NKX2-5 (NK2 homeobox 5)

Gene

• Entrez ID: 1482
• Gene name: NK2 homeobox 5
• Gene symbol: NKX2-5
• Synonyms (NCBI Gene): CHNG5, CSX, CSX1, HLHS2, NKX2.5, NKX2E, NKX4-1, VSD3
• Chromosome: 5
• Chromosome location: 5q35.1
• 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,

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28936670	G>A	Pathogenic, benign, conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs72554028	C>G,T	Benign-likely-benign, likely-benign, pathogenic, benign	Coding sequence variant, synonymous variant, genic downstream transcript variant, missense variant, 3 prime UTR variant
rs77612903	G>A,C,T	Benign, conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, coding sequence variant, synonymous variant, 3 prime UTR variant
rs104893900	G>A	Pathogenic	Missense variant, coding sequence variant, downstream transcript variant, genic downstream transcript variant, 3 prime UTR variant
rs104893901	G>A	Pathogenic	Stop gained, coding sequence variant, downstream transcript variant, genic downstream transcript variant, 3 prime UTR variant
rs104893902	G>A	Pathogenic, uncertain-significance	3 prime UTR variant, coding sequence variant, missense variant, genic downstream transcript variant
rs104893903	G>A	Pathogenic	3 prime UTR variant, coding sequence variant, stop gained, genic downstream transcript variant
rs104893904	C>G	Benign, likely-benign, uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs104893905	G>A	Pathogenic	3 prime UTR variant, coding sequence variant, missense variant, genic downstream transcript variant
rs104893906	G>A	Pathogenic	3 prime UTR variant, coding sequence variant, missense variant, genic downstream transcript variant
rs104893907	A>C,T	Pathogenic	3 prime UTR variant, coding sequence variant, stop gained, genic downstream transcript variant
rs137852683	T>C	Pathogenic	Missense variant, coding sequence variant, 3 prime UTR variant, genic downstream transcript variant
rs137852684	C>A,T	Benign, pathogenic, benign-likely-benign, likely-benign	Missense variant, downstream transcript variant, 3 prime UTR variant, coding sequence variant, genic downstream transcript variant
rs137852685	C>G	Pathogenic	Missense variant, downstream transcript variant, 3 prime UTR variant, coding sequence variant, genic downstream transcript variant
rs137852686	T>C	Pathogenic	Missense variant, coding sequence variant, 3 prime UTR variant, genic downstream transcript variant
rs151314714	C>T	Conflicting-interpretations-of-pathogenicity, benign, likely-benign	Coding sequence variant, synonymous variant
rs201249977	C>A,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	3 prime UTR variant, missense variant, coding sequence variant, genic downstream transcript variant
rs201442000	T>C,G	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs375086983	G>A,T	Pathogenic, uncertain-significance	Genic downstream transcript variant, 3 prime UTR variant, coding sequence variant, missense variant
rs387906773	T>A	Pathogenic	Coding sequence variant, missense variant
rs387906774	G>C,T	Pathogenic	Missense variant, 3 prime UTR variant, genic downstream transcript variant, downstream transcript variant, coding sequence variant
rs387906775	G>C	Pathogenic	Coding sequence variant, missense variant
rs387906776	G>A,C,T	Pathogenic, uncertain-significance	Genic downstream transcript variant, 3 prime UTR variant, coding sequence variant, missense variant
rs397516908	CCG>AT	Likely-pathogenic	3 prime UTR variant, frameshift variant, genic downstream transcript variant, downstream transcript variant, coding sequence variant
rs587782928	T>C	Pathogenic	Missense variant, genic downstream transcript variant, 3 prime UTR variant, coding sequence variant, downstream transcript variant
rs587782929	C>-	Pathogenic	Coding sequence variant, frameshift variant, 3 prime UTR variant, genic downstream transcript variant
rs587782930	ACGCCGTA>-	Pathogenic	Coding sequence variant, frameshift variant, 3 prime UTR variant, genic downstream transcript variant
rs587784066	TG>-	Pathogenic	Genic downstream transcript variant, 3 prime UTR variant, frameshift variant, coding sequence variant, downstream transcript variant
rs587784067	G>-	Pathogenic, uncertain-significance	Coding sequence variant, frameshift variant, 3 prime UTR variant, genic downstream transcript variant
rs606231358	CCAGCTC>-	Pathogenic	Coding sequence variant, frameshift variant
rs606231359	CG>-	Pathogenic	Coding sequence variant, frameshift variant
rs606231360	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs756974215	TTG>-	Pathogenic, uncertain-significance	Genic downstream transcript variant, 3 prime UTR variant, coding sequence variant, inframe deletion
rs773922431	G>A,C,T	Likely-pathogenic	Stop gained, missense variant, genic downstream transcript variant, coding sequence variant, 3 prime UTR variant
rs786205824	C>G,T	Uncertain-significance, pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant, 3 prime UTR variant
rs786205826	->G	Pathogenic	Coding sequence variant, genic downstream transcript variant, frameshift variant, 3 prime UTR variant
rs797044675	->GG	Pathogenic	Coding sequence variant, genic downstream transcript variant, frameshift variant, 3 prime UTR variant
rs797045790	CTG>AACGGTAC	Pathogenic	Genic downstream transcript variant, downstream transcript variant, coding sequence variant, frameshift variant, 3 prime UTR variant
rs797045791	A>C	Pathogenic	Genic downstream transcript variant, missense variant, downstream transcript variant, coding sequence variant, 3 prime UTR variant
rs797045792	C>A	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant, 3 prime UTR variant
rs864321645	C>A	Pathogenic	Genic downstream transcript variant, splice acceptor variant, 3 prime UTR variant, downstream transcript variant
rs864321648	C>T	Pathogenic	Genic downstream transcript variant, missense variant, downstream transcript variant, coding sequence variant, 3 prime UTR variant
rs864321649	G>A,T	Pathogenic	Genic downstream transcript variant, missense variant, downstream transcript variant, coding sequence variant, 3 prime UTR variant
rs864321650	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs876657934	G>C	Likely-pathogenic	Genic downstream transcript variant, intron variant, 3 prime UTR variant, downstream transcript variant
rs876661380	C>A	Uncertain-significance, pathogenic	Splice donor variant
rs876661381	G>-	Pathogenic	Genic downstream transcript variant, downstream transcript variant, coding sequence variant, frameshift variant, 3 prime UTR variant
rs879253754	T>-	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, frameshift variant, 3 prime UTR variant
rs1057520670	G>C	Pathogenic	Genic downstream transcript variant, stop gained, 3 prime UTR variant, coding sequence variant
rs1554093433	G>T	Pathogenic	Coding sequence variant, 3 prime UTR variant, stop gained, genic downstream transcript variant
rs1554093461	CA>-	Likely-pathogenic	Coding sequence variant, 3 prime UTR variant, frameshift variant, genic downstream transcript variant
rs1554093487	G>T	Pathogenic	Downstream transcript variant, stop gained, coding sequence variant, genic downstream transcript variant, 3 prime UTR variant
rs1561619801	->T	Pathogenic	Downstream transcript variant, coding sequence variant, genic downstream transcript variant, frameshift variant, 3 prime UTR variant
rs1561621507	CCTCTGGCTTGAAGGCG>AGGAGGC	Pathogenic	Coding sequence variant, frameshift variant
rs1581108237	A>-	Likely-pathogenic	Frameshift variant, coding sequence variant, genic downstream transcript variant, 3 prime UTR variant
rs1581108437	TGGAA>-	Likely-pathogenic	Frameshift variant, coding sequence variant, genic downstream transcript variant, 3 prime UTR variant
rs1581111034	CTTTCTTTTCGGCTCTAGGGTCCTTGGCTGGGTCGGGGTCGCTGTAGGCACGTGGATAGAAGGCGGGGGCGGCGGGAAAGGCAGACGCACACTTGGCCGGTGAAGGCGCGCGGCCCAGCTCTGCGCGCAGCTCTGGGAGGCCCGGCGCAGCCGCCTCGGGCCCAGCGTAGGCCTCTGGCTTGAAGGCGGCCAGCATGCAGGAGGAGGGCGCCAGGGTCGCCTCCAGGCGGGCAGAGAGCTCTCCGGCGGCAGCCA	Pathogenic	Initiator codon variant, genic upstream transcript variant, upstream transcript variant, 5 prime UTR variant, splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030022	hsa-miR-26b-5p	Microarray	19088304
MIRT050106	hsa-miR-26a-5p	CLASH	23622248
MIRT043120	hsa-miR-324-5p	CLASH	23622248
MIRT039794	hsa-miR-615-3p	CLASH	23622248
MIRT495609	hsa-miR-4747-3p	PAR-CLIP	22291592
MIRT495608	hsa-miR-4493	PAR-CLIP	22291592
MIRT495607	hsa-miR-6820-5p	PAR-CLIP	22291592
MIRT495606	hsa-miR-1538	PAR-CLIP	22291592
MIRT495605	hsa-miR-4745-3p	PAR-CLIP	22291592
MIRT495604	hsa-miR-1908-5p	PAR-CLIP	22291592
MIRT495603	hsa-miR-663a	PAR-CLIP	22291592
MIRT495602	hsa-miR-6787-5p	PAR-CLIP	22291592
MIRT495601	hsa-miR-4747-5p	PAR-CLIP	22291592
MIRT495600	hsa-miR-5196-5p	PAR-CLIP	22291592
MIRT495599	hsa-miR-6881-5p	PAR-CLIP	22291592
MIRT495598	hsa-miR-555	PAR-CLIP	22291592
MIRT495597	hsa-miR-6126	PAR-CLIP	22291592
MIRT495610	hsa-miR-3622b-5p	PAR-CLIP	22291592
MIRT495609	hsa-miR-4747-3p	PAR-CLIP	22291592
MIRT495608	hsa-miR-4493	PAR-CLIP	22291592
MIRT495607	hsa-miR-6820-5p	PAR-CLIP	22291592
MIRT495606	hsa-miR-1538	PAR-CLIP	22291592
MIRT495605	hsa-miR-4745-3p	PAR-CLIP	22291592
MIRT495604	hsa-miR-1908-5p	PAR-CLIP	22291592
MIRT495603	hsa-miR-663a	PAR-CLIP	22291592
MIRT495602	hsa-miR-6787-5p	PAR-CLIP	22291592
MIRT495601	hsa-miR-4747-5p	PAR-CLIP	22291592
MIRT495600	hsa-miR-5196-5p	PAR-CLIP	22291592
MIRT495599	hsa-miR-6881-5p	PAR-CLIP	22291592
MIRT495598	hsa-miR-555	PAR-CLIP	22291592
MIRT495597	hsa-miR-6126	PAR-CLIP	22291592
MIRT495609	hsa-miR-4747-3p	PAR-CLIP	22291592
MIRT495608	hsa-miR-4493	PAR-CLIP	22291592
MIRT495607	hsa-miR-6820-5p	PAR-CLIP	22291592
MIRT495606	hsa-miR-1538	PAR-CLIP	22291592
MIRT495605	hsa-miR-4745-3p	PAR-CLIP	22291592
MIRT495604	hsa-miR-1908-5p	PAR-CLIP	22291592
MIRT495603	hsa-miR-663a	PAR-CLIP	22291592
MIRT495602	hsa-miR-6787-5p	PAR-CLIP	22291592
MIRT495601	hsa-miR-4747-5p	PAR-CLIP	22291592
MIRT495600	hsa-miR-5196-5p	PAR-CLIP	22291592
MIRT495599	hsa-miR-6881-5p	PAR-CLIP	22291592
MIRT495598	hsa-miR-555	PAR-CLIP	22291592
MIRT495597	hsa-miR-6126	PAR-CLIP	22291592
MIRT495610	hsa-miR-3622b-5p	PAR-CLIP	22291592
