, Q9TUB2, Q9W678, Q9W679, Q9WUR6, Q9XSK8

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
ATM	down-regulates	TP63	phosphorylation
CDK2	down-regulates	TP63	phosphorylation
RPS6KB1	down-regulates	TP63	phosphorylation
TGFBR1	unknown	TP63	phosphorylation
TP63	“up-regulates quantity by expression”	PERP	“transcriptional regulation”
SATB2	“down-regulates activity”	TP63	binding
ABL1	“up-regulates quantity by stabilization”	TP63	phosphorylation
CRBN	“down-regulates quantity by destabilization”	TP63	polyubiquitination
TP63	“up-regulates quantity by expression”	SUN1	“transcriptional regulation”
TP63	“up-regulates quantity by expression”	PLEC	“transcriptional regulation”
TP63	“up-regulates quantity by expression”	SYNE3	“transcriptional regulation”
MAPK14	“down-regulates quantity by destabilization”	TP63	phosphorylation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — BLCA, CESC, HNSC, MEL, NBL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	67
Likely pathogenic	52
Uncertain significance	319
Likely benign	219
Benign	76

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1018494	NM_003722.5(TP63):c.796C>T (p.Arg266Ter)	Pathogenic
1024583	NM_003722.5(TP63):c.1861del (p.Ser621fs)	Pathogenic
1062831	NM_003722.5(TP63):c.1050A>T (p.Arg350Ser)	Pathogenic
1451175	NM_003722.5(TP63):c.328C>T (p.Gln110Ter)	Pathogenic
1451179	NM_003722.5(TP63):c.1695C>A (p.Phe565Leu)	Pathogenic
1454691	NM_003722.5(TP63):c.1583dup (p.Leu529fs)	Pathogenic
1677243	NM_003722.5(TP63):c.290G>C (p.Arg97Pro)	Pathogenic
1677244	NM_003722.5(TP63):c.1939C>T (p.Arg647Cys)	Pathogenic
194382	NM_003722.5(TP63):c.1837_1841del (p.Pro613fs)	Pathogenic
2079999	NM_003722.5(TP63):c.1735del (p.Tyr579fs)	Pathogenic
208163	NM_003722.5(TP63):c.740A>G (p.His247Arg)	Pathogenic
208418	NM_003722.5(TP63):c.1037C>G (p.Ala346Gly)	Pathogenic
2446718	NM_003722.5(TP63):c.1703del (p.Gln568fs)	Pathogenic
2579607	NM_003722.5(TP63):c.1039T>C (p.Cys347Arg)	Pathogenic
265276	NM_003722.5(TP63):c.956G>A (p.Arg319His)	Pathogenic
2710369	NM_003722.5(TP63):c.2014C>T (p.Gln672Ter)	Pathogenic
2734605	NM_003722.5(TP63):c.518G>A (p.Gly173Asp)	Pathogenic
2734606	NM_003722.5(TP63):c.932G>A (p.Ser311Asn)	Pathogenic
279913	NM_003722.5(TP63):c.1027C>T (p.Arg343Trp)	Pathogenic
3600613	NM_003722.5(TP63):c.580-2A>G	Pathogenic
3602195	NM_003722.5(TP63):c.1654T>G (p.Phe552Val)	Pathogenic
3650569	NM_003722.5(TP63):c.1851del (p.Arg618fs)	Pathogenic
3659797	NM_003722.5(TP63):c.566C>A (p.Ser189Ter)	Pathogenic
3695316	NM_003722.5(TP63):c.653dup (p.Pro219fs)	Pathogenic
372540	NM_003722.5(TP63):c.1727T>C (p.Ile576Thr)	Pathogenic
3729545	NM_003722.5(TP63):c.1999del (p.Ala667fs)	Pathogenic
379608	NM_003722.5(TP63):c.935G>A (p.Cys312Tyr)	Pathogenic
379830	NM_003722.5(TP63):c.547C>T (p.Gln183Ter)	Pathogenic
3809728	NM_003722.5(TP63):c.1050A>C (p.Arg350Ser)	Pathogenic
3897228	NM_003722.5(TP63):c.858_859delinsCTTCCTG (p.Leu287fs)	Pathogenic

SpliceAI

2303 predictions. Top by Δscore:

