SLFN11
protein-codingschlafen family member 11, the group of Schlafen family
Gene summary
Enables ATP hydrolysis activity and tRNA binding activity. Involved in several processes, including defense response to virus; negative regulation of G1/S transition of mitotic cell cycle; and replication fork arrest. Located in nucleoplasm and site of DNA damage. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~23.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLFN11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001376007.1. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 1 | 127 | 20 | 2 | 150 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 127 | 21 | 3 | 152 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001362936.1 | 4 | MANE Select | |
| Ensembl | ENSP00000510787.1 | 4 | MANE Select | |
| RefSeq | NP_001098057.1 | 4 | Standard | |
| RefSeq | NP_001098058.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cellular response to DNA damage stimulus
- negative regulation of DNA replication
- positive regulation of cell death
- replication fork arrest
- defense response to virus
Molecular Function
- tRNA binding
- helicase activity
- protein binding
- ATP binding
- ATPase activity
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- aggresome
- site of DNA damage
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394566
- Coding exons
- 4
- Length
- 23397
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125745
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.327 | 480 | 460 | 1.04 | 0.0000244 | 5894 |
| Missense (PolyPhen) | 122 | 124.06 | 0.98336 | 1781 | ||
| Synonymous | -1.63 | 199 | 172 | 1.16 | 0.00000924 | 1744 |
| Loss of Function | -0.566 | 26 | 23.1 | 1.13 | 0.00000112 | 318 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000093 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.00029 | 0.00027 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000069 | 0.000065 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibitor of DNA replication that promotes cell death in response to DNA damage (PubMed:22927417, PubMed:26658330, PubMed:29395061). Acts as a guardian of the genome by killing cells with defective replication (PubMed:29395061). Persistently blocks stressed replication forks by opening chromatin across replication initiation sites at stressed replication forks, possibly leading to unwind DNA ahead of the MCM helicase and block fork progression, ultimately leading to cell death (PubMed:29395061). Acts independently of ATR (PubMed:29395061). Also acts as an interferon (IFN)-induced antiviral protein which acts as an inhibitor of retrovirus protein synthesis (PubMed:23000900). Specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1) by acting as a specific inhibitor of the synthesis of retroviruses encoded proteins in a codon-usage-dependent manner (PubMed:23000900). Binds to tRNAs and exploits the unique viral codon bias towards A/T nucleotides (PubMed:23000900). The exact inhibition mechanism is unclear: may either sequester tRNAs, prevent their maturation via post-transcriptional processing or may accelerate their deacylation (PubMed:23000900). Does not inhibit reverse transcription, integration or production and nuclear export of viral RNA (PubMed:23000900). {ECO:0000269|PubMed:22927417, ECO:0000269|PubMed:23000900, ECO:0000269|PubMed:26658330, ECO:0000269|PubMed:29395061}.;
Intolerance Scores
- LoFtool
- 0.316
- RVIS EVS
- 0.09
- RVIS percentile EVS
- 60.71
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.468
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |