NKX25_HUMAN
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 03-AUG-2022, entry version 219.
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 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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 {ECO:0000250|UniProtKB:P42582, ECO:0000269|PubMed:22560297,
CC ECO:0000269|PubMed:22849347, ECO:0000269|PubMed:26926761}.
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).
CC {ECO:0000250|UniProtKB:P42582, ECO:0000269|PubMed:22849347,
CC ECO:0000269|PubMed:26926761}.
CC -!- INTERACTION:
CC P52952; P43694: GATA4; NbExp=2; IntAct=EBI-936601, EBI-7049352;
CC P52952; O00629: KPNA4; NbExp=2; IntAct=EBI-936601, EBI-396343;
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:0000305}.
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}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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="http://atlasgeneticsoncology.org/Genes/NKX25ID42958ch5q35.html";
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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; 68.
DR ComplexPortal; CPX-61; NKX2-5 homodimer 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; P52952; -.
DR PeptideAtlas; P52952; -.
DR PRIDE; P52952; -.
DR ProteomicsDB; 19299; -.
DR ProteomicsDB; 56562; -. [P52952-1]
DR ProteomicsDB; 56563; -. [P52952-2]
DR Antibodypedia; 28950; 520 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 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; EQHQSGL; -.
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 SignaLink; P52952; -.
DR SIGNOR; P52952; -.
DR BioGRID-ORCS; 1482; 27 hits in 1072 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 81 other tissues.
DR ExpressionAtlas; P52952; baseline and differential.
DR Genevisible; P52952; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
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:BHF-UCL.
DR GO; GO:0055013; P:cardiac muscle cell development; ISS:BHF-UCL.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; 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: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: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: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:0045892; P:negative regulation of transcription, DNA-templated; ISS: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: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 from RNA polymerase II promoter; ISS:BHF-UCL.
DR GO; GO:0010735; P:positive regulation of transcription via serum response element binding; ISS:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
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: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 InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR InterPro; IPR033629; NKX-2.5.
DR PANTHER; PTHR24340:SF28; PTHR24340:SF28; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
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; unknown
FT pathological 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 /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; unknown pathological significance; does not
FT affect DNA 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
