C22orf42, short for Chromosome 22 Open Reading Frame 42, is a protein-coding gene located on the long arm of chromosome 22 at position q12 C22orf42 weighs 27.679 kilodaltons and is thought to be widely expressed in biological contexts, including pituitary adenomaCheng, S., Xie, W., Miao, Y., Guo, J., Wang, J., Li, C., & Zhang, Y. (2019, December 3). Identification of key genes in invasive clinically non-functioning pituitary adenoma by integrating analysis of DNA methylation and mrna expression profiles - journal of translational medicine. SpringerLink. https://link.springer.com/article/10.1186/s12967-019-02148-3 , impaired spermatogenesisTang Q;Wu W;Lu Y;Zhou Y;Wu W;Li J;Pan L;Ling X;Pan F; (n.d.). Joint analysis of M6A and mrna expression profiles in the testes of idiopathic nonobstructive azoospermia patients. Frontiers in endocrinology. https://pubmed.ncbi.nlm.nih.gov/36589848/ , and stress responseKalinowski J, Huang Y, Rivas MA, et al. Stress Overload and DNA Methylation in African American Women in the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure Study. Epigenetics Insights. 2022;15. doi:10.1177/25168657221126314. While the main molecular function remains to be discovered, recent studies have suggested C22orf42 may be subject to regulation via methylation and RNA modification mechanisms, which could influence its expression in specific developmental or disease contexts.

Gene

The mRNA transcript for C22orf42 consists of a sequence of 1,378 base nucleotidesU.S. National Library of Medicine. (n.d.-b). Homo sapiens chromosome 22 open reading frame 42 (C22ORF42), mrna - nucleotide - NCBI. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/nuccore/NM_001010859.3 . It contains 9 exons, and the full transcript includes: a nuclear localization signal at the beginning and end of this sequence, multiple predicted phosphorylation sites, multiple internal repeats, a polyA signal sequence located between the 1358 and 1363 base pairs, and a polyA site on the last base pair of transcription.

Protein

Primary Sequence The C22orf42 gene encodes a protein consisting of 251 amino acids.U.S. National Library of Medicine. (n.d.-b). Uncharacterized protein c22orf42 [homo sapiens] - protein - NCBI. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/protein/NP_001010859.1 . The protein is predicted to localize to the cytoplasm and may be involved in intracellular signaling or structural regulation within the testis and the brain. However, these functions remain hypothetical due to limited experimental validation.

Sub-Cellular localization

DeepLocDeepLoc-2.0. https://services.healthtech.dtu.dk/cgi-bin/webface2.cgi?jobid=6886AF2D0013B7385F4C528C&wait=20 approximately predicted a 59% localization to the cytoplasm and approximately 40% to the nucleus, 35% to the cell membrane, and 28% to the mitochondria. Since cytoplasm was the highest prediction, C22orf42 is predicted to be localized in the cytoplasm.

Post-Translational Modifications

Predicted phosphorylation sites in the human C22orf42 protein using NetPhos 3.1NetPhos. Bioinformatic tools and services - DTU health tech. (n.d.-b). https://services.healthtech.dtu.dk/cgi-bin/webface2.cgi?jobid=6886ADB50013B65E0306FB21&wait=20 . Peaks above the magenta threshold line (0.5) indicate high-confidence phosphorylation sites, with serine (red), threonine (green), and tyrosine (blue) residues mapped across the sequence. A notable cluster of predicted serine phosphorylation sites is observed between residues 175 and 225.

Ortholog Sequences

C22orf42 is conserved across primates only and has only one known paralog, DRICH1DRICH1. Genecards. (n.d.). https://www.genecards.org/cgi-bin/carddisp.pl?gene=DRICH1 . Orthologous sequences of C22orf42 were analyzed by sorting them according to their median date of divergence and categorizing them by genus name, common name, taxonomic group, accession number, sequence length (in amino acids), sequence identity to the human protein, and sequence similarity to the human protein. As C22orf42 is a gene exclusive to primates, no orthologs were identified outside this taxonomic group. The Crab-eating macaque (Macaca fascicularis) represents the most distantly related species with a median divergence time of 28.8 million years and a sequence identity of 25.1%. Sequence identities and similarities were determined using the EMBOSS NEEDLEEmbl-Ebi. (n.d.-a). ClustalO. EMBL-Ebi Homepage. https://www.ebi.ac.uk/jdispatcher/msa/clustalo?stype=protein pairwise alignment tool.

+ Orthologs of C22orf42Genus and SpeciesCommon NameTaxonomic Group (Order)Date of Divergence (MYA)Accession #Sequence Length (aa)Sequence Identity (%)Homo sapiensHumanPrimate0NP_001010859.1251100Pan TroglodytesChimpanzeeApes6.4NP_001266945.120781.51Pan piniscusBonoboApes6.4XP_054961926.222181.09Pongo abelii Sumatran OrangutanApes15.2XP_054399340.219276.81Pongo pygmaeusBornean OrangutanApes 15.2XP_054326077.119276.81Macaca nemestrinaSouthern Pig-tailed MacaqueOld World Monkey28.8XP_070936571.134935.3Macaca mulattaIndochinese Rhesus MacaqueOld World Monkey28.8XP_028683601.140529.6Rhinopithecus roxellanaGolden Snub-Nosed MonkeyOld World Monkey28.8 XP_030771153.137626Chlorocebus SabaeusGreen MonkeyOld World Monkey28.8XP_072863228.123224.9Condylura cristataStar-nosed MoleEulipotyphla28.8XP_00467650716725.1

Expression Gene Expression C22orf42 displays a tissue-specific expression profile, with the highest RNA levels detected in the testis ~3.2 RPKM, according to RNA-seq data from the Human Protein Atlas (HPA) across 27 human tissues.U.S. National Library of Medicine. (n.d.-d). C22ORF42 chromosome 22 open reading frame 42 [homo sapiens (human)] - gene - NCBI. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/gene/150297 Sequencing was performed on samples from 95 individuals, and expression values are reported in RPKM (reads per kilobase of transcript per million). Moderate expression was observed in the Stomach, Prostate, and Salivary gland, while most other tissues exhibited minimal or undetectable levels, indicating restricted expression primarily in male reproductive tissues.

Additional insights from the NCBI Gene Expression Omnibus (GEO) dataset GDS2697U.S. National Library of Medicine. (n.d.-f). GDS2697 / 224567_x_at. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS2697%3A224567_x_at reinforce this expression pattern. C22orf42 expression is reduced in patients with Teratozoospermia compared to individuals with normal sperm. In the normal group, expression counts are consistently higher, and percentile ranks remain near the upper quartile. In contrast, the teratozoospermic group exhibits lower expression levels, with several samples falling below the 25th percentile and one showing a complete absence of detectable signal. These findings suggest that C22orf42 may play a role in maintaining normal sperm structure or development and could be disrupted in male infertility disorders.

Protein Expression

Immunochemistry analysis using Thermo ScientificC22orf42 polyclonal antibody. C22orf42 Polyclonal Antibody (PA5-54015). (n.d.). shows C22orf42 protein localization split into two images. The left image displays strong antibody staining in the testis, indicating high protein expression, while the right image shows weak staining in the kidney, reflecting low protein abundance. Antibody binding appears to be primarily cytoplasmic, supporting tissue-specific protein expression.

References