LOCUS       NM_001166176            1924 bp    mRNA    linear   PRI 01-JUL-2013
DEFINITION  Homo sapiens NK2 homeobox 5 (NKX2-5), transcript variant 3, mRNA.
ACCESSION   NM_001166176
VERSION     NM_001166176.1  GI:260898751
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1924)
  AUTHORS   Guntheroth,W., Chun,L., Patton,K.K., Matsushita,M.M., Page,R.L. and
            Raskind,W.H.
  TITLE     Wenckebach periodicity at rest that normalizes with tachycardia in
            a family with a NKX2.5 mutation
  JOURNAL   Am. J. Cardiol. 110 (11), 1646-1650 (2012)
   PUBMED   22920929
  REMARK    GeneRIF: The responsiveness of WP to exercise, the long-term
            stability of the WP rhythm, and the mild asymptomatic structural
            features expand the phenotypic presentation of diseases related to
            mutations in NKX2.5.
REFERENCE   2  (bases 1 to 1924)
  AUTHORS   Qin,X., Xing,Q., Ma,L., Meng,H., Liu,Y., Pang,S. and Yan,B.
  TITLE     Genetic analysis of an enhancer of the NKX2-5 gene in ventricular
            septal defects
  JOURNAL   Gene 508 (1), 106-109 (2012)
   PUBMED   22824467
  REMARK    GeneRIF: Variants within the cardiac enhancer in the NKX2-5 gene is
            not associated with ventricular septal defects.
REFERENCE   3  (bases 1 to 1924)
  AUTHORS   Pradhan,L., Genis,C., Scone,P., Weinberg,E.O., Kasahara,H. and
            Nam,H.J.
  TITLE     Crystal structure of the human NKX2.5 homeodomain in complex with
            DNA target
  JOURNAL   Biochemistry 51 (32), 6312-6319 (2012)
   PUBMED   22849347
  REMARK    GeneRIF: The high resolution crystal structure of NKX2.5 protein
            provides a detailed picture of protein and DNA interactions, which
            allows to predict DNA binding of mutants identified in human
            patients.
REFERENCE   4  (bases 1 to 1924)
  AUTHORS   Brust,E.S., Beltrao,C.B., Chammas,M.C., Watanabe,T., Sapienza,M.T.
            and Marui,S.
  TITLE     Absence of mutations in PAX8, NKX2.5, and TSH receptor genes in
            patients with thyroid dysgenesis
  JOURNAL   Arq Bras Endocrinol Metabol 56 (3), 173-177 (2012)
   PUBMED   22666732
  REMARK    GeneRIF: Absence of mutations in PAX8, NKX2.5, and TSH receptor
            genes demonstrate the rare genetic etiology in sporadic cases of
            thyroid dysgenesis.
REFERENCE   5  (bases 1 to 1924)
  AUTHORS   van Engelen,K., Mommersteeg,M.T., Baars,M.J., Lam,J., Ilgun,A., van
            Trotsenburg,A.S., Smets,A.M., Christoffels,V.M., Mulder,B.J. and
            Postma,A.V.
  TITLE     The ambiguous role of NKX2-5 mutations in thyroid dysgenesis
  JOURNAL   PLoS ONE 7 (12), E52685 (2012)
   PUBMED   23285148
  REMARK    GeneRIF: NKX2-5 mutations do not play a major pathogenic role in
            thyroid dysgenesis, and that genetic testing of NKX2-5 in TD is not
            warranted.
REFERENCE   6  (bases 1 to 1924)
  AUTHORS   Schott,J.J., Benson,D.W., Basson,C.T., Pease,W., Silberbach,G.M.,
            Moak,J.P., Maron,B.J., Seidman,C.E. and Seidman,J.G.
  TITLE     Congenital heart disease caused by mutations in the transcription
            factor NKX2-5
  JOURNAL   Science 281 (5373), 108-111 (1998)
   PUBMED   9651244
REFERENCE   7  (bases 1 to 1924)
  AUTHORS   Durocher,D., Charron,F., Warren,R., Schwartz,R.J. and Nemer,M.
  TITLE     The cardiac transcription factors Nkx2-5 and GATA-4 are mutual
            cofactors
  JOURNAL   EMBO J. 16 (18), 5687-5696 (1997)
   PUBMED   9312027
REFERENCE   8  (bases 1 to 1924)
  AUTHORS   Chen,C.Y. and Schwartz,R.J.
  TITLE     Recruitment of the tinman homolog Nkx-2.5 by serum response factor
            activates cardiac alpha-actin gene transcription
  JOURNAL   Mol. Cell. Biol. 16 (11), 6372-6384 (1996)
   PUBMED   8887666
REFERENCE   9  (bases 1 to 1924)
  AUTHORS   Turbay,D., Wechsler,S.B., Blanchard,K.M. and Izumo,S.
  TITLE     Molecular cloning, chromosomal mapping, and characterization of the
            human cardiac-specific homeobox gene hCsx
  JOURNAL   Mol. Med. 2 (1), 86-96 (1996)
   PUBMED   8900537
REFERENCE   10 (bases 1 to 1924)
  AUTHORS   Shiojima,I., Komuro,I., Inazawa,J., Nakahori,Y., Matsushita,I.,
            Abe,T., Nagai,R. and Yazaki,Y.
  TITLE     Assignment of cardiac homeobox gene CSX to human chromosome 5q34
  JOURNAL   Genomics 27 (1), 204-206 (1995)
   PUBMED   7665173
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA559427.1, AK297844.1,
            AK290615.1 and AI609745.1.
            
            Summary: This gene encodes a homeobox-containing transcription
            factor. This transcription factor functions in heart formation and
            development. Mutations in this gene cause atrial septal defect with
            atrioventricular conduction defect, and also tetralogy of Fallot,
            which are both heart malformation diseases. Mutations in this gene
            can also cause congenital hypothyroidism non-goitrous type 5, a
            non-autoimmune condition. Alternative splicing results in multiple
            transcript variants. [provided by RefSeq, Oct 2009].
            
            Transcript Variant: This variant (3) differs in the 3' coding
            region and 3' UTR, compared to variant 1. The encoded isoform (3)
            has a distinct C-terminus and is shorter than isoform 1.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK297844.1, DC356690.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           ERS025083 [ECO:0000348]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-106               DA559427.1         1-106
            107-1133            AK297844.1         1-1027
            1134-1742           AK290615.1         771-1379
            1743-1924           AI609745.1         1-182               c
FEATURES             Location/Qualifiers
     source          1..1924
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5q34"
     gene            1..1924
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /note="NK2 homeobox 5"
                     /db_xref="GeneID:1482"
                     /db_xref="HGNC:2488"
                     /db_xref="MIM:600584"
     exon            1..563
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /inference="alignment:Splign:1.39.8"
     variation       187
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /replace="c"
                     /replace="t"
                     /db_xref="dbSNP:3729937"
     CDS             230..685
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /note="isoform 3 is encoded by transcript variant 3;
                     tinman paralog; homeobox protein Nkx-2.5; cardiac-specific
                     homeobox 1; homeobox protein NK-2 homolog E; homeobox
                     protein CSX; NK2 transcription factor related, locus 5"
                     /codon_start=1
                     /product="homeobox protein Nkx-2.5 isoform 3"
                     /protein_id="NP_001159648.1"
                     /db_xref="GI:260898752"
                     /db_xref="CCDS:CCDS54949.1"
                     /db_xref="GeneID:1482"
                     /db_xref="HGNC:2488"
                     /db_xref="MIM:600584"
                     /translation="

MFPSPALTPTPFSVKDILNLEQQQRSLAAAGELSARLEATLAPSSCMLAAFKPEAYAGPEAAAPGLPELRAELGRAPSPAKCASAFPAAPAFYPRAYSDPDPAKDPRAEKKGCELPRGQRPPVLFSSALSQPDFLQMLSETCRWLPVHLAE

"
     variation       250
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /replace="a"
                     /replace="c"
                     /db_xref="dbSNP:3729934"
