Aortic aneurysm, familial thoracic 7: genes and variants

Genes linked to Aortic aneurysm, familial thoracic 7

• ACTA2: Actin, aortic smooth muscle

  Its smooth-muscle actin filaments generate contractile force in arteries and visceral organs and help maintain vascular-wall structure. Pathogenic variants are an important cause of familial thoracic aortic aneurysm and dissection and can also produce occlusive vascular disease.

  20 disease-causing and 159 uncertain variants in ACTA2 are linked to Aortic aneurysm, familial thoracic 7.

• MYH11: Myosin-11

  Its smooth-muscle myosin motor generates contractile force in arteries and visceral organs. Pathogenic variants can impair aortic smooth-muscle mechanics and cause familial thoracic aortic aneurysm and dissection, sometimes with patent ductus arteriosus.

  4 disease-causing and 842 uncertain variants in MYH11 are linked to Aortic aneurysm, familial thoracic 7.

• LOX: Protein-lysine 6-oxidase

  It oxidatively initiates covalent crosslinking of collagen and elastin, strengthening arteries and other extracellular matrices. Pathogenic loss-of-function variants can weaken the aortic wall and predispose to familial thoracic aortic aneurysm and dissection.

  3 disease-causing and 24 uncertain variants in LOX are linked to Aortic aneurysm, familial thoracic 7.

• MYLK: Myosin light chain kinase, smooth muscle

  It phosphorylates myosin regulatory light chains to initiate smooth-muscle contraction in blood vessels and visceral tissues. Pathogenic loss-of-function variants can reduce arterial contractile integrity and cause familial thoracic aortic aneurysm and dissection.

  2 disease-causing and 884 uncertain variants in MYLK are linked to Aortic aneurysm, familial thoracic 7.

• PRKG1: cGMP-dependent protein kinase 1

  It transduces cyclic-GMP signals from nitric oxide and natriuretic peptides to promote vascular smooth-muscle relaxation and regulate vascular tone. A recurrent activating variant causes highly penetrant familial thoracic aortic aneurysm and dissection.

  1 disease-causing and 159 uncertain variants in PRKG1 are linked to Aortic aneurysm, familial thoracic 7.

Weakly linked (only a few uncertain records): COL3A1, SLC2A10, SMAD3 and TGFBR1.

Known disease-causing variants in Aortic aneurysm, familial thoracic 7

Uncertain variants in Aortic aneurysm, familial thoracic 7 that look disease-causing

Which prediction tools work for Aortic aneurysm, familial thoracic 7

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• AlphaMissense: 99 out of 100
• REVEL: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MutPred2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 94 out of 100
• phyloP: 89 out of 100
• SIFT: 87 out of 100
• PolyPhen-2: 79 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Familial thoracic aortic aneurysm and aortic dissection is also caused by ACTA2 variants; they fall in the same places as the Aortic aneurysm, familial thoracic 7 variants (8 disease-causing).

Diseases related to Aortic aneurysm, familial thoracic 7

• Familial thoracic aortic aneurysm and aortic dissection, also linked to ACTA2, LOX, MYH11, MYLK and 1 more
• Connective tissue disorder, also linked to MYH11 and MYLK
• Isolated thoracic aortic aneurysm, also linked to ACTA2 and MYH11
• Familial aortopathy, also linked to ACTA2
• Marfan syndrome/loeys-dietz syndrome/familial thoracic aortic aneurysms and dissections, also linked to LOX
• Cutis laxa, also linked to LOX
• Multisystemic smooth muscle dysfunction syndrome, also linked to ACTA2
• Thoracic aortic aneurysm or dissection, also linked to ACTA2
• Congenital aneurysm of ascending aorta, also linked to LOX
• Moyamoya disease, also linked to ACTA2

Frequently asked questions

Which genes are linked to Aortic aneurysm, familial thoracic 7?

In CATVariant, Aortic aneurysm, familial thoracic 7 is linked to 5 analyzed proteins: ACTA2 (Actin, aortic smooth muscle), MYH11 (Myosin-11), LOX (Protein-lysine 6-oxidase), MYLK (Myosin light chain kinase, smooth muscle) and PRKG1 (cGMP-dependent protein kinase 1).

How many genetic variants are linked to Aortic aneurysm, familial thoracic 7?

2,188 variants: 30 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2,072 are of uncertain significance or have conflicting reports.

Which uncertain variants in Aortic aneurysm, familial thoracic 7 look disease-causing?

2 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example ACTA2 R118W and ACTA2 R149H. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Aortic aneurysm, familial thoracic 7?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.99, based on 18 disease-causing and 15 harmless variants).

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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