CHTD4
MCID: CNG404
MIFTS: 39

Congenital Heart Defects, Multiple Types, 4 (CHTD4)

Categories: Cardiovascular diseases, Fetal diseases, Genetic diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Congenital Heart Defects, Multiple Types, 4

MalaCards integrated aliases for Congenital Heart Defects, Multiple Types, 4:

Name: Congenital Heart Defects, Multiple Types, 4 57 72 29 6 70
Chtd4 57 72
Complete Atrioventricular Septal Defect with Ventricular Hypoplasia 58
Complete Atrioventricular Canal Defect with Ventricular Hypoplasia 58
Complete Atrioventricular Septal Defect with Ventricular Imbalance 58
Complete Atrioventricular Septal Defect-Tetralogy of Fallot 58
Complete Atrioventricular Canal Defect-Tetralogy of Fallot 58
Heart Defects, Congenital, Multiple Types, Type 4 39
Unbalanced Complete Atrioventricular Canal 58
Complete Avsd with Ventricular Hypoplasia 58
Complete Avsd-Tetralogy of Fallot 58
Cavc with Ventricular Hypoplasia 58
Cavc-Tetralogy of Fallot 58

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
incomplete penetrance
phenotypic variability
intrafamilial variability

Inheritance:
autosomal dominant


HPO:

31
congenital heart defects, multiple types, 4:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare cardiac malformations
Developmental anomalies during embryogenesis


External Ids:

OMIM® 57 615779
MeSH 44 D006330
ICD10 via Orphanet 33 Q21.2
UMLS 70 C4014310

Summaries for Congenital Heart Defects, Multiple Types, 4

OMIM® : 57 The multiple types of congenital heart defects observed in CHTD4 include atrial, ventricular, and atrioventricular septal defects, double-outlet right ventricle, tetralogy of Fallot, hypoplastic left heart syndrome, aortic stenosis, and coarctation of the aorta. Intrafamilial variability and incomplete penetrance has been reported (Al Turki et al., 2014; Qiao et al., 2018). Some patients exhibit syndromic features such as developmental delay, congenital diaphragmatic hernia, and severe gastroesophageal reflux (High et al., 2016; Upadia et al., 2018). For a discussion of genetic heterogeneity of multiple types of congenital heart defects, see CHTD1 (306955). (615779) (Updated 20-May-2021)

MalaCards based summary : Congenital Heart Defects, Multiple Types, 4, also known as chtd4, is related to double outlet right ventricle and complete atrioventricular canal. An important gene associated with Congenital Heart Defects, Multiple Types, 4 is NR2F2 (Nuclear Receptor Subfamily 2 Group F Member 2), and among its related pathways/superpathways are Factors involved in megakaryocyte development and platelet production and Ectoderm Differentiation. Affiliated tissues include heart, and related phenotypes are coarctation of aorta and hypoplastic left heart

UniProtKB/Swiss-Prot : 72 Congenital heart defects, multiple types, 4: A disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, and patent ductus arteriosus. Some patients also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions.

Related Diseases for Congenital Heart Defects, Multiple Types, 4

Diseases in the Heart Disease family:

Congenital Heart Defects, Multiple Types, 6 Congenital Heart Defects, Multiple Types, 3
Congenital Heart Defects, Multiple Types, 2 Congenital Heart Defects, Multiple Types, 4
Congenital Heart Defects, Multiple Types, 5 Congenital Heart Defects, Multiple Types, 7

Diseases related to Congenital Heart Defects, Multiple Types, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 28)
# Related Disease Score Top Affiliating Genes
1 double outlet right ventricle 29.4 GATA6 GATA4 CRELD1
2 complete atrioventricular canal 10.1
3 total anomalous pulmonary venous return 1 9.9 GATA4 CRELD1
4 dextro-looped transposition of the great arteries 9.9 GATA4 CRELD1
5 holt-oram syndrome 9.8 GATA4 CRELD1
6 malignant childhood germ cell neoplasm 9.8 GATA6 GATA4
7 tricuspid atresia 9.7 GATA6 GATA4
8 pulmonary valve disease 9.7 GATA6 GATA4
9 tricuspid valve disease 9.7 GATA6 GATA4
10 interatrial communication 9.7 GATA6 GATA4
11 46,xy sex reversal 9.7 NR2F2 GATA4
12 endodermal sinus tumor 9.7 GATA6 GATA4
13 pancreatic agenesis 9.7 GATA6 GATA4
14 germ cell and embryonal cancer 9.6 GATA6 GATA4
15 inguinal hernia 9.6 GATA6 GATA4
16 adrenal cortical carcinoma 9.6 GATA6 GATA4
17 ventricular septal defect 9.5 NR2F2 GATA6 GATA4
18 diaphragm disease 9.5 NR2F2 GATA6 GATA4
19 heart septal defect 9.5 GATA6 GATA4 CRELD1
20 patent ductus arteriosus 1 9.5 GATA6 GATA4 CRELD1
21 hypoplastic left heart syndrome 9.5 GATA6 GATA4 CRELD1
22 diaphragmatic hernia, congenital 9.5 NR2F2 GATA6 GATA4
23 atrial heart septal defect 9.5 GATA6 GATA4 CRELD1
24 patent foramen ovale 9.5 GATA6 GATA4 CRELD1
25 familial atrial fibrillation 9.4 GATA6 GATA4
26 partial atrioventricular canal 9.2 NR2F2 GATA6 GATA4 CRELD1
27 atrioventricular septal defect 9.2 NR2F2 GATA6 GATA4 CRELD1
28 tetralogy of fallot 9.2 NR2F2 GATA6 GATA4 CRELD1

Graphical network of the top 20 diseases related to Congenital Heart Defects, Multiple Types, 4:



Diseases related to Congenital Heart Defects, Multiple Types, 4

Symptoms & Phenotypes for Congenital Heart Defects, Multiple Types, 4

Human phenotypes related to Congenital Heart Defects, Multiple Types, 4:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 coarctation of aorta 31 HP:0001680
2 hypoplastic left heart 31 HP:0004383
3 tetralogy of fallot 31 HP:0001636
4 ventricular septal defect 31 HP:0001629
5 atrioventricular canal defect 31 HP:0006695
6 aortic valve stenosis 31 HP:0001650

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Cardiovascular Heart:
atrial septal defect
hypoplastic left heart
tetralogy of fallot
ventricular septal defect
patent foramen ovale
more
Neurologic Central Nervous System:
developmental delay (in some patients)

Abdomen Gastrointestinal:
gastroesophageal reflux, severe (in some patients)

Cardiovascular Vascular:
coarctation of aorta
patent ductus arteriosus

Chest Diaphragm:
diaphragmatic hernia (in some patients)

Clinical features from OMIM®:

615779 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Congenital Heart Defects, Multiple Types, 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.26 CRELD1 GATA4 GATA6 NR2F2
2 embryo MP:0005380 8.92 CRELD1 GATA4 GATA6 NR2F2

Drugs & Therapeutics for Congenital Heart Defects, Multiple Types, 4

Search Clinical Trials , NIH Clinical Center for Congenital Heart Defects, Multiple Types, 4

Genetic Tests for Congenital Heart Defects, Multiple Types, 4

Genetic tests related to Congenital Heart Defects, Multiple Types, 4:

# Genetic test Affiliating Genes
1 Congenital Heart Defects, Multiple Types, 4 29 NR2F2

Anatomical Context for Congenital Heart Defects, Multiple Types, 4

MalaCards organs/tissues related to Congenital Heart Defects, Multiple Types, 4:

40
Heart

Publications for Congenital Heart Defects, Multiple Types, 4

Articles related to Congenital Heart Defects, Multiple Types, 4:

(show all 14)
# Title Authors PMID Year
1
Novel de novo pathogenic variant in the NR2F2 gene in a boy with congenital heart defect and dysmorphic features. 6 57
29663647 2018
2
A novel NR2F2 loss-of-function mutation predisposes to congenital heart defect. 6 57
29222010 2018
3
De novo frameshift mutation in COUP-TFII (NR2F2) in human congenital diaphragmatic hernia. 57 6
27363585 2016
4
Germline but not somatic de novo mutations are common in human congenital diaphragmatic hernia. 57
29570242 2018
5
Prevalence and penetrance of ZFPM2 mutations and deletions causing congenital diaphragmatic hernia. 57
24702427 2015
6
Rare variants in NR2F2 cause congenital heart defects in humans. 57
24702954 2014
7
Breakpoint mapping and array CGH in translocations: comparison of a phenotypically normal and an abnormal cohort. 57
18371933 2008
8
Rare Occurrence of Absent Pulmonary Valve Syndrome in the Setting of Double-Outlet Right Ventricle with Unbalanced Complete Atrioventricular Canal Defect. 61
31049480 2019
9
Major Aortopulmonary Collateral Arteries With Anatomy Other Than Pulmonary Atresia/Ventricular Septal Defect. 61
28527961 2017
10
Outcomes of total cavopulmonary connection for single ventricle palliation. 61
26904211 2016
11
Impact of pharmacotherapy on interstage outcomes in single ventricle infants. 61
21696551 2011
12
Biventricular repair in patients with heterotaxy syndrome. 61
19185155 2009
13
Results of Norwood stage I operation: comparison of hypoplastic left heart syndrome with other malformations. 61
10649212 2000
14
Double-outlet right ventricle with complete atrioventricular canal. 61
9768963 1998

Variations for Congenital Heart Defects, Multiple Types, 4

ClinVar genetic disease variations for Congenital Heart Defects, Multiple Types, 4:

6 (show all 27)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NR2F2 NM_021005.4(NR2F2):c.1022C>A (p.Ser341Tyr) SNV Pathogenic 128232 rs587777371 GRCh37: 15:96880628-96880628
GRCh38: 15:96337399-96337399
2 NR2F2 NM_021005.4(NR2F2):c.614A>T (p.Asn205Ile) SNV Pathogenic 128233 rs587777372 GRCh37: 15:96877476-96877476
GRCh38: 15:96334247-96334247
3 NR2F2 NM_021005.4(NR2F2):c.210_212GCA[6] (p.Gln75dup) Microsatellite Pathogenic 128234 rs780808943 GRCh37: 15:96875542-96875543
GRCh38: 15:96332313-96332314
4 NR2F2 NM_021005.4(NR2F2):c.970+1G>A SNV Pathogenic 128235 rs587777374 GRCh37: 15:96877833-96877833
GRCh38: 15:96334604-96334604
5 NR2F2 NM_021005.4(NR2F2):c.97_103del (p.Pro33fs) Deletion Pathogenic 916034 GRCh37: 15:96875426-96875432
GRCh38: 15:96332197-96332203
6 NR2F2 NM_021005.4(NR2F2):c.856dup (p.Val286fs) Duplication Pathogenic 280543 rs886041730 GRCh37: 15:96877716-96877717
GRCh38: 15:96334487-96334488
7 NR2F2 NM_021005.4(NR2F2):c.217C>T (p.Gln73Ter) SNV Pathogenic 848589 GRCh37: 15:96875551-96875551
GRCh38: 15:96332322-96332322
8 NR2F2 NM_021005.4(NR2F2):c.247G>T (p.Gly83Ter) SNV Pathogenic 446122 rs1555447012 GRCh37: 15:96875581-96875581
GRCh38: 15:96332352-96332352
9 NR2F2 NM_021005.4(NR2F2):c.83_84dup (p.Val29fs) Duplication Likely pathogenic 547880 rs1555446983 GRCh37: 15:96875415-96875416
GRCh38: 15:96332186-96332187
10 NR2F2 GRCh37/hg19 15q26.2(chr15:96878571-96880063)x1 copy number loss Likely pathogenic 548125 GRCh37: 15:96878571-96880063
GRCh38:
11 NR2F2 NM_021005.4(NR2F2):c.746G>A (p.Trp249Ter) SNV Uncertain significance 598763 rs1567138573 GRCh37: 15:96877608-96877608
GRCh38: 15:96334379-96334379
12 NR2F2 NM_021005.4(NR2F2):c.204C>G (p.Ser68Arg) SNV Uncertain significance 640947 rs1381103214 GRCh37: 15:96875538-96875538
GRCh38: 15:96332309-96332309
13 NR2F2 NM_021005.4(NR2F2):c.1000G>C (p.Val334Leu) SNV Uncertain significance 951285 GRCh37: 15:96880606-96880606
GRCh38: 15:96337377-96337377
14 NR2F2 NM_021005.4(NR2F2):c.4G>T (p.Ala2Ser) SNV Uncertain significance 958490 GRCh37: 15:96875338-96875338
GRCh38: 15:96332109-96332109
15 NR2F2 NM_021005.4(NR2F2):c.671T>A (p.Val224Asp) SNV Uncertain significance 966751 GRCh37: 15:96877533-96877533
GRCh38: 15:96334304-96334304
16 NR2F2 NM_021005.4(NR2F2):c.309C>G (p.Phe103Leu) SNV Uncertain significance 1014312 GRCh37: 15:96875643-96875643
GRCh38: 15:96332414-96332414
17 NR2F2 NM_021005.4(NR2F2):c.19A>G (p.Thr7Ala) SNV Uncertain significance 1016890 GRCh37: 15:96875353-96875353
GRCh38: 15:96332124-96332124
18 NR2F2 NM_021005.4(NR2F2):c.682C>T (p.Arg228Trp) SNV Uncertain significance 1038040 GRCh37: 15:96877544-96877544
GRCh38: 15:96334315-96334315
19 NR2F2 NM_021005.4(NR2F2):c.1087C>A (p.Leu363Ile) SNV Uncertain significance 828100 rs1596432381 GRCh37: 15:96880693-96880693
GRCh38: 15:96337464-96337464
20 NR2F2 NM_021005.4(NR2F2):c.948G>T (p.Lys316Asn) SNV Uncertain significance 854815 GRCh37: 15:96877810-96877810
GRCh38: 15:96334581-96334581
21 NR2F2 NM_021005.4(NR2F2):c.276C>T (p.Gly92=) SNV Uncertain significance 854852 GRCh37: 15:96875610-96875610
GRCh38: 15:96332381-96332381
22 NR2F2 NM_021005.4(NR2F2):c.709C>T (p.Gln237Ter) SNV Uncertain significance 241370 rs878855066 GRCh37: 15:96877571-96877571
GRCh38: 15:96334342-96334342
23 NR2F2 NM_021005.4(NR2F2):c.816C>G (p.Ala272=) SNV Likely benign 697865 rs76163938 GRCh37: 15:96877678-96877678
GRCh38: 15:96334449-96334449
24 NR2F2 NM_021005.4(NR2F2):c.882C>T (p.Ile294=) SNV Likely benign 743789 rs1163679972 GRCh37: 15:96877744-96877744
GRCh38: 15:96334515-96334515
25 NR2F2 NM_021005.4(NR2F2):c.129C>G (p.Pro43=) SNV Likely benign 241369 rs551936462 GRCh37: 15:96875463-96875463
GRCh38: 15:96332234-96332234
26 NR2F2 NM_021005.4(NR2F2):c.834G>A (p.Ser278=) SNV Benign 413760 rs199886454 GRCh37: 15:96877696-96877696
GRCh38: 15:96334467-96334467
27 NR2F2 NM_021005.4(NR2F2):c.537C>T (p.Ser179=) SNV Benign 477848 rs143951395 GRCh37: 15:96877399-96877399
GRCh38: 15:96334170-96334170

