SLFN5

Summary

SLFN5 (schlafen family member 5, HGNC:28286) is a protein-coding gene on chromosome 17q12, encoding Schlafen family member 5 (Q08AF3). May have a role in hematopoietic cell differentiation.

Predicted to enable ATP binding activity. Predicted to be involved in cell differentiation. Predicted to be located in nucleus.

Source: NCBI Gene 162394 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 141 total
• MANE Select transcript: NM_144975

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28286
Approved symbol	SLFN5
Name	schlafen family member 5
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	MGC19764
Ensembl gene	ENSG00000166750
Ensembl biotype	protein_coding
OMIM	614952
Entrez	162394

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000299977, ENST00000542451, ENST00000592325, ENST00000884250, ENST00000884251, ENST00000884252

RefSeq mRNA: 2 — MANE Select: NM_144975 NM_001330183, NM_144975

CCDS: CCDS32619, CCDS82106

Canonical transcript exons

ENST00000299977 — 5 exons

Exon	Start	End
ENSE00001106255	35260971	35261096
ENSE00001106258	35258651	35259702
ENSE00001106261	35264183	35264903
ENSE00001245563	35265072	35273655
ENSE00002926419	35243072	35243143

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.9100 / max 1309.2786, expressed in 1706 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160345	46.7196	1706
160347	0.1904	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
visceral pleura	UBERON:0002401	97.13	gold quality
pancreatic ductal cell	CL:0002079	96.74	gold quality
superficial temporal artery	UBERON:0001614	96.67	gold quality
parietal pleura	UBERON:0002400	96.50	gold quality
pylorus	UBERON:0001166	96.43	gold quality
cardia of stomach	UBERON:0001162	96.32	gold quality
buccal mucosa cell	CL:0002336	95.79	gold quality
nasal cavity epithelium	UBERON:0005384	95.59	gold quality
tendon of biceps brachii	UBERON:0008188	95.44	gold quality
nipple	UBERON:0002030	95.16	gold quality
lower lobe of lung	UBERON:0008949	95.01	gold quality
palpebral conjunctiva	UBERON:0001812	94.83	gold quality
superior surface of tongue	UBERON:0007371	94.55	gold quality
epithelium of nasopharynx	UBERON:0001951	94.33	gold quality
nasopharynx	UBERON:0001728	94.31	gold quality
layer of synovial tissue	UBERON:0007616	94.28	gold quality
trigeminal ganglion	UBERON:0001675	94.27	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.26	gold quality
bronchus	UBERON:0002185	94.10	gold quality
bronchial epithelial cell	CL:0002328	94.00	gold quality
seminal vesicle	UBERON:0000998	93.92	gold quality
trachea	UBERON:0003126	93.90	gold quality
thymus	UBERON:0002370	93.82	gold quality
dorsal root ganglion	UBERON:0000044	93.46	gold quality
decidua	UBERON:0002450	93.10	gold quality
urethra	UBERON:0000057	93.05	gold quality
oral cavity	UBERON:0000167	92.44	gold quality
renal medulla	UBERON:0000362	92.40	gold quality
epithelial cell of pancreas	CL:0000083	92.29	gold quality
ventral tegmental area	UBERON:0002691	92.16	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	47.01
E-CURD-112	yes	8.46
E-MTAB-9801	yes	6.11
E-MTAB-9067	yes	5.13
E-GEOD-150728	no	977.32
E-CURD-10	no	562.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

103 targeting SLFN5, 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-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-8068	99.98	73.85	2376
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-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 11)

• SLFN5 knockdown also resulted in increased invasion in three-dimensional collagen, suggesting a dual role for SLFN5 in the regulation of invasion and anchorage-independent growth of melanoma cells. (PMID:20956525)
• SLFN5 exhibits key roles in controlling motility and invasiveness of renal cell carcinoma cells by negatively controlling expression of MMP-1, MMP-13, and several other genes involved in the control of malignant cell motility. (PMID:26012550)
• In this study population, elevated SLFN5 protein expression in patients with intestinal metaplasia correlated with progression to gastric cancer (PMID:27032393)
• Type-I IFN treatment triggers the interaction of STAT1 with SLFN5, and the resulting complex negatively controls STAT1-mediated gene transcription via interferon stimulated response elements (PMID:28671669)
• This is the first study to report that SLFN5 inhibits cancer migration and invasiveness in several common cancer cell lines by repressing MT1-MMP expression via the AKT/GSK-3beta/beta-catenin signalling pathway, suggesting that SLFN5 plays wide inhibitory roles in various cancers. (PMID:30844429)
• Study results demonstrated that overexpression of SLFN5 promoted the morphology transformation of lung cancer cell line A549 from epithelial to mesenchymal, as well as migration and invasion. However, knockdown of SLFN5 resulted in the opposite results. Results suggest that SLFN5 may act as a synergist in lung cancer cell tumorigenesis and progression through beta-catenin/Snail/E-cadherin pathway. (PMID:31472120)
• Human Schlafen 5 regulates reversible epithelial and mesenchymal transitions in breast cancer by suppression of ZEB1 transcription. (PMID:32488136)
• Comparative proteomics identifies Schlafen 5 (SLFN5) as a herpes simplex virus restriction factor that suppresses viral transcription. (PMID:33432153)
• Schlafen 5 as a novel therapeutic target in pancreatic ductal adenocarcinoma. (PMID:33846574)
• SLFN5 Regulates LAT1-Mediated mTOR Activation in Castration-Resistant Prostate Cancer. (PMID:33985973)
• Schlafen 5 suppresses human immunodeficiency virus type 1 transcription by commandeering cellular epigenetic machinery. (PMID:35687115)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slfn5	ENSMUSG00000054404
rattus_norvegicus	Slfn5	ENSRNOG00000021719

