Categories: Cardiovascular system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 600958 (gene) , 615396 (trait) , 115197 (trait)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2005

Cross-species summary: Increase in volume of the muscle tissue of the heart, due to an increase in the size of muscle cells, primarily in the left ventricle and ventricular septum due to recessive variants in the MYBPC3 gene

Species-specific name: Feline familial HCM

Species-specific symbol: HCM

Species-specific description: Information listed here was previously listed under 'OMIA:000515-9685 : Cardiomyopathy, hypertrophic', an entry that now describes generic information about HCM. See also 'OMIA:002951-9685 : Cardiomyopathy, hypertrophic, MYBPC3-related, autosomal dominant' [30/04/2025]. 
The original entry was edited by Meg Sleeper, VMD and Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT and has been updated.

Inheritance: Boeykens et al. (2024) and Longeri et al. (2013) support a recessive mode of inheritance for HCM related to omia.variant:901.

Molecular basis: HCM is genetically heterogeneous in the overall cat population. By sequencing a very likely comparative candidate gene (based on the homologous human disorder), Meurs et al. (2005) identified the causative mutation in Maine Coon cats as a G to C substitution in exon 3, codon 31 of MYBPC3 (omia.variant:901). This changes a conserved amino acid (alanine to proline; A31P), which most likely changes protein conformation. The exact role of this myosin binding protein C, cardiac is still unknown, though it may bind myosin or actin, or interact with other cardiac proteins that form sarcomeres (Meurs et al., 2005).  Meurs et al. (2007) identified the causative mutation in Ragdoll cats as a C to T substitution in the same gene (MYBPC3), which changes the amino acid from arginine to tryptophan (R820W, omia.variant:902, see 'OMIA:002951-9685 : Cardiomyopathy, hypertrophic, MYBPC3-related, autosomal dominant'). As a result, the secondary structure of the myosin binding protein is changed, affecting sarcomere function. Wess et al. (2010) proposed that a third mutation A74T is causative in Maine Coons, but the explanations by Kittleson et al. (2010) and the extensive data of Longeri et al. (2013) have, in essence, disproved this claim. Boeykens et al. (2024) classified the variant MYBPC3:c.91G>C [A31P] as a pathogenic variant using modified American College of Medical Genetics and Genomics guidelines. 

Breeds: Maine Coon (Cat) (VBO_0100154), Maine Coon Polydactyl (Cat) (VBO_0100155), Munchkin (Cat) (VBO_0100169), Pixiebob Longhair (Cat) (VBO_0100192), Scottish Fold (Cat) (VBO_0100209), Siberian (Cat) (VBO_0100223).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).

Associated gene: