ALPK3 Heterozygous Truncating Variants Cause Late-Onset Hypertrophic Cardiomyopathy With Frequent Apical Involvement and Apical Aneurysm

Leora Busse^#^{1

2}, Emily A Huth^#^{1

2}, Maria Roselle Abraham³, Theodore Abraham³, Arun Padmanabhan^{1

2

4}, Julianne Wojciak^{1

2}, Gabrielle Wright⁵, Rajani Aatre⁶, Rachel Campagna⁷, Erika Jackson⁸, Sarah Kreykes⁹, Kimberly Lane¹⁰, Lindsey Sawyer¹¹, Chelsea Pappas¹², Matthew Thomas¹³, Rebecca VanDyke¹⁴, Vasanth Vedantham^{1

2

4}, Emily J Higgs^{1

2}

Affiliations

¹ Cardiovascular Genetics Center (L.B., E.A.H., A.P., J.W., V.V., E.J.H.), University of California, San Francisco.
² Cardiology Division, Cardiovascular Research Institute (L.B., E.A.H., A.P., J.W., V.V., E.J.H.), University of California, San Francisco.
³ University of California, San Francisco Hypertrophic Cardiomyopathy Center of Excellence, Division of Cardiology (M.R.A., T.A.), University of California, San Francisco.
⁴ Department of Medicine and Cardiovascular Research Institute (A.P., V.V.), University of California, San Francisco.
⁵ University of California San Francisco Genetic Counseling Program (G.W.).
⁶ Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor (R.A.).
⁷ Heart and Vascular Center, University of Chicago Medicine, IL (R.C.).
⁸ Knight Cardiovascular Institute, Oregon Health and Science University, Portland (E.J.).
⁹ Cardiovascular Division, University of Minnesota, Minneapolis (S.K.).
¹⁰ Baylor Scott & White The Heart Hospital at Plano, TX (K.L.).
¹¹ Division of Genetics, Department of Pediatrics, Children's Hospital of the Kings Daughters, Norfolk, VA (L.S.).
¹² Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.P.).
¹³ Division of Cardiology, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville (M.T.).
¹⁴ Bluhm Cardiovascular Institute, Northwestern Medicine, Winfield, IL (R.V.D.).

^# Contributed equally.

Leora Busse et al. Circ Genom Precis Med. 2025 Aug.

. 2025 Aug;18(4):e005186.

doi: 10.1161/CIRCGEN.125.005186. Epub 2025 Jun 5.

¹ Cardiovascular Genetics Center (L.B., E.A.H., A.P., J.W., V.V., E.J.H.), University of California, San Francisco.
² Cardiology Division, Cardiovascular Research Institute (L.B., E.A.H., A.P., J.W., V.V., E.J.H.), University of California, San Francisco.
³ University of California, San Francisco Hypertrophic Cardiomyopathy Center of Excellence, Division of Cardiology (M.R.A., T.A.), University of California, San Francisco.
⁴ Department of Medicine and Cardiovascular Research Institute (A.P., V.V.), University of California, San Francisco.
⁵ University of California San Francisco Genetic Counseling Program (G.W.).
⁶ Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor (R.A.).
⁷ Heart and Vascular Center, University of Chicago Medicine, IL (R.C.).
⁸ Knight Cardiovascular Institute, Oregon Health and Science University, Portland (E.J.).
⁹ Cardiovascular Division, University of Minnesota, Minneapolis (S.K.).
¹⁰ Baylor Scott & White The Heart Hospital at Plano, TX (K.L.).
¹¹ Division of Genetics, Department of Pediatrics, Children's Hospital of the Kings Daughters, Norfolk, VA (L.S.).
¹² Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.P.).
¹³ Division of Cardiology, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville (M.T.).
¹⁴ Bluhm Cardiovascular Institute, Northwestern Medicine, Winfield, IL (R.V.D.).

^# Contributed equally.

No abstract available

Keywords: cardiomyopathies; genetics; genotype; humans; phenotype.

Conflict of interest statement

V.V. has received research grants from Tenaya Therapeutics for unrelated projects. The other authors report no conflicts.

ALPK3 heterozygous truncating variants cause late-onset hypertrophic cardiomyopathy with frequent apical involvement and apical aneurysm.
Busse L, Huth EA, Abraham MR, Abraham T, Padmanabhan A, Wojciak J, Wright G, Aatre R, Campagna R, Jackson E, Kreykes S, Lane K, Sawyer L, Stevens C, Thomas M, VanDyke R, Vedantham V, Higgs EJ. Busse L, et al. medRxiv [Preprint]. 2024 Nov 15:2024.11.14.24317359. doi: 10.1101/2024.11.14.24317359. medRxiv. 2024. Update in: Circ Genom Precis Med. 2025 Aug;18(4):e005186. doi: 10.1161/CIRCGEN.125.005186. PMID: 39606411 Free PMC article. Updated. Preprint.