| Tbio | Pituitary homeobox 3 |
Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. In addition to its importance during development, it also has roles in the long-term survival and maintenance of the mdDA neurons. Activates NR4A2/NURR1-mediated transcription of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons. Acts by decreasing the interaction of NR4A2/NURR1 with the corepressor NCOR2/SMRT which acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state. Essential for the normal lens development and differentiation. Plays a critical role in the maintenance of mitotic activity of lens epithelial cells, fiber cell differentiation and in the control of the temporal and spatial activation of fiber cell-specific crystallins. Positively regulates FOXE3 expression and negatively regulates PROX1 in the anterior lens epithelium, preventing activation of CDKN1B/P27Kip1 and CDKN1C/P57Kip2 and thus maintains lens epithelial cells in cell cycle (By similarity).
This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family act as transcription factors. This protein is involved in lens formation during eye development. Mutations of this gene have been associated with anterior segment mesenchymal dysgenesis and congenital cataracts. [provided by RefSeq, Jul 2008]
This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family act as transcription factors. This protein is involved in lens formation during eye development. Mutations of this gene have been associated with anterior segment mesenchymal dysgenesis and congenital cataracts. [provided by RefSeq, Jul 2008]
Comments
| Disease | Target Count |
|---|---|
| CATARACT, POSTERIOR POLAR, 4 (disorder) | 1 |
| Congenital cataract | 1 |
| Microphthalmos | 5 |
| Neurologic Manifestations | 4 |
| Disease | Target Count |
|---|---|
| Cataract | 104 |
| Anterior segment mesenchymal dysgenesis | 2 |
| Cataract 11, multiple types | 1 |
| PMID | Text | |
|---|---|---|
| 24555714 | novel PITX3 mutation c.573del, p.(Ser192Alafs*117), was identified in heterozygous state in a Belgo-Romanian family with a similar phenotype | |
| 24525476 | Meta-analysis suggests that rs3758549, rs2281983, and rs4919621 single nucleotide polymorphisms are not major determinants of the risk for Parkinson's disease | |
| 24394914 | the SNP rs3758549 might contribute to the occurrence of Parkinson disease (PD) in the Asian population, especially early onset PD in the Asian population. | |
| 24172139 | our data demonstrate that key midbrain dopamine regulators (Nurr1, Pitx3, and Lmx1a) play overlapping as well as distinct roles during neurogenesis and neurotransmitter phenotype determination of mDA neurons | |
| 23694789 | Mutations in PITX3 are not a common cause or a risk factor for multisystem atrophy and progressive supranuclear palsy in the Polish population. | |
| 22429667 | Presence of the rs4919621 allele A in PITX3 significantly increases the risk of Parkinson's disease (PD) patients in a Caucasian population, while rs2281983 allele C and rs4919621 allele A were both risk factors in early onset PD. | |
| 22411443 | novel synonymous SNP in PITX3 gene may contribute to PD risk in the Chinese population. | |
| 22309633 | This study provided that NURR1 and PITX3 gene expression is decreased in the peripheral blood lymphocytes of Chinese patients with Parkinson's disease patients. | |
| 22223473 | Deletion of PITX3 is associated with aggressive neurobehavioral phenotype in Smith-Magenis Syndrome. | |
| 22103961 | we report the absence of mutations in all studied genes in four families with phenotypes associating cataract, mental retardation and microcephaly. | |
| 22037506 | The results of this study suggested that these PITX3 SNPs do not contribute to the risk of developing PD in EOPD or LOPD in Chinese. | |
| 21836522 | Data show that BFSP2 and PITX3, hitherto known to cause eye defects only in a dominant fashion, can also present recessively. | |
| 21633712 | The 542delC is a novel mutation in PITX3 causing an isolated posterior polar cataract. | |
| 21565251 | Allele & genotype frequencies did not differ between patients & controls for rs2281983, rs4919621, & rs3758549. These SNP sites do not contribute to the risk of developing PD in late-onset sporadic PD in this Chinese population. | |
