FHL2 Gene - Four and a Half LIM Domains 2 | Function, Mutations & Disease

FHL2 (Four and a Half LIM Domains 2) encodes a member of the four-and-a-half-LIM-only protein family. The protein contains four and a half LIM domains and functions as a transcriptional coactivator or corepressor depending on the cellular context. It interacts with a wide range of transcription factors, nuclear receptors, and signaling molecules, playing roles in cell differentiation, proliferation, migration, and apoptosis. FHL2 is implicated in cardiac hypertrophy, bone development, and various cancers including breast, prostate, and colorectal cancer.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Androgen receptor signaling pathway

• Wnt/β-catenin signaling pathway

• Calcineurin/NFAT signaling pathway

• RhoA/ROCK signaling pathway

• TGF-β signaling pathway

FHL2 is a 279-amino acid protein containing four complete LIM domains and one N-terminal half LIM domain. It lacks a catalytic domain and functions as an adaptor that shuttles between the nucleus and cytoplasm. Through its LIM domains, FHL2 interacts with transcription factors (e.g., androgen receptor, β-catenin, NFAT), kinases, and structural proteins. It modulates gene expression in a context-dependent manner, acting as a coactivator or corepressor. FHL2 is highly expressed in heart and skeletal muscle, and its dysregulation contributes to cancer progression and cardiac hypertrophy.