PITX2 (paired like homeodomain 2)

Gene

• Entrez ID: 5308
• Gene name: Paired like homeodomain 2
• Gene symbol: PITX2
• Synonyms: ARP1, ASGD4, Brx1, IDG2, IGDS, IGDS2, IHG2, IRID2, Otlx2, PTX2, RGS, RIEG, RIEG1, RS
• Chromosome: 4
• Chromosome location: 4q25
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs6533526	G>A	Benign, pathogenic	3 prime UTR variant
rs104893857	A>T	Pathogenic	5 prime UTR variant, missense variant, coding sequence variant
rs104893858	T>C,G	Pathogenic	Missense variant, coding sequence variant
rs104893859	C>G,T	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs104893860	C>T	Pathogenic	Stop gained, coding sequence variant
rs104893861	C>T	Pathogenic	Missense variant, coding sequence variant
rs104893862	C>T	Pathogenic	5 prime UTR variant, missense variant, coding sequence variant
rs121909248	G>A	Pathogenic	Missense variant, coding sequence variant
rs121909249	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs138163892	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs141176394	T>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs387906810	T>C	Pathogenic	Coding sequence variant, missense variant
rs772800095	C>A,G	Pathogenic	Coding sequence variant, missense variant
rs1057519483	GTGGACATGTCCGGGTAGCGGT>-	Pathogenic	5 prime UTR variant, coding sequence variant, initiator codon variant, frameshift variant
rs1057519484	G>A	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs1057519487	GAGCCCGGGACGCCTGTCACTG>-	Pathogenic	Coding sequence variant, frameshift variant
rs1057519488	GA>-	Pathogenic	Coding sequence variant, frameshift variant
rs1057519489	A>T	Pathogenic	Coding sequence variant, stop gained
rs1198152064	T>C,G	Pathogenic	Intron variant
rs1553922583	T>A,C	Likely-pathogenic, pathogenic	Splice acceptor variant
rs1553922891	->T	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1553922901	G>A	Pathogenic	5 prime UTR variant, stop gained, coding sequence variant
rs1560590094	C>G	Pathogenic	Intron variant
rs1578446544	G>C	Pathogenic	Coding sequence variant, stop gained
rs1578450728	A>C	Pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT555582	hsa-miR-494-3p	PAR-CLIP	21572407
MIRT555581	hsa-miR-374b-5p	PAR-CLIP	21572407
MIRT555580	hsa-miR-374a-5p	PAR-CLIP	21572407
MIRT555579	hsa-miR-377-3p	PAR-CLIP	21572407
MIRT555577	hsa-miR-4517	PAR-CLIP	21572407
MIRT555578	hsa-miR-5583-3p	PAR-CLIP	21572407
MIRT555576	hsa-miR-369-3p	PAR-CLIP	21572407
MIRT555574	hsa-miR-5692b	PAR-CLIP	21572407
MIRT555575	hsa-miR-5692c	PAR-CLIP	21572407
MIRT555573	hsa-miR-153-5p	PAR-CLIP	21572407
MIRT555582	hsa-miR-494-3p	PAR-CLIP	21572407
MIRT555581	hsa-miR-374b-5p	PAR-CLIP	21572407
MIRT555580	hsa-miR-374a-5p	PAR-CLIP	21572407
MIRT555579	hsa-miR-377-3p	PAR-CLIP	21572407
MIRT555577	hsa-miR-4517	PAR-CLIP	21572407
MIRT555578	hsa-miR-5583-3p	PAR-CLIP	21572407
MIRT555576	hsa-miR-369-3p	PAR-CLIP	21572407
MIRT555574	hsa-miR-5692b	PAR-CLIP	21572407
MIRT555575	hsa-miR-5692c	PAR-CLIP	21572407
MIRT555573	hsa-miR-153-5p	PAR-CLIP	21572407
MIRT2069710	hsa-miR-498	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription regulatory region sequence-specific DNA binding	IDA	9685346
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IDA	9685346
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001102	Function	RNA polymerase II activating transcription factor binding	IPI	9685346
GO:0003253	Process	Cardiac neural crest cell migration involved in outflow tract morphogenesis	ISS
GO:0003700	Function	DNA-binding transcription factor activity	IDA	15385555
GO:0005515	Function	Protein binding	IPI	16449236, 19174163, 23088713, 25241761
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IDA	19251162
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005667	Component	Transcription regulator complex	IDA	15385555
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IDA	15385555, 23975681
GO:0007368	Process	Determination of left/right symmetry	ISS
GO:0008134	Function	Transcription factor binding	IPI	15385555
GO:0009653	Process	Anatomical structure morphogenesis	IBA	21873635
GO:0035315	Process	Hair cell differentiation	IC	19251162
GO:0035993	Process	Deltoid tuberosity development	IMP	18312615
GO:0042476	Process	Odontogenesis	IMP	14630904
GO:0043010	Process	Camera-type eye development	IMP	9618168
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	9685346, 19251162
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	TAS
GO:0048536	Process	Spleen development	ISS
GO:0060126	Process	Somatotropin secreting cell differentiation	TAS	10372733
GO:0060127	Process	Prolactin secreting cell differentiation	TAS	10372733
GO:0060971	Process	Embryonic heart tube left/right pattern formation	ISS
GO:0061072	Process	Iris morphogenesis	IMP	9437321
GO:0061325	Process	Cell proliferation involved in outflow tract morphogenesis	ISS
GO:0070986	Process	Left/right axis specification	ISS
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 601542
• HGNC: 9005
• e!Ensembl: ENSG00000164093

Protein

• UniProt ID: Q99697
• Protein name: Pituitary homeobox 2 (ALL1-responsive protein ARP1) (Homeobox protein PITX2) (Paired-like homeodomain transcription factor 2) (RIEG bicoid-related homeobox transcription factor) (Solurshin)
• Protein 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 mR
• PDB: 2L7F, 2L7M, 2LKX
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00046	Homeodomain	86 → 142	Homeodomain	Domain
  PF03826	OAR	275 → 292	OAR motif	Motif

• Sequence:

  METNCRKLVSACVQLGVQPAAVECLFSKDSEIKKVEFTDSPESRKEAASSKFFPRQHPGA
  NEKDKSQQGKNEDVGAEDPSKKKRQRRQRTHFTSQQLQELEATFQRNRYPDMSTREEIAV
  WTNLTEARVRVWFKNRRAKWRKRERNQQAELCKNGFGPQFNGLMQPYDDMYPGYSYNNWA
  AKGLTSASLSTKSFPFFNSMNVNPLSSQSMFSPPNSISSMSMSSSMVPSAVTGVPGSSLN
  SLNNLNNLSSPSLNSAVPTPACPYAPPTPPYVYRDTCNSSLASLRLKAKQHSSFGYASVQ
  NPASNLSACQYAVDRPV

• Sequence length: 317

Pathways

KEGG:

TGF-beta signaling pathway

Reactome:

