PITX2

Summary

PITX2 (paired like homeodomain 2, HGNC:9005) is a protein-coding gene on chromosome 4q25, encoding Pituitary homeobox 2 (Q99697). May play a role in myoblast differentiation. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. The encoded protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes, is involved in the development of the eye, tooth and abdominal organs, and acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. Mutations in this gene are associated with Axenfeld-Rieger syndrome, iridogoniodysgenesis syndrome, and sporadic cases of Peters anomaly. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Alternatively spliced transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 5308 — RefSeq curated summary.

At a glance

• Gene–disease (curated): anterior segment dysgenesis 4 (Definitive, ClinGen) — +9 more curated relationships
• GWAS associations: 65
• Clinical variants (ClinVar): 257 total — 58 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 67
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 146 downstream targets (CollecTRI)
• MANE Select transcript: NM_000325

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9005
Approved symbol	PITX2
Name	paired like homeodomain 2
Location	4q25
Locus type	gene with protein product
Status	Approved
Aliases	IGDS, RS, Brx1, Otlx2, ARP1
Ensembl gene	ENSG00000164093
Ensembl biotype	protein_coding
OMIM	601542
Entrez	5308

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000354925, ENST00000355080, ENST00000394595, ENST00000511837, ENST00000511990, ENST00000556049, ENST00000557119, ENST00000607868, ENST00000613094, ENST00000614423, ENST00000616641, ENST00000644488, ENST00000644743, ENST00000645131

RefSeq mRNA: 6 — MANE Select: NM_000325 NM_000325, NM_001204397, NM_001204398, NM_001204399, NM_153426, NM_153427

CCDS: CCDS3692, CCDS3693, CCDS3694

Canonical transcript exons

ENST00000644743 — 3 exons

Exon	Start	End
ENSE00001121567	110621164	110621369
ENSE00001903507	110617423	110618688
ENSE00003821783	110622256	110623077

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 96.56.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7457 / max 131.9031, expressed in 788 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53633	1.8153	591
53636	1.1461	387
53634	0.3338	180
53635	0.1581	83
53632	0.1328	59
53631	0.1181	32
53639	0.0389	23
53640	0.0026	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingiva	UBERON:0001828	96.56	gold quality
biceps brachii	UBERON:0001507	96.14	gold quality
gingival epithelium	UBERON:0001949	96.12	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.88	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.88	gold quality
body of tongue	UBERON:0011876	93.90	gold quality
gastrocnemius	UBERON:0001388	93.80	gold quality
muscle of leg	UBERON:0001383	91.94	gold quality
muscle organ	UBERON:0001630	91.69	gold quality
skeletal muscle tissue	UBERON:0001134	91.47	gold quality
vastus lateralis	UBERON:0001379	90.83	gold quality
quadriceps femoris	UBERON:0001377	90.30	gold quality
pituitary gland	UBERON:0000007	88.49	gold quality
placenta	UBERON:0001987	86.91	gold quality
deltoid	UBERON:0001476	86.55	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.15	gold quality
lower esophagus	UBERON:0013473	86.10	gold quality
penis	UBERON:0000989	85.23	gold quality
adenohypophysis	UBERON:0002196	85.20	gold quality
vermiform appendix	UBERON:0001154	85.00	gold quality
periodontal ligament	UBERON:0008266	84.71	silver quality
muscle tissue	UBERON:0002385	84.61	gold quality
tongue	UBERON:0001723	84.55	gold quality
mammalian vulva	UBERON:0000997	84.14	gold quality
mouth mucosa	UBERON:0003729	82.77	gold quality
caecum	UBERON:0001153	82.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.48	gold quality
urinary bladder	UBERON:0001255	82.27	gold quality
tibialis anterior	UBERON:0001385	81.87	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	918.41
E-MTAB-10485	yes	582.50
E-GEOD-124472	yes	489.17
E-GEOD-135922	yes	56.86
E-MTAB-9388	yes	12.44
E-ANND-3	yes	12.02

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

146 targets.

Target	Regulation
ABCB1	Unknown
ADIPOQ
ADK
AHR
AHSG
ALDH5A1
AMELX
APOA1
APOA2
APOB
APOC2
APOC3
ARAP1
ARG1
ATP11C
CASR
CAT
CCNA1
CCND2
CD81
CD82
CD9
CDKN1A	Unknown
CETP
CHEK2
CHI3L1
CRP
CRY1
CSH1
CXCL6	Activation

JASPAR motifs

Motif	Name	Family
MA1547.1	PITX2	Paired-related HD factors
MA1547.2	PITX2	Paired-related HD factors

JASPAR matrix evidence (PMIDs): PMID:9685346

Upstream regulators (CollecTRI, top): BMP4, CREB1, CTNNB1, HNF4A, LEF1, LHX6, MEF2A, MSX2, NFIX, NKX2-5, PAX3, PITX2, SMAD2, SOX9, TBX1, TFAP2A, USF2

miRNA regulators (miRDB)

119 targeting PITX2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548A-5P	99.94	71.27	3482

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• mutational analysis in early-onset glaucoma (PMID:11774072)
• PITX2 gene is responsible for a significant portion of Axenfeld-Rieger syndrome in the Brazilian population. (PMID:11821690)
• the paired-like homeobox transcription factors Pitx1 and Pitx2 are factors functionally activating the proximal human prolactin promoter (hPRL-164luc) (PMID:12223489)
• Four novel mutations in the PITX2 gene in patients with Axenfeld-Rieger syndrome. Two mutations were found in the homeobox and two were found in the region downstream of the homeobox. (PMID:12381896)
• The position 50 residue in the PITX2 homeodomain plays an important role in both DNA binding and dimerization activities. (PMID:12612071)
• plays a critical role in directing cardiac asymmetric morphogenesis; correlates with double outlet right ventricle in laterality mutants; Pitx2 loss of function experiments cause severe cardiovascular defects. (PMID:12732450)
• oligodontia of Rieger syndrome of Chinese family linked to mutation (PMID:14630904)
• role for Pitx2 in regulating regionally specific terminal neuronal differentiation in the developing ventrolateral thalamus and midbrain (PMID:14975719)
• A deletion of thymine (T) 1261 was identified, creating a frameshift mutation in codon 227. (PMID:15255117)
• promoter- and cell-specific functional interaction between PITX2 and MEF2A (PMID:15466416)
• linkage of chromosome 4q24-q26 to RDC and identification of a missense mutation in PITX2 in 17 disease affected individuals (PMID:15591271)
• LEF-1 expression is regulated through PITX2, LEF-1 and beta-catenin direct physical interactions (PMID:15728254)
• This is the first structure of a native lysine50 class homeodomain; analysis of PITX2 residues mutated in Rieger syndrome indicates that many of these residues are involved in DNA binding, while others are involved in formation of the hydrophobic core. (PMID:15895993)
• This review of Axenfeld-Rieger syndrome highlights the production of mutant homeobox transcription factor PITX2 in at least four different transcriptional and splicing isoforms, with different biological properties. (PMID:16274491)
• Ultimately, PITX2 loss of function mutations have a compound effect: the reduced expression of PITX2 target genes coupled with the extensive activation of FOXC1-regulated targets in Axenfeld-Rieger syndrome. (PMID:16449236)
• The results indicate that the PITX2 C-terminal domain has inhibitory activity and support the notion that Axenfeld-Rieger Syndrome may also be caused by gain-of-function mutations. (PMID:16498627)
• The frequency of mutations in the FOXC1, GJA1, PITX2, and CYP1B1 genes in this study were 25%, 12.5%, 0% and 0%, respectively. (PMID:16638984)
• Direct evidence to support aberrant RNA splicing in PITX2 mutants as the mechanism underlying the Axenfeld-Rieger syndrome in some patients. (PMID:16834779)
• Gene analysis revealed a novel PITX2 mutation and a polymorphism in a family with Axenfeld-Rieger anomaly or syndrome and Fuchs’ endothelial dystrophy. (PMID:16876867)
• The findings in the present study clearly demonstrate that FOXC1 and PITX2 mutations are responsible for a significant proportion of Axenfeld-Rieger malformations in Germany. (PMID:16936096)
• The results show that PITX2/Pitx2 mutation results in reduced corneal thickness and provides the first example of reduced CCT (central corneal thickness) in a genetic subtype of glaucoma. (PMID:17065505)
• Occurrence of precocious glaucoma in human patients affected by Axenfeld-Rieger syndrome caused by PITX2 mutations. (PMID:17167399)
• Patients with FOXC1 mutations have the mildest prognosis for glaucoma development, whereas patients with PITX2 defects and patients with FOXC1 duplication have a more severe prognosis for glaucoma development than do patients with FOXC1 mutations. (PMID:17197537)
• PITX2, BARX1, and FOXC1 mutations were absent in De Hauwere syndrome and suggest that De Hauwere syndrome is caused by a different gene. (PMID:17486624)
• In addition, no pathogenic sequence variations were found in DCN, DSPG3, LUM, PITX2 and FOXC1, which have also been implicated in corneal and anterior segment dysgenesis. (PMID:17558846)
• Cytogenetically invisible microdeletions involving PITX2 in Rieger syndrome. (PMID:17850355)
• DNA hypermethylation of PITX2 is a marker of poor prognosis in untreated lymph node-negative hormone receptor-positive breast cancer patients. (PMID:17965955)
• The tendon, muscle, and bone anomalies further support a role of Pitx2 in forelimb development. (PMID:18312615)
• Sella turcica bridge in combination with PITX2 mutation would suspect that anomalies are typical symptoms of ARS. Sella turcica anomalies in association with craniofacial/dental aberrations might be important indicators for ARS caused by PITX2 mutation. (PMID:18331556)
• The exclusion of these genes as likely candidates supports the hypothesis that the ocular phenotype associated with peters’ anomaly segregating in this family is a distinct, new, autosomal dominant entity in the anterior segment dysgenesis spectrum. (PMID:18616618)
• Evaluate paraffin-embedded tumor tissue testing of PITX2 DNA methylation as a marker for outcome prediction in tamoxifen-treated, node-negative breast cancer patients. (PMID:18711169)
• Data show that RGS13 inhibits CREB-dependent transcription of target genes through disruption of complexes formed at the promoter. (PMID:18775326)
• Localization of the PITX2 gene expression in human eye cells in the course of prenatal development (PMID:18946986)
• A novel p.W86C mutation in PITX2 in a Chinese family with Axenfeld-Rieger syndrome, was found. (PMID:19052653)
• Proteomic and genomic analysis of PITX2 interacting and regulating networks are reported. (PMID:19174163)
• PITX2 homeobox mutations predictably resulted in decreased function of the protein. (PMID:19218601)
• Patients with greater than median PITX2 methylation in the tumors were 4 times more likely to experience biochemical recurrence within 8 years after surgery than patients with less than average methylation (PMID:19233404)
• Our results implicate the potential importance of Pitx2 as a beta-catenin downstream modulator in hair growth control. (PMID:19251162)
• A brief review of the clinical features and the relevant diagnostic approaches, together with a detailed review of published PITX2 and FOXC1 mutations in Axenfeld-Rieger syndrome, is given. (PMID:19513095)
• These data suggest PAWR is a novel PITX2-interacting protein that regulates PITX2 activity in ocular cells. (PMID:19801652)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pitx2	ENSMUSG00000028023

