Submission declined on 17 June 2026 by ChrysGalley (talk). There are two main issues that need to be fixed: (a) you can't have direct URLs in articles as you have in Abnormal physiological conditions. The last section, Clinical significance, there is big gap between what is said there and robust sourcing. At the moment it contravenes WP:MEDRS. If you would like to continue working on the submission, click on the "Edit" tab at the top of the window. If you have not resolved the issues listed above, your draft will be declined again and potentially deleted. If you need extra help, please ask us a question at the AfC Help Desk or get live help from experienced editors. Please do not remove reviewer comments or this notice until the submission is accepted. Where to get help If you need help editing or submitting your draft, please ask us a question at the AfC Help Desk or get live help from experienced editors. These venues are only for help with editing and the submission process, not to get reviews. If you need feedback on your draft, or if the review is taking a lot of time, you can try asking for help on the talk page of a relevant WikiProject. Some WikiProjects are more active than others so a speedy reply is not guaranteed. How to improve a draft Wikipedia:Contributing to Wikipedia – a basic overview on how to edit Wikipedia. Help:Wikitext – how to use the markup Help:Referencing for beginners – how to include references Wikipedia:Article development – how to develop your article Wikipedia:Writing better articles – how to improve your article Wikipedia:Verifiability – make sure your article includes reliable third-party sources You can also browse Wikipedia:Featured articles and Wikipedia:Good articles to find examples of Wikipedia's best writing on topics similar to your proposed article. Improving your odds of a speedy review To improve your odds of a faster review, tag your draft with relevant WikiProject tags using the button below. This will let reviewers know a new draft has been submitted in their area of interest. For instance, if you wrote about a female astronomer, you would want to add the Biography, Astronomy, and Women scientists tags. Add tags to your draft Editor resources Easy tools: Citation bot (help) | Advanced: Fix bare URLs Declined by ChrysGalley 54 days ago. Last edited by Citation bot 54 days ago. Reviewer: Inform author. Resubmit Please note that if the issues are not fixed, the draft will be declined again.

Transmembrane protein 74B (TMEM74B) which is also known as C20orf46 is a protein which in humans is encoded by the TMEM74B gene. TMEM74B is involved in protein binding and is localized to the plasma membrane.^[1]

The human TMEM74B gene is on chromosome 20 (20p13)^[2]. It is located on the minus strand, spanning approximately 8,849 base pairs. It is flanked upstream by the RAD21L1 (Rad21 Cohesion Complex Component Like 1), which encodes a nuclear cohesion complex protein critical for chromosome pairing, sister chromatid cohesion, and DNA repair during meiosis.^[3] Downstream, it is flanked by the PSMF1 (Proteasome Inhibitor Subunit 1) which encodes a structural regulator that binds and inhibits the 20s proteasome complex to modulate intracellular protein degradation and turnover.^[4]

A multiple dataset analysis of the 3 RNA-sequence data sets from the gene database record at NCBI for human TMEM74B^[5][6][7], microarray NCBI GEO profiles GDS3113^[8], GDS3834^[9], and GDS1096^[10] across all tissues, and in situ hybridization data^[11], indicates that under normal physiological conditions human TMEM74B is expressed at overall low to moderate levels and is tissue specific^[12]. The highest expressed tissues overall were the small intestine and duodenum within the gastrointestinal tract, fetal and developing tissues in the central nervous system, and at specific somatic barrier tissues such as the lungs and placenta.

Analyzation of microarray NCBI GEO profiles of abnormal physiological conditions; high and low chromosomal instability phenotypes in stage 2 and 3 colorectal cancers, type 2 diabetes pancreatic beta cells, and human herpes virus infection of primary pulmonary microvascular cells indicated that under abnormal and unstable physiological conditions such as viral stress^[13], metabolic disease^[14], or high chromosomal instability^[15] TMEM74B is expressed at higher levels.^[13][14][15]

Human TMEM74B has 17 transcript variants^[16] that encode 7 protein isoforms^[17]. 9 of these transcript variants are human reviewed alternative variants that all together encode 2 protein isoforms. The other 8 transcript variants which were identified by computational modeling and await manual curation encode 5 protein isoforms. The primary referenced transcript is variant 2 (NM_001304748.2) which has a length of 1876 nucleotides, contains 3 exons and encodes isoform 1 (NP_001291677.1).

The primary referenced protein isoform of human TMEM74B, isoform 1, is encoded by transcript variant 2 and is composed of 256 amino acids and has an approximate molecular weight of 27.6 kDa^[18]. The calculated isoelectric point (pI) for the complete sequence is 6.97^[19]. This neutral score is atypical for a human transmembrane protein, which tend to skew basic with isoelectric points in the 8.5-9.5 range^[20]. Statistical Analysis of Protein Sequences (SAPS) demonstrated that this global neutrality is maintained by highly polarized, offsetting, structural microdomains^[21]. The protein has a highly polarized structure with a neutral global scale that is a result of basic regulatory cluster balancing out the heavily acidic disordered loops and slightly acidic transmembrane cores.^{[22] [23]}

Amino acid sequence analysis of human TMEM74B on PSORT^[24] and DeepLoc 2.0^[25] indicated that the subcellular localization shares an equal distribution probability between the endoplasmic reticulum, plasma membrane, and lysosome. The tools predicted the presence of both a signal peptide and 2 highly hydrophobic transmembrane segments. Secondary structure analysis via JPred^[26] confirmed the presence of 2 tightly packed parallel transmembrane alpha helices .

There is a single paralog for human TMEM74B which is human TMEM74 shown below. There is a 45% identity and 57% similarity between the two. The main function of its paralog is to regulate and induce autophagy^[27].

The human TMEM74B gene possesses hundreds of documented orthologs distributed widely across vertebrate lineages, including diverse classes of mammals, birds, amphibians, and fish.^[28] As shown in the table below, TMEM74B is overall moderately to highly conserved across species even in the instance of 429 MYA of divergence.

Below is a phylogenetic tree showing the evolutionary history of TMEM74B and its orthologs. The evolutionary divergence times for these species span from approximately 87 million years ago for closely related mammalian lineages to 429 MYA for basal fish lineages.

Genomic and expression profiling links variations and dysregulation of the TMEM74B locus to four distinct pathological conditions spanning developmental, hematological, psychiatric, and ophthalmic phenotypes^[29]. It is associated with;

• Twin-To-Twin Transfusion Syndrome; a complication of monochorionic twin pregnancies that arise from unbalanced placental vascular anastomoses that result in unidirectional shunting of blood from 1 twin to the other^[30]
• Neonatal Anemia; an anemia in newborns characterized by an abnormally low red blood cell count for neonates^[31]
• Body Dysmorphic Disorder ; a somatoform mental disorder with pervasive and intrusive beliefs about one's perceived defects or flaws in appearance that results in severe emotional distress and impairment in functioning.^[32]
• Achromatopsia; a retinal disorder that results from absence/severe dysfunction of cone photoreceptors, producing marked impairment of color vision and central visual function.^[33]