RPRML is a single-exon and intronless gene located on the reverse strand of chromosome 17 between nucleotides 46,978,156 and 46,979,253 (GRCh38.p13 assembly). The gene spans 1.098 kb of genomic DNA within a dense CpG island.

The mRNA is 1.098 kb in length. Transcription is regulated by DNA methylation (Alarcon et al., 2020). According to the Genotype-Tissue Expression (GTEx) database (www.gtexportal.org), RPRML is expressed at very low levels in most tissues and mainly expressed in brain compartments.

RPRML is yet poorly known.

RPRML open reading frame encodes a 120-amino acid protein with an estimated molecular mass of 12.3 kDa. Predicted post-translational modifications include two N-glycosylation sites at amino acids 2 and 27, a sumoylation site at position 93, and two serine- phosphorylation sites at positions 9 and 108 (Amigo et al., 2018).

RPRML protein expression has been reported in glandular and foveolar epithelial cells of the gastric mucosa (Alarcón et al., 2020).

Bioinformatic predictions indicates it contains a single-pass transmembrane domain located between amino acids 67 and 87 (Amigo et al., 2018). However, immunohistochemical evidence and ectopic overexpression experiments indicate it is predominantly localized in the cytoplasm (Alarcón et al. 2020).

RPRML is expressed during normal embryonic development of zebrafish and is required for the formation of hematopoietic progenitors during hematovascular development (Figueroa et al,. 2017 and Stanic et al., 2019). In humans, it has tumor suppressor properties and when ectopically overexpressed in the AGS gastric cancer cell line it inhibits cell cycle progression at G2/M phase, reduces cell proliferation, clonogenic capacity and anchorage-independent growth (Alarcón et al. 2020). In gastric tumors, the loss of RPRML protein expression is associated with reduced apoptotic marker (Alarcón et al. 2020). RPRML expression in colorectal cancer cells is dependent on FRMD5 and CTNNB1 (β-catenin) expression, both components of the canonical Wnt signaling pathway (Zhu et al., 2017). The biological and pathological function of RPRML remains to be fully elucidated.

RPRML is a member of the Reprimo (RPRM) gene family. In humans, it shares 52.5% amino acid sequence identity with RPRM, mainly in the C-terminal domain (Wichmann et al., 2016).

No pathogenic mutations have been reported. However, its locus at 17q21 is often affected by chromosome rearrangements and segmental amplifications in multiple tumors.