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), PAX7 (ENSG00000009709), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), RHOXF1 (ENSG00000101883), CRX (ENSG00000105392), EVX1 (ENSG00000106038), PAX4 (ENSG00000106331), NOBOX (ENSG00000106410), PITX3 (ENSG00000107859), PHOX2B (ENSG00000109132), OTX1 (ENSG00000115507), PRRX1 (ENSG00000116132), VSX2 (ENSG00000119614), ESX1 (ENSG00000123576), PAX8 (ENSG00000125618), PAX1 (ENSG00000125813), RHOXF2 (ENSG00000131721), GSC (ENSG00000133937), RAX (ENSG00000134438), PAX3 (ENSG00000135903), ALX3 (ENSG00000156150), HESX1 (ENSG00000163666), UNCX (ENSG00000164853), PHOX2A (ENSG00000165462), OTX2 (ENSG00000165588), DRGX (ENSG00000165606), PRRX2 (ENSG00000167157), SHOX2 (ENSG00000168779), OTP (ENSG00000171540), RAX2 (ENSG00000173976), EVX2 (ENSG00000174279), PROP1 (ENSG00000175325), ISX (ENSG00000175329), ALX1 (ENSG00000180318), MIXL1 (ENSG00000185155), SHOX (ENSG00000185960)

Protein

Protein identifiers

Pituitary homeobox 2 — Q99697 (reviewed: Q99697)

Alternative names: ALL1-responsive protein ARP1, Homeobox protein PITX2, Paired-like homeodomain transcription factor 2, RIEG bicoid-related homeobox transcription factor, Solurshin

All UniProt accessions (6): A0A8J9C2I7, A0A8J9G9V2, D6RBG8, D6RFI4, Q99697, U3KQ81

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in myoblast differentiation. When unphosphorylated, associates with an ELAVL1-containing complex, which stabilizes cyclin mRNA and ensuring cell proliferation. Phosphorylation by AKT2 impairs this association, leading to CCND1 mRNA destabilization and progression towards differentiation. Involved in the establishment of left-right asymmetry in the developing embryo.

Subunit / interactions. Interacts with EFEMP2. Interacts (when unphosphorylated on Thr-90) with ELAVL1/HUR.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Phosphorylated at Thr-90 by AKT2, but not AKT1. Phosphorylation impairs its association with a CCND1 mRNA-stabilizing complex, thus shortening the half-life of CCND1.