Variant	Effect	Δscore
3:189789839:TGAGG:T	donor_loss	1.0000
3:189789843:GTAA:G	donor_loss	1.0000
3:189864211:A:AG	acceptor_gain	1.0000
3:189864211:ACT:A	acceptor_gain	1.0000
3:189864211:ACTG:A	acceptor_gain	1.0000
3:189864213:T:A	acceptor_gain	1.0000
3:189864214:G:A	acceptor_gain	1.0000
3:189864227:A:G	acceptor_gain	1.0000
3:189864414:CGAGG:C	donor_gain	1.0000
3:189864415:GAGG:G	donor_gain	1.0000
3:189864415:GAGGG:G	donor_gain	1.0000
3:189864416:AGGGT:A	donor_loss	1.0000
3:189864417:GG:G	donor_gain	1.0000
3:189864418:GG:G	donor_gain	1.0000
3:189864419:G:GG	donor_gain	1.0000
3:189864419:GT:G	donor_loss	1.0000
3:189864420:T:A	donor_loss	1.0000
3:189866672:T:TA	acceptor_gain	1.0000
3:189866680:A:AG	acceptor_gain	1.0000
3:189866681:G:GT	acceptor_gain	1.0000
3:189866681:GGAC:G	acceptor_gain	1.0000
3:189866681:GGACA:G	acceptor_gain	1.0000
3:189866760:G:GT	donor_gain	1.0000
3:189866795:CAG:C	donor_loss	1.0000
3:189866796:AG:A	donor_loss	1.0000
3:189866797:GG:G	donor_loss	1.0000
3:189866798:G:C	donor_loss	1.0000
3:189866799:T:A	donor_loss	1.0000
3:189867939:GAGA:G	donor_gain	1.0000
3:189867941:GA:G	donor_gain	1.0000

AlphaMissense

4516 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:189808441:T:A	I165N	1.000
3:189808443:C:T	P166S	1.000
3:189808444:C:A	P166H	1.000
3:189808444:C:G	P166R	1.000
3:189808451:C:A	N168K	1.000
3:189808451:C:G	N168K	1.000
3:189808458:T:G	Y171D	1.000
3:189808464:G:C	G173R	1.000
3:189808464:G:T	G173C	1.000
3:189808465:G:A	G173D	1.000
3:189808465:G:T	G173V	1.000
3:189808476:T:C	F177L	1.000
3:189808477:T:C	F177S	1.000
3:189808478:C:A	F177L	1.000
3:189808478:C:G	F177L	1.000
3:189808483:T:A	V179E	1.000
3:189808488:T:C	F181L	1.000
3:189808489:T:C	F181S	1.000
3:189808490:C:A	F181L	1.000
3:189808490:C:G	F181L	1.000
3:189808500:A:C	S185R	1.000
3:189808502:C:A	S185R	1.000
3:189808502:C:G	S185R	1.000
3:189808507:C:A	A187D	1.000
3:189808509:A:C	K188Q	1.000
3:189808509:A:G	K188E	1.000
3:189808510:A:C	K188T	1.000
3:189808510:A:T	K188M	1.000
3:189808511:G:C	K188N	1.000
3:189808511:G:T	K188N	1.000

dbSNP variants (sampled 300 via entrez): RS1000035181 (3:189634532 T>C), RS1000047945 (3:189721416 C>G,T), RS1000056453 (3:189672416 C>T), RS1000077405 (3:189714726 T>C), RS1000084786 (3:189800350 A>G), RS1000104822 (3:189799696 A>G), RS1000122625 (3:189595311 T>C), RS1000133869 (3:189633173 A>G), RS1000139167 (3:189683572 T>C), RS1000143662 (3:189881695 C>A,G,T), RS1000155602 (3:189895322 C>T), RS1000156068 (3:189764821 T>C), RS1000175625 (3:189638188 T>A), RS1000192623 (3:189678842 C>A,T), RS1000196164 (3:189761146 C>G)

Disease associations

OMIM: gene MIM:603273 | disease phenotypes: MIM:603543, MIM:103285, MIM:106260, MIM:129400, MIM:604292, MIM:605289, MIM:618149, MIM:620311, MIM:600057, MIM:106250, MIM:609129, MIM:305100