TFAP2 (AP-2) family regulates transcription of other transcription factors

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Aniridia	Aniridia	rs1565200471, rs121907912, rs121907915, rs121907913, rs121907914, rs1131692318, rs121907916, rs121907917, rs794726661, rs121907918, rs121907920, rs121907922, rs121907927, rs121907928, rs878852979, rs121907929, rs397514640, rs398123295, rs606231388, rs864309681, rs886041222, rs886041221, rs1057517785, rs1057517783, rs757259413, rs1057517780, rs1131692319, rs1131692317, rs1131692316, rs1131692315, rs1131692314, rs1131692313, rs1131692312, rs1131692310, rs1131692309, rs1131692308, rs1131692307, rs1131692306, rs1131692305, rs1131692304, rs1131692303, rs1131692302, rs1131692301, rs1131692300, rs1131692299, rs1131692298, rs1131692297, rs1131692296, rs1131692295, rs1131692294, rs1131692293, rs1131692292, rs1131692291, rs1131692290, rs1554985709, rs1131692289, rs141873759, rs1131692287, rs1131692286, rs1131692285, rs1131692284, rs1131692282, rs1554985714, rs1554984996, rs1554983586, rs1554982537, rs1554983229, rs1554983571, rs1554985305, rs1554985378, rs1554985737, rs1554986754, rs1554985028, rs1411880763, rs1554985320, rs1565264372, rs1565264387, rs1565264399, rs1554986858, rs1565277245, rs1565245598, rs1565246499, rs1565238322, rs1592416305, rs1592563428, rs1592348310, rs750848278, rs1592348542, rs1592348901, rs1592349567, rs1592367444, rs1592367623, rs1592369407, rs1592369500, rs1592369895, rs1592370052, rs1592409736, rs1592409876, rs1592410582, rs1592411896, rs1592414464, rs1592415563, rs1592415745, rs1592415868, rs1592415958, rs1592416453, rs1592420967, rs1592421398, rs1592433022, rs1592433545, rs1592433606, rs1592434096, rs1592435423, rs151086737, rs1592530126, rs1592530379, rs1592530521, rs1592531953, rs1592532084, rs1592532169, rs1554985100, rs1592542273, rs1592542705, rs1357628990, rs1592542942, rs1592543032, rs1592543499, rs1592543841, rs769095184, rs1592544327, rs1592544553, rs759557055, rs1592545392, rs760490431, rs763807196, rs1592545972, rs1592546024, rs1592546120, rs1592546273, rs1592562717, rs1592562836, rs1592562910, rs1592563047, rs1592563240, rs1592563333, rs1592563636, rs1592563721, rs1592564013, rs1592564157, rs1592564219, rs1592564366, rs1388158419, rs1592610205, rs1592350356, rs1592370265, rs1592412022, rs1592416538, rs1592421981, rs1592422097, rs1592435527, rs1592435632, rs1592435653, rs1592532561, rs1592532580, rs1592542002, rs1592542060, rs1592546340, rs1592546566, rs1592546589, rs1592564908, rs1592614756, rs1592654547, rs1592610121, rs1954534591
Anterior pituitary dysgenesis	ANTERIOR SEGMENT DYSGENESIS 4, PETERS ANOMALY SUBTYPE	rs1553922583
Anterior segment dysgenesis	Irido-corneo-trabecular dysgenesis (disorder), IRIDOGONIODYSGENESIS, TYPE 2, ANTERIOR SEGMENT DYSGENESIS 5	rs121907917, rs72549387, rs121909248, rs104893861, rs104893862, rs80358194, rs2113111009, rs104893957, rs104893958, rs104893954, rs587778873, rs587778874, rs878853070, rs752281590, rs369858688, rs1057519477, rs1057519480, rs1131692284, rs1554100953, rs1183655796, rs1558489563, rs121907913, rs72549376	10051017, 10051017, 20881294, 9437321, 9618168, 11487566, 8944018, 11487566
Atrial fibrillation	Atrial Fibrillation, ATRIAL FIBRILLATION, FAMILIAL, 1 (disorder), Familial atrial fibrillation	rs120074192, rs121908590, rs121908593, rs121434558, rs587776851, rs387906612, rs387906613, rs387906614, rs387906615, rs199472687, rs199472705, rs199473324, rs587777336, rs587777339, rs587777557, rs587777558, rs587777559, rs587777560, rs886037778, rs769405762, rs770372675	29892015, 30061737, 24333117
Axenfeld anomaly	Axenfeld anomaly (disorder), Axenfeld-Rieger syndrome, Rieger eye malformation sequence, Axenfeld-Rieger Syndrome, Type 1	rs104893857, rs1560590094, rs104893858, rs1198152064, rs104893859, rs104893860, rs121909249, rs104893862, rs104893957, rs104893951, rs104893952, rs104893953, rs121909339, rs387906810, rs372857241, rs376405759, rs886039568, rs1057519489, rs1057519488, rs1057519487, rs1057519483, rs1057519484, rs1057519471, rs1057519472, rs1057519475, rs1057519478, rs1057519479, rs1057519480, rs1057519481, rs1057519482, rs760676014, rs1085307884, rs368260972, rs1554101000, rs1553922583, rs1554100963, rs1241813534, rs1554101058, rs1183655796, rs772800095, rs1581373890, rs1581373773, rs1728998905, rs1762521548, rs1762522833, rs2230096, rs1762525473, rs1762536800	24433355, 19513095, 19513095, 15378534, 10937553, 10502778, 11487566, 8944018, 12381896, 14630904, 10644443, 14623826, 16936096
Cataract	Cataract	rs118203965, rs118203966, rs104893685, rs121908938, rs104894175, rs121909048, rs28937573, rs121909049, rs121909050, rs74315488, rs80358200, rs80358203, rs121434643, rs56141211, rs132630322, rs121917775, rs121917735, rs121917736, rs137853199, rs137853200, rs121917867, rs121917869, rs121913555, rs104893736, rs121909595, rs121909596, rs121909597, rs28931605, rs121909598, rs104893618, rs1695062782, rs74315486, rs74315487, rs74315490, rs74315489, rs745938679, rs1566402656, rs74315439, rs74315441, rs121912973, rs121917823, rs1593332981, rs121917825, rs121917827, rs113994108, rs387906963, rs387906964, rs1240503246, rs387906965, rs387906966, rs750207077, rs387907336, rs387907337, rs387907342, rs140332366, rs397514703, rs398122937, rs398122378, rs398122392, rs398122944, rs137853924, rs398122947, rs397515623, rs397515624, rs397515625, rs397515626, rs398122948, rs587778872, rs398123066, rs587777601, rs370424081, rs786205221, rs786205222, rs864309684, rs864309688, rs864309701, rs864309689, rs864309690, rs864309681, rs864309686, rs864309696, rs864309693, rs864309687, rs864309691, rs864309692, rs864309695, rs864309678, rs864309685, rs864309700, rs864309698, rs864309683, rs864309682, rs864309679, rs111534978, rs864309680, rs864309702, rs864622780, rs756898971, rs869312732, rs775038545, rs878852983, rs1114167312, rs1114167313, rs1114167314, rs1114167315, rs1114167307, rs886041410, rs886041412, rs1057518738, rs1057517926, rs1057518878, rs1057519616, rs12799308, rs1064793935, rs1064797219, rs1085307126, rs1085307127, rs765628635, rs1114167427, rs1114167433, rs1554744860, rs1554743428, rs747093432, rs1411557416, rs1555179713, rs1481963503, rs1555549755, rs1456161420, rs1555547008, rs1555889308, rs1555888762, rs766522434, rs1264025914, rs1553585262, rs1567671947, rs1337897299, rs764945940, rs1307969607, rs949335475, rs1184095219, rs776129797, rs1569203234, rs1567668570, rs749141857, rs764098604, rs1184398243, rs1578956689, rs1568480054, rs1564745688, rs1564722302, rs1564723150, rs1571175950, rs1569602837, rs1576552712, rs1575369255, rs981126461, rs1570403798, rs200557771, rs1477743112, rs1651879427, rs1651881222, rs1651919374, rs2024441691, rs148284531, rs1246080692
Congenital heart defects	Congenital Heart Defects	rs267607101, rs121434422, rs387906498, rs397509416, rs587777371, rs587777372, rs587777374, rs367537998, rs797044882, rs886041730, rs768027510, rs1064793873, rs1555447012, rs1554263268, rs1554263321, rs1555223294, rs782051102, rs1555896779, rs1555896778, rs1555897088, rs374016704, rs1555446983, rs1479104927, rs1562443558, rs755445139, rs1581616817, rs1581655293, rs1899172049	10499585
Glaucoma	Glaucoma, Glaucoma of childhood	rs121918355, rs1566660365, rs1566635134, rs121918356, rs1566634475, rs28936700, rs55771538, rs28936701, rs104893622, rs55989760, rs72549387, rs104893628, rs2125316417, rs104893629, rs74315328, rs121909193, rs74315330, rs74315329, rs74315332, rs74315334, rs74315336, rs74315338, rs74315341, rs121909194, rs74315331, rs1558603396, rs387907175, rs587778873, rs587778875, rs104894979, rs137854895, rs766425037, rs72549380, rs148542782, rs541217363, rs753021890, rs771076928, rs56010818, rs777678299, rs1446110883, rs1573274915, rs1587545234, rs751768343, rs944452644
Isolated somatotropin deficiency	Isolated somatotropin deficiency	rs797044450, rs71640277, rs863223306, rs2144738731, rs863223307, rs2144739370, rs863223309, rs863223310, rs137853223, rs2144739380, rs2144739391
Nystagmus	Nystagmus	rs137852207, rs137852208, rs1928435502, rs137852209, rs137852210, rs1929191668, rs137852211, rs137852212, rs2124209414, rs387906720, rs387906721, rs1602791884, rs786205896

