Hypoplastic left heart syndrome: genes and variants
Hypoplastic left heart syndrome is linked to 3 analyzed proteins (MYH6, GJA1 and NKX2-5). 1 DNA variants are known to cause it; 13 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: hypoplastic left heart syndrome 1; hypoplastic left heart syndrome 2
Genes linked to Hypoplastic left heart syndrome
MYH6: Myosin-6
Its alpha-myosin motor contributes to ATP-dependent force generation in the cardiac sarcomere, particularly in atrial myocardium. Pathogenic variants can cause cardiomyopathy, congenital heart defects, and selected conduction-system disorders.
1 disease-causing and 0 uncertain variants in MYH6 are linked to Hypoplastic left heart syndrome.
GJA1: Gap junction alpha-1 protein
It forms connexin 43 gap junctions that permit direct electrical and metabolic communication between neighboring cells in heart, bone, skin, and many other tissues. Pathogenic variants cause oculodentodigital dysplasia and related syndromes with craniofacial, dental, limb, and sometimes cardiac abnormalities.
0 disease-causing and 8 uncertain variants in GJA1 are linked to Hypoplastic left heart syndrome.
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.
0 disease-causing and 5 uncertain variants in NKX2-5 are linked to Hypoplastic left heart syndrome.
Weakly linked (only a few uncertain records): NOTCH1.
Known disease-causing variants in Hypoplastic left heart syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| MYH6 G408D | 408 | Myosin motor | Disease-causing (★) |
Diseases related to Hypoplastic left heart syndrome
- Atrial septal defect, also linked to MYH6 and NKX2-5
- Hypertrophic cardiomyopathy, also linked to MYH6
- Primary dilated cardiomyopathy, also linked to MYH6
- Oculodentodigital dysplasia, also linked to GJA1
- Primary familial hypertrophic cardiomyopathy, also linked to MYH6
- Hypothyroidism, congenital, nongoitrous, 2, also linked to NKX2-5
- Primary familial dilated cardiomyopathy, also linked to MYH6
- Sick sinus syndrome 2, autosomal dominant, also linked to MYH6
- Familial isolated dilated cardiomyopathy, also linked to MYH6
- Ventricular septal defect, also linked to NKX2-5
- Familial atrioventricular septal defect, also linked to GJA1
- Dilated cardiomyopathy 1EE, also linked to MYH6
Frequently asked questions
Which genes are linked to Hypoplastic left heart syndrome?
In CATVariant, Hypoplastic left heart syndrome is linked to 3 analyzed proteins: MYH6 (Myosin-6), GJA1 (Gap junction alpha-1 protein) and NKX2-5 (Homeobox protein Nkx-2.5).
How many genetic variants are linked to Hypoplastic left heart syndrome?
22 variants: 1 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 13 are of uncertain significance or have conflicting reports.
Which uncertain variants in Hypoplastic left heart syndrome 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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