Here we want to draw some attention to one of the rather unknown but interesting genes that we have encountered, the TMEM253 gene specifically expressed in the intestine.

The intestine is part of the gastrointestinal tract and the major site of food breakdown and nutrient absorption. The small intestine is an approximately 5.5-meter-long organ, including the duodenum, jejunum, and ileum, where lipids and carbohydrates in the semifluid mass from the stomach are degraded by bile and pancreatic fluids and here most of the absorption of nutrients from food takes place. The cecum, colon and rectum make up the 1.5 meters long large intestine where gut microbiota ferment unabsorbed material and remaining water, electrolytes and vitamins are absorbed. Transcriptome analysis shows that 75% of all human proteins are expressed in this important organ system with almost 400 genes showing enriched expression in the intestine compared to other tissue types.

Many of the intestine enriched genes are well-known with known functions, but among them we also find TMEM253, a rather unknown gene with few publications and neither known function nor protein evidence in UniProt. That this "Gene Doe" has a function in the intestine is however strongly suggested by the expression profile in both bulk and single cell RNA seq showing enrichment in intestine and more specifically distal and proximal enterocytes. Expression clustering and correlation of tissue and single cell RNA seq data further show TMEM253 to cluster together with other genes known to be related to absorption in small intestine and enterocytes. Immunohistochemical staining of the protein confirms these findings by showing high and specific expression in enterocytes in duodenum, small intestine, colon and rectum.