MIRT495609	hsa-miR-4747-3p	PAR-CLIP	22291592
MIRT495608	hsa-miR-4493	PAR-CLIP	22291592
MIRT495607	hsa-miR-6820-5p	PAR-CLIP	22291592
MIRT495606	hsa-miR-1538	PAR-CLIP	22291592
MIRT495605	hsa-miR-4745-3p	PAR-CLIP	22291592
MIRT495604	hsa-miR-1908-5p	PAR-CLIP	22291592
MIRT495603	hsa-miR-663a	PAR-CLIP	22291592
MIRT495602	hsa-miR-6787-5p	PAR-CLIP	22291592
MIRT495601	hsa-miR-4747-5p	PAR-CLIP	22291592
MIRT495600	hsa-miR-5196-5p	PAR-CLIP	22291592
MIRT495599	hsa-miR-6881-5p	PAR-CLIP	22291592
MIRT495598	hsa-miR-555	PAR-CLIP	22291592
MIRT495597	hsa-miR-6126	PAR-CLIP	22291592
MIRT1186554	hsa-miR-1257	CLIP-seq
MIRT1186555	hsa-miR-4433	CLIP-seq
MIRT1186556	hsa-miR-4722-5p	CLIP-seq
MIRT2054064	hsa-miR-1225-3p	CLIP-seq
MIRT2054065	hsa-miR-3127-3p	CLIP-seq
MIRT2054066	hsa-miR-3689a-3p	CLIP-seq
MIRT2054067	hsa-miR-3689c	CLIP-seq
MIRT2054068	hsa-miR-4300	CLIP-seq
MIRT2054069	hsa-miR-4425	CLIP-seq
MIRT2054070	hsa-miR-4713-5p	CLIP-seq
MIRT2054071	hsa-miR-4740-3p	CLIP-seq
MIRT2054072	hsa-miR-920	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IMP	19479054
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	ISS	8900537
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription cis-regulatory region binding	IDA	19479054, 29899023
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	22849347, 26926761
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IMP	15649947
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS	8900537
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001216	Function	DNA-binding transcription activator activity	IDA	29325903
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	19578358
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	15649947
GO:0001570	Process	Vasculogenesis	IEA
GO:0001570	Process	Vasculogenesis	ISS	8900537
GO:0001947	Process	Heart looping	IEA
GO:0001947	Process	Heart looping	ISS	8900537
GO:0003007	Process	Heart morphogenesis	IEA
GO:0003007	Process	Heart morphogenesis	ISS	8900537
GO:0003148	Process	Outflow tract septum morphogenesis	IMP	20807224
GO:0003151	Process	Outflow tract morphogenesis	IEA
GO:0003161	Process	Cardiac conduction system development	IEA
GO:0003161	Process	Cardiac conduction system development	IMP	15109497
GO:0003161	Process	Cardiac conduction system development	IMP	27207958
GO:0003162	Process	Atrioventricular node development	IEA
GO:0003162	Process	Atrioventricular node development	ISS
GO:0003166	Process	Bundle of His development	IEA
GO:0003166	Process	Bundle of His development	ISS
GO:0003168	Process	Purkinje myocyte differentiation	IEA
GO:0003180	Process	Aortic valve morphogenesis	TAS	29325903
GO:0003208	Process	Cardiac ventricle morphogenesis	IEA
GO:0003211	Process	Cardiac ventricle formation	IEA
GO:0003221	Process	Right ventricular cardiac muscle tissue morphogenesis	IMP	20807224
GO:0003222	Process	Ventricular trabecula myocardium morphogenesis	IEA
GO:0003228	Process	Atrial cardiac muscle tissue development	IEA
GO:0003228	Process	Atrial cardiac muscle tissue development	ISS
GO:0003278	Process	Apoptotic process involved in heart morphogenesis	IEA
GO:0003285	Process	Septum secundum development	IMP	10587520
GO:0003342	Process	Proepicardium development	IEA
GO:0003350	Process	Pulmonary myocardium development	IEA
GO:0003677	Function	DNA binding	IDA	9858576
GO:0003677	Function	DNA binding	IEA
GO:0003682	Function	Chromatin binding	IDA	16678093
GO:0003682	Function	Chromatin binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IDA	9312027
GO:0003700	Function	DNA-binding transcription factor activity	IDA	9858576, 10948187, 11431700
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IMP	11431700
GO:0005515	Function	Protein binding	IPI	9312027, 10075728, 11431700, 12499378, 14757752, 18579533, 19797053, 26926761, 29899023, 32296183
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	9858576, 10948187, 29899023
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005667	Component	Transcription regulator complex	IC	9312027
GO:0005667	Component	Transcription regulator complex	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA
GO:0006355	Process	Regulation of DNA-templated transcription	IDA	22849347
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IEA
GO:0006366	Process	Transcription by RNA polymerase II	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0007507	Process	Heart development	IEA
GO:0007507	Process	Heart development	ISO
GO:0007512	Process	Adult heart development	IEA
GO:0007512	Process	Adult heart development	IMP	9651244
GO:0008283	Process	Cell population proliferation	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	ISS	8900537
GO:0010628	Process	Positive regulation of gene expression	IEA
GO:0010667	Process	Negative regulation of cardiac muscle cell apoptotic process	IEA
GO:0010667	Process	Negative regulation of cardiac muscle cell apoptotic process	IMP	11889119
GO:0010765	Process	Positive regulation of sodium ion transport	IEA
GO:0010765	Process	Positive regulation of sodium ion transport	ISS	8900537
GO:0010832	Process	Negative regulation of myotube differentiation	IMP	15653675
GO:0030097	Process	Hemopoiesis	IEA
GO:0030097	Process	Hemopoiesis	ISS	8900537
GO:0030154	Process	Cell differentiation	IBA
GO:0030154	Process	Cell differentiation	ISS	8900537
GO:0030855	Process	Epithelial cell differentiation	IEA
GO:0030878	Process	Thyroid gland development	IEA
GO:0030878	Process	Thyroid gland development	IMP	16418214
GO:0032991	Component	Protein-containing complex	IDA	26926761
GO:0032993	Component	Protein-DNA complex	IDA	22849347
GO:0035050	Process	Embryonic heart tube development	IEA
GO:0035050	Process	Embryonic heart tube development	ISS	8900537
GO:0042803	Function	Protein homodimerization activity	IEA
GO:0043066	Process	Negative regulation of apoptotic process	ISS	8900537
GO:0043565	Function	Sequence-specific DNA binding	IDA	10948187
GO:0045666	Process	Positive regulation of neuron differentiation	IMP	15653675
GO:0045823	Process	Positive regulation of heart contraction	IEA
GO:0045823	Process	Positive regulation of heart contraction	ISS
GO:0045892	Process	Negative regulation of DNA-templated transcription	ISS	8900537
GO:0045893	Process	Positive regulation of DNA-templated transcription	IDA	11431700
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	ISS	8900537
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	10948187, 19578358, 29325903
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IGI	16678093
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	11431700, 15649947, 18079734, 19479054, 29899023
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS	8900537
GO:0048536	Process	Spleen development	IEA
GO:0048536	Process	Spleen development	IMP	22560297
GO:0048536	Process	Spleen development	ISS	8900537
GO:0048738	Process	Cardiac muscle tissue development	IEA
GO:0050673	Process	Epithelial cell proliferation	IEA
GO:0050679	Process	Positive regulation of epithelial cell proliferation	IEA
GO:0051891	Process	Positive regulation of cardioblast differentiation	IEA
GO:0051891	Process	Positive regulation of cardioblast differentiation	ISS	8900537
GO:0055005	Process	Ventricular cardiac myofibril assembly	IEA
GO:0055007	Process	Cardiac muscle cell differentiation	IEA
GO:0055008	Process	Cardiac muscle tissue morphogenesis	IEA
GO:0055008	Process	Cardiac muscle tissue morphogenesis	IMP	11889119
GO:0055008	Process	Cardiac muscle tissue morphogenesis	ISS
GO:0055013	Process	Cardiac muscle cell development	IEA
GO:0055013	Process	Cardiac muscle cell development	ISS
GO:0055014	Process	Atrial cardiac muscle cell development	ISS	8900537
GO:0055015	Process	Ventricular cardiac muscle cell development	ISS	8900537
GO:0055117	Process	Regulation of cardiac muscle contraction	IEA
GO:0055117	Process	Regulation of cardiac muscle contraction	ISS	8900537
GO:0060037	Process	Pharyngeal system development	IEA
GO:0060037	Process	Pharyngeal system development	ISS	8900537
GO:0060038	Process	Cardiac muscle cell proliferation	IEA
GO:0060043	Process	Regulation of cardiac muscle cell proliferation	IEA
GO:0060047	Process	Heart contraction	IEA
GO:0060048	Process	Cardiac muscle contraction	IEA
GO:0060261	Process	Positive regulation of transcription initiation by RNA polymerase II	IEA
GO:0060261	Process	Positive regulation of transcription initiation by RNA polymerase II	ISS	8900537
GO:0060347	Process	Heart trabecula formation	IEA
GO:0060411	Process	Cardiac septum morphogenesis	IEA
GO:0060411	Process	Cardiac septum morphogenesis	ISO
GO:0060412	Process	Ventricular septum morphogenesis	IMP	10587520, 20807224
GO:0060413	Process	Atrial septum morphogenesis	IMP	9651244, 10587520
GO:0060928	Process	Atrioventricular node cell development	IEA
GO:0060929	Process	Atrioventricular node cell fate commitment	IEA
GO:0060971	Process	Embryonic heart tube left/right pattern formation	IEA
GO:0061629	Function	RNA polymerase II-specific DNA-binding transcription factor binding	IPI	9858576, 11431700
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IEA
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	ISS
GO:0090575	Component	RNA polymerase II transcription regulator complex	IDA	9312027
GO:1903779	Process	Regulation of cardiac conduction	IEA
GO:1903779	Process	Regulation of cardiac conduction	ISS	8900537
GO:1904019	Process	Epithelial cell apoptotic process	IEA
GO:1904036	Process	Negative regulation of epithelial cell apoptotic process	IEA
GO:1990664	Component	Nkx-2.5 complex	IPI	22849347
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 600584
• HGNC: 2488
• e!Ensembl: ENSG00000183072

Protein

• UniProt ID: P52952
• Protein name: Homeobox protein Nkx-2.5 (Cardiac-specific homeobox) (Homeobox protein CSX) (Homeobox protein NK-2 homolog E)
• Protein function: Transcription factor required for the development of the heart and the spleen (PubMed:22560297). During heart development, acts as a transcriptional activator of NPPA/ANF in cooperation with GATA4 (By similarity). May cooperate with TBX2 to nega
• PDB: 3RKQ, 4S0H, 6WC2, 6WC5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00046	Homeodomain	139 → 195	Homeodomain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed only in the heart.
