RNF212 Gene - Meiotic Recombination, Fertility, and Genetic Variants | NCBI, UniProt, OMIM

RNF212 (Ring Finger Protein 212) encodes a RING finger domain-containing protein that is essential for meiotic recombination. It acts as a dosage-sensitive regulator of crossover formation during meiosis, promoting the stabilization of crossover-specific recombination intermediates. RNF212 is orthologous to the yeast Zip3 and C. elegans ZHP-3 proteins. The protein localizes to meiotic chromosomes and is required for the formation of synaptonemal complex and crossover interference. Variants in RNF212 have been associated with human infertility and reproductive aging.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

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

• Synaptonemal complex assembly (Reactome: R-HSA-1500620)

• Formation of crossover intermediates (Reactome: R-HSA-5696398)

RNF212 is a 305-amino acid RING finger protein that localizes to meiotic chromosomes. It contains a RING-type zinc finger domain (residues 30-70) required for E3 ubiquitin ligase activity and protein-protein interactions. The protein is essential for stabilizing crossover-specific recombination intermediates during meiosis. RNF212 interacts with other meiotic proteins such as MSH4, MSH5, and SYCP1. Its expression is highest in testis and ovary, consistent with its role in gametogenesis. Structural studies indicate that the RING domain coordinates two zinc ions and mediates ubiquitination of target proteins involved in crossover designation.