Left ventricular noncompaction (LVNC) is a heterogeneous disorder with unclear genetic causes and an unknown mechanism. eIF3a

an important member of the Eukaryotic translation initiation factor 3 (eIF3) family

is involved in multiple biological processes

including cell proliferation and migration during myocardial development

suggesting it could play a role in LVNC development. To investigate the association between a novel variant (c.1145 A- 

>

 G) in eIF3a and LVNC

and explore potential mechanisms that could lead to the development of LVNC. A novel eIF3a variant

c.1145 A- 

>

 G

was identified by whole-exome sequencing in a familial pedigree with LVNC. Adenovirus vectors containing wild-type eIF3a and the mutated version were constructed and co-infected into H9C2 cells. Cell proliferation

apoptosis

cell migration

and differentiation

as well as phosphorylation of ERK1/2 were studied and were measured by proliferation assays

flow cytometry

real-time PCR and Western blot

respectively. The eIF3a mutation inhibited the proliferation of H9C2 cells

induced apoptosis

promoted cell migration

and inhibited the differentiation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The effect of the eIF3a mutation may be attributed to a decrease in expression of p-ERK1/2. A novel

eIF3a

gene mutation disrupted the p-ERK1/2 pathway and caused decreased myocardium proliferation

differentiation

accelerated migration.This finding may provide some insight into the mechanism involved in LVNC development.