Paralogs (6): SLFN13 (ENSG00000154760), SLFNL1 (ENSG00000171790), SLFN12 (ENSG00000172123), SLFN11 (ENSG00000172716), SLFN12L (ENSG00000205045), SLFN14 (ENSG00000236320)

Protein

Protein identifiers

Schlafen family member 5 — Q08AF3 (reviewed: Q08AF3)

All UniProt accessions (2): B4E128, Q08AF3

UniProt curated annotations — full annotation on UniProt →

Function. May have a role in hematopoietic cell differentiation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q08AF3-1	1	yes
Q08AF3-2	2

RefSeq proteins (2): NP_001317112, NP_659412* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007421	Schlafen_AlbA_2_dom	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, PF17057, PF21026

UniProt features (75 total): strand 34, helix 24, turn 8, sequence variant 3, splice variant 2, chain 1, binding site 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7Q3Z	X-RAY DIFFRACTION	1.85
7CUX	X-RAY DIFFRACTION	3.29
6RR9	X-RAY DIFFRACTION	3.43
7PPJ	ELECTRON MICROSCOPY	3.44

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08AF3-F1	87.90	0.61

Functional residue map

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

Ligand- & substrate-binding residues (1): 578–585

Post-translational modifications (1): 59

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 175 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, FOSTER_TOLERANT_MACROPHAGE_UP, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, DOUGLAS_BMI1_TARGETS_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, CUI_TCF21_TARGETS_2_DN, GOBP_RRNA_CATABOLIC_PROCESS, GAVIN_FOXP3_TARGETS_CLUSTER_P2, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, WANG_SMARCE1_TARGETS_UP, GOMF_RIBONUCLEOPROTEIN_COMPLEX_BINDING, LIU_COMMON_CANCER_GENES

GO Biological Process (2): rRNA catabolic process (GO:0016075), cell differentiation (GO:0030154)

GO Molecular Function (4): RNA nuclease activity (GO:0004540), ATP binding (GO:0005524), ribosome binding (GO:0043022), nucleotide binding (GO:0000166)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA catabolic process	1
rRNA metabolic process	1
cellular developmental process	1
nuclease activity	1
catalytic activity, acting on RNA	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoprotein complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLFN5	CLLU1-AS1	Q5K130	512
SLFN5	SAMD10	Q9BYL1	446
SLFN5	CCDC126	Q96EE4	432
SLFN5	BPIFA3	Q9BQP9	411
SLFN5	ZNF880	Q6PDB4	410
SLFN5	METTL27	Q8N6F8	400
SLFN5	XRRA1	Q6P2D8	398
SLFN5	SIRAL2	Q9NWS6	370
SLFN5	FAM53A	Q6NSI3	370
SLFN5	ZNF266	Q14584	367
SLFN5	TMEM106A	Q96A25	355
SLFN5	MXRA7	P84157	324
SLFN5	ZNF239	Q16600	324
SLFN5	Q8N1N5	Q8N1N5	321
SLFN5	STK35	Q8TDR2	305

IntAct

42 interactions, top by confidence:

A	B	Type	Score
PRSS22	PPM1A	psi-mi:“MI:0914”(association)	0.560
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530
NOTCH1	CNOT1	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
SOX2	CBX4	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
IGHD	POTEF	psi-mi:“MI:0914”(association)	0.350
SLFN5	BEND3	psi-mi:“MI:0914”(association)	0.350
B4GALT2	LENG9	psi-mi:“MI:0914”(association)	0.350
CLEC4E	ESYT2	psi-mi:“MI:0914”(association)	0.350
GPR45	VWA8	psi-mi:“MI:0914”(association)	0.350
GML	POTEF	psi-mi:“MI:0914”(association)	0.350
PLEKHG7	MROH6	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
D2HGDH	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
SULT1C4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PUDP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
OPALIN	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SF3B3	MYO9A	psi-mi:“MI:0914”(association)	0.350
NSUN5P1		psi-mi:“MI:0914”(association)	0.350
BAG2	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
SNX21	ACOT8	psi-mi:“MI:0914”(association)	0.350
BSG	TNPO2	psi-mi:“MI:0914”(association)	0.350
RAMP3	MGST3	psi-mi:“MI:0914”(association)	0.350
CTAG1A	PER1	psi-mi:“MI:0914”(association)	0.350
PRSS50	TUBB	psi-mi:“MI:0914”(association)	0.350
IGHD	OBSL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): SLFN5 (Biochemical Activity), SLFN5 (Biochemical Activity), SLFN5 (Affinity Capture-MS), SLFN5 (Affinity Capture-MS), SLFN5 (Affinity Capture-MS), SLFN5 (Negative Genetic), SLFN13 (Affinity Capture-MS), SLFN5 (Affinity Capture-MS), BEND3 (Affinity Capture-MS), SLFN5 (Affinity Capture-MS), SLFN5 (Affinity Capture-MS), SLFN5 (Affinity Capture-MS), SLFN5 (Affinity Capture-MS), SLFN5 (Affinity Capture-MS), SLFN5 (Affinity Capture-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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	127
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

940 predictions. Top by Δscore:

Variant	Effect	Δscore
17:35243140:GCGG:G	donor_gain	1.0000
17:35243141:CGGG:C	donor_loss	0.9900
17:35243142:GG:G	donor_gain	0.9900
17:35243142:GGGT:G	donor_loss	0.9900
17:35243143:GG:G	donor_gain	0.9900
17:35243144:GTA:G	donor_loss	0.9900
17:35243145:T:C	donor_loss	0.9900
17:35258650:GGA:G	acceptor_gain	0.9900
17:35258829:G:GG	donor_gain	0.9900
17:35259690:G:GT	donor_gain	0.9900
17:35259708:G:GT	donor_gain	0.9900
17:35260969:A:G	acceptor_gain	0.9900
17:35260970:G:GC	acceptor_loss	0.9900
17:35260970:G:GG	acceptor_gain	0.9900
17:35260970:GA:G	acceptor_gain	0.9900
17:35260970:GAC:G	acceptor_gain	0.9900
17:35260970:GACC:G	acceptor_gain	0.9900
17:35260970:GACCT:G	acceptor_gain	0.9900
17:35265070:A:AG	acceptor_gain	0.9900
17:35265071:G:GG	acceptor_gain	0.9900
17:35243144:G:GG	donor_gain	0.9800
17:35258826:GCA:G	donor_gain	0.9800
17:35259698:CCCAG:C	donor_loss	0.9800
17:35259700:CAG:C	donor_loss	0.9800
17:35259701:AG:A	donor_loss	0.9800
17:35260968:A:AG	acceptor_gain	0.9800
17:35261092:TCCAG:T	donor_loss	0.9800
17:35261093:CCAG:C	donor_loss	0.9800
17:35261094:CAGGT:C	donor_loss	0.9800
17:35261095:AGGTA:A	donor_loss	0.9800

AlphaMissense

5879 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:35264317:T:A	W425R	0.988
17:35264317:T:C	W425R	0.988
17:35259606:T:C	F306L	0.978
17:35259608:T:A	F306L	0.978
17:35259608:T:G	F306L	0.978
17:35264365:G:C	A441P	0.973
17:35265754:T:C	F848L	0.973
17:35265756:T:A	F848L	0.973
17:35265756:T:G	F848L	0.973
17:35264319:G:C	W425C	0.969
17:35264319:G:T	W425C	0.969
17:35264469:G:C	K475N	0.964
17:35264469:G:T	K475N	0.964
17:35258982:T:C	F98L	0.962
17:35258984:T:A	F98L	0.962
17:35258984:T:G	F98L	0.962
17:35259672:T:A	W328R	0.961
17:35259672:T:C	W328R	0.961
17:35265193:T:A	W661R	0.960
17:35265193:T:C	W661R	0.960
17:35265781:T:C	F857L	0.958
17:35265783:T:A	F857L	0.958
17:35265783:T:G	F857L	0.958
17:35264369:T:C	L442P	0.957
17:35264465:T:C	L474S	0.955
17:35264366:C:A	A441D	0.952
17:35258847:T:C	S53P	0.951
17:35264767:T:C	F575L	0.951
17:35264769:T:A	F575L	0.951
17:35264769:T:G	F575L	0.951

dbSNP variants (sampled 300 via entrez): RS1000068940 (17:35252816 C>T), RS1000135414 (17:35254122 G>A), RS1000169207 (17:35253649 A>G), RS1000502839 (17:35252131 TAA>T), RS1000533898 (17:35251853 A>G), RS1000612832 (17:35270122 A>T), RS1000716162 (17:35263292 G>A), RS1000748798 (17:35269865 C>T), RS1000812635 (17:35245320 G>A), RS1000833815 (17:35263998 T>G), RS1000880398 (17:35246712 AGGCGTGGTGGTG>A), RS1000918613 (17:35246602 C>T), RS1001137399 (17:35262265 A>C), RS1001181285 (17:35245627 T>A,C), RS1001317008 (17:35253137 T>A)

Disease associations

OMIM: gene MIM:614952 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	6
Acetaminophen	affects cotreatment, increases expression	5
(+)-JQ1 compound	decreases expression, increases expression	4
Cyclosporine	increases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Arsenic Trioxide	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Ethinyl Estradiol	affects expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
Genistein	increases expression, affects expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
OTX015	increases expression	1
mivebresib	increases expression	1
TAK-243	decreases sumoylation	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	decreases expression, increases methylation	1

Clinical trials (associated diseases)

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