• Sequence:

  MFPSPALTPTPFSVKDILNLEQQQRSLAAAGELSARLEATLAPSSCMLAAFKPEAYAGPE
  AAAPGLPELRAELGRAPSPAKCASAFPAAPAFYPRAYSDPDPAKDPRAEKKELCALQKAV
  ELEKTEADNAERPRARRRRKPRVLFSQAQVYELERRFKQQRYLSAPERDQLASVLKLTST
  QVKIWFQNRRYKCKRQRQDQTLELVGLPPPPPPPARRIAVPVLVRDGKPCLGDSAPYAPA
  YGVGLNPYGYNAYPAYPGYGGAACSPGYSCTAAYPAGPSPAQPATAAANNNFVNFGVGDL
  NAVQSPGIPQSNSGVSTLHGIRAW

• Sequence length: 324

Pathways

Reactome:

YAP1- and WWTR1 (TAZ)-stimulated gene expression
Physiological factors

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormal cardiovascular system morphology	Pathogenic	rs797045792, rs797045791, rs797045790	RCV000193839 RCV000192960 RCV000195107	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Atrial septal defect	Likely pathogenic; Pathogenic	rs1554093433	RCV000626863	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Atrial septal defect 7	Likely pathogenic; Pathogenic	rs1761346424, rs2113901873, rs2113901504, rs2113901862, rs2113905914, rs2113905948, rs2113906009, rs758539727, rs2113906336, rs2113902216, rs2113906167, rs397516909, rs2113901553, rs2113901956, rs797045791, rs2113901025, rs2113902320, rs2113902012, rs2113906234, rs2113906022, rs2113901953, rs587782928, rs587782929, rs587782930, rs587784067, rs2480073143, rs2480072807, rs2480079168, rs756377692, rs797045792, rs760723447, rs2480072174, rs2480073440, rs104893900, rs104893901, rs104893903, rs606231358, rs606231359, rs137852683, rs606231360, rs104893907, rs879253754, rs2480071984, rs2480079410, rs2480072950, rs2480071978, rs2480079215, rs2480072130, rs2480072407, rs2480079337, rs2480072423, rs2480072428, rs773922431, rs387906773, rs72554028, rs1554093487, rs1554093433, rs1554093461, rs1561621507, rs1561619801, rs1581108237, rs1581111034, rs1456289029, rs1761430125, rs1761434175, rs1761438700	RCV001313496 RCV001376992 RCV001385601 RCV001383345 RCV001381274 RCV001380091 RCV001730133 RCV001913579 RCV001967917 RCV001904166 RCV001999853 RCV001994587 RCV001938276 RCV001911633 RCV002023478 RCV002007293 RCV001951013 RCV001885642 RCV001944124 RCV001941194 RCV001981524 RCV001895301 RCV001942526 RCV000144176 RCV000144177 RCV000144178 RCV000550275 RCV002472192 RCV003037133 RCV002801455 RCV002819875 RCV002894266 RCV002889896 RCV003025938 RCV003051877 RCV000009568 RCV000009569 RCV000009570 RCV000009577 RCV000009578 RCV000009579 RCV000009581 RCV000009583 RCV000234875 RCV000240621 RCV003340736 RCV003510652 RCV003511220 RCV003510006 RCV003509980 RCV003510133 RCV003510261 RCV003620674 RCV003621020 RCV003869443 RCV003619678 RCV000023020 RCV000588165 RCV003767784 RCV001049571 RCV000644449 RCV000690794 RCV000707466 RCV000818694 RCV000818509 RCV001052873 RCV001058874 RCV001222867 RCV001216063	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Atrioventricular septal defect, somatic	Pathogenic	rs137852683, rs137852686	RCV000009580 RCV000009586	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cardiovascular phenotype	Likely pathogenic; Pathogenic	rs2113906336, rs397516909, rs2113906234, rs2480079337, rs2480072423, rs1554093487	RCV002397979 RCV005374896 RCV003303443 RCV004371647 RCV004985493 RCV000621937	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Congenital heart disease	Likely pathogenic; Pathogenic	rs864321649, rs864321648, rs864321645, rs864321650	RCV000203525 RCV000203502 RCV000203558 RCV000203543	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Heart, malformation of	Likely pathogenic	rs876657934, rs397516908	RCV000219333 RCV000037965	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypothyroidism, congenital, nongoitrous, 5	Likely pathogenic	rs1761374435	RCV001775361	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Malformation of the heart and great vessels	Likely pathogenic; Pathogenic	rs587784067, rs587784066	RCV000146756 RCV000146752	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
NKX2-5-related disorder	Likely pathogenic; Pathogenic	rs587784067	RCV003965106	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Noncompaction cardiomyopathy	Likely pathogenic; Pathogenic	rs1554093433	RCV000626863	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Primary dilated cardiomyopathy	Likely pathogenic; Pathogenic	rs1554093433	RCV000626863	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Tetralogy of Fallot	Likely pathogenic; Pathogenic	rs864321649, rs2480073228, rs1761360431	RCV004813078 RCV003315207 RCV001261993	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ventricular fibrillation	Likely pathogenic; Pathogenic	rs1554093433	RCV000626863	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ventricular septal defect 3	Pathogenic	rs387906775	RCV000023024	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Aortic arch interruption	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AORTIC VALVE DISEASE 2	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATHYREOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FLUTTER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL SEPTAL DEFECT 7 WITH OR WITHOUT ATRIOVENTRICULAR CONDUCTION DEFECTS	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL SEPTAL DEFECT, ATRIOVENTRICULAR CONDUCTION DEFECT SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL SEPTAL DEFECT, OSTIUM SECUNDUM TYPE	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL SEPTAL DEFECT-ATRIOVENTRICULAR CONDUCTION DEFECTS SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL SEPTAL DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIOVENTRICULAR BLOCK	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOEMBOLIC STROKE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMEGALY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHY, DILATED	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CEREBROVASCULAR ACCIDENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ABSENCE OF THYROID GLAND	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ATROPHY OF THYROID	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HYPOTHYROIDISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HYPOTHYROIDISM DUE TO ABSENCE OF THYROID GLAND	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HYPOTHYROIDISM WITHOUT GOITER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL SEPTAL DEFECT OF HEART	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONOTRUNCAL CARDIAC DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Conotruncal heart malformations	Uncertain significance	ClinVar CTD, ClinVar, GenCC, HPO CTD, ClinVar, GenCC, HPO CTD, ClinVar, GenCC, HPO	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