Disease relevance. Axenfeld-Rieger syndrome 1 (RIEG1) [MIM:180500] An autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals. Additional features include aniridia, maxillary hypoplasia, hypodontia, anal stenosis, redundant periumbilical skin. The disease is caused by variants affecting the gene represented in this entry. Anterior segment dysgenesis 4 (ASGD4) [MIM:137600] A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD4 is an autosomal dominant disease. The disease is caused by variants affecting the gene represented in this entry. Ring dermoid of cornea (RDC) [MIM:180550] An ocular disorder characterized by bilateral annular limbal dermoids (growths with a skin-like structure) with corneal and conjunctival extension. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the paired homeobox family. Bicoid subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q99697-1	PTX2B, ARP1B	yes
Q99697-2	PTX2C, ARP1C
Q99697-3	PTX2A, ARP1A

RefSeq proteins (6): NP_000316, NP_001191326, NP_001191327, NP_001191328, NP_700475, NP_700476 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR003654	OAR_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR016233	Homeobox_Pitx/unc30	Family
IPR017970	Homeobox_CS	Conserved_site

Pfam: PF00046, PF03826

UniProt features (36 total): sequence variant 16, sequence conflict 4, helix 3, compositionally biased region 3, splice variant 2, short sequence motif 2, strand 2, chain 1, DNA-binding region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2L7F	SOLUTION NMR
2L7M	SOLUTION NMR
2LKX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99697-F1	62.59	0.19

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 90

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8866906	TFAP2 (AP-2) family regulates transcription of other transcription factors

MSigDB gene sets: 0 (showing top):

GO Biological Process (53): negative regulation of transcription by RNA polymerase II (GO:0000122), branching involved in blood vessel morphogenesis (GO:0001569), vasculogenesis (GO:0001570), in utero embryonic development (GO:0001701), neuron migration (GO:0001764), extraocular skeletal muscle development (GO:0002074), outflow tract morphogenesis (GO:0003151), atrioventricular valve development (GO:0003171), cardiac neural crest cell migration involved in outflow tract morphogenesis (GO:0003253), pulmonary myocardium development (GO:0003350), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), determination of left/right symmetry (GO:0007368), positive regulation of cell population proliferation (GO:0008284), anatomical structure morphogenesis (GO:0009653), Wnt signaling pathway (GO:0016055), subthalamic nucleus development (GO:0021763), hypothalamus cell migration (GO:0021855), regulation of cell migration (GO:0030334), embryonic camera-type eye development (GO:0031076), embryonic hindlimb morphogenesis (GO:0035116), hair cell differentiation (GO:0035315), vascular associated smooth muscle cell differentiation (GO:0035886), deltoid tuberosity development (GO:0035993), odontogenesis (GO:0042476), camera-type eye development (GO:0043010), positive regulation of transcription by RNA polymerase II (GO:0045944), spleen development (GO:0048536), embryonic digestive tract morphogenesis (GO:0048557), atrial cardiac muscle tissue morphogenesis (GO:0055009), ventricular cardiac muscle cell development (GO:0055015), somatotropin secreting cell differentiation (GO:0060126), prolactin secreting cell differentiation (GO:0060127), ventricular septum morphogenesis (GO:0060412), left lung morphogenesis (GO:0060460), pulmonary vein morphogenesis (GO:0060577), superior vena cava morphogenesis (GO:0060578), embryonic heart tube left/right pattern formation (GO:0060971), endodermal digestive tract morphogenesis (GO:0061031), iris morphogenesis (GO:0061072)

GO Molecular Function (17): transcription cis-regulatory region binding (GO:0000976), 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 repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), chromatin DNA binding (GO:0031490), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), ribonucleoprotein complex binding (GO:0043021), phosphoprotein binding (GO:0051219), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA-binding transcription factor binding (GO:0140297), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), chromatin binding (GO:0003682), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
blood vessel morphogenesis	2
camera-type eye development	2
regulation of DNA-templated transcription	2
DNA binding	2
protein binding	2
binding	2
negative regulation of DNA-templated transcription	1
angiogenesis	1
branching morphogenesis of an epithelial tube	1
cell differentiation	1
chordate embryonic development	1
generation of neurons	1
skeletal muscle tissue development	1
skeletal muscle organ development	1
heart morphogenesis	1
anatomical structure morphogenesis	1
heart valve development	1
neural crest cell migration	1
outflow tract morphogenesis	1
cell migration involved in heart development	1
cardiac neural crest cell development involved in outflow tract morphogenesis	1
striated muscle tissue development	1
venous blood vessel development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
determination of bilateral symmetry	1
left/right pattern formation	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
developmental process	1
anatomical structure development	1
cell surface receptor signaling pathway	1
subthalamus development	1

