Alternative titles; symbolsCHROMOSOME 16 OPEN READING FRAME 75; C16ORF75BLM-ASSOCIATED PROTEIN, 18-KD; BLAP18HGNC Approved Gene Symbol: RMI2Cytogenetic location:...
Alternative titles; symbols
HGNC Approved Gene Symbol: RMI2
Cytogenetic location: 16p13.13 Genomic coordinates (GRCh38): 16:11,345,458-11,351,759 (from NCBI)
RMI2 is a component of the BLM (RECQL3; 604610) complex, which plays a role in homologous recombination-dependent DNA repair and is essential for genome stability (Xu et al., 2008).
▼ Cloning and Expression
Xu et al. (2008) and Singh et al. (2008) independently identified RMI2 as a component of the BLM complex purified from cultured human cell lines. The deduced 147-amino acid protein has a single oligonucleotide-binding (OB)-fold domain. RMI2 had an apparent molecular mass of 18 to 20 kD by SDS-PAGE. RMI2 orthologs were detected in vertebrates and plants, but not in lower organisms.
▼ Gene Function
Xu et al. (2008) found that RMI1 (610404) and RMI2 were present in approximately stoichiometric amounts with other BLM complex components, including topoisomerase-3-alpha (TOP3A; 601243), RPA (see RPA1; 179835), and BLAP250. RMI2 also associated with RMI1 and TOP3A in a second complex. RMI1 and RMI2 interacted directly, and both were essential for stability of the BLM complex. Depletion of either RMI1 or RMI2 depleted the other protein by 80 to 90%. Chicken DT40 cells depleted of Rmi2 displayed elevated sister chromatid exchange, but other functions of the BLM complex appeared intact. Mutation analysis revealed that interaction between human RMI2 and BLM was essential for suppression of sister chromatid exchange. Singh et al. (2008) presented similar findings and found that RMI2 was required for the targeting of the BLM complex to chromatin and for assembly of BLM foci in response to replication stress. They also showed that RMI2, like BLM, was phosphorylated during mitosis.
Hartz (2008) mapped the RMI2 gene to chromosome 16p13.13 based on an alignment of the RMI2 sequence (GenBank BC013040) with the genomic sequence (build 36.1).
▼ Molecular Genetics
Associations Pending Confirmation
In 2 sibs, born of consanguineous Pakistani parents, with a Bloom syndrome-like phenotype (see BLM, 210900), Hudson et al. (2016) identified a homozygous 80-kb deletion at chromosome 16p13.13, resulting in the deletion of the entire RMI2 gene and the microRNA gene MIR548H2. The deletion, which was found by microarray analysis, segregated with the disorder in the family. Patient cells showed increased chromosome and/or chromatid breaks, increased sister chromatid exchange, increased micronuclei, and increased chromatin threads or bridges compared to controls, suggesting genomic instability. Similar abnormalities were observed in RMI2-null cells. Although removal of RMI2 had a profound effect on the stability of BLM (604610), it was not essential to the enzymatic capability of the BTR complex, which may explain the milder phenotype in these patients. The patients were 6 and 4 years of age. Both had cafe-au-lait spots apparent from infancy, but only the younger sib had pre- and postnatal growth restriction and gastroesophageal reflux.