DELETION 5Q35 SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DILATED CARDIOMYOPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Double outlet right ventricle	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
FAMILIAL ATRIAL FIBRILLATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL BICUSPID AORTIC VALVE	—	Disgenet, GWAS catalog Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial isolated congenital asplenia	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HEART SEPTAL DEFECTS, VENTRICULAR	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY ATRIAL FIBRILLATION	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY BUNDLE BRANCH SYSTEM DEFECT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertrophic cardiomyopathy	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HYPOPLASTIC LEFT HEART SYNDROME	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypoplastic left heart syndrome 2	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar ClinVar, Disgenet, HPO ClinVar, Disgenet, HPO ClinVar, Disgenet, HPO	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
INTERRUPTED AORTIC ARCH	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lissencephaly due to TUBA1A mutation	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Long QT syndrome	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOTONIC DYSTROPHY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NKX2.5-related congenital, conduction and myopathic heart disease	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Persistent truncus arteriosus	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Reclassified - variant of unknown significance	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Single ventricle	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
small Atrial septal defect	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPLENIC HYPOPLASIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STROKE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENTRICULAR SEPTAL DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Cerebrovascular Accidents	Stroke	CTD_human_DG	29531354		★☆☆☆☆ Found in Text Mining only
Aneurysm of aortic arch	Aneurysm Of Aortic Arch	HPO_DG			★☆☆☆☆ Found in Text Mining only
Aortic coarctation	Aortic Coarctation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Aortic valve calcification	Aortic valve calcification	ORPHANET_DG	25438918		★☆☆☆☆ Found in Text Mining only
Aortic valve calcification	Aortic valve calcification	HPO_DG			★☆☆☆☆ Found in Text Mining only
Aortic Valve Disease 1	Aortic valve calcification	ORPHANET_DG	25438918		★☆☆☆☆ Found in Text Mining only
Aortic valve disorder	Aortic Valve Disease	ORPHANET_DG	25438918		★☆☆☆☆ Found in Text Mining only
Aortic Valve Insufficiency	Aortic Valve Insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Aortic Valve Stenosis	Aortic Valve Sclerosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	27993833		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	27993833		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	BEFREE	16896344, 20022124, 24120998, 24782644, 27035640, 31609246		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Fibrillation	Atrial Fibrillation	CTD_human_DG	20062060, 29892015, 30061737		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Fibrillation	Atrial Fibrillation	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 1 (disorder)	Atrial Fibrillation	ORPHANET_DG	22818067, 23525379		★☆☆☆☆ Found in Text Mining only
ATRIAL SEPTAL DEFECT 1	Atrial Septal Defect	BEFREE	27752029		★☆☆☆☆ Found in Text Mining only
ATRIAL SEPTAL DEFECT 7 WITH OR WITHOUT ATRIOVENTRICULAR CONDUCTION DEFECTS	Atrial septal defect with atrioventricular conduction defects	UNIPROT_DG	10587520, 14607454, 15342699, 15810002, 9651244		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL SEPTAL DEFECT 7 WITH OR WITHOUT ATRIOVENTRICULAR CONDUCTION DEFECTS	Atrial septal defect with atrioventricular conduction defects	GENOMICS_ENGLAND_DG	15109497		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL SEPTAL DEFECT 7 WITH OR WITHOUT ATRIOVENTRICULAR CONDUCTION DEFECTS	Atrial septal defect with atrioventricular conduction defects	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Septal Defect with Atrioventricular Conduction Defects	Atrial septal defect with atrioventricular conduction defects	ORPHANET_DG	18375255, 19049681		★☆☆☆☆ Found in Text Mining only
Atrial Septal Defect with Atrioventricular Conduction Defects	Atrial septal defect with atrioventricular conduction defects	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Atrial septal defect, ostium secundum type	Atrial Septal Defect	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial septal defect-atrioventricular conduction defects syndrome	Atrial septal defect with atrioventricular conduction defects	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Septal Defects	Atrial Septal Defect	BEFREE	12074273, 12798584, 16470726, 16896344, 18375255, 20659440, 21188375, 22824467, 26297999, 26679770, 27752029, 28259982, 30354339, 30982828		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Septal Defects	Atrial Septal Defect	LHGDN	12798584		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Septal Defects	Atrial Septal Defect	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrioventricular Block	Atrioventricular block	BEFREE	16896344, 25742962, 26226998, 26679770, 30354339		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrioventricular Septal Defect	Atrioventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	27752029		★☆☆☆☆ Found in Text Mining only
Bicuspid aortic valve	Bicuspid aortic valve	BEFREE	16733161, 26708639		★☆☆☆☆ Found in Text Mining only
Bicuspid aortic valve	Bicuspid aortic valve	ORPHANET_DG	25438918		★☆☆☆☆ Found in Text Mining only
