Variant "TP63:p.Arg318His"
Search results: 2 records
Variant information
Gene:
TP63 
Variant:
TP63:p.Arg318His 
dbSNP ID:
no data 
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
2 
Reference:
1 
Effect type:
Penetrance and Expressivity(2)  
Modifier effect:
Altered phenotype(2)  
Details：
  • Target disease:
    Ectodermal Dysplasia (DOID_2121)
    Effect type:
    Penetrance and Expressivity 
    Modifier effect:
    Altered phenotype 
    Evidence:
    Study on animal models 
    Effect:
    TP63/Trp63 give rise to two classes of transcripts, TAp63 and ΔNp63. TAp63 is a strong modifier of EEC-associated phenotypes with regard to both penetrance and expressivity
    Reference:
    PMID23775923
    Title:
    An allelic series of Trp63 mutations defines TAp63 as a modifier of EEC syndrome.
    Species studied:
    Human
    Abstract:
    Human Ectrodactyly, Ectodermal dysplasia, Clefting (EEC) syndrome is an autosomal dominant developmental disorder defined by limb deformities, skin defects, and craniofacial clefting. Although associated with heterozygous missense mutations in TP63, the genetic basis underlying the variable expressivity and incomplete penetrance of EEC is unknown. Here, we show that mice heterozygous for an allele encoding the Trp63 p.Arg318His mutation, which corresponds to the human TP63 p.Arg279His mutation found in patients with EEC, have features of human EEC. Using an allelic series, we discovered that whereas clefting and skin defects are caused by loss of Trp63 function, limb anomalies are due to gain- and/or dominant-negative effects of Trp63. Furthermore, we identify TAp63 as a strong modifier of EEC-associated phenotypes with regard to both penetrance and expressivity.
  • Target disease:
    Ectrodactyly, Ectodermal Dysplasia, And Cleft Lip-Palate Syndrome (DOID_0060784,DOID_0060783,DOID_0060773)
    Effect type:
    Penetrance and Expressivity 
    Modifier effect:
    Altered phenotype 
    Evidence:
    Study on animal models 
    Effect:
    TP63/Trp63 give rise to two classes of transcripts, TAp63 and ΔNp63. TAp63 is a strong modifier of EEC-associated phenotypes with regard to both penetrance and expressivity
    Reference:
    PMID23775923
    Title:
    An allelic series of Trp63 mutations defines TAp63 as a modifier of EEC syndrome.
    Species studied:
    Human
    Abstract:
    Human Ectrodactyly, Ectodermal dysplasia, Clefting (EEC) syndrome is an autosomal dominant developmental disorder defined by limb deformities, skin defects, and craniofacial clefting. Although associated with heterozygous missense mutations in TP63, the genetic basis underlying the variable expressivity and incomplete penetrance of EEC is unknown. Here, we show that mice heterozygous for an allele encoding the Trp63 p.Arg318His mutation, which corresponds to the human TP63 p.Arg279His mutation found in patients with EEC, have features of human EEC. Using an allelic series, we discovered that whereas clefting and skin defects are caused by loss of Trp63 function, limb anomalies are due to gain- and/or dominant-negative effects of Trp63. Furthermore, we identify TAp63 as a strong modifier of EEC-associated phenotypes with regard to both penetrance and expressivity.