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Fam184A
Gene

FAM184A (family with sequence similarity 184 member A [Homo sapiens]) has multiple aliases including C6orf60, Chromosome 6 Open Reading Frame 60, LOC79632, and FLJ13942. FAM184A has 18 exons, 1 polyadenylation site, is oriented on the minus strand, and is located on the long arm of chromosome 6 at 6q22.31 (119,470,552 to 119,280,992). FAM184A is part of the FAM184 gene family and has one paralog, FAM184B.

Protein

Transcription of FAM184A produces 12 different mRNAs, 2 unspliced variants which are believed to be non-coding, and 10 alternatively spliced variants. The length of isoform 1 is 1,140 amino acids long and the calculated molecular weight is 132.8 kDa. Isoform 1 contains four conserved domains: chromosome segregation protein SMC (common bacterial type), V-type ATPase subunit family, DUF342 (protein of unknown function), and FAM184. Other domains of significance in isoform 1 are two coiled-coil domains. The four human tissues with highest FAM184A expression are the testis, placenta, lungs, and brain.

Evolutionary History

Considered conserved in tetrapods, FAM184A also has orthologs in a range of organisms including members of many of the recently updated major clades , TSAR, haptista, cryptista, archaeplastia, metamonada, CRuMs, and amorphea. The absence of orthologs in additional clades may be solely based on limited sequence data available; based on the proposed updated eukaryotic phylogenetic tree, FAM184A was present in the most recent common eukaryotic ancestral organisms.

Role in Cancer

Differential gene expression (DGE) of FAM184A has been associated with numerous cancer types including endometrial, prostate, breast, and leukemia. Regarding endometrial cancer, FAM184A serves as one of seven genes that comprise a prognostic signature for survival in patients with high expression of the gene being classified as “risky.”

In the Brain

Several papers have also shown evidence of FAM184A’s involvement in the brain. FAM184A expression was identified as a marker in the substantia nigra (an area of the midbrain) of adult mice, representing a potential for insight into the susceptibility for the collapse of the substantia nigra dopaminergic neurons in Parkinson’s Disease (Hook 2017). In human cells, neural progenitor/stem cells expressing MEF2CA showed upregulated FAM184A when compared to control cells (vector-control) (Chan 2015). MEF2CA is a constitutively-active form of MEF2 (myocyte enhancer factor 2) and increases MEF2 activity.

Association with Psychiatric Disorders

GWAS and methods analyzing gene expression have implicated the involvement of FAM184A in psychiatric disorders. In a study performed in males with a variety of psychiatric disorders, researchers found increased FAM184A expression in individuals exhibiting both suicidal ideation and behaviors (1/76 genes). Another study showed FAM184A was a risk locus for a range of mood disorders based on the presence of 37 SNP variants in affected individuals (BP I and II, schizoaffective disorder, major depression, and single-episode major depression).

Viral Interactions

FAM184A has also been found to be involved in the human host-flavivirus protein-protein interaction network, where NS3 in dengue virus 2 (DENV) and NS5 in tick-borne encephalitis (TBEV) interact with FAM184A. NS3 and NS5 make up the primary enzymatic components of the viral replication complex and the identification of proteins involved in this network represent potential novel therapeutic targets.