Bicuspid aortic valve	Bicuspid aortic valve	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bundle-Branch Block	Bundle Branch Block	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cardiac defects	Cardiac Defects	BEFREE	17685485		★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	BEFREE	15109497, 23661673, 29332214		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Dilated	Cardiomyopathy	BEFREE	28690296		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathy, Dilated	Cardiomyopathy	CTD_human_DG	28973413		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	BEFREE	25503402, 25725155, 28690296		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	CTD_human_DG	28973413		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	29342503		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	19464101		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cerebrovascular accident	Stroke	CTD_human_DG	29531354		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Choroid Plexus Carcinoma	Choroid Plexus Carcinoma	BEFREE	28580685		★☆☆☆☆ Found in Text Mining only
Chromosome 5, monosomy 5q35	Monosomy 5q35	ORPHANET_DG	17910075		★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathies	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Clinodactyly of the 5th finger	Camptodactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Complete atrioventricular block	Complete Atrioventricular Block	BEFREE	15109497		★☆☆☆☆ Found in Text Mining only
Conduction disorder of the heart	Conduction Disorder Of The Heart	BEFREE	12112663, 15109497, 15850572, 16470726, 23661673, 29282804		★☆☆☆☆ Found in Text Mining only
Congenital absence of spleen	Asplenia	BEFREE	22560297		★☆☆☆☆ Found in Text Mining only
Congenital exomphalos	Congenital Exomphalos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	12112663, 17685485, 17891434, 22193390, 25028484, 26226998, 27152669, 29282804		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital heart disease	Congenital Heart Disease	BEFREE	10096597, 10903346, 11431700, 12074273, 12798584, 15109497, 15161646, 15917268, 15925411, 16138909, 16418214, 17350578, 17891520, 19181906, 19967350, 20433683, 20659440, 20725931, 22179962, 22449847, 22885181, 23285148, 23661673, 23936479, 24376681, 24880466, 25742962, 26180509, 26823822, 27033241, 28189763, 30121862, 30611920, 30834692, 9651244		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Congenital hypoplasia of aortic arch	Hypoplastic aortic arch	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Hypothyroidism	Congenital Hypothyroidism	BEFREE	20157192		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Hypothyroidism	Congenital Hypothyroidism	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Myotonic Dystrophy	Congenital Myotonic Dystrophy	CTD_human_DG	18084293		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
CONOTRUNCAL HEART MALFORMATIONS (disorder)	Conotruncal heart defect	UNIPROT_DG	14607454, 17891434		★☆☆☆☆ Found in Text Mining only
CONOTRUNCAL HEART MALFORMATIONS (disorder)	Conotruncal heart defect	GENOMICS_ENGLAND_DG	22155005		★☆☆☆☆ Found in Text Mining only
CONOTRUNCAL HEART MALFORMATIONS (disorder)	Conotruncal heart defect	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	12845333, 15161646, 15925411, 17350578, 19371212, 20725931, 22011241, 22179962, 22576768, 22824467, 23285148, 23644027, 23936479, 24376681, 24880466, 25524324, 26180509, 26679770, 26823822, 27033241, 27426723, 29282804, 29332214, 30121862		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Deletion 5q35	Deletion 5q36	Orphanet			★☆☆☆☆ Found in Text Mining only
Double Outlet Right Ventricle	Double Outlet Right Ventricle	BEFREE	18456715		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Double Outlet Right Ventricle	Double Outlet Right Ventricle	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Down Syndrome	Down Syndrome	BEFREE	25524324		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dystrophia myotonica 2	Myotonic dystrophy	CTD_human_DG	18084293		★☆☆☆☆ Found in Text Mining only
Ebstein Anomaly	Ebstein anomaly of the tricuspid valve	BEFREE	12074273, 16470726		★☆☆☆☆ Found in Text Mining only
Exophthalmos	Proptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial atrial fibrillation	Atrial Fibrillation	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial dilated cardiomyopathy	Cardiomyopathy	BEFREE	25503402		★☆☆☆☆ Found in Text Mining only
Familial progressive cardiac conduction defect	Progressive Cardiac Conduction Defect	Orphanet			★☆☆☆☆ Found in Text Mining only
Foramen Ovale, Patent	Patent foramen ovale	BEFREE	12798584, 19464101, 27752029		★☆☆☆☆ Found in Text Mining only
Foramen Ovale, Patent	Patent foramen ovale	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gastrointestinal Stromal Tumors	Gastrointestinal stromal tumor	BEFREE	21192842		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Heart Block	Heart Block	BEFREE	12074273, 12798584		★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart Diseases	LHGDN	12074273, 14607454, 16138909, 17891520		★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart Diseases	BEFREE	12112663, 23661673		★☆☆☆☆ Found in Text Mining only
Heart Septal Defects	Heart Septal Defects	BEFREE	19181906, 30834692		★☆☆☆☆ Found in Text Mining only
Heart Septal Defects	Heart Septal Defects	HPO_DG			★☆☆☆☆ Found in Text Mining only
Heart Septal Defects	Heart Septal Defects	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Hereditary bundle branch system defect	Hereditary Bundle Branch System Defect	ORPHANET_DG	22179962		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Holt-Oram syndrome	Holt-Oram Syndrome	BEFREE	11431700		★☆☆☆☆ Found in Text Mining only
Hypersomnia	Hypersomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	29342503		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplastic Left Heart Syndrome	Hypoplastic Left Heart Syndrome	BEFREE	12798584		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypoplastic Left Heart Syndrome	Hypoplastic Left Heart Syndrome	LHGDN	12798584		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypoplastic Left Heart Syndrome	Hypoplastic Left Heart Syndrome	ORPHANET_DG	12798584, 14607454, 20456451		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypoplastic Left Heart Syndrome	Hypoplastic Left Heart Syndrome	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypoplastic Left Heart Syndrome	Hypoplastic Left Heart Syndrome	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOPLASTIC LEFT HEART SYNDROME 1	Hypoplastic Left Heart Syndrome	BEFREE	12798584, 25050861, 28793912		★☆☆☆☆ Found in Text Mining only
