SLFN13

Summary

SLFN13 (schlafen family member 13, HGNC:26481) is a protein-coding gene on chromosome 17q12, encoding Schlafen family member 13 (Q68D06). Endoribonuclease that cleaves tRNAs and rRNAs.

Enables RNA endonuclease activity. Involved in rRNA catabolic process and tRNA decay. Located in cytoplasm.

Source: NCBI Gene 146857 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 193 total
• MANE Select transcript: NM_144682

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26481
Approved symbol	SLFN13
Name	schlafen family member 13
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31952
Ensembl gene	ENSG00000154760
Ensembl biotype	protein_coding
OMIM	614957
Entrez	146857

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000285013, ENST00000524511, ENST00000526483, ENST00000526861, ENST00000530782, ENST00000531588, ENST00000532210, ENST00000532774, ENST00000533791, ENST00000534689, ENST00000542635, ENST00000855083, ENST00000855084, ENST00000855085

RefSeq mRNA: 1 — MANE Select: NM_144682 NM_144682

CCDS: CCDS32620

Canonical transcript exons

ENST00000285013 — 6 exons

Exon	Start	End
ENSE00001235439	35435096	35441366
ENSE00001235446	35444615	35445693
ENSE00001518812	35447268	35447414
ENSE00003473260	35441563	35442286
ENSE00003641414	35443789	35443920
ENSE00003851049	35448722	35448766

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 97.01.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9405 / max 122.0338, expressed in 425 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165370	1.9405	425

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.01	gold quality
bronchial epithelial cell	CL:0002328	93.12	gold quality
bronchus	UBERON:0002185	91.84	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.86	gold quality
bone marrow cell	CL:0002092	90.72	gold quality
oviduct epithelium	UBERON:0004804	90.17	gold quality
granulocyte	CL:0000094	88.88	gold quality
minor salivary gland	UBERON:0001830	87.39	gold quality
fallopian tube	UBERON:0003889	86.58	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.59	gold quality
vermiform appendix	UBERON:0001154	85.50	gold quality
saliva-secreting gland	UBERON:0001044	85.17	gold quality
spleen	UBERON:0002106	84.68	gold quality
bone marrow	UBERON:0002371	83.62	gold quality
gall bladder	UBERON:0002110	83.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.60	gold quality
rectum	UBERON:0001052	82.16	gold quality
descending thoracic aorta	UBERON:0002345	82.11	gold quality
lymph node	UBERON:0000029	81.63	gold quality
mouth mucosa	UBERON:0003729	81.55	gold quality
left lobe of thyroid gland	UBERON:0001120	81.43	gold quality
right lobe of thyroid gland	UBERON:0001119	80.53	gold quality
thyroid gland	UBERON:0002046	80.45	gold quality
body of stomach	UBERON:0001161	80.20	gold quality
endocervix	UBERON:0000458	80.06	gold quality
left uterine tube	UBERON:0001303	79.78	gold quality
smooth muscle tissue	UBERON:0001135	79.65	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.53	gold quality
thoracic aorta	UBERON:0001515	79.40	gold quality
tonsil	UBERON:0002372	79.17	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	31.62
E-MTAB-6678	yes	27.48
E-ANND-3	yes	10.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

152 targeting SLFN13, 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-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3671	99.90	73.04	3897

Literature-anchored findings (GeneRIF, showing 1)

• The cytoplasmically localized SLFN13 inhibits protein synthesis in 293T cells and restricts HIV replication in a nucleolytic activity-dependent manner. (PMID:29563550)

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): SLFN5 (ENSG00000166750), SLFNL1 (ENSG00000171790), SLFN12 (ENSG00000172123), SLFN11 (ENSG00000172716), SLFN12L (ENSG00000205045), SLFN14 (ENSG00000236320)

Protein

Protein identifiers

Schlafen family member 13 — Q68D06 (reviewed: Q68D06)

Alternative names: Schlafen-13

All UniProt accessions (5): Q68D06, E9PKT7, E9PM29, E9PMV5, K7EPV8

UniProt curated annotations — full annotation on UniProt →

Function. Endoribonuclease that cleaves tRNAs and rRNAs. Cleaves tRNAs 11 nucleotides from the 3’-terminus at the acceptor stem. Does not act on tRNA(Sec). Able to restrict HIV-1 virus replication; ability to inhibit HIV-1 replication is dependent on endoribonuclease activity.

Subcellular location. Cytoplasm.

Cofactor. Can also use Mn(2+).

