SLFN12L

Summary

SLFN12L (schlafen family member 12 like, HGNC:33920) is a protein-coding gene on chromosome 17q12, encoding Schlafen family member 12-like (Q6IEE8).

Predicted to be located in membrane.

Source: NCBI Gene 100506736 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 102 total
• MANE Select transcript: NM_001363830

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33920
Approved symbol	SLFN12L
Name	schlafen family member 12 like
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205045
Ensembl biotype	protein_coding
OMIM	614956
Entrez	100506736

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000260908, ENST00000587436, ENST00000590802, ENST00000628453, ENST00000714259

RefSeq mRNA: 2 — MANE Select: NM_001363830 NM_001195790, NM_001363830

CCDS: CCDS56026, CCDS86591

Canonical transcript exons

ENST00000628453 — 5 exons

Exon	Start	End
ENSE00001401199	35522279	35522969
ENSE00001416641	35464254	35475485
ENSE00001477533	35478075	35478185
ENSE00001477537	35479117	35480195
ENSE00001477540	35537573	35537678

Expression profiles

Bgee: expression breadth ubiquitous, 123 present calls, max score 90.55.

FANTOM5 (CAGE): breadth broad, TPM avg 6.0732 / max 314.1613, expressed in 403 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165378	3.8368	178
165380	0.7861	149
165381	0.4611	98
165379	0.4226	88
165376	0.3117	160
165377	0.1461	52
165375	0.1069	53
165373	0.0020	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	90.55	gold quality
blood	UBERON:0000178	81.55	gold quality
spleen	UBERON:0002106	78.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.94	silver quality
lymph node	UBERON:0000029	75.94	gold quality
vermiform appendix	UBERON:0001154	71.06	gold quality
bone marrow cell	CL:0002092	70.93	gold quality
bone marrow	UBERON:0002371	70.37	gold quality
tonsil	UBERON:0002372	68.81	gold quality
small intestine Peyer’s patch	UBERON:0003454	67.32	gold quality
duodenum	UBERON:0002114	67.10	gold quality
small intestine	UBERON:0002108	66.38	gold quality
gall bladder	UBERON:0002110	66.34	gold quality
lung	UBERON:0002048	65.93	gold quality
right lung	UBERON:0002167	65.55	gold quality
upper lobe of left lung	UBERON:0008952	65.40	gold quality
mucosa of transverse colon	UBERON:0004991	65.37	gold quality
endometrium	UBERON:0001295	64.79	gold quality
omental fat pad	UBERON:0010414	64.38	gold quality
leukocyte	CL:0000738	64.25	gold quality
monocyte	CL:0000576	62.52	gold quality
right lobe of liver	UBERON:0001114	61.55	gold quality
adipose tissue	UBERON:0001013	61.50	gold quality
right atrium auricular region	UBERON:0006631	61.37	gold quality
sural nerve	UBERON:0015488	60.67	gold quality
rectum	UBERON:0001052	60.63	gold quality
lower esophagus mucosa	UBERON:0035834	60.37	gold quality
liver	UBERON:0002107	60.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	59.53	gold quality
thoracic mammary gland	UBERON:0005200	59.31	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-120	yes	513.02
E-MTAB-7008	yes	154.75
E-MTAB-5061	yes	14.71
E-ANND-3	yes	4.99
E-MTAB-9067	no	637.16
E-MTAB-10137	no	77.26
E-GEOD-99795	no	22.52

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• in the stomachs of H. pylori-infected patients, the human SLFN4 ortholog SLFN12L colocalized to cells that expressed myeloid-derived suppressor cell surface markers CD15+CD33+HLA-DRlo (PMID:27427984)
• Schlafen 12 (SLFN12) is a cytosolic protein that stimulates sucrase-isomaltase (SI) expression. (PMID:30875077)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slfn4	ENSMUSG00000000204
mus_musculus	Slfn3	ENSMUSG00000018986
mus_musculus	Slfn2	ENSMUSG00000072620
mus_musculus	Slfn1	ENSMUSG00000078763
rattus_norvegicus	Slfn2	ENSRNOG00000037113
rattus_norvegicus	Slfn1	ENSRNOG00000048053
rattus_norvegicus	Slfn4l1	ENSRNOG00000062983

Paralogs (6): SLFN13 (ENSG00000154760), SLFN5 (ENSG00000166750), SLFNL1 (ENSG00000171790), SLFN12 (ENSG00000172123), SLFN11 (ENSG00000172716), SLFN14 (ENSG00000236320)

Protein

Protein identifiers

Schlafen family member 12-like — Q6IEE8 (reviewed: Q6IEE8)

All UniProt accessions (2): A0A499FJ85, A0A8I5QCZ1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the Schlafen family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6IEE8-1	1	yes
Q6IEE8-2	2

RefSeq proteins (2): NP_001182719, NP_001350759* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007421	Schlafen_AlbA_2_dom	Domain
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 (8 total): sequence variant 4, chain 1, transmembrane region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IEE8-F1	81.70	0.51

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RRNA_CATABOLIC_PROCESS, GOMF_RIBONUCLEOPROTEIN_COMPLEX_BINDING, GOMF_RIBOSOME_BINDING, GOMF_PROTEIN_CONTAINING_COMPLEX_BINDING, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, GSE10239_NAIVE_VS_KLRG1INT_EFF_CD8_TCELL_UP, GSE10239_NAIVE_VS_KLRG1HIGH_EFF_CD8_TCELL_UP, GSE10239_MEMORY_VS_KLRG1HIGH_EFF_CD8_TCELL_UP, GOBP_RRNA_METABOLIC_PROCESS, GSE13306_TREG_VS_TCONV_SPLEEN_DN, chr17q12, GSE14769_UNSTIM_VS_40MIN_LPS_BMDM_DN

GO Biological Process (1): rRNA catabolic process (GO:0016075)

GO Molecular Function (2): RNA nuclease activity (GO:0004540), ribosome binding (GO:0043022)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA catabolic process	1
rRNA metabolic process	1
nuclease activity	1
catalytic activity, acting on RNA	1
ribonucleoprotein complex binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLFN12L	C18orf63	Q68DL7	507
SLFN12L	GLI1	P08151	480
SLFN12L	A0A087WV05	A0A087WV05	480
SLFN12L	SLFNL1	Q499Z3	392
SLFN12L	A0A0U1RQV1	A0A0U1RQV1	359
SLFN12L	ZNF471	Q9BX82	346
SLFN12L	TFF2	Q03403	324
SLFN12L	ZNF667	Q5HYK9	323
SLFN12L	FNDC3B	Q53EP0	297
SLFN12L	CTSF	Q9UBX1	291
SLFN12L	CCDC91	Q7Z6B0	290
SLFN12L	C16orf54	Q6UWD8	289
SLFN12L	MYBL1	P10243	276
SLFN12L	PCDHGB2	Q9Y5G2	272
SLFN12L	ZNF8	P17098	269

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (4): SLFN12L (Affinity Capture-MS), SLFN12L (Cross-Linking-MS (XL-MS)), SLFN12L (Affinity Capture-MS), SLFN12L (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

491 predictions. Top by Δscore:

Variant	Effect	Δscore
17:35479094:ATTG:A	donor_gain	0.9900
17:35479109:T:TA	donor_gain	0.9900
17:35487722:GAAC:G	donor_loss	0.9900
17:35487723:AACCT:A	donor_loss	0.9900
17:35487724:ACCT:A	donor_loss	0.9900
17:35487725:C:CA	donor_loss	0.9900
17:35487788:T:A	donor_gain	0.9900
17:35478186:C:CC	acceptor_gain	0.9800
17:35478196:A:C	acceptor_gain	0.9800
17:35479066:T:TA	donor_gain	0.9800
17:35479105:T:TA	donor_gain	0.9800
17:35478182:CATA:C	acceptor_gain	0.9700
17:35478199:T:C	acceptor_gain	0.9700
17:35479088:AT:A	donor_gain	0.9700
17:35479089:T:TA	donor_gain	0.9700
17:35479170:A:C	donor_gain	0.9700
17:35479268:T:TA	donor_gain	0.9700
17:35487725:CCTGG:C	donor_gain	0.9700
17:35478196:A:AC	acceptor_gain	0.9600
17:35480191:CTTTT:C	acceptor_gain	0.9600
17:35487724:A:AC	donor_gain	0.9600
17:35487725:C:CC	donor_gain	0.9600
17:35487749:CTCT:C	donor_gain	0.9600
17:35487750:TCTT:T	donor_gain	0.9600
17:35487751:CTTC:C	donor_gain	0.9600
17:35475483:GCCC:G	acceptor_loss	0.9500
17:35475487:T:G	acceptor_loss	0.9500
17:35479094:A:AC	donor_gain	0.9500
17:35479149:T:A	donor_gain	0.9500
17:35475486:C:CC	acceptor_gain	0.9400

AlphaMissense

4081 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:35479211:A:C	F333L	0.990
17:35479211:A:T	F333L	0.990
17:35479213:A:G	F333L	0.990
17:35479147:A:G	W355R	0.973
17:35479147:A:T	W355R	0.973
17:35480072:T:A	R46S	0.971
17:35480072:T:G	R46S	0.971
17:35475351:A:G	W447R	0.970
17:35475351:A:T	W447R	0.970
17:35479469:A:C	F247L	0.969
17:35479469:A:T	F247L	0.969
17:35479471:A:G	F247L	0.969
17:35475303:C:G	A463P	0.966
17:35479555:A:G	S219P	0.965
17:35479226:G:C	F328L	0.963
17:35479226:G:T	F328L	0.963
17:35479228:A:G	F328L	0.963
17:35479463:A:C	N249K	0.963
17:35479463:A:T	N249K	0.963
17:35479769:T:A	R147S	0.963
17:35479769:T:G	R147S	0.963
17:35479467:G:T	A248E	0.962
17:35479535:T:A	K225N	0.960
17:35479535:T:G	K225N	0.960
17:35479721:G:C	F163L	0.960
17:35479721:G:T	F163L	0.960
17:35479723:A:G	F163L	0.960
17:35479212:A:C	F333C	0.958
17:35479838:A:C	F124L	0.957
17:35479838:A:T	F124L	0.957

dbSNP variants (sampled 300 via entrez): RS1000033791 (17:35528681 C>G,T), RS1000064225 (17:35505840 G>A), RS1000166071 (17:35491271 C>A,T), RS1000255750 (17:35528852 T>C), RS1000261669 (17:35480418 C>A), RS1000301372 (17:35500934 T>C), RS1000303145 (17:35485881 T>C), RS1000351717 (17:35500671 G>T), RS1000355156 (17:35485624 T>C), RS1000368962 (17:35522984 A>G), RS1000414672 (17:35480253 T>A,C), RS1000452947 (17:35511269 C>G,T), RS1000500875 (17:35468428 A>T), RS1000529643 (17:35481598 G>T), RS1000565011 (17:35505410 C>G,T)

Disease associations

OMIM: gene MIM:614956 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000779_5	Depression (quantitative trait)	2.000000e-06
GCST004619_45	Reticulocyte fraction of red cells	5.000000e-53
GCST004622_49	Reticulocyte count	2.000000e-49
GCST005991_42	Platelet count	1.000000e-12
GCST90002381_113	Eosinophil count	1.000000e-12
GCST90002382_415	Eosinophil percentage of white cells	1.000000e-17
GCST90002385_410	High light scatter reticulocyte count	4.000000e-41
GCST90002386_182	High light scatter reticulocyte percentage of red cells	2.000000e-42
GCST90002398_268	Neutrophil count	2.000000e-09
GCST90002404_158	Red cell distribution width	2.000000e-15
GCST90002405_400	Reticulocyte count	1.000000e-62
GCST90002406_455	Reticulocyte fraction of red cells	1.000000e-75

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004309	platelet count
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
monomethylarsonous acid	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases expression	1
Catechin	affects cotreatment, decreases expression	1
Dinitrochlorobenzene	affects binding	1
Lipopolysaccharides	decreases expression, decreases reaction	1
Plant Extracts	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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