Protein interactions and networks

STRING

2274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PITX2	FOXC1	Q12948	988
PITX2	LEFTY2	O00292	920
PITX2	CTNNB1	P35222	890
PITX2	LEFTY1	O75610	868
PITX2	CYP1B1	Q16678	832
PITX2	SHH	Q15465	779
PITX2	POU1F1	P28069	758
PITX2	HCN4	Q9Y3Q4	755
PITX2	BMP4	P12644	748
PITX2	OSR2	Q8N2R0	747
PITX2	PAX9	P55771	745
PITX2	TBX5	Q99593	736
PITX2	ZFHX3	Q15911	720
PITX2	LEF1	Q9UJU2	698
PITX2	LHX3	Q9UBR4	694

IntAct

31 interactions, top by confidence:

A	B	Type	Score
PITX2	Hoxa1	psi-mi:“MI:0915”(physical association)	0.570
Hoxa1	PITX2	psi-mi:“MI:0915”(physical association)	0.570
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
IER2	KPNA3	psi-mi:“MI:0914”(association)	0.530
YBX1	PITX2	psi-mi:“MI:0915”(physical association)	0.500
CTNNB1	PITX2	psi-mi:“MI:2364”(proximity)	0.480
PITX2	PITX2	psi-mi:“MI:0407”(direct interaction)	0.440
PITX2	CDC37	psi-mi:“MI:0915”(physical association)	0.400
CCL11	PITX2	psi-mi:“MI:0915”(physical association)	0.370
	PITX2	psi-mi:“MI:0915”(physical association)	0.370
PITX2	TRIM25	psi-mi:“MI:0915”(physical association)	0.370
PITX2	ZNHIT3	psi-mi:“MI:0915”(physical association)	0.370
FOXC2	ZNF536	psi-mi:“MI:0914”(association)	0.350
RBPJ	SAMD1	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
NOP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
PITX2	AHCYL1	psi-mi:“MI:0914”(association)	0.350
NOP2	NVL	psi-mi:“MI:0914”(association)	0.350
PITX2	NCL	psi-mi:“MI:0914”(association)	0.350
RFC2	PITX2	psi-mi:“MI:0915”(physical association)	0.000
PITX2	GPR158	psi-mi:“MI:0915”(physical association)	0.000
PITX2	PRKACB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (84): AHCYL2 (Affinity Capture-MS), AHCYL1 (Affinity Capture-MS), LRRC46 (Affinity Capture-MS), PITX2 (Affinity Capture-MS), PITX2 (PCA), Hoxa1 (Affinity Capture-Western), CTNNB1 (Co-localization), PITX2 (Affinity Capture-MS), PITX2 (Affinity Capture-MS), AHCYL2 (Affinity Capture-MS), LRRC46 (Affinity Capture-MS), PITX2 (Affinity Capture-MS), AHCYL1 (Affinity Capture-MS), PITX2 (Affinity Capture-RNA), PITX2 (Two-hybrid)

ESM2 similar proteins: A3RK74, A3RK75, A4L7N3, B3LYS5, B3P0K6, B4HF64, B4MB78, E1BPQ1, F1R8Z9, G3V7R4, O43524, O93353, O93385, P23512, P32183, P35584, P56673, P70314, P78337, P97474, Q12778, Q28EM1, Q32NP8, Q3BJS1, Q66JJ0, Q68EZ2, Q68F77, Q6EUW1, Q6EUW2, Q6QU75, Q810W5, Q8IZQ8, Q8K3Q3, Q8R5I7, Q91813, Q91981, Q96NZ1, Q99697, Q99NA7, Q9CXC9

Diamond homologs: A1A546, A1YEY5, A1YFI3, A1YG57, A1YGA2, A2T733, A2T777, A2T7P4, A6NFQ7, A6NJG6, A6NJT0, A6NNA5, A6YP92, F1NEA7, G5EC89, O08934, O14813, O15266, O15499, O35085, O35160, O35690, O35750, O42115, O42250, O43186, O54751, O60902, O70137, O73592, O75364, O93385, O95076, O97670, P21711, P22810, P29454, P32242, P53544, P53545

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PITX2	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
PAX3	“up-regulates quantity by expression”	PITX2	“transcriptional regulation”
LEF1	“up-regulates quantity by expression”	PITX2	“transcriptional regulation”
PITX2	“down-regulates quantity by repression”	TBX1	“transcriptional regulation”
PITX2	“down-regulates quantity by repression”	GNRH1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	17
Uncertain significance	94
Likely benign	29
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1398374	NM_000325.6(PITX2):c.316G>T (p.Glu106Ter)	Pathogenic
1455159	NM_000325.6(PITX2):c.700_716dup (p.Thr239_Gly240insCysProGlnGlnTer)	Pathogenic
1456258	NC_000004.11:g.(?111539281)(111554154_?)del	Pathogenic
1458040	NM_000325.6(PITX2):c.448_449del (p.Arg150fs)	Pathogenic
1693121	NM_000325.6(PITX2):c.220C>T (p.Gln74Ter)	Pathogenic
1693122	NM_000325.6(PITX2):c.503_506del (p.Asn168fs)	Pathogenic
1693123	NM_000325.6(PITX2):c.515del (p.Gln172fs)	Pathogenic
1693124	NM_000325.6(PITX2):c.525del (p.Asp175fs)	Pathogenic
1693125	NM_000325.6(PITX2):c.557G>A (p.Trp186Ter)	Pathogenic
1693126	NM_000325.6(PITX2):c.663del (p.Asn222fs)	Pathogenic
1693127	NM_000325.6(PITX2):c.790del (p.Val264fs)	Pathogenic
1693128	NM_000325.6(PITX2):c.791_792dup (p.Pro265fs)	Pathogenic
1693129	NM_000325.6(PITX2):c.867_889del (p.Ser290fs)	Pathogenic
1693130	NM_000325.6(PITX2):c.293dup (p.His98fs)	Pathogenic
1693133	NM_000325.6(PITX2):c.417G>T (p.Trp139Cys)	Pathogenic
1693135	NM_000325.6(PITX2):c.428G>C (p.Arg143Pro)	Pathogenic
1693136	NM_000325.6(PITX2):c.302_303del (p.Ser101fs)	Pathogenic
1693146	NM_000325.6(PITX2):c.384G>A (p.Trp128Ter)	Pathogenic
1693156	NM_000325.6(PITX2):c.412-1G>A	Pathogenic
2019449	NM_000325.6(PITX2):c.470_476dup (p.Cys159Ter)	Pathogenic
2203569	NM_000325.6(PITX2):c.350C>G (p.Pro117Arg)	Pathogenic
2942566	NM_000325.6(PITX2):c.376G>C (p.Ala126Pro)	Pathogenic
2950646	NM_000325.6(PITX2):c.250G>T (p.Glu84Ter)	Pathogenic
30197	NM_000325.6(PITX2):c.421A>G (p.Lys141Glu)	Pathogenic
3337461	NM_000325.6(PITX2):c.206-1G>A	Pathogenic
3366291	NM_000325.6(PITX2):c.634del (p.Leu212fs)	Pathogenic
375436	NM_000325.6(PITX2):c.343_364del (p.Arg115fs)	Pathogenic
375437	NM_000325.6(PITX2):c.350C>T (p.Pro117Leu)	Pathogenic
375440	NM_000325.6(PITX2):c.714_735del (p.Thr239fs)	Pathogenic
375441	NM_000325.6(PITX2):c.784_785del (p.Ser262fs)	Pathogenic

SpliceAI

501 predictions. Top by Δscore:

Variant	Effect	Δscore
4:110618697:G:T	acceptor_gain	1.0000
4:110621158:TCCTA:T	donor_loss	1.0000
4:110621159:CCTA:C	donor_loss	1.0000
4:110621160:CTACC:C	donor_loss	1.0000
4:110621161:TACCC:T	donor_loss	1.0000
4:110621162:A:AC	donor_gain	1.0000
4:110621162:A:T	donor_loss	1.0000
4:110621162:AC:A	donor_gain	1.0000
4:110621163:C:CC	donor_gain	1.0000
4:110621163:C:CT	donor_loss	1.0000
4:110621163:CC:C	donor_gain	1.0000
4:110621177:T:TA	donor_gain	1.0000
4:110621366:TTCT:T	acceptor_gain	1.0000
4:110621368:CT:C	acceptor_gain	1.0000
4:110621369:TC:T	acceptor_loss	1.0000
4:110621370:C:CC	acceptor_gain	1.0000
4:110621371:T:A	acceptor_loss	1.0000
4:110621378:G:T	acceptor_gain	1.0000
4:110618684:CAAAC:C	acceptor_gain	0.9900
4:110618689:C:G	acceptor_loss	0.9900
4:110618690:T:A	acceptor_loss	0.9900
4:110618696:CGGT:C	acceptor_gain	0.9900
4:110618699:T:C	acceptor_gain	0.9900
4:110618699:T:TC	acceptor_gain	0.9900
4:110618705:C:CT	acceptor_gain	0.9900
4:110618706:A:T	acceptor_gain	0.9900
4:110621365:TTTCT:T	acceptor_gain	0.9900
4:110621377:C:CT	acceptor_gain	0.9900
4:110622253:TA:T	donor_loss	0.9900
4:110622254:A:AC	donor_gain	0.9900

