The most common congenital heart defect, present in roughly 1 in 100 to 1 in 200 people. A large genome-wide study's real headline is a biological pathway — cilia and a cell-trafficking complex — validated in animal models, with the variant on this page a separate locus from the same study.
A bicuspid aortic valve (BAV) has two leaflets instead of the normal three, present from birth. It is the most common congenital heart defect, affecting roughly 0.5 to 1.2% of the population, and it raises long-term risk of aortic stenosis (a narrowed, stiffened valve) and aortic dilation, sometimes requiring valve surgery later in life.
The study behind this page compared 2,131 BAV patients against 2,728 controls in a genome-wide discovery-and-replication design. Its central finding, and the reason it was published in a major cardiology journal, is biological rather than statistical: the associated loci cluster near genes that regulate primary cilia (small sensory structures nearly every cell has) and the exocyst complex, a cellular machine that directs proteins to the right place inside a developing cell. The authors did not stop at the statistical association — they knocked out and then rescued the relevant genes in zebrafish and mouse models, and reproduced bicuspid valves, valvular stenosis, and calcification, giving the finding a level of mechanistic support well beyond a typical GWAS.
rs7543130, near PALMD, is a separate locus this same discovery-and-replication study identified at genome-wide significance. The source paper's own headline narrative is about the cilia/exocyst pathway described above; this page states that plainly rather than implying PALMD itself is one of the named cilia or exocyst genes, which the paper's abstract does not claim.
2026-09-12 · Larsen LA, Christensen ST, et al. TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development. PLOS Biology. 2026;24(8):e3003902. DOI:10.1371/journal.pbio.3003902
A University of Copenhagen team found that three proteins -- TAK1, TAB2 and PKA-C-alpha -- form a signaling hub inside the primary cilium (a microscopic antenna-like structure most cells have) that controls heart development, by analyzing genetic data from several thousand people with syndromic congenital heart disease and validating rare mutations in zebrafish, human cells and mouse stem cells. This is a mechanistically related finding to, not the same specific disease as, this catalogue's bicuspid-aortic-valve page: that page's own source study found bicuspid aortic valve tied to defects in cilia and the exocyst complex specifically, while this new study is about syndromic congenital heart disease more broadly, via a different set of ciliary genes (TAK1/TAB2/PKA-Cα, not the earlier study's named exocyst/cilia genes), with effects the authors say may extend to the brain, kidneys and skeleton too. None of TAK1, TAB2 or PKA-Cα are yet catalogued here, and this is rare-mutation case data rather than a common-variant GWAS finding, so no new variant page was added -- filed here as a real, honest reinforcement of the cilia-and-heart-development theme already on this catalogue, not as evidence about bicuspid aortic valve specifically.
A bicuspid aortic valve is diagnosed by echocardiogram, often found incidentally or during workup for a heart murmur — not by genetic testing. Management is monitoring by regular echocardiogram for valve function and the aorta's diameter, with surgery (valve repair or replacement) if stenosis, regurgitation, or aortic dilation become severe enough. None of that pathway depends on genotype.
The variant here is not the study's mechanistic story. This study's real contribution — validated in animal models — is a cilia/exocyst pathway link to BAV. rs7543130/PALMD is a separate genome-wide-significant locus from the same dataset, not itself described in the source paper as part of that pathway.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Bicuspid Aortic Valve comes down to these specific, well-studied positions — not a diagnosis.
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Bicuspid Aortic Valve. MyGeneLog™. https://www.mygenelog.com/conditions/bicuspid-aortic-valve
Not on its own. The same study's real mechanistic finding — validated in zebrafish and mouse models — is a link to primary-cilia and exocyst-complex genes. The variant on this page, near PALMD, is a separate genome-wide-significant locus from the same dataset, not part of that validated pathway.
It is the most common congenital heart defect, present in roughly 1 in 100 to 1 in 200 people.
By echocardiogram, often incidentally — and then followed with regular imaging to watch for stenosis or aortic dilation, with surgery if either becomes severe. None of this depends on genotype.
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