SLFN11

Summary

SLFN11 (schlafen family member 11, HGNC:26633) is a protein-coding gene on chromosome 17q12, encoding Schlafen family member 11 (Q7Z7L1). Inhibitor of DNA replication that promotes cell death in response to DNA damage. In precision oncology, SLFN11 EXPRESSION confers sensitivity to Temozolomide + Talazoparib in Lung Small Cell Carcinoma (CIViC Level D); 2 further curated variant–drug associations are listed below.

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 cytosol; nucleoplasm; and site of DNA damage.

Source: NCBI Gene 91607 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 155 total — 1 likely-pathogenic
• Druggable target: yes
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• MANE Select transcript: NM_001376007

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26633
Approved symbol	SLFN11
Name	schlafen family member 11
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34922
Ensembl gene	ENSG00000172716
Ensembl biotype	protein_coding
OMIM	614953
Entrez	91607

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 3 retained_intron

ENST00000308377, ENST00000394566, ENST00000427966, ENST00000430814, ENST00000441608, ENST00000498396, ENST00000586099, ENST00000588579, ENST00000589562, ENST00000589811, ENST00000591682, ENST00000592108, ENST00000592122, ENST00000685675, ENST00000884394, ENST00000884395, ENST00000884396, ENST00000884397, ENST00000884398, ENST00000884399, ENST00000937300, ENST00000951852, ENST00000951853, ENST00000951854

RefSeq mRNA: 16 — MANE Select: NM_001376007 NM_001104587, NM_001104588, NM_001104589, NM_001104590, NM_001376007, NM_001376008, NM_001376009, NM_001376010, NM_001376011, NM_001387158, NM_001387159, NM_001387160, NM_001387161, NM_001387162, NM_001387163, NM_152270

CCDS: CCDS11294

Canonical transcript exons

ENST00000685675 — 7 exons

Exon	Start	End
ENSE00001186646	35360243	35360371
ENSE00001186651	35362739	35363826
ENSE00001518837	35350305	35353139
ENSE00001518838	35366947	35367063
ENSE00001518841	35367603	35367700
ENSE00002404167	35353336	35354059
ENSE00003926230	35373474	35373621

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 94.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.0686 / max 319.7694, expressed in 1194 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165359	7.0686	1194

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	94.48	gold quality
leukocyte	CL:0000738	94.16	gold quality
calcaneal tendon	UBERON:0003701	93.52	gold quality
sural nerve	UBERON:0015488	92.39	gold quality
omental fat pad	UBERON:0010414	91.99	gold quality
peritoneum	UBERON:0002358	91.94	gold quality
bone marrow cell	CL:0002092	91.89	gold quality
right lobe of thyroid gland	UBERON:0001119	90.88	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.70	gold quality
left uterine tube	UBERON:0001303	90.62	gold quality
left lobe of thyroid gland	UBERON:0001120	90.29	gold quality
granulocyte	CL:0000094	90.17	gold quality
vermiform appendix	UBERON:0001154	89.98	gold quality
upper lobe of left lung	UBERON:0008952	89.91	gold quality
thyroid gland	UBERON:0002046	89.84	gold quality
right ovary	UBERON:0002118	89.76	gold quality
gall bladder	UBERON:0002110	89.56	gold quality
endocervix	UBERON:0000458	89.49	gold quality
tibial nerve	UBERON:0001323	89.49	gold quality
right lung	UBERON:0002167	89.39	gold quality
left ovary	UBERON:0002119	89.23	gold quality
upper lobe of lung	UBERON:0008948	89.19	gold quality
smooth muscle tissue	UBERON:0001135	88.93	gold quality
tendon	UBERON:0000043	88.60	gold quality
apex of heart	UBERON:0002098	88.54	gold quality
descending thoracic aorta	UBERON:0002345	88.54	gold quality
spleen	UBERON:0002106	87.90	gold quality
corpus epididymis	UBERON:0004359	87.90	gold quality
right coronary artery	UBERON:0001625	87.88	gold quality
thoracic aorta	UBERON:0001515	87.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.15
E-MTAB-7303	no	8.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting SLFN11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4760-5P	99.80	69.88	1619

Literature-anchored findings (GeneRIF, showing 38)

• SLFN11 expression is causally associated with the activity of DNA-damaging agents in cancer cells, and has a broad expression range in colon and ovarian adenocarcinomas. (PMID:22927417)
• SLFN11 selectively inhibits viral protein synthesis in HIV-infected cells by means of codon-bias discrimination (PMID:23000900)
• SLFN11 has a role as a transcriptional target of EWS-FLI1 and is a determinant of drug response in Ewing sarcoma (PMID:25779942)
• SLFN11 expression predicts good better survival in colorectal cancer patients with KRAS exon 2 wild type who have received oxaliplatin based adjuvant chemotherapy. (PMID:26525741)
• the results identify SLFN11 epigenetic inactivation as a predictor of resistance to platinum drugs in human cancer. (PMID:26625211)
• SLFN11 inhibits checkpoint maintenance and homologous recombination repair by promoting the destabilization of the RPA-ssDNA complex, thereby sensitizing cancer cell lines expressing high endogenous levels of SLFN11 to DNA-damaging agents. (PMID:26658330)
• SLFN11 is a relevant predictive biomarker of sensitivity to PARP inhibitor monotherapy in SCLC and we identify combinatorial therapy with TMZ as a particularly promising therapeutic strategy that warrants further clinical investigation (PMID:27440269)
• SLFN11 contributes to the sensitivity of Ewing sarcoma cells to inhibition of ribonucleotide reductase M2 (PMID:27557498)
• DNA methylation at SLFN11 cg10911913 was positively associated with measured levels of all 3 PM2.5 species. (PMID:27982729)
• In vivo silencing of SLFN11 was associated with marked deposition of H3K27me3, a histone modification placed by EZH2, within the gene body of SLFN11, inducing local chromatin condensation and gene silencing. (PMID:28196596)
• SLFN11 is frequently methylated in human colorectal cancer, and the expression of SLFN11 is regulated by promoter region methylation. Methylation of SLFN11 reduced the sensitivity of CRC cells to cisplatin. (PMID:28403629)
• Authors conclude that SLFN11 is recruited to stressed replication forks carrying extended RPA filaments where it blocks replication by changing chromatin structure across replication sites. (PMID:29395061)
• Our study uncovered a novel mechanism of codon-specific translational inhibition via SLFN11-dependent tRNA cleavage in the DNA damage response and supports the notion that SLFN11-deficient tumor cells can be resensitized to DNA-damaging agents by targeting ATR or tRNA-Leu-TAA. (PMID:30374083)
• Depletion of Schlafen 11 (Slfn11) increases the replication of (+)ssRNA viruses from the Flavivirus genus but has no significant effect on the replication of the (-)ssRNA viruses. Quantification of the ratio of genome-containing viral particles to PFU indicates that Slfn11 impairs West Nile virus (WNV) infectivity. Slfn11 prevents WNV-induced downregulation of a subset of tRNAs for the translation of viral polyprotein. (PMID:31118262)
• a consistent and evident pattern emerges, highlighting the strong correlation of SLFN11 with the immune system in BC, as well as its meaningful associations with clearly distinct clinico-pathological BC phenotypes and clinical outcome (PMID:31222709)
• our work has identified both the mechanism of SLFN11 activation and PPP1CC as the enzyme responsible for its activation. Our findings open up future studies of the PPP1CC subunit(s) involved in SLFN11 activation and the putative kinase(s) that inactivates SLFN11. (PMID:31395656)
• Analyses of multiple breast, lung, and ovarian cancer patient cohorts treated with chemotherapy confirmed SLFN11 mRNA expression as a predictive biomarker of longer overall survival and improved tumor response. (PMID:31682620)
• BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers. (PMID:32075943)
• SLFN11 Expression in Advanced Prostate Cancer and Response to Platinum-based Chemotherapy. (PMID:32127465)
• Chromatin Remodeling and Immediate Early Gene Activation by SLFN11 in Response to Replication Stress. (PMID:32209474)
• SLFN11 inhibits hepatocellular carcinoma tumorigenesis and metastasis by targeting RPS4X via mTOR pathway. (PMID:32292519)
• Immunohistochemical analysis of SLFN11 expression uncovers potential non-responders to DNA-damaging agents overlooked by tissue RNA-seq. (PMID:32474729)
• SLFN11 promotes stalled fork degradation that underlies the phenotype in Fanconi anemia cells. (PMID:32735670)
• Epigenetic suppression of SLFN11 in germinal center B-cells during B-cell development. (PMID:33513156)
• SLFN11 promotes CDT1 degradation by CUL4 in response to replicative DNA damage, while its absence leads to synthetic lethality with ATR/CHK1 inhibitors. (PMID:33536335)
• Schlafen 11 predicts response to platinum-based chemotherapy in gastric cancers. (PMID:33785877)
• A wake-up call for cancer DNA damage: the role of Schlafen 11 (SLFN11) across multiple cancers. (PMID:34294893)
• SLFN11 is Widely Expressed in Pediatric Sarcoma and Induces Variable Sensitization to Replicative Stress Caused By DNA-Damaging Agents. (PMID:34413129)
• SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer. (PMID:34549724)
• Retrospective analysis of Schlafen11 (SLFN11) to predict the outcomes to therapies affecting the DNA damage response. (PMID:34663950)
• FK228 potentiates topotecan activity against small cell lung cancer cells via induction of SLFN11. (PMID:34893686)
• Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex. (PMID:35105802)
• Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer. (PMID:35440668)
• Mechanistic understanding of human SLFN11. (PMID:36115853)
• SLFN11 negatively regulates non-canonical NFkB signaling to promote glioblastoma progression. (PMID:36382088)
• Mouse Slfn8 and Slfn9 genes complement human cells lacking SLFN11 during the replication stress response. (PMID:37833372)
• SLFN11 promotes clear cell renal cell carcinoma progression via the PI3K/AKT signaling pathway. (PMID:38206539)
• Schlafen 11 triggers innate immune responses through its ribonuclease activity upon detection of single-stranded DNA. (PMID:38875319)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slfn8	ENSMUSG00000035208
mus_musculus	Slfn9	ENSMUSG00000069793
mus_musculus	Slfn10	ENSMUSG00000072621
rattus_norvegicus	Slfn9	ENSRNOG00000021412

Paralogs (6): SLFN13 (ENSG00000154760), SLFN5 (ENSG00000166750), SLFNL1 (ENSG00000171790), SLFN12 (ENSG00000172123), SLFN12L (ENSG00000205045), SLFN14 (ENSG00000236320)

Protein

Protein identifiers

Schlafen family member 11 — Q7Z7L1 (reviewed: Q7Z7L1)

All UniProt accessions (9): Q7Z7L1, C9J902, C9JDG6, C9JUT2, K7EIM3, K7EJJ3, K7EKT7, K7ER38, K7ES87

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of DNA replication that promotes cell death in response to DNA damage. Acts as a guardian of the genome by killing cells with defective replication. 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. Upon DNA damage, inhibits translation of ATR or ATM based on distinct codon usage without disrupting early DNA damage response signaling. Antiviral restriction factor with manganese-dependent type II tRNA endoribonuclease. A single tRNA molecule is bound and cleaved by the SLFN11 dimer. 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. Impairs the replication of human cytomegalovirus (HCMV) and some Flaviviruses. Exploits the unique viral codon bias towards A/T nucleotides. Also acts as an interferon (IFN)-induced antiviral protein which acts as an inhibitor of retrovirus protein synthesis.

Subunit / interactions. Homodimer. Interacts with MCM3. Interacts with DHX9. Interacts with RPA1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Exhibits a wider expression range in ovarian and colon adenocarcinoma than in their corresponding healthy tissues.

Domain organisation. The N-terminus contains an endonuclease domain. The C-terminus displays homology to superfamily I DNA/RNA helicases, although it is in an autoinhibited conformation.

Induction. Down-regulated in small cell lung cancer (SCLC) cells resistant to PARP inhibitor drugs. Up-regulated by type I interferons, poly-IC and poly-dAdT.

Miscellaneous. Dominant determinant of sensitivity to DNA-damaging anticancer drugs: acts by mediating cell death in response to DNA damage induced by anticancer drugs. Down-regulated in a number of chemoresistant tumors.

Similarity. Belongs to the Schlafen family. Subgroup III subfamily.

RefSeq proteins (16): NP_001098057, NP_001098058, NP_001098059, NP_001098060, NP_001362936, NP_001362937, NP_001362938, NP_001362939, NP_001362940, NP_001374087, NP_001374088, NP_001374089, NP_001374090, NP_001374091, NP_001374092, NP_689483 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007421	Schlafen_AlbA_2_dom	Domain
IPR018647	SLFN_3-like_DNA/RNA_helicase	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR029684	Schlafen	Family
IPR031450	Poxin-SLFN/SLFN_N	Domain
IPR038461	Schlafen_AlbA_2_dom_sf	Homologous_superfamily
IPR048729	SLFN_GTPase-like	Domain

Pfam: PF04326, PF09848, PF17057, PF21026

UniProt features (108 total): strand 39, helix 37, mutagenesis site 9, binding site 7, turn 6, sequence variant 4, sequence conflict 4, chain 1, active site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
9ERF	ELECTRON MICROSCOPY	2.64
7ZEL	ELECTRON MICROSCOPY	2.8
9ERE	ELECTRON MICROSCOPY	2.82
9GMX	ELECTRON MICROSCOPY	2.82
9GMW	ELECTRON MICROSCOPY	3
7ZES	ELECTRON MICROSCOPY	3.1
7ZEP	ELECTRON MICROSCOPY	3.2
9ERD	ELECTRON MICROSCOPY	3.72

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7L1-F1	86.90	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 216

Ligand- & substrate-binding residues (7): 209; 214; 285; 287; 321; 322; 599–606

Mutagenesis-validated functional residues (9):

Position	Phenotype
209	complete loss of endonuclease activity.
214	complete loss of endonuclease activity.
216	complete loss of endonuclease activity.
234	no effect on endonuclease activity.
252	slight increase in endonuclease activity.
605	abolishes atpase activity without affecting its role in dna damage response; when associated with a-668.
668	abolishes atpase activity without affecting its role in dna damage response; when associated with m-605.
669	abolishes atpase activity, leading to abolish ability to inhibit dna replication without affecting subcellular location.
753	complete loss of trna cleavage and ssdna binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOMF_ENDONUCLEASE_ACTIVITY, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOMF_NUCLEASE_ACTIVITY, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (7): immune system process (GO:0002376), chromatin remodeling (GO:0006338), DNA damage response (GO:0006974), negative regulation of DNA replication (GO:0008156), replication fork arrest (GO:0043111), defense response to virus (GO:0051607), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134)

GO Molecular Function (12): tRNA binding (GO:0000049), DNA binding (GO:0003677), helicase activity (GO:0004386), endonuclease activity (GO:0004519), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), RNA binding (GO:0003723), catalytic activity (GO:0003824), nuclease activity (GO:0004518), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), site of DNA damage (GO:0090734), chromosome (GO:0005694), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nucleic acid binding	2
catalytic activity, acting on a nucleic acid	2
ATP-dependent activity	2
biological_process	1
chromatin organization	1
cellular response to stress	1
DNA replication	1
regulation of DNA replication	1
negative regulation of DNA metabolic process	1
DNA-templated DNA replication maintenance of fidelity	1
negative regulation of DNA-templated DNA replication	1
defense response	1
response to virus	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
RNA binding	1
nucleic acid conformation isomerase activity	1
nuclease activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
chromosome	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLFN11	RPA3	P35244	582
SLFN11	RPA1	P27694	576
SLFN11	SAMHD1	Q9Y3Z3	545
SLFN11	PARP1	P09874	544
SLFN11	BARD1	Q99728	531
SLFN11	TOP1	P11387	522
SLFN11	TRIM5	Q9C035	497
SLFN11	IFI16	Q16666	494
SLFN11	GBP5	Q96PP8	486
SLFN11	ISG15	P05161	474
SLFN11	MX2	P20592	461
SLFN11	APOBEC3G	Q9HC16	461
SLFN11	CH25H	O95992	458
SLFN11	BST2	Q10589	447
SLFN11	IFITM2	Q01629	445

IntAct

19 interactions, top by confidence:

A	B	Type	Score
SLFN11	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
NOTCH1	CNOT1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
SOX2	DDX39A	psi-mi:“MI:0914”(association)	0.350
PPM1A	BCKDK	psi-mi:“MI:0914”(association)	0.350
PPM1E	NDUFA4	psi-mi:“MI:0914”(association)	0.350
G3BP1	AGPS	psi-mi:“MI:0914”(association)	0.350
NUTM2F	IRF6	psi-mi:“MI:0914”(association)	0.350
SPDYE4	RPS10-NUDT3	psi-mi:“MI:0914”(association)	0.350
TEK	KIF2A	psi-mi:“MI:0914”(association)	0.350
C1QA	VWA8	psi-mi:“MI:0914”(association)	0.350
SLC18A3	ORC4	psi-mi:“MI:0914”(association)	0.350
SLC2A2	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
	TTC8	psi-mi:“MI:0914”(association)	0.350
PPP1R15A	BARD1	psi-mi:“MI:0914”(association)	0.350
CEP43	RIPK2	psi-mi:“MI:2364”(proximity)	0.270
CIAO1	SLFN11	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (404): SLFN11 (Affinity Capture-MS), SLFN11 (Proximity Label-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Affinity Capture-MS), SLFN11 (Positive Genetic)

ESM2 similar proteins: A0A140LIF8, A0JN92, A1Z198, A6H603, B1ARD6, B1ARD8, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E1BPN0, G1SRW8, O02799, P0C7P3, P52630, Q08AF3, Q0GKD5, Q0P3U3, Q149M9, Q1LXZ7, Q1LZ50, Q2LKU9, Q2LKV5, Q2LKW6, Q32KW9, Q5I0J8, Q5NCI0, Q5RCZ8, Q5RFJ8, Q5SY16, Q5U311, Q60766, Q63035, Q68D06, Q6AYC2, Q6AYF9, Q6IEE8, Q6NXR0, Q7Z7L1

Diamond homologs: A0A7H0DNF0, B1ARD6, B1ARD8, G1SRW8, P0C7P3, Q08AF3, Q5RCZ8, Q5U311, Q68D06, Q6IEE8, Q7Z7L1, Q8CBA2, Q8IYM2, Q8V4S4, Q9Z0I6, Q9Z0I7, V9GXG1, Q8QMP8, Q01226, P21000

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

155 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	126
Likely benign	22
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
982226	NM_001376007.1(SLFN11):c.2603T>C (p.Ile868Thr)	Likely pathogenic

SpliceAI

899 predictions. Top by Δscore:

Variant	Effect	Δscore
17:35353137:TCA:T	acceptor_gain	1.0000
17:35353138:CA:C	acceptor_gain	1.0000
17:35353138:CAC:C	acceptor_gain	1.0000
17:35353140:C:CC	acceptor_gain	1.0000
17:35354060:C:CC	acceptor_gain	1.0000
17:35360373:T:C	acceptor_gain	1.0000
17:35373462:C:CA	donor_gain	1.0000
17:35353135:TATCA:T	acceptor_gain	0.9900
17:35353137:TCAC:T	acceptor_loss	0.9900
17:35353139:ACTG:A	acceptor_loss	0.9900
17:35353140:C:CA	acceptor_loss	0.9900
17:35353141:T:A	acceptor_loss	0.9900
17:35354064:A:C	acceptor_gain	0.9900
17:35354066:G:C	acceptor_gain	0.9900
17:35360372:C:CC	acceptor_gain	0.9900
17:35360373:T:TC	acceptor_gain	0.9900
17:35362734:CTTAC:C	donor_loss	0.9900
17:35362735:TTA:T	donor_loss	0.9900
17:35362736:TA:T	donor_loss	0.9900
17:35362737:ACCTG:A	donor_loss	0.9900
17:35362738:CC:C	donor_loss	0.9900
17:35363827:C:CC	acceptor_gain	0.9900
17:35353330:GCTTA:G	donor_loss	0.9800
17:35353331:CTTA:C	donor_loss	0.9800
17:35353332:TTA:T	donor_loss	0.9800
17:35353333:TA:T	donor_loss	0.9800
17:35353335:C:CG	donor_loss	0.9800
17:35354064:A:AC	acceptor_gain	0.9800
17:35360369:GAT:G	acceptor_gain	0.9800
17:35373130:AGTGG:A	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000048814 (17:35366438 C>G), RS1000162730 (17:35366854 T>C,G), RS1000254082 (17:35373766 C>T), RS1000358944 (17:35355346 G>C), RS1000370390 (17:35361211 T>C), RS1000474785 (17:35354930 G>A), RS1000549184 (17:35366802 T>A,G), RS1000570925 (17:35365660 T>C), RS1000606783 (17:35361604 G>A,T), RS1000702373 (17:35359675 C>A), RS1000950871 (17:35357754 AATATAAATATATAAT>A), RS1001018302 (17:35372116 T>C), RS1001053385 (17:35373549 A>C,G), RS1001156921 (17:35360515 C>A,T), RS1001273939 (17:35371769 G>C)

Disease associations

OMIM: gene MIM:614953 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (1): Moyamoya angiopathy (Orphanet:477768)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006528_4	Barrett’s esophagus x pack-years of smoking exposure interaction	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006526	pack-years measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725095 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
SLFN11 EXPRESSION	Temozolomide + Talazoparib	Lung Small Cell Carcinoma	Sensitivity/Response	CIViC D	EID5883
SLFN11 EXPRESSION	Niraparib + Temozolomide	Ewing Sarcoma	Sensitivity/Response	CIViC D	EID5884
SLFN11 EXPRESSION	7-Ethyl-10-Hydroxycamptothecin	Colorectal Cancer	Sensitivity/Response	CIViC D	EID870

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	6
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	increases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	increases expression	1
Dasatinib	decreases expression	1
Temozolomide	increases expression	1
Vorinostat	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Calcitriol	increases expression	1
Copper	affects binding, decreases expression	1
Cytarabine	increases expression	1
Disulfiram	decreases expression, affects binding	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697389	Binding	Inhibition of SLFN11 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7ZC	Abcam Raji SLFN11 KO	Cancer cell line	Male
CVCL_C0A5	Abcam THP-1 SLFN11 KO	Cancer cell line	Male
CVCL_C6N5	A673-SLFN11-KO	Cancer cell line	Female
CVCL_C6N6	ES8-SLFN11-KO	Cancer cell line	Male
CVCL_C6N7	JN-DSRCT-SLFN11-KO	Cancer cell line	Male
CVCL_C7BT	Abcam PC-3 SLFN11 KO	Cancer cell line	Male
CVCL_D8AM	Ubigene A-549 SLFN11 KO	Cancer cell line	Male
CVCL_TP40	HAP1 SLFN11 (-) 1	Cancer cell line	Male
CVCL_XT49	HAP1 SLFN11 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.