Gene: TP63

Alternate names for this Gene: AIS|B(p51A)|B(p51B)|EEC3|KET|LMS|NBP|OFC8|RHS|SHFM4|TP53CP|TP53L|TP73L|p40|p51|p53CP|p63|p73H|p73L

Gene Summary: 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.

Gene is located in Chromosome: 3

Location in Chromosome : 3q28

Description of this Gene: tumor protein p63

Type of Gene: protein-coding

rs10937405 in TP63 gene and Adenocarcinoma of lung (disorder) PMID 22797724 2012 A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population.

PMID 20871597 2010 The combined analyses identified two susceptibility loci for lung adenocarcinoma: TERT (rs2736100, combined P = 2.91 × 10⁻¹¹), odds ratio (OR) = 1.27) and TP63 (rs10937405, combined P = 7.26 × 10⁻¹²), OR = 1.31).

PMID 31326317 2019 Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations.

PMID 28604730 2017 Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

PMID 24880342 2014 We also showed an association between common variation at 3q28 (TP63, rs13314271, OR = 1.13, P = 7.22 × 10(-10)) and lung adenocarcinoma that had been previously reported only in Asians.

PMID 27501781 2016 Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma.

rs797044484 in TP63 gene and Blepharitis PMID 19903181 2010 Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

rs797044484 in TP63 gene and Blepharophimosis PMID 19903181 2010 Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

rs13080835 in TP63 gene and Carcinoma of lung PMID 28604730 2017 Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

PMID 23143601 2012 Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia.

PMID 31009812 2019 Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region.

PMID 21725308 2011 The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10(-20) and P = 1.0 × 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10(-11) and P = 6.2 × 10(-13), respectively).

rs76479869 in TP63 gene and Cleft Palate PMID 28054174 2017 Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate.

rs797044484 in TP63 gene and Cleft lip or lips PMID 19903181 2010 Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

rs797044484 in TP63 gene and Cleft palate, isolated PMID 19903181 2010 Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

rs76479869 in TP63 gene and Cleft upper lip PMID 28054174 2017 Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate.

rs797044484 in TP63 gene and Corneal Ulcer PMID 19903181 2010 Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

rs1205536026 in TP63 gene and ECTRODACTYLY, ECTODERMAL DYSPLASIA, AND CLEFT LIP/PALATE SYNDROME 3 PMID 10839977 2000 Split-hand/split-foot malformation is caused by mutations in the p63 gene on 3q27.

PMID 12838557 2003 EEC syndrome type 3 with a heterozygous germline mutation in the P63 gene and B cell lymphoma.

PMID 11462173 2001 p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation.

PMID 10535733 1999 Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome.

PMID 19903181 2010 Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

PMID 26380986 2015 Use of Targeted Exome Sequencing for Molecular Diagnosis of Skeletal Disorders.

rs121908842 in TP63 gene and Hay-Wells syndrome PMID 11159940 2001 Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63.

rs797044484 in TP63 gene and Hypodontia PMID 19903181 2010 Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

rs797044484 in TP63 gene and Hypothyroidism PMID 19903181 2010 Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

rs13314271 in TP63 gene and Malignant neoplasm of lung PMID 24880342 2014 Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.

PMID 21725308 2011 The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10(-20) and P = 1.0 × 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10(-11) and P = 6.2 × 10(-13), respectively).

PMID 23143601 2012 Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia.

rs11375254 in TP63 gene and Non-Small Cell Lung Carcinoma PMID 31326317 2019 Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations.

rs9817981 in TP63 gene and Non-alcoholic Fatty Liver Disease PMID 21423719 2011 Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

rs121908847 in TP63 gene and OROFACIAL CLEFT 8 PMID 16740912 2006 A mutation of the p63 gene in non-syndromic cleft lip.

rs797044484 in TP63 gene and Obstruction of nasolacrimal duct PMID 19903181 2010 Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

rs76479869 in TP63 gene and Oral cleft PMID 28054174 2017 Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate.

rs9854771 in TP63 gene and Pancreatic carcinoma PMID 29422604 2018 Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

PMID 26098869 2015 Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer.

rs17505102 in TP63 gene and Precursor Cell Lymphoblastic Leukemia Lymphoma PMID 22076464 2012 Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia.

rs17447439 in TP63 gene and Primary biliary cirrhosis PMID 23000144 2012 Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.

rs28512356 in TP63 gene and Psoriasis PMID 25903422 2015 Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.

rs121908840 in TP63 gene and RAPP-HODGKIN SYNDROME PMID 12939657 2003 The Rapp-Hodgkin syndrome results from mutations of the TP63 gene.

PMID 15200513 2004 Molecular evidence that AEC syndrome and Rapp-Hodgkin syndrome are variable expression of a single genetic disorder.

PMID 12766194 2003 Heterozygous mutation in the SAM domain of p63 underlies Rapp-Hodgkin ectodermal dysplasia.

rs121908838 in TP63 gene and SPLIT-HAND/FOOT MALFORMATION 4 PMID 11462173 2001 p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation.

PMID 10839977 2000 Split-hand/split-foot malformation is caused by mutations in the p63 gene on 3q27.

rs797044484 in TP63 gene and Sensorineural hearing loss, bilateral PMID 19903181 2010 Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

rs11375254 in TP63 gene and Squamous cell carcinoma of lung PMID 31326317 2019 Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations.

rs4687074 in TP63 gene and Systolic Pressure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.