UniProtKB/Swiss-Prot genetic disease variations for Congenital Heart Defects, Multiple Types, 4:

72
# Symbol AA change Variation ID SNP ID
1 NR2F2 p.Asp170Val VAR_071767
2 NR2F2 p.Asn205Ile VAR_071768 rs587777372
3 NR2F2 p.Glu251Asp VAR_071769
4 NR2F2 p.Ser341Tyr VAR_071770 rs587777371
5 NR2F2 p.Ala412Ser VAR_071771 rs201527820

Expression for Congenital Heart Defects, Multiple Types, 4

Search GEO for disease gene expression data for Congenital Heart Defects, Multiple Types, 4.

Pathways for Congenital Heart Defects, Multiple Types, 4

Pathways related to Congenital Heart Defects, Multiple Types, 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.52 GATA6 GATA4
2 11.42 NR2F2 GATA6
3 10.78 GATA6 GATA4
4 10.64 GATA6 GATA4
5 10.29 GATA6 GATA4

GO Terms for Congenital Heart Defects, Multiple Types, 4

Cellular components related to Congenital Heart Defects, Multiple Types, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 8.8 NR2F2 GATA6 GATA4

Biological processes related to Congenital Heart Defects, Multiple Types, 4 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 9.63 NR2F2 GATA6 GATA4
2 positive regulation of transcription, DNA-templated GO:0045893 9.54 NR2F2 GATA6 GATA4
3 in utero embryonic development GO:0001701 9.49 NR2F2 GATA6
4 blood coagulation GO:0007596 9.48 GATA6 GATA4
5 positive regulation of angiogenesis GO:0045766 9.43 GATA6 GATA4
6 male gonad development GO:0008584 9.4 GATA6 GATA4
7 cell fate commitment GO:0045165 9.32 GATA6 GATA4
8 cardiac muscle cell differentiation GO:0055007 9.26 GATA6 GATA4
9 endocardial cushion development GO:0003197 9.16 GATA4 CRELD1
10 intestinal epithelial cell differentiation GO:0060575 8.96 GATA6 GATA4
11 positive regulation of cardioblast differentiation GO:0051891 8.62 GATA6 GATA4

Molecular functions related to Congenital Heart Defects, Multiple Types, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.43 NR2F2 GATA6 GATA4
2 zinc ion binding GO:0008270 9.33 NR2F2 GATA6 GATA4
3 transcription regulatory region sequence-specific DNA binding GO:0000976 9.32 GATA6 GATA4
4 DNA-binding transcription factor activity GO:0003700 9.13 NR2F2 GATA6 GATA4
5 sequence-specific DNA binding GO:0043565 8.8 NR2F2 GATA6 GATA4

Sources for Congenital Heart Defects, Multiple Types, 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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