C9orf25

Chromosome 9 open reading frame 25 (C9orf25) is a domain that encodes the FAM219A gene.^[5] The terms FAM219A and C9orf25 are aliases and can be used interchangeably. The function of this gene is not yet completely understood.

FAM219A
Identifiers
Aliases	FAM219A, C9orf25, bA573M23.5, family with sequence similarity 219 member A
External IDs	MGI: 1919151; HomoloGene: 51830; GeneCards: FAM219A; OMA:FAM219A - orthologs
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9p13.3 Start 34,398,184 bp[1] End 34,458,570 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 A5 Start 41,517,691 bp[2] End 41,569,538 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone superior vestibular nucleus ventral tegmental area inferior ganglion of vagus nerve pons hypothalamus prefrontal cortex substantia nigra thalamus C1 segment Top expressed in primary visual cortex superior frontal gyrus dentate gyrus of hippocampal formation granule cell neural layer of retina muscle of thigh granulocyte lip ventricular zone cerebellar cortex spermatocyte More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 203259 71901 Ensembl ENSG00000164970 ENSMUSG00000028439 UniProt Q8IW50 Q9D772 RefSeq (mRNA) NM_001184940 NM_001184941 NM_001184942 NM_001184943 NM_001184944 NM_001184945 NM_147202 NM_001159583 NM_027993 RefSeq (protein) NP_001171869 NP_001171870 NP_001171871 NP_001171872 NP_001171874 NP_671735 NP_001153055 NP_082269 NP_001364030 NP_001364031 NP_001364032 NP_001364033 NP_001364034 Location (UCSC) Chr 9: 34.4 – 34.46 Mb Chr 4: 41.52 – 41.57 Mb PubMed search [3] [4]
Wikidata
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Gene

Location of C9orf25 on the - strand of Chromosome 9

Location

In humans, C9orf25 is located at the 9p13.3 position on chromosome 9.^[6] The gene is encoded on the sense strand (-) spanning the chromosomal locus from base pair 34,502,909 to 34,398,027.^[5][7] The span of the gene is 104,882 base pairs^{[8][9][10][11][12][13][14]}

Transcript variants

In humans there are 8 main transcript variants of the FAM219A gene.^[7] All of these transcripts have varying lengths and splice sites with transcript variant 1 being the longest and most abundant.^[5][7] Only four of these transcripts encode for a protein product.^[15]

Homology

Speed of evolution of C9orf25 in some orthologs compared to evolution of Cytochrome C and Fibrinogen^[16]

Orthologs

The C9orf25 gene has orthologs in a wide variety of Eukaryotic organisms, including invertebrates. This gene has not been found in plants, fungi or protists.^[17] C9orf25 is a slowly evolving gene.^[16] It is also highly conserved throughout all of its known orthologs.

Paralogs

C9orf25 has a paralog FAM219B which is located on the long arm of chromosome 9 and is 198 amino acids long.^[18] The C9orf25 and FAM219B genes duplicated and diverged between 684 and 797 million years ago.

Protein

General properties

The C9orf25 protein is composed of 185 amino acids. It has a molecular weight of 20.4 kilodaltons and an isoelectric point of 4.47.^[19] It is a member of the FAM219 super family. The entire protein is still considered to be a domain of unknown function.

Protein localization

C9orf25 has no signal sequence and remains in the cytosol.^[19]

Conserved motifs and post-translational modifications

The following are experimental post-transitional modifications for the C9orf25 protein:^[20]

• 6 predicted Serine phosphorylation sites
• 1 predicted Tyrosine phosphorylation site
• 1 predicted prenylation site

Secondary structure of the FAM219A gene

Secondary structure

The secondary structure of the gene is predicted to have two stretches of alpha helices and one beta strand. The majority of the secondary structure of gene is random coils.^[21]

Expression

The C9orf25 gene has medium to high expression in most tissues of the body.^[22] The gene has particularly high expression in the nervous, digestive and male reproductive systems.^[23]

Interacting proteins

The C9orf25 gene has many different interactions with a variety of other proteins that have an assortment of functions.^[24][25] The main ones that are listed on at least two reviewed sources are shown below.

Interactor Gene	Full Protein Name	Method	Description	Clinical Significance (Potential)
LIMS3	LIM Zinc finger domain	Two hybrid pooling approach	Senescent cell antigen containing protein
PDE6D	Rhodopsin sensitive cGMP phosphodiesterase subunit	Two hybrid pooling approach	Regulates the activity of the RAS protein in the cytosol	Joubert Syndrome
NIPSNAP3A	NipSnap homolog 3A	Two Hybrid	Involved in the Acetylation and phosphorylation process
CSNK1A1	Casein Kinase 1 Alpha 1	Two Hybrid	Serine/Threonine protein kinase. Participates in S phase checkpoint arrest by phosphorylating Claspin	NSEOE
SPRY2	Protein Sprouty Homolog 2	Two Hybrid	Antagonist of fibroblast growth factor	IgA nephropathy 3
BTRC	F-box/WD repeat containing protein	Affinity Capture	Substrate recognition component of SCF ubiquitin-protein ligase (phosphorolation dependent ubiquination)	CD4 (HIV-1) degregation
MTA1	Metastasis Associated Protein 1	Affinity Capture	Cancer associated. DNA binding transcription factor activity	Esophageal and Breast cancer
MTA3	Metastasis Associated Protein 3	Affinity Capture	Maintains epithelial architecture. Regulation of E-cadherin levels	Cancers related to epithelial cells

Clinical significance

Expression and amount of C9orf25 present in prostate cells ^[22]

The C9orf25 protein is associated with several disease causing proteins, however does not seem to be responsible for disease on its own.^[6][15] The gene seems to have higher expression in metastatic cells.^[22]