1. Gene Aliases

Rattus norvegicus: Cdk107, LOC102553282, schlafen 3, schlafen 4, Slfn3, uncharacterized LOC102553282. Orthologous to human SLFN12 (schlafen family member 12) gene [https://rgd.mcw.edu/rgdweb/report/gene/main.html?id=620455]

Mus musculus: AI450778; OTTMUSCASG00059415; OTTMUSPWKG00059399; OTTMUSWSBG00059306; Schlafen family member 4 [https://rgd.mcw.edu/rgdweb/report/gene/main.html?id=1615945]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

apoptotic signaling pathway: Slfn4 human orthologous SLFN12 was shown to be involved in apoptotic signaling. Estrogen-related hormones induce apoptosis by stabilizing Schlafen-12 protein turnover [PMID: 31420216]. Multiple PDE3A modulators act as molecular glues promoting PDE3A-SLFN12 interaction and induce SLFN12 dephosphorylation and cell death [PMID: 35104454].

response to bacterium: Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a bacterium [https://www.ebi.ac.uk/QuickGO/term/GO:0009617#:~:text=response to bacterium&text=Any process that results in,a stimulus from a bacterium.]. Listeria monocytogenes is a foodborne pathogen that crosses the intestinal barrier and disseminates within the host. miR-200b is repressed during L. monocytogenes infection, while Slf4 mRNA expression anticorrelates with that of miR-200b. These data indicate Slf4 might be involved in process of bacterium responses in the intestine of humanized mouse [PMID: 23012479].

GO terms:

apoptotic signaling pathway [The series of molecular signals which triggers the apoptotic death of a cell. The pathway starts with reception of a signal, and ends when the execution phase of apoptosis is triggered.|This term can be used to annotate gene products involved in apoptotic events happening downstream of the cross-talk point between the extrinsic and intrinsic apoptotic pathways. The cross-talk starts when caspase-8 cleaves Bid and truncated Bid interacts with mitochondria. From this point on it is not possible to distinguish between extrinsic and intrinsic pathways. GO:0097190]

lung alveolus development [The process whose specific outcome is the progression of the alveolus over time, from its formation to the mature structure. The alveolus is a sac for holding air in the lungs; formed by the terminal dilation of air passageways. GO:0048286]

rRNA catabolic process [The chemical reactions and pathways resulting in the breakdown of rRNA, ribosomal RNA, a structural constituent of ribosomes. GO:0016075]

response to bacterium [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a bacterium. GO:0009617]

MSigDB Signatures:

No relevant human or rat signatures were found in MSigDB

7. Gene Descriptions

NCBI Gene Summary: Predicted to act upstream of or within negative regulation of cell population proliferation. [provided by Alliance of Genome Resources, Apr 2022]

GeneCards Summary: SLFN12 (Schlafen Family Member 12) is a Protein Coding gene. Diseases associated with SLFN12 include Bleeding Disorder, Platelet-Type, 20 and Mpox. Among its related pathways are 17q12 copy number variation syndrome. An important paralog of this gene is SLFN12L.

UniProtKB/Swiss-Prot Summary: Ribonuclease which is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling [PMID: 31420216, PMID: 35104454, PMID: 34272366, PMID: 34707099]. May play a role in cell differentiation [PMID: 30045019].

8. Cellular Location of Gene Product

Estimation of protein expression could not be performed. View primary data. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000172123/subcellular]

9. Mechanistic Information

Summary

Slfn4 functions as a negative regulator of cell population proliferation in the intestine [CS: 9]. When downregulated, as seen in the colonic mucosa of aged rats or during exposure to certain intestinal toxins, its absence leads to dysregulated cellular proliferation [CS: 8]. This dysregulation is likely due to the loss of Slfn4's inhibitory influence on cell growth pathways [CS: 7]. Typically, Slfn4 maintains homeostasis by ensuring a controlled rate of cellular turnover [CS: 8], but its reduction disrupts this balance, potentially leading to excessive cell proliferation and contributing to pathologies like hyperplasia or cancer [CS: 6].

The upregulation of Slfn4 in response to cyclic strain in rat small intestine epithelial cells signifies its role in intestinal epithelial differentiation [CS: 7]. This upregulation likely functions as a protective response to stress, where Slfn4 promotes the maturation and specialization of epithelial cells [CS: 6]. Enhanced epithelial differentiation, facilitated by Slfn4, helps maintain the integrity of the intestinal barrier and optimizes absorptive functions [CS: 8], counteracting the disruptive effects of intestinal stressors and toxins [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: low tissue specificity [https://www.proteinatlas.org/ENSG00000172123/tissue]

Cell type enchanced: adipocytes, nk-cells (cell type enhanced) [https://www.proteinatlas.org/ENSG00000172123/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: