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FLASH GENE

Symbol

PITX3

contributors: mct - updated : 27-03-2019

HGNC name	paired-like homeodomain 3
HGNC id	9006

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	11.29 kb     4 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	a muscle-specific promoter situated between the first exon and exon 2 that contains the initiator ATG codon

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - D10S1710 - D10S1240 - PITX3 - D10S1697 - D10S1267 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005029 4 - 1407 NP_005020 31 302 - 1998 9620774

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue       Nervous brain midbrain substantia nigra     Homo sapiens Visual eye lens     highly Homo sapiens   eye anterior segment       Homo sapiens   eye uvea choroid       eye extrinsic muscle       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

Text	developing eye, midbrain region, tongue, incisor primordia, condensing mesenchyme around the sternum and vertebrae and in the head muscles (

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	POU specific and POU homeo domains (helix-turn-helix)
	an OAR domain

HOMOLOGY

interspecies	ortholog to Pitx3, Mus musculus
	ortholog to Pitx3, Rattus norvegicus
	ortholog to pitx3, Danio rerio
	ortholog to PITX3, Pan troglodytes

Homologene

FAMILY	RIEG/PITX homeobox family
	paired homeobox family
	bicoid subfamily

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	involved in lens formation during eye development
	regulating gene expression and controlling cell differentiation
	inducing the late maturation of midbrain dopamine neurons
	transcription factor which has a key role in lens and anterior segment development
	critical homeodomain transcription factor for the proper development and survival of mesodiencephalic dopaminergic (mdDA) neurons
	critical mediator of GDNF-induced BDNF expression in nigrostriatal dopaminergic neurons
	is critical for the survival of midbrain dopaminergic (mDA) neurons
	transcription factor PITX3 is expressed selectively in midbrain dopaminergic neurons susceptible to neurodegenerative stress
	key midbrain dopamine (mDA) regulators (NR4A2, PITX3, and LMX1A) play overlapping as well as distinct roles during neurogenesis and neurotransmitter phenotype determination of mDA neurons
	is a bicoid-related homeodomain transcription factor critical for the development of the ocular lens, mesencephalic dopaminergic neurons and skeletal muscle
	PITX2 and PITX3 are key regulators of the intracellular redox state preventing DNA damage as cells undergo differentiation
	is specifically required for dopamine-related function and, if impaired, PITX3 could contribute during the pathogenesis of Parkinson disease
	regulated levels of PITX3 and EN1 control the size and rostral/caudal-identity of the Mesodiencephalic dopaminergic (mdDA) neuronal population

CELLULAR PROCESS	cell life, differentiation
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development

text	lens formation during eye development
	histogenesis and organogenesis

PATHWAY

metabolism

signaling

sensory transduction/vision

photoreception

a component

INTERACTION

DNA

RNA

small molecule

protein	nuclear receptor related 1, NR4A2 (
	transcription regulatory role for FOXP1 on the PITX3 gene in mammalian stem cells
	directly regulates FOXE3 during early lens development
	LMO3 is a Ssubstantia nigra -specific co-regulator of PITX3-dependent transcription

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

ASMD2 , CTPP2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in patients with Parkinson disease

Susceptibility

to PD dementia (PDD) and visuospatial dysfunction in idiopathic Parkinson disease (PD)

Variant & Polymorphism SNP	common polymorphism in the PITX3 gene affects the risk of developing PD dementia (PDD) and visuospatial dysfunction in idiopathic Parkinson disease (PD)

Candidate gene
Marker	PITX3 DNA methylation is an independent prognostic biomarker for overall survival in patients with head and neck squamous cell carcinoma
Therapy target

ANIMAL & CELL MODELS

	lack of Pitx3 in mice causes the preferential loss of substantia nigra pars compacta (SNc) mdDA neurons that are most affected in Parkinson disease
	Pitx3-deficient mice exhibit severe but selective developmental loss of mDA neurons, with accompanying locomotor deficits resembling those seen in Parkinson's disease (PD) models
	expression of truncated Pitx3 in the developing lens leads to microphthalmia and aphakia in mice
	Pitx3(-/-) mice displayed abnormal motor activities, including impaired motor coordination and decreased locomotion