Heterogeneous nuclear ribonucleoprotein H2 (HNRNPH2)

Heterogeneous nuclear ribonucleoprotein H2 (HNRNPH2) is a ubiquitously expressed RNA-binding protein that complexes with heterogeneous nuclear RNA (hnRNA) in the nucleus, regulating pre-mRNA processing, alternative splicing, and aspects of mRNA metabolism and transport[1][2][4]. It contains three quasi-RRM domains for RNA binding and shuttles between the nucleus and cytoplasm. HNRNPH2 plays a key role in the control of alternative splicing, including in the telomerase reverse transcriptase pathway, thereby influencing cancer cell survival by modulating apoptosis resistance and telomerase activity[2]. Pathogenic mutations in HNRNPH2, particularly affecting the nuclear localization signal, cause a neurodevelopmental disorder characterized by intellectual disability, developmental delays, epilepsy, and musculoskeletal symptoms[3][5]. These disease phenotypes stem from protein mislocalization to RNA granules and disruption of activity-dependent gene expression, rather than from simple protein loss. Therapeutic approaches under investigation include antisense oligonucleotides to knock down mutant HNRNPH2 and restore gene expression balance via upregulation of the paralog HNRNPH1[3][5]. The protein is also implicated in X-linked agammaglobulinemia and Fabry disease[1][2][4].

Other names

HNRNPH'FTP3HNRPH2hnRNP H2hnRNP H'hnRNPH'MRXSBNRPH2epididymis secretory sperm binding proteinheterogeneous nuclear ribonucleoprotein H-primeFTP-3heterogeneous nuclear ribonucleoprotein H2 (H')

Antisense oligonucleotides: reduce expression of mutant HNRNPH2, restoring functional compensation by HNRNPH1