Chromosome 21, open reading frame 140 (C21orf140) is a protein which in humans is encoded by the C21orf140 gene. Its primary alias is Family With Sequence Similarity 243 Member A (FAM243A).
Gene 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.
Expression patterns 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.
Transcript and regulation C21orf140 has a single transcript, an mRNA that is 961 nucleotides long. 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.
In the coding region, sequences conserved in mammalian orthologs overlap with some identified transcription factor binding sites, including JUN, TFAP4, ETV1, and ZBTB18.
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.
Protein The C21orf140 protein contains 251 amino acids and a calculated molecular weight of ~29 kDa. Its theoretical isoelectric point is pH = 8.7. There is one known isoform. It is the sole member of the FAM243 protein family in humans, according to a UniProt query. It contains less alanine (3.6%) and less histidine (0.8%) than the average human protein.
Protein motifs
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.
Post-translational modifications The human C21orf140 protein is bioinformatically predicted to contain two phosphorylated serine residues, three phosphorylatedthreonine residues, and an N-glycosylated asparagine. Additionally, four cysteine pairs are predicted to form disulfide bonds. No protein modifications have been experimentally confirmed. +Predicted Human C21orf140 PTMsPredicted PTM Residue Location(s)Possible Functionphosphoserine16, 188activation or signalingphosphothreonine32, 57, 236activation or signalingN-glycosylated asparagine228protein sorting or foldingcysteine-cysteine disulfide bond26/73, 109/119, 157/176, 201/213protein tertiary structure formation 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.
Secondary and tertiary structures
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.
Protein interactions The C21orf140 protein has no known interactions with other human proteins other than co-mentions in an article listed in PubMed.
Evolutionary history
Paralogs An NCBI protein BLAST search against the human genome shows no paralogs of C21orf140 in humans.
Orthologs An NCBI protein BLAST search 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. +Selected Orthologs of Human C21orf140 ProteinScientific nameCommon nameTaxonomic groupMedian date of human divergence (MYA)NCBI Accession numberProtein size (aa)Sequence identity to human (%)Sequence similarity to human (%)Homo sapiensHumanPrimates0NP_001269466251100100Mus musculusHouse mouseRodentia87NP_08352825170.585.3Equus caballusDomestic horsePerissodactyla94XP_01459197924378.186.1Phocoena sinusVaquitaCetacea94XP_0324871422567787.5Indicator indicatorGreater honeyguideAves319XP_05424732525347.468.4Gallus gallusRed junglefowlAves319XP_00493459331640.257.6Crocodylus porosusSaltwater crocodileReptilia319XP_01938458725257.573.8Gekko japonicusSchlegel's Japanese geckoReptilia319XP_01527892525256.673.4Ascaphus trueiCoastal tailed frogAmphibia352XP_07544941025049.467.7Microcaecilia unicolorN/AAmphibia352XP_03005838925547.767.3Huso husoBeluga sturgeonActinopterygii429KAK647358325339.854.2Tachysurus fulvidracoYellow catfishActinopterygii429XP_02699174225227.643.5Heterodontus francisciHorn sharkChondrichthyes462XP_06790308925743.159.9Hemitrygon akajeiRed stingrayChondrichthyes462XP_07291596727336.653.3Vanessa atalantaRed admiralInsecta686XP_04754462348713.923.9Aphis gossypiiCotton aphidInsecta686XP_02783908046013.622.9Mytilus galloprovincialisMediterranean musselBivalvia686VDI4031654914.222.6Eriocheir sinensisChinese mitten crabCrustacea686XP_05072233153011.520.4Dysidea avaraN/APorifera758XP_06588373625220.134Amphimedon queenslandicaN/APorifera758XP_01140683345716.226.5
Clinical significance 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. 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. A 2022 oncogenomic study associated tumoral C21orf140 mutations with a lack of lasting benefit from hyperthermic intraperitoneal chemotherapy for gastric cancer.
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