GenCC curated gene-disease

Disease	Classification	Inheritance
ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3	Definitive	Autosomal dominant
ankyloblepharon-ectodermal defects-cleft lip/palate syndrome	Definitive	Autosomal dominant
limb-mammary syndrome	Definitive	Autosomal dominant
ADULT syndrome	Definitive	Autosomal dominant
Rapp-Hodgkin syndrome	Definitive	Autosomal dominant
premature ovarian failure 21	Strong	Autosomal dominant
TP63-related ectodermal dysplasia spectrum with limb and orofacial malformations	Strong	Autosomal dominant
split hand-foot malformation 4	Moderate	Autosomal dominant
EEC syndrome	Supportive	Autosomal dominant
split hand-foot malformation	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3	Definitive	AD

Mondo (19): limb-mammary syndrome (MONDO:0011334), ADULT syndrome (MONDO:0007072), ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (MONDO:0007124), Rapp-Hodgkin syndrome (MONDO:0007508), ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3 (MONDO:0011428), split hand-foot malformation 4 (MONDO:0011535), orofacial cleft 8 (MONDO:0029145), premature ovarian failure 21 (MONDO:0957216), bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039), prostate cancer (MONDO:0008315), premature menopause (MONDO:0001119), skeletal dysplasia (MONDO:0018230), ankyloblepharon filiforme adnatum-cleft palate syndrome (MONDO:0007123), auditory neuropathy (MONDO:0021944), TP63-related ectodermal dysplasia spectrum with limb and orofacial malformations (MONDO:1040001)

Orphanet (13): Limb-mammary syndrome (Orphanet:69085), Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (Orphanet:1071), EEC syndrome (Orphanet:1896), Isolated split hand-split foot malformation (Orphanet:2440), ADULT syndrome (Orphanet:978), Classic bladder exstrophy (Orphanet:93930), Familial prostate cancer (Orphanet:1331), Primary bone dysplasia (Orphanet:364526), Ankyloblepharon filiforme adnatum-cleft palate syndrome (Orphanet:1072), Male infertility with spermatogenesis disorder (Orphanet:399775), Ectodermal dysplasia syndrome (Orphanet:79373), Muscular dystrophy (Orphanet:98473), Rapp-Hodgkin syndrome (Orphanet:3022)

HPO phenotypes

254 total (30 of 254 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000015	Bladder diverticulum
HP:0000021	Megacystis
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000039	Epispadias
HP:0000044	Hypogonadotropic hypogonadism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000056	Abnormal clitoris morphology
HP:0000059	Hypoplastic labia majora
HP:0000068	Urethral atresia
HP:0000069	Abnormality of the ureter
HP:0000070	Ureterocele
HP:0000072	Hydroureter
HP:0000076	Vesicoureteral reflux
HP:0000081	Duplicated collecting system
HP:0000104	Renal agenesis
HP:0000110	Renal dysplasia
HP:0000126	Hydronephrosis
HP:0000145	Transverse vaginal septum
HP:0000151	Aplasia of the uterus
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000198	Absence of Stensen duct
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000231_1	Urinary bladder cancer	1.000000e-07
GCST000573_2	Brain imaging	1.000000e-06
GCST000639_3	Urinary bladder cancer	6.000000e-08
GCST000810_1	Lung adenocarcinoma	7.000000e-12
GCST000842_1	Bladder cancer	2.000000e-10
GCST001140_1	Lung cancer	7.000000e-26
GCST001320_1	Acute lymphoblastic leukemia (childhood)	3.000000e-08
GCST001320_24	Acute lymphoblastic leukemia (childhood)	2.000000e-08
GCST001320_26	Acute lymphoblastic leukemia (childhood)	9.000000e-09
GCST001609_2	Lung adenocarcinoma	7.000000e-17
GCST001740_1	Lung cancer	4.000000e-09
GCST002240_2	Bladder cancer	2.000000e-11
GCST002466_5	Lung cancer	7.000000e-10
GCST002874_26	Psoriasis	8.000000e-06
GCST002874_30	Psoriasis	4.000000e-08
GCST002991_16	Pancreatic cancer	2.000000e-08
GCST003268_23	Psoriasis vulgaris	3.000000e-06
GCST003327_8	Squamous cell carcinoma	1.000000e-11
GCST003605_4	EGFR mutation-positive lung adenocarcinoma	9.000000e-13
GCST004744_38	Lung adenocarcinoma	7.000000e-12
GCST004748_38	Lung cancer	1.000000e-06
GCST005434_22	Pancreatic cancer	5.000000e-08
GCST005752_55	Systemic lupus erythematosus	2.000000e-06
GCST007977_2	Postoperative stroke after cardiac surgery	4.000000e-07
GCST008376_2	Lung cancer in never smokers	9.000000e-07
GCST008834_14	Non-small cell lung cancer	1.000000e-20
GCST009391_1626	Metabolite levels	9.000000e-06
GCST009532_2	Circulating leptin levels in high cardiovascular risk	3.000000e-06
GCST010148_6	Cutaneous squamous cell carcinoma	6.000000e-15
GCST011456_2	Serum CC16 levels	5.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:1001494	psoriasis vulgaris
EFO:0009951	response to surgery
EFO:0009956	post-operative stroke
EFO:0010549	xanthosine measurement
EFO:0005000	leptin measurement
EFO:1001927	cutaneous squamous cell carcinoma
EFO:0005080	CC16 measurement

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D004476	Ectodermal Dysplasia	C16.131.077.350; C16.131.831.350; C16.320.850.250; C17.800.804.350; C17.800.827.250
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C536373	Ankyloblepharon filiforme adnatum (supp.)
C538268	Auditory neuropathy (supp.)
C565799	Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip-Palate Syndrome 3 (supp.)
C536189	Ectrodactyly-cleft lip-palate syndrome (supp.)
C535847	Hay-Wells syndrome (supp.)
C535903	Limb-mammary syndrome (supp.)
C538052	Propping Zerres syndrome (supp.)
C535289	Rapp-Hodgkin syndrome (supp.)
C565344	Split-Hand-Foot Malformation 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	decreases response to substance, increases expression, increases activity, increases phosphorylation, affects binding (+5 more)	8
sodium arsenite	affects expression, decreases expression, increases abundance	4
Silicon Dioxide	affects expression, affects reaction, decreases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	4
Valproic Acid	affects cotreatment, increases expression	4
trichostatin A	decreases reaction, increases expression, affects reaction, increases response to substance, increases activity (+2 more)	3
Benzo(a)pyrene	decreases methylation, affects response to substance, affects methylation	3
Particulate Matter	increases abundance, affects cotreatment, increases expression, decreases expression	3
kaempferol	increases expression	2
bisphenol A	affects cotreatment, increases methylation, increases expression	2
arsenite	decreases expression, increases abundance, increases expression	2
nickel chloride	decreases expression, decreases reaction, increases expression, increases reaction, decreases activity (+1 more)	2
chrysin	increases expression	2
chloropicrin	decreases expression	2
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects cotreatment, decreases expression, increases expression, increases reaction, increases cleavage	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, affects response to substance	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Quercetin	increases expression	2
Smoke	decreases expression, affects response to substance, increases abundance	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	2
Silver Compounds	affects cotreatment, increases expression, decreases expression	2
Cadmium Chloride	decreases activity, affects binding, decreases reaction, decreases expression	2
Topotecan	increases cleavage, affects cotreatment, decreases expression, increases expression, increases reaction	2
Luteolin	increases expression	2
bisphenol F	affects cotreatment, increases methylation	1
naringenin	affects cotreatment, increases expression	1
quercitrin	decreases expression	1
afimoxifene	increases expression	1
cobaltous chloride	decreases activity, affects binding, decreases reaction	1

Cellosaurus cell lines

9 cell lines: 7 cancer cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_1059	A2058	Cancer cell line	Male
CVCL_1280	HH [Human lymphoma]	Cancer cell line	Male
CVCL_2127	MOTN-1	Cancer cell line	Female
CVCL_B8RA	Abcam HCT 116 TP63 KO	Cancer cell line	Male
CVCL_B9CC	Abcam MCF-7 TP63 KO	Cancer cell line	Female
CVCL_B9TP	Abcam A-549 TP63 KO	Cancer cell line	Male
CVCL_E3EB	10101	Cancer cell line	Male
CVCL_RJ95	UNIPDi002-A	Induced pluripotent stem cell	Female
CVCL_RJ96	UNIPDi003-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

301 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer