SLFN12
Chr 17schlafen family member 12
Also known as: SLFN3
Enables RNA nuclease activity and ribosome binding activity. Involved in apoptotic signaling pathway and rRNA catabolic process. Part of cytosol and nucleus. [provided by Alliance of Genome Resources, Jul 2025]
Clinical Summary— SLFN12
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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
7 Pathogenic / Likely Pathogenic· 82 VUS of 104 total submissions
Some data sources returned errors (1)
pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.35LOEUF
pLI 0.000
Z-score 0.63
OE 0.81 (0.51–1.35)
Highly tolerant — LoF variants common in population
Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.10Z-score
OE missense 0.98 (0.89–1.08)
293 obs / 297.7 exp
Mild missense constraint
Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.81 (0.51–1.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.89–1.08)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 11 / 13.5Missense obs/exp: 293 / 297.7Syn Z: -0.06
ClinVar Variant Classifications
104 submitted variants in ClinVar
Classification Summary
Pathogenic7
VUS82
Likely Benign12
Benign3
7
Pathogenic
82
VUS
12
Likely Benign
3
Benign
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 7 | 0 | 7 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 75 | 7 | 0 | 82 |
Likely Benign | 0 | 10 | 2 | 0 | 12 |
Benign | 0 | 0 | 3 | 0 | 3 |
| Total | 0 | 85 | 19 | 0 | 104 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLFN12 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
SCHLAFEN FAMILY, MEMBER 12; SLFN12
MIM #614955 · *
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Deciphering the Role of SLFN12: A Novel Biomarker for Predicting Immunotherapy Outcomes in Glioma Patients Through Artificial Intelligence.
Chen Z et al.·J Cell Mol Med
2024Open AccessCohort
First-in-Human Dose-Escalation Study of the First-in-Class PDE3A-SLFN12 Complex Inducer BAY 2666605 in Patients with Advanced Solid Tumors Coexpressing SLFN12 and PDE3A.
Papadopoulos KP et al.·Clin Cancer Res
2024Open AccessCohort
SLFN12 Expression Significantly Effects the Response to Chemotherapy Drugs in Triple-Negative Breast Cancer.
Brown SR et al.·Cancers (Basel)
2024Open Access
Discovery of BAY 2666605, a Molecular Glue for PDE3A and SLFN12.
Lewis TA et al.·ACS Med Chem Lett
2024
A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors.
Takaki EO et al.·Clin Cancer Res
2024Open Access
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
Schlafen Family Intra-Regulation by IFN-alpha2 in Triple-Negative Breast Cancer
Brown SR et al.·Cancers (Basel)
2023
Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase
Garvie CW et al.·Nat Commun
2021
A complex puzzle: Regulation of SLFN12 RNase activity by phosphorylation.
Greulich H·Cell Chem Biol
2022
RNA Sequencing of Intestinal Enterocytes Pre- and Post-Roux-en-Y Gastric Bypass Reveals Alteration in Gene Expression Related to Enterocyte Differentiation, Restitution, and Obesity with Regulation by Schlafen 12
Vomhof-DeKrey EE et al.·Cells
2022
Multiple PDE3A modulators act as molecular glues promoting PDE3A-SLFN12 interaction and induce SLFN12 dephosphorylation and cell death.
Yan B et al.·Cell Chem Biol
2022
Overview of Structural and Functional Insights of SLFN12 Associated With Different Diseases.
Tilmisani M et al.·Cureus
2024Review
Velcrin-induced selective cleavage of tRNALeu(TAA) by SLFN12 causes cancer cell death.
Lee S et al.·Nat Chem Biol
2022
Top 8 full-text resultsSearch PubTator3 ↗
External Resources
Links to major genomics databases and tools