MORC1 Gene: Function, Mutations, and Role in Spermatogenesis | NCBI, UniProt, OMIM

MORC1 (MORC family CW-type zinc finger 1) is a protein-coding gene located on chromosome 3q13.13. It encodes a nuclear protein containing a CW-type zinc finger domain and an ATPase domain, which is involved in chromatin remodeling and transcriptional repression. MORC1 plays a critical role in meiotic progression and spermatogenesis, particularly in the silencing of unsynapsed chromatin during male meiosis. It is essential for male fertility, as loss-of-function mutations lead to meiotic arrest and azoospermia. The protein also participates in epigenetic regulation through interaction with histone modifiers and DNA methylation pathways.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Meiotic recombination (Reactome: R-HSA-912446)

• Chromatin modifying enzymes (Reactome: R-HSA-3247509)

• Epigenetic regulation of gene expression (KEGG: hsa05202)

The MORC1 protein (UniProt Q86V20) is a 1,032-amino acid nuclear protein that belongs to the MORC family. It contains an N-terminal CW-type zinc finger domain that mediates interaction with methylated histones (H3K4me3), a central ATPase domain (GHKL-type) essential for chromatin remodeling, and a C-terminal coiled-coil region involved in homodimerization. MORC1 functions as a transcriptional repressor by promoting heterochromatin formation and silencing unsynapsed chromatin during male meiosis. It is highly expressed in testicular germ cells, particularly in pachytene spermatocytes. Loss of MORC1 leads to defective meiotic sex chromosome inactivation (MSCI), meiotic arrest, and apoptosis of spermatocytes, resulting in non-obstructive azoospermia and male infertility.