     variation       292
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /replace="a"
                     /replace="g"
                     /db_xref="dbSNP:2277923"
     variation       502
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /replace="c"
                     /replace="t"
                     /db_xref="dbSNP:72554030"
     exon            564..1924
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /inference="alignment:Splign:1.39.8"
     variation       918
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /replace="c"
                     /replace="t"
                     /db_xref="dbSNP:72554027"
     variation       1020
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /replace="c"
                     /replace="g"
                     /db_xref="dbSNP:3729938"
     variation       1090
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /replace="c"
                     /replace="g"
                     /db_xref="dbSNP:3729753"
     variation       1116
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /replace="c"
                     /replace="t"
                     /db_xref="dbSNP:3729754"
     STS             1491..1692
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /standard_name="RH80828"
                     /db_xref="UniSTS:85708"
     variation       1794
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
                     /replace="g"
                     /replace="t"
                     /db_xref="dbSNP:11552707"
     polyA_signal    1901..1906
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
     polyA_site      1919
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
     polyA_site      1924
                     /gene="NKX2-5"
                     /gene_synonym="CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E;
                     NKX4-1; VSD3"
ORIGIN      

gctcctgtcatcgaggcccctggcccaatggcaggctgagtccccctcctctggcctggtcccgcctctcctgccccttgtgctcagcgctacctgctgcccggacacatccagagctggccgacgggtgcgcgggcgggcggcggcaccatgcagggaagctgccaggggccgtgggcagcgccgctttctgccgcccacctggcgctgtgagactggcgctgccaccatgttccccagccctgctctcacgcccacgcccttctcagtcaaagacatcctaaacctggaacagcagcagcgcagcctggctgccgccggagagctctctgcccgcctggaggcgaccctggcgccctcctcctgcatgctggccgccttcaagccagaggcctacgctgggcccgaggcggctgcgccgggcctcccagagctgcgcgcagagctgggccgcgcgccttcaccggccaagtgtgcgtctgcctttcccgccgcccccgccttctatccacgtgcctacagcgaccccgacccagccaaggaccctagagccgaaaagaaagggtgtgaactgccccgagggcagagacctcccgttttgttctccagcgccttgagccagcctgactttctacaaatgctgagtgagacgtgtcggtggctcccagtgcacttggcagagtgagccgcagccagctgggcgctccaggcaggacacagtggcctccacgaggatcccttaccattactgtgcggccgcgctccgtaggtcaagccgctcttaccaagcgtctctctgcctctctgttccccctcagagctgtgcgcgctgcagaaggcggtggagctggagaagacagaggcggacaacgcggagcggccccgggcgcgacggcggaggaagccgcgcgtgctcttctcgcaggcgcaggtctatgagctggagcggcgcttcaagcagcagcggtacctgtcggcccccgaacgcgaccagctggccagcgtgctgaaactcacgtccacgcaggtcaagatctggttccagaaccggcgctacaagtgcaagcggcagcggcaggaccagactctggagctggtggggctgcccccgccgccgccgccgcctgcccgcaggatcgcggtgccagtgctggtgcgcgatggcaagccatgcctaggggactcggcgccctacgcgcctgcctacggcgtgggcctcaatccctacggttataacgcctaccccgcctatccgggttacggcggcgcggcctgcagccctggctacagctgcactgccgcttaccccgccgggccttccccagcgcagccggccactgccgccgccaacaacaacttcgtgaacttcggcgtcggggacttgaatgcggttcagagccccgggattccgcagagcaactcgggagtgtccacgctgcatggtatccgagcctggtagggaagggacccgcgtggcgcgaccctgaccgatcccacctcaacagctccctgactctcggggggagaaggggctcccaacatgaccctgagtcccctggattttgcattcactcctgcggagacctaggaactttttctgtcccacgcgcgtttgttcttgcgcacgggagagtttgtggcggcgattatgcagcgtgcaatgagtgatcctgcagcctggtgtcttagctgtccccccaggagtgccctccgagagtccatgggcacccccggttggaactgggactgagctcgggcacgcagggcctgagatctggccgcccattccgcgagccagggccgggcgcccgggcctttgctatctcgccgtcgcccgcccacgcacccacccgtatttatgtttttacctattgctgtaagaaatgacgatccccttcccattaaagagagtgcgttgaccccg

//

ANNOTATIONS from NCBI Entrez Gene (20130726):
            GeneID:1482 -> Molecular function: GO:0001104 [RNA polymerase II transcription cofactor activity] evidence: IEA
            GeneID:1482 -> Molecular function: GO:0001190 [RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription] evidence: IEA
            GeneID:1482 -> Molecular function: GO:0003677 [DNA binding] evidence: IDA
            GeneID:1482 -> Molecular function: GO:0003682 [chromatin binding] evidence: IDA
            GeneID:1482 -> Molecular function: GO:0003700 [sequence-specific DNA binding transcription factor activity] evidence: IDA
            GeneID:1482 -> Molecular function: GO:0003700 [sequence-specific DNA binding transcription factor activity] evidence: IMP
            GeneID:1482 -> Molecular function: GO:0003705 [RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity] evidence: IEA
            GeneID:1482 -> Molecular function: GO:0005515 [protein binding] evidence: IPI
            GeneID:1482 -> Molecular function: GO:0008134 [transcription factor binding] evidence: IPI
            GeneID:1482 -> Molecular function: GO:0010736 [serum response element binding] evidence: ISS
            GeneID:1482 -> Molecular function: GO:0042803 [protein homodimerization activity] evidence: IEA
            GeneID:1482 -> Molecular function: GO:0043565 [sequence-specific DNA binding] evidence: IDA
            GeneID:1482 -> Molecular function: GO:0044212 [transcription regulatory region DNA binding] evidence: IDA
            GeneID:1482 -> Molecular function: GO:0046982 [protein heterodimerization activity] evidence: ISS
            GeneID:1482 -> Biological process: GO:0000122 [negative regulation of transcription from RNA polymerase II promoter] evidence: IMP
            GeneID:1482 -> Biological process: GO:0000122 [negative regulation of transcription from RNA polymerase II promoter] evidence: ISS
            GeneID:1482 -> Biological process: GO:0001570 [vasculogenesis] evidence: ISS
            GeneID:1482 -> Biological process: GO:0001947 [heart looping] evidence: ISS
            GeneID:1482 -> Biological process: GO:0003007 [heart morphogenesis] evidence: ISS
            GeneID:1482 -> Biological process: GO:0003148 [outflow tract septum morphogenesis] evidence: IMP
            GeneID:1482 -> Biological process: GO:0003161 [cardiac conduction system development] evidence: IMP
            GeneID:1482 -> Biological process: GO:0003166 [bundle of His development] evidence: IEA
            GeneID:1482 -> Biological process: GO:0003168 [Purkinje myocyte differentiation] evidence: IEA
            GeneID:1482 -> Biological process: GO:0003211 [cardiac ventricle formation] evidence: IEA
            GeneID:1482 -> Biological process: GO:0003221 [right ventricular cardiac muscle tissue morphogenesis] evidence: IMP
            GeneID:1482 -> Biological process: GO:0003222 [ventricular trabecula myocardium morphogenesis] evidence: IEA
            GeneID:1482 -> Biological process: GO:0003278 [apoptotic process involved in heart morphogenesis] evidence: IEA
            GeneID:1482 -> Biological process: GO:0003285 [septum secundum development] evidence: IMP
            GeneID:1482 -> Biological process: GO:0003342 [proepicardium development] evidence: IEA
            GeneID:1482 -> Biological process: GO:0003350 [pulmonary myocardium development] evidence: IEA
            GeneID:1482 -> Biological process: GO:0007512 [adult heart development] evidence: IMP
            GeneID:1482 -> Biological process: GO:0008284 [positive regulation of cell proliferation] evidence: ISS
            GeneID:1482 -> Biological process: GO:0010667 [negative regulation of cardiac muscle cell apoptotic process] evidence: IMP
            GeneID:1482 -> Biological process: GO:0010735 [positive regulation of transcription via serum response element binding] evidence: ISS
            GeneID:1482 -> Biological process: GO:0010765 [positive regulation of sodium ion transport] evidence: ISS
            GeneID:1482 -> Biological process: GO:0010832 [negative regulation of myotube differentiation] evidence: IMP
            GeneID:1482 -> Biological process: GO:0030097 [hemopoiesis] evidence: ISS
            GeneID:1482 -> Biological process: GO:0030154 [cell differentiation] evidence: ISS
            GeneID:1482 -> Biological process: GO:0030509 [BMP signaling pathway] evidence: IEA
            GeneID:1482 -> Biological process: GO:0030878 [thyroid gland development] evidence: IMP
            GeneID:1482 -> Biological process: GO:0035050 [embryonic heart tube development] evidence: ISS
            GeneID:1482 -> Biological process: GO:0043066 [negative regulation of apoptotic process] evidence: ISS
            GeneID:1482 -> Biological process: GO:0045214 [sarcomere organization] evidence: IEA
            GeneID:1482 -> Biological process: GO:0045666 [positive regulation of neuron differentiation] evidence: IMP
            GeneID:1482 -> Biological process: GO:0045823 [positive regulation of heart contraction] evidence: ISS
            GeneID:1482 -> Biological process: GO:0045892 [negative regulation of transcription, DNA-dependent] evidence: ISS
            GeneID:1482 -> Biological process: GO:0045893 [positive regulation of transcription, DNA-dependent] evidence: IDA
            GeneID:1482 -> Biological process: GO:0045893 [positive regulation of transcription, DNA-dependent] evidence: ISS
            GeneID:1482 -> Biological process: GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] evidence: IDA
            GeneID:1482 -> Biological process: GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] evidence: IGI
            GeneID:1482 -> Biological process: GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] evidence: IMP
            GeneID:1482 -> Biological process: GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] evidence: ISS
            GeneID:1482 -> Biological process: GO:0048536 [spleen development] evidence: IMP
            GeneID:1482 -> Biological process: GO:0048536 [spleen development] evidence: ISS
            GeneID:1482 -> Biological process: GO:0051891 [positive regulation of cardioblast differentiation] evidence: ISS
            GeneID:1482 -> Biological process: GO:0055005 [ventricular cardiac myofibril assembly] evidence: IEA
            GeneID:1482 -> Biological process: GO:0055007 [cardiac muscle cell differentiation] evidence: ISS
            GeneID:1482 -> Biological process: GO:0055008 [cardiac muscle tissue morphogenesis] evidence: IMP
            GeneID:1482 -> Biological process: GO:0055014 [atrial cardiac muscle cell development] evidence: ISS
            GeneID:1482 -> Biological process: GO:0055015 [ventricular cardiac muscle cell development] evidence: ISS
            GeneID:1482 -> Biological process: GO:0055117 [regulation of cardiac muscle contraction] evidence: ISS
            GeneID:1482 -> Biological process: GO:0060037 [pharyngeal system development] evidence: ISS
            GeneID:1482 -> Biological process: GO:0060038 [cardiac muscle cell proliferation] evidence: IEA
            GeneID:1482 -> Biological process: GO:0060043 [regulation of cardiac muscle cell proliferation] evidence: IEA
            GeneID:1482 -> Biological process: GO:0060048 [cardiac muscle contraction] evidence: IEA
            GeneID:1482 -> Biological process: GO:0060070 [canonical Wnt receptor signaling pathway] evidence: IEA
            GeneID:1482 -> Biological process: GO:0060261 [positive regulation of transcription initiation from RNA polymerase II promoter] evidence: ISS
            GeneID:1482 -> Biological process: GO:0060347 [heart trabecula formation] evidence: IEA
            GeneID:1482 -> Biological process: GO:0060412 [ventricular septum morphogenesis] evidence: IMP
            GeneID:1482 -> Biological process: GO:0060413 [atrial septum morphogenesis] evidence: IMP
            GeneID:1482 -> Biological process: GO:0060928 [atrioventricular node cell development] evidence: IEA
            GeneID:1482 -> Biological process: GO:0060929 [atrioventricular node cell fate commitment] evidence: IEA
            GeneID:1482 -> Biological process: GO:0060971 [embryonic heart tube left/right pattern formation] evidence: IEA
            GeneID:1482 -> Biological process: GO:0090090 [negative regulation of canonical Wnt receptor signaling pathway] evidence: ISS
            GeneID:1482 -> Biological process: GO:1901387 [positive regulation of voltage-gated calcium channel activity] evidence: ISS
            GeneID:1482 -> Cellular component: GO:0005634 [nucleus] evidence: IDA
            GeneID:1482 -> Cellular component: GO:0005667 [transcription factor complex] evidence: IC
            GeneID:1482 -> Cellular component: GO:0005737 [cytoplasm] evidence: IEA