TMEM198
Identifiers
Aliases	TMEM198, TMEM198A, transmembrane protein 198
External IDs	MGI: 2443133; GeneCards: TMEM198
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q35 Start 219,543,663 bp[1] End 219,550,595 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 C4 Start 75,456,176 bp[2] End 75,462,349 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in prefrontal cortex anterior pituitary right frontal lobe right hemisphere of cerebellum right ovary left ovary cingulate gyrus anterior cingulate cortex dorsolateral prefrontal cortex ganglionic eminence Top expressed in visual cortex piriform cortex primary motor cortex primary visual cortex cingulate gyrus superior frontal gyrus superior cervical ganglion prefrontal cortex subiculum olfactory tubercle More reference expression data BioGPS n/a
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 130612 319998 Ensembl ENSG00000188760 ENSMUSG00000051703 UniProt Q66K66 Q8BG75 RefSeq (mRNA) NM_001303098 NM_001005209 NM_177056 RefSeq (protein) NP_001005209 NP_001290027 NP_796030 Location (UCSC) Chr 2: 219.54 – 219.55 Mb Chr 1: 75.46 – 75.46 Mb PubMed search [3] [4]
Wikidata
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TMEM198 (Transmembrane Protein 198)  is a protein in humans encoded by the TMEM198  gene, also known as TMEM198A. TMEM198 is known to promote LRP6 phosphorylation by casein kinases.^[5] Furthermore, a knockdown of TMEM198 in Vero cells significantly reduces the production of PEDV and SADS.^[6] Porcine Epidemic Diarrhea Virus (PEDV) and Swine Acute Diarrhea Syndrome Coronavirus (SADS) are both coronaviruses that infect pigs.

TMEM198 gene is located on chromosome 2 (2q35), with a plus orientation.^[7]

TMEM198 has 5 exons and spans 6,568  bp, with the coding region 1,083  bp. The fifth exon is hard to discern, which is due to being too small to detect and/or located near the UTR regions. TMEM198 is principally observed in the Brain ( expressed at 2.52), Ovary (4.71), and testes (2.19).^[8] The overexpression of TMEM198 promotes tumor growth,^[9] which leads to cancers such as Rectosigmoid Cancer.

In the gene neighborhood of the human gene TMEM198, there are notable genes located such as: Acid-sensing ion channel  4  (ASIC4), inhibin subunit alpha (INHA), and GDP-Mannose Pyrophosphorylase A  (GMPPA)  are all upstream of TMEM198. While  Chondroitin Polymerizing Factor (CHPF), ODS1, and ASIC4 Antisense RNA 1 (ASCIC4-AS1) are all downstream.

TMEM198 is 360 amino acids long, with long untranslated regions (UTRs). The conceptual translation of TMEM198 depicts multiple transmembrane regions as well as phosphorylation sites.

The first 3 labeled missense mutations do not affect major proteins. This was determined with multiple sequence alignment to identify the most conserved proteins among multiple vertebrates. However, the last two missense mutations affect a protein that is highly conserved within all tested vertebrates, highlighting its importance.

In humans, TMEM198 has a molecular weight of 39.3kDa and a theoretical pI of approximately 10.0. TMEM198 is predicted to be positively charged at physiological pH. TMEM198 also has a high Leu% (16.7%), thus making TMEM198 hydrophobic.

TMEM198 has 15 alternate splice variants and 3 distinct transcript variants. The 3 main transcript variants encode the same protein, NP_001005209.1, thus making TMEM198 only have one protein isoform.

The structure of TMEM198 can be noted to have alpha helices as the area with main confidence, while the beta sheets are of lower confidence in the true structure.

There are 6 transmembrane helices (hydrophobic alpha helices). This is to be considered as more evidence shows that TMEM198 has 7 transmembrane helices, with the seventh one having a lower probability^[10] of appearing as compared to the first 6.

Dis1 and Dis2 are regions with no fixed 3d structure. It’s located at the C-terminus end of the protein, in the cytoplasm, thus making it the protein's signaling end. UniProt^[11] does note that the protein is involved in Wnt signalling via LRP6. The first 35 amino acids at the N- terminal of TMEM198 are necessary for viral replication as well as the formation of DMVs (Double-Membrane Vesicles)^[12]

The following table provides a few details on orthologs of the human version of TMEM198. To save space, not all of these orthologs are included in the multiple sequence alignment. Only the listed vertebrates were included. These orthologs were identified through TimeTree ^[13] and BLAST^[14] searches. The table is categorized by increasing date of divergence from the human lineage, with Hazel plant being the furthest known ortholog of TMEM198.

A major trend of the Ortholog table is that as the date of divergence from the human lineage increases, so does the sequence length. There are a few outliers to this trend, but it is otherwise notable.

TMEM198 has no known paralog in the human genome.

The multiple sequence alignment (MSA) box-frame format. It demonstrates that TMEM198 is highly conserved across a wide range of vertebrate species, including mammals, fish, amphibians, and a bird (long-tailed hermit used as an outlier). (The American eel may not be a true TMEM198 ortholog given its FASTA header mislabeling). The consistency score of 96^[15] indicates high confidence in the alignment, meaning the residue positions are strongly supported across pairwise comparisons.

The Phylogenetic tree^[16] depicts the evolutionary relationships among 15 vertebrate species from the Ortholog table, excluding Hazel, as it will exaggerate the results. The furthest relative in this phylogenetic tree is Anguilla rostrata.