C6orf163

C6orf163 is a human protein encoded by the C6orf163 gene.

Gene
C6orf163 is a 20.6 kb gene encoded on the plus strand of chromosome 6 (6q15). C6orf163 is predicted to be part of a readthrough locus with its neighboring genes on the plus strand, SMIM8 (small integral membrane protein 8, also known as C6orf162), LINC01590 (long intergenic non-coding RNA 1590), and CFAP206 (cilia and flagella associated protein 206).

Transcript
C6orf163 has been observed to be near-ubiquitously expressed at low levels in RNA-seq datasets. It is expressed most highly in the testes. There are 4 isoforms of C6orf163, the most common of which has 5 exons. The splice variants differ by truncation on the 5' end. An additional unspliced mRNA variant has been identified, but it does not appear to code for a protein.

Throughout early development, C6orf163 is expressed at moderate levels in many tissues. Its expression is highest at 10 weeks gestational time and decreases as development progresses.

Protein
The human C6orf163 protein is 329 amino acids long and has a molecular weight of 38 kDa. Its predicted isoelectric point is 6.49. According to the structural prediction from Alphafold, it mainly consists of a long alpha helical region, which is a relatively rare structure in human proteins. The long alpha helical structure is well conserved among orthologs.

C6orf163 contains a predicted leucine zipper motif from amino acids 247 to 269. This motif is typically involved in DNA binding, and is commonly found in transcription factors and other regulatory proteins. Leucine zippers form dimers to bind DNA, so the presence of this motif suggests that C6orf163 may exist as a dimer. C6orf163 has been experimentally found to undergo phosphorylation at 7 different residues and ubiquitination at 1 residue. Additionally, it has been computationally predicted to undergo sumoylation, lycine acetylation, and mucin-type O-GlcNac glycosylation.

C6orf163 has been found to interact with the protein DRC6 (Dynein regulatory complex subunit 6, also known as F-box and leucine rich repeat protein 13), which is a ubiquitin ligase that forms part of the SCF-type E3 ubiquitin ligase complex. DRC6 has been found to be involved in regulation of ciliary and flagellar motility.

C6orf163 has a nuclear localization signal from amino acids 310 to 316. Antibody staining has shown C6orf163 to be localized to the nucleus and cytoplasm.

Evolution
The C6orf163 protein is highly conserved among animals. Orthologs of C6orf163 have been identified in mammals, birds, reptiles, amphibians, fish, and some invertebrates including mollusks, echinoderms, and lancelets. The most distant c6orf163 ortholog identified is in the Japanese mud snail, Batillaria attramentaria. This ortholog has 23% sequence identity with the human protein.

Homo sapiens C6orf163 has no known paralogs in humans.

Clinical significance
A genome-wide association study analyzing genetic predictors of long-term treatment outcome for bipolar disorder showed that SNPs near C6orf163 were associated with the total number of manic and depressive episodes during follow up treatment and the number of depressive episodes during follow up, suggesting that C6orf163 may be involved in susceptibility to bipolar disorder.