ID NKX25_HUMAN Reviewed; 324 AA. AC P52952; A8K3K0; B4DNB6; E9PBU6; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 24-JAN-2024, entry version 227. DE RecName: Full=Homeobox protein Nkx-2.5; DE AltName: Full=Cardiac-specific homeobox; DE AltName: Full=Homeobox protein CSX; DE AltName: Full=Homeobox protein NK-2 homolog E; GN Name=NKX2-5; Synonyms=CSX, NKX2.5, NKX2E; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Heart; RX PubMed=8900537; DOI=10.1007/bf03402205; RA Turbay D., Wechsler S.B., Blanchard K.M., Izumo S.; RT "Molecular cloning, chromosomal mapping, and characterization of the human RT cardiac-specific homeobox gene hCsx."; RL Mol. Med. 2:86-96(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal lung; RA Tate G., Mitsuya T.; RT "Human Nkx-2.5 gene."; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT RP ASP-74. RC TISSUE=Heart; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas, and Spleen; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP DEVELOPMENTAL STAGE. RX PubMed=21403123; DOI=10.1161/circulationaha.110.980607; RA Sizarov A., Ya J., de Boer B.A., Lamers W.H., Christoffels V.M., RA Moorman A.F.; RT "Formation of the building plan of the human heart: morphogenesis, growth, RT and differentiation."; RL Circulation 123:1125-1135(2011). RN [8] RP FUNCTION, VARIANT HIS-236, AND CHARACTERIZATION OF VARIANT HIS-236. RX PubMed=22560297; DOI=10.1016/j.devcel.2012.02.009; RA Koss M., Bolze A., Brendolan A., Saggese M., Capellini T.D., Bojilova E., RA Boisson B., Prall O.W., Elliott D.A., Solloway M., Lenti E., Hidaka C., RA Chang C.P., Mahlaoui N., Harvey R.P., Casanova J.L., Selleri L.; RT "Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-5/p15 RT module."; RL Dev. Cell 22:913-926(2012). RN [9] RP FUNCTION, INTERACTION WITH NEDD9, AND SUBCELLULAR LOCATION. RX PubMed=29899023; DOI=10.1126/scitranslmed.aap7294; RA Samokhin A.O., Stephens T., Wertheim B.M., Wang R.S., Vargas S.O., RA Yung L.M., Cao M., Brown M., Arons E., Dieffenbach P.B., Fewell J.G., RA Matar M., Bowman F.P., Haley K.J., Alba G.A., Marino S.M., Kumar R., RA Rosas I.O., Waxman A.B., Oldham W.M., Khanna D., Graham B.B., Seo S., RA Gladyshev V.N., Yu P.B., Fredenburgh L.E., Loscalzo J., Leopold J.A., RA Maron B.A.; RT "NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary RT arterial hypertension."; RL Sci. Transl. Med. 10:0-0(2018). RN [10] RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 138-194 OF MUTANT SER-193 OF RP HOMODIMER IN COMPLEX WITH DNA, SUBUNIT, AND DNA-BINDING. RX PubMed=22849347; DOI=10.1021/bi300849c; RA Pradhan L., Genis C., Scone P., Weinberg E.O., Kasahara H., Nam H.J.; RT "Crystal structure of the human NKX2.5 homeodomain in complex with DNA RT target."; RL Biochemistry 51:6312-6319(2012). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF 142-194 IN COMPLEX WITH TBX5 AND RP DNA, INTERACTION WITH TBX5, AND DNA-BINDING. RX PubMed=26926761; DOI=10.1021/acs.biochem.6b00171; RA Pradhan L., Gopal S., Li S., Ashur S., Suryanarayanan S., Kasahara H., RA Nam H.J.; RT "Intermolecular interactions of cardiac transcription factors NKX2.5 and RT TBX5."; RL Biochemistry 55:1702-1710(2016). RN [12] RP VARIANT ASD7 MET-178. RX PubMed=9651244; DOI=10.1126/science.281.5373.108; RA Schott J.-J., Benson D.W., Basson C.T., Pease W., Silberbach G.M., RA Moak J.P., Maron B.J., Seidman C.E., Seidman J.G.; RT "Congenital heart disease caused by mutations in the transcription factor RT NKX2-5."; RL Science 281:108-111(1998). RN [13] RP VARIANT TOF CYS-25, AND VARIANTS ASD7 LYS-188; GLY-189 AND CYS-191. RX PubMed=10587520; DOI=10.1172/jci8154; RA Benson D.W., Silberbach G.M., Kavanaugh-McHugh A., Cottrill C., Zhang Y., RA Riggs S., Smalls O., Johnson M.C., Watson M.S., Seidman J.G., Seidman C.E., RA Plowden J., Kugler J.D.; RT "Mutations in the cardiac transcription factor NKX2.5 affect diverse RT cardiac developmental pathways."; RL J. Clin. Invest. 104:1567-1573(1999). RN [14] RP VARIANTS TOF GLN-21; CYS-25; CYS-216 AND VAL-219. RX PubMed=11714651; DOI=10.1161/hc4601.098427; RA Goldmuntz E., Geiger E., Benson D.W.; RT "NKX2.5 mutations in patients with tetralogy of fallot."; RL Circulation 104:2565-2568(2001). RN [15] RP VARIANTS ASD7 ILE-15; VAL-63; GLU-127 AND THR-275, VARIANTS TOF GLN-21; RP PRO-22; CYS-25; CYS-216; VAL-219 AND THR-323, VARIANT CTMH ASN-291 DEL, RP VARIANT HLHS2 CYS-25, AND INVOLVEMENT IN CONGENITAL HEART MALFORMATIONS. RX PubMed=14607454; DOI=10.1016/j.jacc.2003.05.004; RA McElhinney D.B., Geiger E., Blinder J., Benson D.W., Goldmuntz E.; RT "NKX2.5 mutations in patients with congenital heart disease."; RL J. Am. Coll. Cardiol. 42:1650-1655(2003). RN [16] RP VARIANTS ASD7 PRO-7; SER-19; CYS-25; PRO-45; LEU-51; PRO-69; LEU-77; RP SER-114; ARG-114; ARG-118; ARG-124; VAL-126; SER-133; THR-135; PRO-144; RP MET-178; GLU-183; THR-192; ARG-192; ARG-194; GLU-205; VAL-219; ASN-226; RP HIS-248; PRO-279; PHE-279; VAL-281; VAL-286; HIS-294; GLY-299; GLY-305; RP SER-320 AND GLN-322. RX PubMed=15342699; DOI=10.1136/jmg.2003.017483; RA Reamon-Buettner S.M., Borlak J.; RT "Somatic NKX2-5 mutations as a novel mechanism of disease in complex RT congenital heart disease."; RL J. Med. Genet. 41:684-690(2004). RN [17] RP VARIANTS ASD7 ILE-15; GLN-21; PRO-22; CYS-25; VAL-63; GLU-127; CYS-142; RP MET-178; HIS-187; LYS-188; GLY-189; CYS-190; CYS-191; CYS-216; VAL-219; RP THR-275 AND THR-323, AND VARIANT HLHS2 CYS-25. RX PubMed=15810002; DOI=10.1002/ajmg.a.30684; RA Hirayama-Yamada K., Kamisago M., Akimoto K., Aotsuka H., Nakamura Y., RA Tomita H., Furutani M., Imamura S., Takao A., Nakazawa M., Matsuoka R.; RT "Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal RT defect."; RL Am. J. Med. Genet. A 135:47-52(2005). RN [18] RP VARIANTS CHNG5 CYS-25; SER-119 AND PRO-161, AND CHARACTERIZATION OF RP VARIANTS CHNG5 CYS-25; SER-119 AND PRO-161. RX PubMed=16418214; DOI=10.1210/jc.2005-1350; RA Dentice M., Cordeddu V., Rosica A., Ferrara A.M., Santarpia L., RA Salvatore D., Chiovato L., Perri A., Moschini L., Fazzini C., Olivieri A., RA Costa P., Stoppioni V., Baserga M., De Felice M., Sorcini M., Fenzi G., RA Di Lauro R., Tartaglia M., Macchia P.E.; RT "Missense mutation in the transcription factor NKX2-5: a novel molecular RT event in the pathogenesis of thyroid dysgenesis."; RL J. Clin. Endocrinol. Metab. 91:1428-1433(2006). RN [19] RP VARIANT CTHM CYS-25. RX PubMed=17891434; DOI=10.1007/s00246-007-9058-2; RA Akcaboy M.I., Cengiz F.B., Inceoglu B., Ucar T., Atalay S., Tutar E., RA Tekin M.; RT "The effect of p.Arg25Cys alteration in NKX2-5 on conotruncal heart RT anomalies: mutation or polymorphism?"; RL Pediatr. Cardiol. 29:126-129(2008). RN [20] RP VARIANT VSD3 GLN-283. RX PubMed=21110066; DOI=10.1007/s10709-010-9522-4; RA Peng T., Wang L., Zhou S.F., Li X.; RT "Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with RT non-familial congenital heart disease."; RL Genetica 138:1231-1240(2010). RN [21] RP VARIANT TOF CYS-25. RX PubMed=19948535; DOI=10.1136/jmg.2009.070391; RA Rauch R., Hofbeck M., Zweier C., Koch A., Zink S., Trautmann U., Hoyer J., RA Kaulitz R., Singer H., Rauch A.; RT "Comprehensive genotype-phenotype analysis in 230 patients with tetralogy RT of Fallot."; RL J. Med. Genet. 47:321-331(2010). RN [22] RP VARIANT VSD3 ALA-59, AND CHARACTERIZATION OF VARIANT VSD3 ALA-59. RX PubMed=21165553; DOI=10.3892/ijmm.2010.585; RA Wang J., Xin Y.F., Liu X.Y., Liu Z.M., Wang X.Z., Yang Y.Q.; RT "A novel NKX2-5 mutation in familial ventricular septal defect."; RL Int. J. Mol. Med. 27:369-375(2011). CC -!- FUNCTION: Transcription factor required for the development of the CC heart and the spleen (PubMed:22560297). During heart development, acts CC as a transcriptional activator of NPPA/ANF in cooperation with GATA4 CC (By similarity). May cooperate with TBX2 to negatively modulate CC expression of NPPA/ANF in the atrioventricular canal (By similarity). CC Binds to the core DNA motif of NPPA promoter (PubMed:22849347, CC PubMed:26926761). Together with PBX1, required for spleen development CC through a mechanism that involves CDKN2B repression (PubMed:22560297). CC Positively regulates transcription of genes such as COL3A1 and MMP2, CC resulting in increased pulmonary endothelial fibrosis in response to CC hypoxia (PubMed:29899023). {ECO:0000250|UniProtKB:P42582, CC ECO:0000269|PubMed:22560297, ECO:0000269|PubMed:22849347, CC ECO:0000269|PubMed:26926761, ECO:0000269|PubMed:29899023}. CC -!- SUBUNIT: Homodimer (via the homeobox); binds DNA as homodimer CC (PubMed:22849347). Interacts (via the homeobox) with TBX5 (via the T- CC box); this complex binds DNA (PubMed:26926761). Interacts with HIPK1 CC and HIPK2, but not HIPK3. Interacts with the C-terminal zinc finger of CC GATA4 through its homeobox domain. Also interacts with JARID2 which CC represses its ability to activate transcription of ANF. Interacts with CC FBLIM1. Interacts with TBX18 (By similarity). Interacts with histone CC methyltransferase NSD2 (via HMG box) (By similarity). Interacts with CC NEDD9 (PubMed:29899023). Interacts with TBX1 (By similarity). CC {ECO:0000250|UniProtKB:P42582, ECO:0000269|PubMed:22849347, CC ECO:0000269|PubMed:26926761, ECO:0000269|PubMed:29899023}. CC -!- INTERACTION: CC P52952; P43694: GATA4; NbExp=2; IntAct=EBI-936601, EBI-7049352; CC P52952; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-936601, EBI-10261141; CC P52952; Q93062-3: RBPMS; NbExp=3; IntAct=EBI-936601, EBI-740343; CC P52952; O15266-2: SHOX; NbExp=3; IntAct=EBI-936601, EBI-12825957; CC P52952; Q99593-1: TBX5; NbExp=6; IntAct=EBI-936601, EBI-304423; CC P52952; Q15642-2: TRIP10; NbExp=3; IntAct=EBI-936601, EBI-6550597; CC P52952; Q71FD7: Fblim1; Xeno; NbExp=4; IntAct=EBI-936601, EBI-8346526; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29899023}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P52952-1; Sequence=Displayed; CC Name=2; CC IsoId=P52952-2; Sequence=VSP_043492, VSP_043493; CC Name=3; CC IsoId=P52952-3; Sequence=VSP_045481, VSP_045482; CC -!- TISSUE SPECIFICITY: Expressed only in the heart. CC -!- DEVELOPMENTAL STAGE: Expressed at embryonic stages 10 to 11 in the CC nondifferentiated mesodermal cells at the venous and arterial poles, as CC well as cells of the dorsal coelomic wall and ruptured mesocardium (at CC protein level) (PubMed:21403123). Expressed by all myocardial cells at CC embryonic stages 10 to 11 (at protein level) (PubMed:21403123). CC {ECO:0000269|PubMed:21403123}. CC -!- DOMAIN: The homeobox domain binds to double-stranded DNA CC (PubMed:22849347). {ECO:0000269|PubMed:22849347}. CC -!- DISEASE: Atrial septal defect 7, with or without atrioventricular CC conduction defects (ASD7) [MIM:108900]: A congenital heart malformation CC characterized by incomplete closure of the wall between the atria CC resulting in blood flow from the left to the right atria, and CC atrioventricular conduction defects in some cases. CC {ECO:0000269|PubMed:10587520, ECO:0000269|PubMed:14607454, CC ECO:0000269|PubMed:15342699, ECO:0000269|PubMed:15810002, CC ECO:0000269|PubMed:9651244}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Tetralogy of Fallot (TOF) [MIM:187500]: A congenital heart CC anomaly which consists of pulmonary stenosis, ventricular septal CC defect, dextroposition of the aorta (aorta is on the right side instead CC of the left) and hypertrophy of the right ventricle. In this condition, CC blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into CC the body often causing cyanosis. {ECO:0000269|PubMed:10587520, CC ECO:0000269|PubMed:11714651, ECO:0000269|PubMed:14607454, CC ECO:0000269|PubMed:19948535}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A group CC of congenital heart defects involving the outflow tracts. Examples CC include truncus arteriosus communis, double-outlet right ventricle and CC transposition of great arteries. Truncus arteriosus communis is CC characterized by a single outflow tract instead of a separate aorta and CC pulmonary artery. In transposition of the great arteries, the aorta CC arises from the right ventricle and the pulmonary artery from the left CC ventricle. In double outlet of the right ventricle, both the pulmonary CC artery and aorta arise from the right ventricle. CC {ECO:0000269|PubMed:14607454, ECO:0000269|PubMed:17891434}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Hypothyroidism, congenital, non-goitrous, 5 (CHNG5) CC [MIM:225250]: A non-autoimmune condition characterized by resistance to CC thyroid-stimulating hormone (TSH) leading to increased levels of plasma CC TSH and low levels of thyroid hormone. CHNG5 presents variable severity CC depending on the completeness of the defect. Most patients are CC euthyroid and asymptomatic, with a normal sized thyroid gland. Only a CC subset of patients develop hypothyroidism and present a hypoplastic CC thyroid gland. {ECO:0000269|PubMed:16418214}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Ventricular septal defect 3 (VSD3) [MIM:614432]: A common form CC of congenital cardiovascular anomaly that may occur alone or in CC combination with other cardiac malformations. It can affect any portion CC of the ventricular septum, resulting in abnormal communications between CC the two lower chambers of the heart. Classification is based on CC location of the communication, such as perimembranous, inlet, outlet CC (infundibular), central muscular, marginal muscular, or apical muscular CC defect. Large defects that go unrepaired may give rise to cardiac CC enlargement, congestive heart failure, pulmonary hypertension, CC Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, CC and even sudden cardiac death. {ECO:0000269|PubMed:21110066, CC ECO:0000269|PubMed:21165553}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Hypoplastic left heart syndrome 2 (HLHS2) [MIM:614435]: A CC syndrome due to defective development of the aorta proximal to the CC entrance of the ductus arteriosus, and hypoplasia of the left ventricle CC and mitral valve. As a result of the abnormal circulation, the ductus CC arteriosus and foramen ovale are patent and the right atrium, right CC ventricle, and pulmonary artery are enlarged. CC {ECO:0000269|PubMed:14607454, ECO:0000269|PubMed:15810002}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42958/NKX25"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U34962; AAC50470.1; -; mRNA. DR EMBL; AB021133; BAA35181.1; -; mRNA. DR EMBL; AK297844; BAG60178.1; -; mRNA. DR EMBL; AK290615; BAF83304.1; -; mRNA. DR EMBL; AK309495; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC008412; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471062; EAW61404.1; -; Genomic_DNA. DR EMBL; BC025711; AAH25711.1; -; mRNA. DR CCDS; CCDS4387.1; -. [P52952-1] DR CCDS; CCDS54949.1; -. [P52952-2] DR CCDS; CCDS54950.1; -. [P52952-3] DR RefSeq; NP_001159647.1; NM_001166175.1. [P52952-3] DR RefSeq; NP_001159648.1; NM_001166176.1. [P52952-2] DR RefSeq; NP_004378.1; NM_004387.3. [P52952-1] DR PDB; 3RKQ; X-ray; 1.70 A; A/B=138-192. DR PDB; 4S0H; X-ray; 2.82 A; B/F=142-192. DR PDB; 6WC2; X-ray; 2.10 A; M/N/O=137-197. DR PDB; 6WC5; X-ray; 2.90 A; I/N=140-196. DR PDBsum; 3RKQ; -. DR PDBsum; 4S0H; -. DR PDBsum; 6WC2; -. DR PDBsum; 6WC5; -. DR AlphaFoldDB; P52952; -. DR SMR; P52952; -. DR BioGRID; 107864; 69. DR ComplexPortal; CPX-61; NKX2-5 transcription factor complex. DR IntAct; P52952; 59. DR MINT; P52952; -. DR STRING; 9606.ENSP00000327758; -. DR iPTMnet; P52952; -. DR PhosphoSitePlus; P52952; -. DR BioMuta; NKX2-5; -. DR DMDM; 1708211; -. DR MassIVE; P52952; -. DR PaxDb; 9606-ENSP00000327758; -. DR PeptideAtlas; P52952; -. DR ProteomicsDB; 19299; -. DR ProteomicsDB; 56562; -. [P52952-1] DR ProteomicsDB; 56563; -. [P52952-2] DR Pumba; P52952; -. DR Antibodypedia; 28950; 553 antibodies from 41 providers. DR DNASU; 1482; -. DR Ensembl; ENST00000329198.5; ENSP00000327758.4; ENSG00000183072.10. [P52952-1] DR Ensembl; ENST00000424406.2; ENSP00000395378.2; ENSG00000183072.10. [P52952-3] DR Ensembl; ENST00000521848.1; ENSP00000427906.1; ENSG00000183072.10. [P52952-2] DR GeneID; 1482; -. DR KEGG; hsa:1482; -. DR MANE-Select; ENST00000329198.5; ENSP00000327758.4; NM_004387.4; NP_004378.1. DR UCSC; uc003mcm.3; human. [P52952-1] DR AGR; HGNC:2488; -. DR CTD; 1482; -. DR DisGeNET; 1482; -. DR GeneCards; NKX2-5; -. DR HGNC; HGNC:2488; NKX2-5. DR HPA; ENSG00000183072; Tissue enriched (heart). DR MalaCards; NKX2-5; -. DR MIM; 108900; phenotype. DR MIM; 187500; phenotype. DR MIM; 217095; phenotype. DR MIM; 225250; phenotype. DR MIM; 600584; gene. DR MIM; 614432; phenotype. DR MIM; 614435; phenotype. DR neXtProt; NX_P52952; -. DR OpenTargets; ENSG00000183072; -. DR Orphanet; 95713; Athyreosis. DR Orphanet; 99103; Atrial septal defect, ostium secundum type. DR Orphanet; 1479; Atrial septal defect-atrioventricular conduction defects syndrome. DR Orphanet; 1627; Deletion 5q35. DR Orphanet; 334; Familial atrial fibrillation. DR Orphanet; 402075; Familial bicuspid aortic valve. DR Orphanet; 101351; Familial isolated congenital asplenia. DR Orphanet; 871; Familial progressive cardiac conduction defect. DR Orphanet; 2248; Hypoplastic left heart syndrome. DR Orphanet; 1480; NON RARE IN EUROPE: Ventricular septal defect. DR Orphanet; 3303; Tetralogy of Fallot. DR Orphanet; 95712; Thyroid ectopia. DR PharmGKB; PA24202; -. DR VEuPathDB; HostDB:ENSG00000183072; -. DR eggNOG; KOG0842; Eukaryota. DR GeneTree; ENSGT00940000158996; -. DR HOGENOM; CLU_049543_0_0_1; -. DR InParanoid; P52952; -. DR OMA; NYPSMQP; -. DR OrthoDB; 461623at2759; -. DR PhylomeDB; P52952; -. DR TreeFam; TF351204; -. DR PathwayCommons; P52952; -. DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression. DR Reactome; R-HSA-5578768; Physiological factors. DR Reactome; R-HSA-9733709; Cardiogenesis. DR SignaLink; P52952; -. DR SIGNOR; P52952; -. DR BioGRID-ORCS; 1482; 27 hits in 1150 CRISPR screens. DR GeneWiki; NKX2-5; -. DR GenomeRNAi; 1482; -. DR Pharos; P52952; Tbio. DR PRO; PR:P52952; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P52952; Protein. DR Bgee; ENSG00000183072; Expressed in apex of heart and 82 other cell types or tissues. DR ExpressionAtlas; P52952; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:1990664; C:Nkx-2.5 complex; IPI:ComplexPortal. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0032993; C:protein-DNA complex; IDA:UniProtKB. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL. DR GO; GO:0005667; C:transcription regulator complex; IC:BHF-UCL. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:BHF-UCL. DR GO; GO:0001216; F:DNA-binding transcription activator activity; IDA:BHF-UCL. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0007512; P:adult heart development; IMP:BHF-UCL. DR GO; GO:0003180; P:aortic valve morphogenesis; TAS:BHF-UCL. DR GO; GO:0003278; P:apoptotic process involved in heart morphogenesis; IEA:Ensembl. DR GO; GO:0055014; P:atrial cardiac muscle cell development; ISS:BHF-UCL. DR GO; GO:0003228; P:atrial cardiac muscle tissue development; ISS:BHF-UCL. DR GO; GO:0060413; P:atrial septum morphogenesis; IMP:BHF-UCL. DR GO; GO:0060928; P:atrioventricular node cell development; IEA:Ensembl. DR GO; GO:0060929; P:atrioventricular node cell fate commitment; IEA:Ensembl. DR GO; GO:0003162; P:atrioventricular node development; ISS:BHF-UCL. DR GO; GO:0003166; P:bundle of His development; ISS:BHF-UCL. DR GO; GO:0003161; P:cardiac conduction system development; IMP:MGI. DR GO; GO:0055013; P:cardiac muscle cell development; ISS:BHF-UCL. DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0060048; P:cardiac muscle contraction; IEA:Ensembl. DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; IMP:BHF-UCL. DR GO; GO:0060411; P:cardiac septum morphogenesis; ISO:ComplexPortal. DR GO; GO:0003211; P:cardiac ventricle formation; IEA:Ensembl. DR GO; GO:0030154; P:cell differentiation; ISS:BHF-UCL. DR GO; GO:0035050; P:embryonic heart tube development; ISS:BHF-UCL. DR GO; GO:0060971; P:embryonic heart tube left/right pattern formation; IEA:Ensembl. DR GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl. DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl. DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0007507; P:heart development; ISO:ComplexPortal. DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL. DR GO; GO:0003007; P:heart morphogenesis; ISS:BHF-UCL. DR GO; GO:0060347; P:heart trabecula formation; IEA:Ensembl. DR GO; GO:0030097; P:hemopoiesis; ISS:BHF-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:BHF-UCL. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISS:BHF-UCL. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:BHF-UCL. DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IEA:Ensembl. DR GO; GO:0010832; P:negative regulation of myotube differentiation; IMP:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0003148; P:outflow tract septum morphogenesis; IMP:BHF-UCL. DR GO; GO:0060037; P:pharyngeal system development; ISS:BHF-UCL. DR GO; GO:0051891; P:positive regulation of cardioblast differentiation; ISS:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0045823; P:positive regulation of heart contraction; ISS:BHF-UCL. DR GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:BHF-UCL. DR GO; GO:0010765; P:positive regulation of sodium ion transport; ISS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:0003342; P:proepicardium development; IEA:Ensembl. DR GO; GO:0003350; P:pulmonary myocardium development; IEA:Ensembl. DR GO; GO:0003168; P:Purkinje myocyte differentiation; IEA:Ensembl. DR GO; GO:1903779; P:regulation of cardiac conduction; ISS:BHF-UCL. DR GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISS:BHF-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0003221; P:right ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL. DR GO; GO:0003285; P:septum secundum development; IMP:BHF-UCL. DR GO; GO:0048536; P:spleen development; IMP:UniProtKB. DR GO; GO:0030878; P:thyroid gland development; IMP:BHF-UCL. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0001570; P:vasculogenesis; ISS:BHF-UCL. DR GO; GO:0055015; P:ventricular cardiac muscle cell development; ISS:BHF-UCL. DR GO; GO:0055005; P:ventricular cardiac myofibril assembly; IEA:Ensembl. DR GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL. DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IEA:Ensembl. DR CDD; cd00086; homeodomain; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR020479; Homeobox_metazoa. DR PANTHER; PTHR24340; HOMEOBOX PROTEIN NKX; 1. DR PANTHER; PTHR24340:SF28; HOMEOBOX PROTEIN NKX-2.5; 1. DR Pfam; PF00046; Homeodomain; 1. DR PRINTS; PR00024; HOMEOBOX. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR Genevisible; P52952; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Atrial septal defect; KW Congenital hypothyroidism; Developmental protein; Disease variant; KW DNA-binding; Homeobox; Nucleus; Reference proteome. FT CHAIN 1..324 FT /note="Homeobox protein Nkx-2.5" FT /id="PRO_0000048937" FT DNA_BIND 138..197 FT /note="Homeobox" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108, FT ECO:0000269|PubMed:22849347, ECO:0000269|PubMed:26926761" FT VAR_SEQ 112..151 FT /note="ELCALQKAVELEKTEADNAERPRARRRRKPRVLFSQAQVY -> GCELPRGQ FT RPPVLFSSALSQPDFLQMLSETCRWLPVHLAE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043492" FT VAR_SEQ 112 FT /note="E -> A (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045481" FT VAR_SEQ 113..324 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045482" FT VAR_SEQ 152..324 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043493" FT VARIANT 7 FT /note="L -> P (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038212" FT VARIANT 15 FT /note="K -> I (in ASD7; dbSNP:rs387906773)" FT /evidence="ECO:0000269|PubMed:14607454, FT ECO:0000269|PubMed:15810002" FT /id="VAR_038213" FT VARIANT 16 FT /note="D -> A (in dbSNP:rs17052019)" FT /id="VAR_049581" FT VARIANT 19 FT /note="N -> S (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038214" FT VARIANT 21 FT /note="E -> Q (in TOF and ASD7; dbSNP:rs104893904)" FT /evidence="ECO:0000269|PubMed:11714651, FT ECO:0000269|PubMed:14607454, ECO:0000269|PubMed:15810002" FT /id="VAR_038215" FT VARIANT 22 FT /note="Q -> P (in ASD7 and TOF; dbSNP:rs201442000)" FT /evidence="ECO:0000269|PubMed:14607454, FT ECO:0000269|PubMed:15810002" FT /id="VAR_038216" FT VARIANT 25 FT /note="R -> C (in ASD7, TOF, CHNG5, HLHS2 and CTHM; FT uncertain significance; exhibits significant functional FT impairment with reduction of transactivation properties and FT dominant-negative effect; the mutant protein activity on FT the DIO2, TG and TPO promoters is significantly impaired; FT dbSNP:rs28936670)" FT /evidence="ECO:0000269|PubMed:10587520, FT ECO:0000269|PubMed:11714651, ECO:0000269|PubMed:14607454, FT ECO:0000269|PubMed:15342699, ECO:0000269|PubMed:15810002, FT ECO:0000269|PubMed:16418214, ECO:0000269|PubMed:17891434, FT ECO:0000269|PubMed:19948535" FT /id="VAR_010116" FT VARIANT 45 FT /note="S -> P (in ASD7; somatic mutation; FT dbSNP:rs779548360)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038217" FT VARIANT 51 FT /note="F -> L (in ASD7; somatic mutation; FT dbSNP:rs753937287)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038218" FT VARIANT 59 FT /note="P -> A (in VSD3; significantly reduced activation of FT NPPA gene compared to wild-type; dbSNP:rs387906775)" FT /evidence="ECO:0000269|PubMed:21165553" FT /id="VAR_067586" FT VARIANT 63 FT /note="A -> V (in ASD7; dbSNP:rs530270916)" FT /evidence="ECO:0000269|PubMed:14607454, FT ECO:0000269|PubMed:15810002" FT /id="VAR_038219" FT VARIANT 69 FT /note="L -> P (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038220" FT VARIANT 74 FT /note="G -> D (in dbSNP:rs201362118)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_069058" FT VARIANT 77 FT /note="P -> L (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038221" FT VARIANT 114 FT /note="C -> R (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038222" FT VARIANT 114 FT /note="C -> S (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038223" FT VARIANT 118 FT /note="K -> R (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038224" FT VARIANT 119 FT /note="A -> S (in CHNG5; exhibits a significant functional FT impairment with reduction of transactivation properties and FT dominant-negative effect which was associated with reduced FT DNA binding; dbSNP:rs137852684)" FT /evidence="ECO:0000269|PubMed:16418214" FT /id="VAR_047869" FT VARIANT 124 FT /note="K -> R (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038225" FT VARIANT 126 FT /note="E -> V (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038226" FT VARIANT 127 FT /note="A -> E (in ASD7; dbSNP:rs387906774)" FT /evidence="ECO:0000269|PubMed:14607454, FT ECO:0000269|PubMed:15810002" FT /id="VAR_038227" FT VARIANT 133 FT /note="P -> S (in ASD7; somatic mutation; FT dbSNP:rs1184594159)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038228" FT VARIANT 135 FT /note="A -> T (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038229" FT VARIANT 142 FT /note="R -> C (in ASD7)" FT /evidence="ECO:0000269|PubMed:15810002" FT /id="VAR_038230" FT VARIANT 144 FT /note="L -> P (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038231" FT VARIANT 161 FT /note="R -> P (in CHNG5; exhibits a significant functional FT impairment with reduction of transactivation properties and FT dominant-negative effect which was associated with reduced FT DNA binding; dbSNP:rs137852685)" FT /evidence="ECO:0000269|PubMed:16418214" FT /id="VAR_047870" FT VARIANT 178 FT /note="T -> M (in ASD7; dbSNP:rs104893900)" FT /evidence="ECO:0000269|PubMed:15342699, FT ECO:0000269|PubMed:15810002, ECO:0000269|PubMed:9651244" FT /id="VAR_003752" FT VARIANT 183 FT /note="K -> E (in ASD7; somatic mutation; FT dbSNP:rs137852686)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038232" FT VARIANT 187 FT /note="Q -> H (in ASD7)" FT /evidence="ECO:0000269|PubMed:15810002" FT /id="VAR_038233" FT VARIANT 188 FT /note="N -> K (in ASD7)" FT /evidence="ECO:0000269|PubMed:10587520, FT ECO:0000269|PubMed:15810002" FT /id="VAR_010117" FT VARIANT 189 FT /note="R -> G (in ASD7)" FT /evidence="ECO:0000269|PubMed:10587520, FT ECO:0000269|PubMed:15810002" FT /id="VAR_010118" FT VARIANT 190 FT /note="R -> C (in ASD7; dbSNP:rs104893906)" FT /evidence="ECO:0000269|PubMed:15810002" FT /id="VAR_038234" FT VARIANT 191 FT /note="Y -> C (in ASD7)" FT /evidence="ECO:0000269|PubMed:10587520, FT ECO:0000269|PubMed:15810002" FT /id="VAR_010119" FT VARIANT 192 FT /note="K -> R (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038235" FT VARIANT 192 FT /note="K -> T (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038236" FT VARIANT 194 FT /note="K -> R (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038237" FT VARIANT 205 FT /note="V -> E (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038238" FT VARIANT 216 FT /note="R -> C (in TOF and ASD7; dbSNP:rs104893905)" FT /evidence="ECO:0000269|PubMed:11714651, FT ECO:0000269|PubMed:14607454, ECO:0000269|PubMed:15810002" FT /id="VAR_038239" FT VARIANT 219 FT /note="A -> V (in ASD7 and TOF; somatic mutation; FT dbSNP:rs104893902)" FT /evidence="ECO:0000269|PubMed:11714651, FT ECO:0000269|PubMed:14607454, ECO:0000269|PubMed:15342699, FT ECO:0000269|PubMed:15810002" FT /id="VAR_038240" FT VARIANT 226 FT /note="D -> N (in ASD7; somatic mutation; FT dbSNP:rs760528062)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038241" FT VARIANT 236 FT /note="P -> H (found in patients with isolated congenital FT asplenia; uncertain significance; does not affect DNA FT binding; impairs transactivation activity; FT dbSNP:rs397515399)" FT /evidence="ECO:0000269|PubMed:22560297" FT /id="VAR_069590" FT VARIANT 248 FT /note="Y -> H (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038242" FT VARIANT 275 FT /note="P -> T (in ASD7; dbSNP:rs368366482)" FT /evidence="ECO:0000269|PubMed:14607454, FT ECO:0000269|PubMed:15810002" FT /id="VAR_038243" FT VARIANT 279 FT /note="S -> F (in ASD7; somatic mutation; FT dbSNP:rs1223599871)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038244" FT VARIANT 279 FT /note="S -> P (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038245" FT VARIANT 281 FT /note="A -> V (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038246" FT VARIANT 283 FT /note="P -> Q (in VSD3; dbSNP:rs375086983)" FT /evidence="ECO:0000269|PubMed:21110066" FT /id="VAR_067587" FT VARIANT 286 FT /note="A -> V (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038247" FT VARIANT 291 FT /note="Missing (in CTMH; dbSNP:rs756974215)" FT /evidence="ECO:0000269|PubMed:14607454" FT /id="VAR_067588" FT VARIANT 294 FT /note="N -> H (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038248" FT VARIANT 299 FT /note="D -> G (in ASD7; somatic mutation; FT dbSNP:rs137852683)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038249" FT VARIANT 305 FT /note="S -> G (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038250" FT VARIANT 320 FT /note="G -> S (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038251" FT VARIANT 322 FT /note="R -> Q (in ASD7; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15342699" FT /id="VAR_038252" FT VARIANT 323 FT /note="A -> T (in ASD7 and TOF)" FT /evidence="ECO:0000269|PubMed:14607454, FT ECO:0000269|PubMed:15810002" FT /id="VAR_038253" FT HELIX 147..157 FT /evidence="ECO:0007829|PDB:3RKQ" FT HELIX 165..175 FT /evidence="ECO:0007829|PDB:3RKQ" FT HELIX 179..193 FT /evidence="ECO:0007829|PDB:3RKQ" SQ SEQUENCE 324 AA; 34918 MW; ACCC9C2F9C292586 CRC64; MFPSPALTPT PFSVKDILNL EQQQRSLAAA GELSARLEAT LAPSSCMLAA FKPEAYAGPE AAAPGLPELR AELGRAPSPA KCASAFPAAP AFYPRAYSDP DPAKDPRAEK KELCALQKAV ELEKTEADNA ERPRARRRRK PRVLFSQAQV YELERRFKQQ RYLSAPERDQ LASVLKLTST QVKIWFQNRR YKCKRQRQDQ TLELVGLPPP PPPPARRIAV PVLVRDGKPC LGDSAPYAPA YGVGLNPYGY NAYPAYPGYG GAACSPGYSC TAAYPAGPSP AQPATAAANN NFVNFGVGDL NAVQSPGIPQ SNSGVSTLHG IRAW //