User:Timmal122/sandbox

This is the user sandbox of Timmal122. A user sandbox is a subpage of the user's user page. It serves as a testing spot and page development space for the user and is not an encyclopedia article. Create or edit your own sandbox here.

Other sandboxes: Main sandbox | Template sandbox

Finished writing a draft article? Are you ready to request review of it by an experienced editor for possible inclusion in Wikipedia? Submit your draft for review!

C9orf40

Introduction

C9orf40 (chromosome 9 open reading frame 40) is a gene in humans located on the minus strand of chromosome 9 at cytogenetic band 9q21.13. It encodes a 194-amino acid intracellular protein with currently uncharacterized molecular function. The gene is broadly conserved across vertebrates and is classified as a Tdark protein by the Illuminating the Druggable Genome project, indicating low functional annotation but potential biological relevance.

Gene

C9orf40 spans approximately 2.6 kb on chromosome 9 and consists of two exons. It is located within a structurally variable region at 9q21.13, which has been associated with neurodevelopmental phenotypes and certain forms of glioma. The gene is transcribed in the minus orientation and does not overlap with any known protein-coding genes.

Transcript

C9orf40 is expressed as a single known mRNA isoform (NM_017998.3) that includes two exons and multiple polyadenylation signal sequences. No alternative splicing events have been confirmed. The transcript is predicted to be post-transcriptionally regulated through features in the 3′ untranslated region.

Protein

The C9orf40 gene encodes a protein of 194 amino acids with a predicted molecular weight of 20.9 kDa. It lacks annotated transmembrane domains or known functional domains, and its structure is predicted to be largely intrinsically disordered. High-throughput phosphoproteomic studies have identified phosphorylation at Ser69 and Ser76, suggesting post-translational regulation in signaling contexts such as EGF stimulation^[1].

A conserved PPXY motif and potential destruction box at the C-terminus suggest roles in regulated protein degradation and interactions with WW-domain containing proteins.

Expression

Although its expression profile is not fully defined, data from GTEx and the Human Protein Atlas suggest low-to-moderate expression across multiple tissues, including brain and testis. Notably, C9orf40 has been implicated in tumor-associated regulatory networks in glioblastoma and low-grade glioma.

Homology and Evolution

Orthologs of C9orf40 are conserved across a wide range of vertebrates and some chordates. Sequence identity is highest among primates (e.g., 97.5% between human and chimpanzee), followed by moderate similarity in reptiles and amphibians (33–38%), and much lower conservation in more distantly related species such as lancelets (Branchiostoma belcheri, ~10%). A putative ortholog in the flowering plant Pontederia vaginalis displays <2% similarity and is likely non-functional or spuriously annotated.

Figure 1. Multiple sequence alignment of C9orf40 orthologs. Primate sequences show near-complete conservation, while distant species like Pontederia vaginalis exhibit minimal similarity.

Clinical Significance

Deletion of C9orf40 has been reported in patients with epilepsy and intellectual disability^[2]. The gene is also implicated in glioma through ceRNA networks involving long non-coding RNAs and microRNAs^[3].

References

^ Olsen JV, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Cell 127(3): 635–648. [1]
^ Boudry-Labis E, et al. (2013). "A 9q21.13 microdeletion in a girl with epilepsy and mental retardation." Ann Otolaryngol Chir Cervicofac. 130(4): 199–202.
^ Zadorozhna M, et al. (2023). "On the way to revealing the functional significance of uncharacterized CxORFx open reading frame proteins in human cancers." Int J Mol Sci. 24(12): 10190. [2]

[1] Olsen JV, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Cell 127(3): 635–648. [1]

[2] Boudry-Labis E, et al. (2013). "A 9q21.13 microdeletion in a girl with epilepsy and mental retardation." Ann Otolaryngol Chir Cervicofac. 130(4): 199–202.

[3] Zadorozhna M, et al. (2023). "On the way to revealing the functional significance of uncharacterized CxORFx open reading frame proteins in human cancers." Int J Mol Sci. 24(12): 10190. [2]

[1]

[2]

[3]