Immunoglobulin mu DNA-binding protein 2 (IGHMBP2)

Immunoglobulin mu DNA-binding protein 2 (IGHMBP2) is a member of the helicase superfamily 1 (SF1) that functions as an ATP-dependent 5' to 3' DNA/RNA helicase [1, 3]. It plays a vital role in various cellular processes, including RNA metabolism, ribosome biogenesis, translation initiation, and DNA replication [1, 4]. Although ubiquitously expressed, IGHMBP2 is particularly critical for the survival and maintenance of alpha-motor neurons in the spinal cord [4, 11]. Mutations in the IGHMBP2 gene are the primary cause of severe neuromuscular disorders, most notably spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth disease type 2S (CMT2S) [6, 10]. SMARD1 is characterized by early-onset muscle weakness and life-threatening diaphragmatic paralysis, while CMT2S presents as a milder, progressive axonal neuropathy [10, 11]. Currently, there are no FDA-approved treatments, but therapeutic development is actively pursuing gene replacement therapies (e.g., AAV9-IGHMBP2) and antisense oligonucleotides (e.g., VCA-894A) to restore functional protein levels and helicase activity [17, 24].

Other names

IGHMBP2DNA-binding protein SMUBP-2Cardiac transcription factor 1 (CATF1)Glial factor 1 (GF-1)Zinc finger AN1-type domain 7 (ZFAND7)HMN6SMARD1CMT2SHMNR1SMBP2HCSA