HYPOPLASTIC LEFT HEART SYNDROME 2	Hypoplastic Left Heart Syndrome	UNIPROT_DG	14607454, 15810002		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HYPOPLASTIC LEFT HEART SYNDROME 2	Hypoplastic Left Heart Syndrome	GENOMICS_ENGLAND_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 5 (disorder)	Congenital hypothyroidism, nongoitrous	UNIPROT_DG	16418214		★☆☆☆☆ Found in Text Mining only
HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 5 (disorder)	Congenital hypothyroidism, nongoitrous	GENOMICS_ENGLAND_DG	16418214		★☆☆☆☆ Found in Text Mining only
HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 5 (disorder)	Congenital hypothyroidism, nongoitrous	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Ischemic stroke	Ischemic Stroke	BEFREE	31168961		★☆☆☆☆ Found in Text Mining only
Left ventricular noncompaction cardiomyopathy	Cardiomyopathy	BEFREE	31342111		★☆☆☆☆ Found in Text Mining only
leiomyosarcoma	Leiomyosarcoma	BEFREE	21192842		★☆☆☆☆ Found in Text Mining only
Limb Deformities, Congenital	Congenital anomaly of limb	BEFREE	11431700		★☆☆☆☆ Found in Text Mining only
Long narrow head	Dolichocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lymphoproliferative Disorders	Lymphoproliferative Disorder	BEFREE	18492690		★☆☆☆☆ Found in Text Mining only
Lymphoproliferative Disorders	Lymphoproliferative Disorder	LHGDN	18492690		★☆☆☆☆ Found in Text Mining only
Macroglossia	Macroglossia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	17606710, 18446232, 20606036		★☆☆☆☆ Found in Text Mining only
Mitral Valve Stenosis	Mitral Valve Stenosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Muscular ventricular septum defect	Muscular ventricular septal defect	BEFREE	25028484		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	29545582		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myotonic Dystrophy	Myotonic dystrophy	BEFREE	18084293		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myotonic Dystrophy	Myotonic dystrophy	CTD_human_DG	18084293		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOTONIC DYSTROPHY 1	Myotonic dystrophy	BEFREE	18084293, 25168381		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	23637834		★☆☆☆☆ Found in Text Mining only
Non-compaction cardiomyopathy	Noncompaction cardiomyopathy	BEFREE	29979676		★☆☆☆☆ Found in Text Mining only
Ostium secundum atrial septal defect	Secundum atrial septal defect	BEFREE	12798584, 19464101, 27752029		★☆☆☆☆ Found in Text Mining only
Ostium secundum atrial septal defect	Secundum atrial septal defect	ORPHANET_DG	15810002, 21285290		★☆☆☆☆ Found in Text Mining only
Ostium secundum atrial septal defect	Secundum atrial septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Paroxysmal atrial fibrillation	Paroxysmal atrial fibrillation	CTD_human_DG	20062060, 29892015, 30061737		★☆☆☆☆ Found in Text Mining only
Patent ductus arteriosus	Patent ductus arteriosus	BEFREE	30834692		★☆☆☆☆ Found in Text Mining only
Patent ductus arteriosus	Patent ductus arteriosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peutz-Jeghers Syndrome	Peutz-Jeghers Syndrome	BEFREE	21940722		★☆☆☆☆ Found in Text Mining only
POLYDACTYLY, POSTAXIAL	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Precursor Cell Lymphoblastic Leukemia Lymphoma	Lymphoblastic Leukemia	LHGDN	17308084		★☆☆☆☆ Found in Text Mining only
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	BEFREE	14500364, 15194534, 16531254, 17308084, 18079734, 19835636, 21261500		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	17606710, 18446232, 20606036		★☆☆☆☆ Found in Text Mining only
Pyloric Stenosis, Hypertrophic	Congenital hypertrophic pyloric stenosis	BEFREE	22306654		★☆☆☆☆ Found in Text Mining only
Scleroderma	Scleroderma	BEFREE	29342503		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Splenic Hypoplasia	Splenic Hypoplasia	BEFREE	22560297		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Splenic Hypoplasia	Splenic Hypoplasia	ORPHANET_DG	22560297		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Systemic Scleroderma	Scleroderma	BEFREE	29342503		★☆☆☆☆ Found in Text Mining only
Tetralogy of Fallot	Tetralogy of Fallot	UNIPROT_DG	10587520, 11714651, 14607454		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Tetralogy of Fallot	Tetralogy of Fallot	BEFREE	12798584, 17891434, 21519287, 22672592, 22824467, 24182332		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Tetralogy of Fallot	Tetralogy of Fallot	ORPHANET_DG	29045289		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Tetralogy of Fallot	Tetralogy of Fallot	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Tetralogy of Fallot	Tetralogy of Fallot	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Tetralogy of Fallot	Tetralogy of Fallot	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Tetralogy of Fallot	Tetralogy of Fallot	GENOMICS_ENGLAND_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Thyroid Agenesis	Thyroid Agenesis	ORPHANET_DG	16418214		★☆☆☆☆ Found in Text Mining only
Thyroid Agenesis	Thyroid Agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyroid Dysgenesis	Thyroid Dysgenesis	BEFREE	16418214, 23285148		★☆☆☆☆ Found in Text Mining only
Thyroid Dysgenesis	Thyroid Dysgenesis	LHGDN	18976153		★☆☆☆☆ Found in Text Mining only
Thyroid Hypoplasia	Thyroid Hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Transposition of Great Vessels	Transposition Of Great Vessels	HPO_DG			★☆☆☆☆ Found in Text Mining only
Truncus Arteriosus, Persistent	Persistent truncus arteriosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ventricular arrhythmia	Ventricular arrhythmia	BEFREE	24880466		★☆☆☆☆ Found in Text Mining only
VENTRICULAR SEPTAL DEFECT 3	Ventricular septal defect	UNIPROT_DG	21110066, 21165553		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
VENTRICULAR SEPTAL DEFECT 3	Ventricular septal defect	GENOMICS_ENGLAND_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ventricular Septal Defects	Ventricular septal defect	LHGDN	15917268		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ventricular Septal Defects	Ventricular septal defect	BEFREE	20659440, 21165553, 22576768, 22824467, 23644027, 25524324, 26297999, 28406175		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ventricular Septal Defects	Ventricular septal defect	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ventricular Septal Defects	Ventricular septal defect	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations