Ventricular septal defect: genes and variants
Ventricular septal defect is linked to 2 analyzed proteins (GATA4 and NKX2-5). 2 DNA variants are known to cause it; 22 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: ventricular septal defect 1; ventricular septal defect 3
Genes linked to Ventricular septal defect
GATA4: Transcription factor GATA-4
It controls cardiac development and adult cardiac gene expression and also contributes to gonadal and gastrointestinal development. Heterozygous pathogenic variants can cause congenital heart defects, particularly septal defects, and occasionally cardiomyopathy or disorders of sex development.
1 disease-causing and 8 uncertain variants in GATA4 are linked to Ventricular septal defect.
NKX2-5: Homeobox protein Nkx-2.5
It specifies myocardial lineages and maintains genes needed for adult conduction and contractile function. Heterozygous pathogenic variants can cause congenital heart defects, especially atrial septal defects, often with progressive conduction disease.
1 disease-causing and 13 uncertain variants in NKX2-5 are linked to Ventricular septal defect.
Weakly linked (only a few uncertain records): MYCN and TBX5.
Known disease-causing variants in Ventricular septal defect
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| GATA4 G296R | 296 | Disease-causing | |
| NKX2-5 P59A | 59 | Disease-causing |
Same protein, different disease
- Atrioventricular septal defect 4 is also caused by GATA4 variants; they fall mostly in different places as the Ventricular septal defect variants (7 disease-causing).
- Atrial septal defect is also caused by GATA4 variants; they fall partly in the same places as the Ventricular septal defect variants (5 disease-causing).
- Testicular anomalies with or without congenital heart disease is also caused by GATA4 variants; they fall mostly in different places as the Ventricular septal defect variants (3 disease-causing).
- Atrial septal defect is also caused by NKX2-5 variants; they fall mostly in different places as the Ventricular septal defect variants (14 disease-causing).
Diseases related to Ventricular septal defect
- Atrial septal defect, also linked to GATA4 and NKX2-5
- Hypothyroidism, congenital, nongoitrous, 2, also linked to NKX2-5
- Atrioventricular septal defect 4, also linked to GATA4
- Testicular anomalies with or without congenital heart disease, also linked to GATA4
- Hypoplastic left heart syndrome, also linked to NKX2-5
Frequently asked questions
Which genes are linked to Ventricular septal defect?
In CATVariant, Ventricular septal defect is linked to 2 analyzed proteins: GATA4 (Transcription factor GATA-4) and NKX2-5 (Homeobox protein Nkx-2.5).
How many genetic variants are linked to Ventricular septal defect?
39 variants: 2 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 22 are of uncertain significance or have conflicting reports.
Which uncertain variants in Ventricular septal defect look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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