Domain organisation. Shows a pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N’-domain that may clamp base-paired RNAs.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q68D06-1	1	yes
Q68D06-2	2

RefSeq proteins (1): NP_653283* (*=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 (17 total): sequence variant 5, binding site 4, mutagenesis site 3, active site 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68D06-F1	87.77	0.64

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 (2): 208; 213

Ligand- & substrate-binding residues (4): 284; 286; 321; 599–606

Mutagenesis-validated functional residues (3):

Position	Phenotype
208	abolished endoribonuclease activity.
213	abolished endoribonuclease activity.
251	reduced endoribonuclease activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOMF_RNA_ENDONUCLEASE_ACTIVITY, FOSTER_TOLERANT_MACROPHAGE_UP, LIAO_METASTASIS, SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP, GOBP_DEFENSE_RESPONSE_TO_VIRUS, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, GOBP_RRNA_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_VIRUS, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP

GO Biological Process (3): rRNA catabolic process (GO:0016075), tRNA decay (GO:0016078), defense response to virus (GO:0051607)

GO Molecular Function (10): tRNA binding (GO:0000049), RNA endonuclease activity (GO:0004521), ATP binding (GO:0005524), zinc ion binding (GO:0008270), hydrolase activity (GO:0016787), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), metal ion binding (GO:0046872)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA catabolic process	2
rRNA metabolic process	1
tRNA metabolic process	1
defense response	1
response to virus	1
RNA binding	1
endonuclease activity	1
RNA nuclease activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
catalytic activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLFN13	EVA1B	Q9NVM1	768
SLFN13	OASL	Q15646	444
SLFN13	OAS1	P00973	431
SLFN13	RSAD2	Q8WXG1	418
SLFN13	CMPK2	Q5EBM0	412
SLFN13	IFIT3	O14879	412
SLFN13	IFIT1	P09914	398
SLFN13	AFAP1L1	Q8TED9	393
SLFN13	ACBD6	Q9BR61	378
SLFN13	VCL	P18206	346
SLFN13	TMEM218	A2RU14	328
SLFN13	MOB3C	Q70IA8	323
SLFN13	MX1	P20591	322
SLFN13	FAM24B	Q8N5W8	321
SLFN13	ZNF572	Q7Z3I7	310

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SLFN5	BEND3	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): SLFN13 (Affinity Capture-MS), SLFN13 (Affinity Capture-MS), SLFN13 (Proximity Label-MS), SLFN13 (Proximity Label-MS)

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, P20999, P21000, Q01225, Q01226, Q08AF3, Q5RCZ8, Q68D06, Q6IEE8, Q6J362, Q8CBA2, Q8IYM2, Q8QMP8, Q8V4S4, Q9Z0I6, Q9Z0I7, V9GXG1, B1ARD8, G1SRW8, P0C7P3, Q5U311, Q7Z7L1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	152
Likely benign	21
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

829 predictions. Top by Δscore:

Variant	Effect	Δscore
17:35441558:CTTA:C	donor_loss	1.0000
17:35441559:TTAC:T	donor_loss	1.0000
17:35441560:TA:T	donor_loss	1.0000
17:35441562:C:A	donor_loss	1.0000
17:35442287:C:CC	acceptor_gain	1.0000
17:35444715:C:CT	acceptor_gain	1.0000
17:35447327:T:TA	donor_gain	1.0000
17:35447350:T:TA	donor_gain	1.0000
17:35447351:C:A	donor_gain	1.0000
17:35448721:CCT:C	donor_gain	1.0000
17:35441367:C:CC	acceptor_gain	0.9900
17:35441557:GCTTA:G	donor_loss	0.9900
17:35442282:TGGAA:T	acceptor_gain	0.9900
17:35442284:GAAC:G	acceptor_loss	0.9900
17:35442288:T:C	acceptor_loss	0.9900
17:35442292:C:CT	acceptor_gain	0.9900
17:35442293:A:T	acceptor_gain	0.9900
17:35444707:G:T	acceptor_gain	0.9900
17:35447349:TTCC:T	donor_gain	0.9900
17:35447350:TCCC:T	donor_gain	0.9900
17:35448716:TCTTA:T	donor_loss	0.9900
17:35448717:CTTAC:C	donor_loss	0.9900
17:35448718:TTA:T	donor_loss	0.9900
17:35448719:TACCT:T	donor_loss	0.9900
17:35448720:A:AC	donor_gain	0.9900
17:35448720:ACCTC:A	donor_loss	0.9900
17:35448721:C:A	donor_loss	0.9900
17:35448721:C:CC	donor_gain	0.9900
17:35441365:CA:C	acceptor_gain	0.9800
17:35441561:A:AC	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000028843 (17:35434724 G>A), RS1000064066 (17:35446935 G>A,C), RS1000368026 (17:35446582 T>A,C), RS1000517387 (17:35450591 G>T), RS1000761277 (17:35446772 T>A), RS1001879844 (17:35444101 T>A), RS1001902525 (17:35449957 A>G), RS1002354202 (17:35437199 T>C), RS1002525372 (17:35448527 A>G), RS1002778003 (17:35443691 A>C), RS1002804106 (17:35448323 C>T), RS1002885146 (17:35449663 A>G), RS1003051720 (17:35448713 C>G), RS1003552685 (17:35442600 C>G,T), RS1003922347 (17:35444532 G>A,T)

Disease associations

OMIM: gene MIM:614957 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	5
sodium arsenite	decreases expression, increases expression	2
entinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
bisphenol A	affects methylation	1
trichostatin A	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
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Demecolcine	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Vanadates	decreases expression	1
Vincristine	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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