Unknown
Disease name	Disease term	dbSNP ID	References
Congenital keratoglobus	Congenital keratoglobus
Conjunctival dermolipoma	Conjunctival dermolipoma
Corneal astigmatism	Regular astigmatism - corneal
Disorder of eye	Disorder of eye
Glaucoma, congenital	Hydrophthalmos
Hypodontia	Hypodontia
Hypoplasia of iris	Hypoplasia of iris
Hypoplasia of the maxilla	Hypoplasia of the maxilla
Hypospadias	Hypospadias
Imperforate anus	Anus, Imperforate
Microcornea	Microcornea
Microdontia	Microdontia (disorder)
Odontome	Odontome		10499585
Paroxysmal atrial fibrillation	Paroxysmal atrial fibrillation	rs199865688, rs397515994, rs757096307	30061737
Polycoria	Polycoria
Posterior embryotoxon	Posterior embryotoxon
Rieger syndrome	Rieger syndrome		24433355, 19513095
Ring dermoid of cornea	RING DERMOID OF CORNEA		11487566, 15591271, 22224469
Somatotropin deficiency	Somatotropin deficiency
Strabismus	Strabismus
Stroke	Cerebrovascular accident, Acute Cerebrovascular Accidents		29531354
Subcapsular cataract	Subcapsular cataract
Synechiae	Anterior synechiae