| 21524731 | This study suggested that the PITX3 gene rs3758549 polymorphism may increase the susceptibility of Parkinson's disease in chinese. | |
| 21469209 | This study found that rs2281983 and rs4919621 appeared to confer susceptibility to Parkinson's disease, especially in early-onset Parkinson's disease and familial Parkinson's disease. | |
| 21138504 | The single nucleotide polymorphism rs3758549 (C >T substitution) in the Pitx3 gene is a potential risk for sporadic Parkinson disease (PD), especially early-onset PD in Chinese Han population. | |
| 20570600 | Genetic variation in PITX3 may increase the risk of developing schizophrenia. | |
| 20570600 | Observational study of gene-disease association. (HuGE Navigator) | |
| 20468068 | Observational study of gene-disease association. (HuGE Navigator) | |
| 20376326 | The absence of PITX3 mutations in a family presenting congenital cataract and mental retardation, is reported. | |
| 19394114 | PITX3 may play a role in the pathogenesis of Parkinson disease. | |
| 19394114 | Observational study of gene-disease association. (HuGE Navigator) | |
| 19345444 | The result of this study found a strong association between the PITX3 promoter rs3758549 polymorphism and Parkinson's disease. | |
| 19345444 | Observational study of gene-disease association. (HuGE Navigator) | |
| 19204726 | Observational study of gene-disease association. (HuGE Navigator) | |
| 19058789 | Observational study of gene-disease association. (HuGE Navigator) | |
| 18989383 | Duplication of a segment of PITX3 can result in severe symptoms leading to functional blindness while in other individuals in the same family or in other families, the same duplication leads to treatable cataract with minimal visual impairment. | |
| 18420308 | The A-allele of a HapMap tagging SNP (rs4919621) that was genotyped in a population of Parkinson's disease (PD) patients, was significantly more common in PD patients with an early age of onset. | |
| 18420308 | Observational study of gene-disease association. (HuGE Navigator) | |
| 17905480 | We provide evidence for a novel, strong and reproducible association of the PITX3 promoter SNP rs3758549: C>T (p=0.004) with Parkinson Disease. | |
| 17905480 | Observational study of gene-disease association. (HuGE Navigator) | |
| 17888164 | The G219fs mutation was found in multiple families affected with congenital cataracts along with anterior segment malformations. The S13N mutant showed only minor alteration and may represent a rare polymorphism in the PITX3 gene. | |
| 17017509 | we discuss the role of Pitx3 in molecular mechanisms involved in the regional specification, neuronal specification and differentiation of mDA neurons--REVIEW | |
| 16636655 | The 657ins17bp duplication of the PITX3 gene is the cause of the cataract phenotype in the large pedigree. | |
| 16565358 | This is the first report of homozygous PITX3 mutations in humans. The phenotype in these individuals highlights the role of PITX3 in ocular and central nervous system (CNS) development. | |
| 16477036 | Nurr1 and Pitx3 cooperatively promote terminal maturation to the midbrain dopamine neuron phenotype in murine and human ES cell cultures. | |
| 16272057 | we mapped dominant congenital posterior polar cataracts to chromosome 10q24. On sequencing the coding region of PITX3, we found a 17-base-pair duplication in exon 4. | |
| 15286169 | A family with posterior polar cataract with a novel deletion mutation in PITX3. | |
| 11994226 | Meta-analysis and HuGE review of genotype prevalence and gene-disease association. (HuGE Navigator) |
MEFGLLSEAEARSPALSLSDAGTPHPQLPEHGCKGQEHSDSEKASASLPGGSPEDGSLKKKQRRQRTHFT 1 - 70 SQQLQELEATFQRNRYPDMSTREEIAVWTNLTEARVRVWFKNRRAKWRKRERSQQAELCKGSFAAPLGGL 71 - 140 VPPYEEVYPGYSYGNWPPKALAPPLAAKTFPFAFNSVNVGPLASQPVFSPPSSIAASMVPSAAAAPGTVP 141 - 210 GPGALQGLGGGPPGLAPAAVSSGAVSCPYASAAAAAAAAASSPYVYRDPCNSSLASLRLKAKQHASFSYP 211 - 280 AVHGPPPAANLSPCQYAVERPV 281 - 302 //
| PMID | Year | Title | |
|---|---|---|---|
| 24555714 | 2014 | Novel and recurrent PITX3 mutations in Belgian families with autosomal dominant congenital cataract and anterior segment dysgenesis have similar phenotypic and functional characteristics. | |
| 24525476 | 2014 | PITX3 and risk for Parkinson's disease: a systematic review and meta-analysis. | |
| 24431302 | 2014 | Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease. | |
| 24394914 | 2014 | Association between PITX3 promoter polymorphism and risk of Parkinson's disease: the impact of ethnicity and onset age. | |
| 24172139 | 2014 | Functional roles of Nurr1, Pitx3, and Lmx1a in neurogenesis and phenotype specification of dopamine neurons during in vitro differentiation of embryonic stem cells. | |
| 23694789 | 2013 | Analysis of PITX3 gene in patients with multisystem atrophy, progressive supranuclear palsy and corticobasal degeneration. | |
| 22429667 | 2012 | Meta-analysis of association between PITX3 gene polymorphism and Parkinson's disease. | |
| 22411443 | 2012 | A novel synonymous SNP in PITX3 is associated with Parkinson's disease in Chinese population. | |
| 22309633 | 2012 | Decreased NURR1 and PITX3 gene expression in Chinese patients with Parkinson's disease. | |
| 22223473 | 2012 | Clinical improvement of the aggressive neurobehavioral phenotype in a patient with a deletion of PITX3 and the absence of L-DOPA in the cerebrospinal fluid. | |
| 22103961 | 2011 | Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation. | |
| 22037506 | 2011 | PITX3 polymorphism is not associated with Parkinson's disease in a Chinese population. | |
| 21836522 | 2011 | Novel recessive BFSP2 and PITX3 mutations: insights into mutational mechanisms from consanguineous populations. | |
| 21633712 | 2011 | A novel 1-bp deletion in PITX3 causing congenital posterior polar cataract. | |
| 21565251 | 2011 | Genetic variants of the PITX3 gene are not associated with late-onset sporadic Parkinson's disease in a Chinese population. | |
| 21524731 | 2011 | PITX3 gene polymorphism is associated with Parkinson's disease in Chinese population. | |
| 21469209 | 2011 | Systematic genetic analysis of the PITX3 gene in patients with Parkinson disease. | |
| 21138504 | 2011 | The transcription factor Pitx3 is a risk modifier for Parkinson's disease in a Chinese Han population. | |
| 20570600 | 2010 | Preliminary evidence that polymorphisms in dopamine-related transcription factors LMX1A, LMX1B and PITX3 are associated with schizophrenia. | |
| 20468068 | 2010 | Analysis of the Micro-RNA-133 and PITX3 genes in Parkinson's disease. | |
| 20376326 | 2010 | Absence of PITX3 mutation in a Tunisian family with congenital cataract and mental retardation. | |
| 19413330 | 2009 | Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. | |
| 19394114 | 2011 | Transcription factor PITX3 gene in Parkinson's disease. | |
| 19345444 | 2011 | Association of transcription factor polymorphisms PITX3 and EN1 with Parkinson's disease. | |
| 19204726 | 2009 | Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease. | |
| 19058789 | 2009 | A common variant in DRD3 receptor is associated with autism spectrum disorder. | |
| 18989383 | 2008 | Anterior segment mesenchymal dysgenesis in a large Australian family is associated with the recurrent 17 bp duplication in PITX3. | |
| 18420308 | 2010 | PITX3 polymorphism is associated with early onset Parkinson's disease. | |
| 17905480 | 2009 | The transcription factor PITX3 is associated with sporadic Parkinson's disease. | |
| 17888164 | 2007 | Functional analysis of human mutations in homeodomain transcription factor PITX3. | |
| 17017509 | 2006 | The role of Pitx3 in survival of midbrain dopaminergic neurons. | |
| 16636655 | 2006 | The PITX3 gene in posterior polar congenital cataract in Australia. | |
| 16565358 | 2006 | Heterozygous and homozygous mutations in PITX3 in a large Lebanese family with posterior polar cataracts and neurodevelopmental abnormalities. | |
| 16477036 | 2006 | Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. | |
| 16272057 | 2005 | Posterior polar cataract: genetic analysis of a large family. | |
| 15489334 | 2004 | The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | |
| 15286169 | 2004 | Recurrent 17 bp duplication in PITX3 is primarily associated with posterior polar cataract (CPP4). | |
| 15164054 | 2004 | The DNA sequence and comparative analysis of human chromosome 10. | |
| 12477932 | 2002 | Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. | |
| 11994226 | 2002 | Androgen receptor CAG repeats and prostate cancer. | |
| 9620774 | 1998 | A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. | |
| 6801987 | 1982 | Variable expressivity of autosomal dominant anterior segment mesenchymal dysgenesis in six generations. |
