MCM9 Gene: Function, Mutations, and Associated Diseases | NCBI, UniProt, ClinVar

MCM9 (Minichromosome Maintenance 9) is a protein-coding gene that encodes a member of the minichromosome maintenance (MCM) protein family. Unlike canonical MCM proteins involved in DNA replication initiation, MCM9 functions primarily in DNA homologous recombination repair and maintenance of genome stability. It forms a complex with MCM8 that is essential for homologous recombination-mediated DNA double-strand break repair and meiotic recombination. MCM9 is also critical for replication fork stability and telomere maintenance. Loss-of-function mutations in MCM9 cause primary ovarian insufficiency and are associated with increased cancer risk.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Homologous recombination repair (Reactome: R-HSA-5693568)

• Meiotic recombination (Reactome: R-HSA-1500620)

• DNA double-strand break repair (KEGG: hsa03440)

• Fanconi anemia pathway (KEGG: hsa03460)

MCM9 is a 1143-amino acid protein (UniProt Q9NXL9) belonging to the MCM family of AAA+ ATPases. It contains an MCM N-terminal domain and a C-terminal winged-helix domain. MCM9 forms a stable complex with MCM8, which together function as a DNA helicase essential for homologous recombination repair. The MCM8-MCM9 complex promotes the extension of recombination intermediates and facilitates the repair of DNA double-strand breaks. MCM9 is also involved in replication fork stabilization and telomere maintenance. Its expression is highest in testis and ovary, consistent with its critical role in meiosis. Mutations in MCM9 cause primary ovarian insufficiency and increase susceptibility to various cancers.