AlphaMissense

2126 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:110618225:C:G	R285T	1.000
4:110618228:A:G	L284P	1.000
4:110618645:C:G	R145P	1.000
4:110618646:G:T	R145S	1.000
4:110618653:C:A	K142N	1.000
4:110618653:C:G	K142N	1.000
4:110618655:T:C	K142E	1.000
4:110618656:T:A	R141S	1.000
4:110618656:T:G	R141S	1.000
4:110618657:C:A	R141I	1.000
4:110618657:C:G	R141T	1.000
4:110618658:T:C	R141G	1.000
4:110618659:C:A	W140C	1.000
4:110618659:C:G	W140C	1.000
4:110618660:C:G	W140S	1.000
4:110618661:A:G	W140R	1.000
4:110618661:A:T	W140R	1.000
4:110618662:T:A	K139N	1.000
4:110618662:T:G	K139N	1.000
4:110618663:T:A	K139I	1.000
4:110618664:T:C	K139E	1.000
4:110618664:T:G	K139Q	1.000
4:110618666:G:A	A138V	1.000
4:110618666:G:T	A138D	1.000
4:110618667:C:G	A138P	1.000
4:110618667:C:T	A138T	1.000
4:110618669:C:G	R137P	1.000
4:110618669:C:T	R137Q	1.000
4:110618670:G:A	R137W	1.000
4:110618670:G:C	R137G	1.000

dbSNP variants (sampled 300 via entrez): RS1000202866 (4:110628058 T>C), RS1000266046 (4:110621875 C>G,T), RS1000312043 (4:110633249 A>G), RS1000362390 (4:110639362 A>T), RS1000380473 (4:110633564 T>C), RS1000538052 (4:110627683 T>G), RS1000578561 (4:110622954 G>A), RS1000843296 (4:110638226 T>C), RS1000900355 (4:110635442 C>T), RS1000936372 (4:110638594 C>T), RS1001136531 (4:110629404 C>G,T), RS1001138887 (4:110622134 C>A,G,T), RS1001204015 (4:110626869 G>A), RS1001222598 (4:110619859 C>A), RS1001444477 (4:110626655 C>A)

Disease associations

OMIM: gene MIM:601542 | disease phenotypes: MIM:137600, MIM:180500, MIM:116200, MIM:180550, MIM:604229, MIM:109120, MIM:194200, MIM:608583, MIM:107250

GenCC curated gene-disease

Disease	Classification	Inheritance
Axenfeld-Rieger syndrome type 1	Definitive	Autosomal dominant
anterior segment dysgenesis 4	Definitive	Autosomal dominant
ring dermoid of cornea	Strong	Autosomal dominant
disorder of visual system	Strong	Autosomal dominant
aniridia	Moderate	Autosomal dominant
familial atrial fibrillation	Supportive	Autosomal dominant
Axenfeld-Rieger syndrome	Supportive	Autosomal dominant
Rieger anomaly	Supportive	Autosomal dominant
Axenfeld anomaly	Supportive	Autosomal dominant
Peters anomaly	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
anterior segment dysgenesis 4	Definitive	AD

Mondo (19): anterior segment dysgenesis 4 (MONDO:0007662), Axenfeld-Rieger syndrome type 1 (MONDO:0008386), prostate cancer (MONDO:0008315), cataract (MONDO:0005129), ring dermoid of cornea (MONDO:0008387), Peters anomaly (MONDO:0011414), Axenfeld-Rieger anomaly with partially absent eye muscles, distinctive face, hydrocephaly, and skeletal abnormalities (MONDO:0007180), lung adenocarcinoma (MONDO:0005061), pituitary stalk interruption syndrome (MONDO:0019828), intellectual disability (MONDO:0001071), Axenfeld-Rieger syndrome (MONDO:0019187), Wolff-Parkinson-White syndrome (MONDO:0008685), Rieger anomaly (MONDO:0019628), atrial fibrillation, familial, 1 (MONDO:0012066), anterior segment dysgenesis (MONDO:0019503)

Orphanet (11): Axenfeld-Rieger syndrome (Orphanet:782), Rieger anomaly (Orphanet:91483), Familial prostate cancer (Orphanet:1331), Peters anomaly (Orphanet:708), Ring dermoid of cornea (Orphanet:91481), Pituitary stalk interruption syndrome (Orphanet:95496), Anterior segment developmental anomaly (Orphanet:88632), De Hauwere syndrome (Orphanet:1831), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

