C21orf140

Chromosome 21, open reading frame 140 (C21orf140)^[5] is a protein which in humans is encoded by the C21orf140 gene.^[6] Its primary alias is Family With Sequence Similarity 243 Member A (FAM243A).^[7]

C21orf140 is 961 base pairs long, located in chromosome 21 of the human genome at the coordinates 21q22.12 on the minus strand, position 34,400,112 to 34,401,072. It contains only one exon.^[6]

C21orf140 is widely expressed in most tissues, with the stomach and retina showing the highest expression levels. Little to no expression has been found in the parathyroid gland, rectum, epididymis, seminal vesicle, smooth muscle, tonsil, and thymus. Additionally, expression is seen in many regions of the brain, with the highest levels in the white matter and choroid plexus.^[8]

C21orf140 has a single transcript, an mRNA that is 961 nucleotides long.^[9] It has no 5' untranslated region (UTR).

Despite its lack of a 5' UTR, there are RBMX and PABPC1 RNA binding protein sites in the 60 nucleotides upstream of the C21orf140 start codon.^[10]

In the coding region, sequences conserved in mammalian orthologs overlap with some identified transcription factor binding sites, including JUN, TFAP4, ETV1, and ZBTB18.^[11]

The 3' UTR contains binding sites for the microRNAs miR-9-5p, miR-1294, miR-9986, miR-647, miR-628-3p, and miR-590-3p.^[10]

The C21orf140 protein contains 251 amino acids and a calculated molecular weight of ~29 kDa. Its theoretical isoelectric point is pH = 8.7.^[12] There is one known isoform. It is the sole member of the FAM243 protein family in humans, according to a UniProt query.^[13] It contains less alanine (3.6%) and less histidine (0.8%) than the average human protein.^[14]

The C21orf140 protein is predicted to contain mixed charge cluster from residues 110 to 141. The periodic pattern "LXX" repeats four times from residues 27 to 38. Another periodic pattern, “SXXXXLXXX," repeats four times from residues 154 to 193 (the letter X stands in for any amino acid). A predicted bipartite nuclear localization signal spans from residues 113 to 127.

The human C21orf140 protein is bioinformatically predicted to contain two phosphorylated serine residues, three phosphorylatedthreonine residues, and an N-glycosylated asparagine.^[15] Additionally, four cysteine pairs are predicted to form disulfide bonds.^[16] No protein modifications have been experimentally confirmed.^[5]

Though it has not been found yet, there may be a cleavage site to separate the portion of the protein containing the bipartite nuclear localization signal from the portion containing the N-glycosylated asparagine, allowing the former to be sorted to the nucleus and the latter to exist in the extracellular space.

The C21orf140 protein is predicted to contain a globular domain from residues 2 to 167. Residues 168 to 182 and 243 to 251 are predicted to be disordered regions.^[19]

The C21orf140 protein has no known interactions with other human proteins other than co-mentions in an article listed in PubMed.^[20]

An NCBI protein BLAST search against the human genome shows no paralogs of C21orf140 in humans.^[21]

An NCBI protein BLAST search^[21] shows orthologs of C21orf140 in mammals, birds, reptiles, amphibians, bony and cartilaginous fish, bivalves, insects, and sponges. A list of selected orthologs is shown below. C21orf140 has been moderately conserved across its evolutionary history. C21orf140 likely appeared around 758 million years ago in an ancient invertebrate ancestor, as evidenced by the most distant orthologs found in sponges of the phylum Porifera.

C21orf140 has been mentioned in the scientific literature in contexts with implications for human health. A 2024 proteomics study found that C21orf140 is downregulated in individuals with obsessive-compulsive disorder.^[22] A 2024 GWAS study mapped C21orf140 and its SNPs as one of twenty genes in a shared genetic risk cluster linked with conditions including schizophrenia, substance abuse disorders, bipolar disorder, and depression.^[23] A 2022 oncogenomic study associated tumoral C21orf140 mutations with a lack of lasting benefit from hyperthermic intraperitoneal chemotherapy for gastric cancer.^[24]