67 total (30 of 67 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000047	Hypospadias
HP:0000164	Abnormality of the dentition
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000327	Hypoplasia of the maxilla
HP:0000336	Prominent supraorbital ridges
HP:0000365	Hearing impairment
HP:0000431	Wide nasal bridge
HP:0000481	Abnormal cornea morphology
HP:0000482	Microcornea
HP:0000485	Megalocornea
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000502	Abnormal conjunctiva morphology
HP:0000506	Telecanthus
HP:0000523	Subcapsular cataract
HP:0000526	Aniridia
HP:0000558	Rieger anomaly
HP:0000593	Abnormal anterior chamber morphology
HP:0000627	Posterior embryotoxon
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000659	Peters anomaly
HP:0000668	Hypodontia
HP:0000677	Oligodontia
HP:0000691	Microdontia
HP:0000824	Decreased response to growth hormone stimulation test

GWAS associations

65 associations (top):

Study	Trait	p-value
GCST000051_1	Atrial fibrillation/atrial flutter	7.000000e-11
GCST000051_2	Atrial fibrillation/atrial flutter	3.000000e-41
GCST000445_3	Atrial fibrillation	4.000000e-63
GCST000602_1	Atrial fibrillation	3.000000e-28
GCST001499_2	Atrial fibrillation	2.000000e-74
GCST001706_3	Stroke (ischemic)	2.000000e-07
GCST001706_4	Stroke (ischemic)	3.000000e-16
GCST002286_1	Ischemic stroke	3.000000e-08
GCST003075_117	Cognitive decline rate in late mild cognitive impairment	4.000000e-06
GCST003075_44	Cognitive decline rate in late mild cognitive impairment	9.000000e-07
GCST003257_1	Ischemic stroke (cardioembolic)	3.000000e-32
GCST003258_2	Ischemic stroke	3.000000e-14
GCST003490_1	Ischemic stroke (cardioembolic)	1.000000e-25
GCST004295_4	Atrial fibrillation	3.000000e-155
GCST004296_4	Atrial fibrillation	2.000000e-62
GCST004297_12	Atrial fibrillation	7.000000e-136
GCST004298_1	Atrial fibrillation	8.000000e-46
GCST004299_1	Atrial fibrillation	4.000000e-08
GCST004300_2	Incident atrial fibrillation	8.000000e-57
GCST004301_1	Prevalent atrial fibrillation	7.000000e-92
GCST004352_4	Early onset atrial fibrillation	6.000000e-38
GCST004373_12	Atrial fibrillation	2.000000e-134
GCST004373_2	Atrial fibrillation	1.000000e-126
GCST004373_3	Atrial fibrillation	2.000000e-34
GCST004748_40	Lung cancer	2.000000e-06
GCST005170_49	Intraocular pressure	3.000000e-10
GCST005306_8	Atrial fibrillation	2.000000e-39
GCST006061_122	Atrial fibrillation	7.000000e-71
GCST006061_129	Atrial fibrillation	2.000000e-39
GCST006061_133	Atrial fibrillation	8.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:1001493	cardiac embolism
EFO:0004695	intraocular pressure measurement
EFO:0006527	smoking status measurement
EFO:1001976	cardioembolic stroke
EFO:0004327	electrocardiography

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D015783	Aniridia	C11.250.060; C11.270.060; C11.941.375.060; C16.131.384.079; C16.320.290.078
D002386	Cataract	C11.510.245
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
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
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C538261	Atrial fibrillation, familial 1 (supp.)
C566234	Axenfeld-Rieger Anomaly with Partially Absent Eye Muscles, Distinctive Face, Hydrocephaly, and Skeletal Abnormalities (supp.)
C535679	Axenfeld-Rieger syndrome (supp.)
C537884	Peters anomaly (supp.)
C535684	Ring dermoid of cornea (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	8
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
sodium arsenite	increases abundance, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Cadmium	decreases expression, increases abundance	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
tetrabromobisphenol A	increases expression	1
butylbenzyl phthalate	decreases expression	1
hydroquinone	decreases expression	1
mercuric bromide	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Amphotericin B	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cytarabine	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1

Cellosaurus cell lines

9 cell lines: 5 induced pluripotent stem cell, 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5J2	SEES3-1V human PITX2, clone1	Embryonic stem cell	Male
CVCL_A5J3	SEES3-1V human PITX2, clone2	Embryonic stem cell	Male
CVCL_A5J4	SEES3-1V human PITX2, clone3	Embryonic stem cell	Male
CVCL_C3LC	KSCBi018-A-6	Induced pluripotent stem cell	Male
CVCL_C3LD	KSCBi018-A-7	Induced pluripotent stem cell	Male
CVCL_D8T3	Ubigene HCT 116 PITX2 KO	Cancer cell line	Male
CVCL_QX64	MPIMBMi011-A-3	Induced pluripotent stem cell	Male
CVCL_QX65	MPIMBMi011-A-4	Induced pluripotent stem cell	Male
CVCL_QX80	UNIBSi003-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

322 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