SLX1A

Summary

SLX1A (structure-specific endonuclease subunit SLX1A, HGNC:20922) is a protein-coding gene on chromosome 16p11.2, encoding Structure-specific endonuclease subunit SLX1 (Q9BQ83). Catalytic subunit of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination.

This gene encodes a protein that is an important regulator of genome stability. The protein represents the catalytic subunit of the SLX1-SLX4 structure-specific endonuclease, which can resolve DNA secondary structures that are formed during repair and recombination processes. Two identical copies of this gene are located on the p arm of chromosome 16 due to a segmental duplication; this record represents the more centromeric copy. Alternative splicing results in multiple transcript variants. Read-through transcription also occurs between this gene and the downstream SULT1A3 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3) gene.

Source: NCBI Gene 548593 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_001014999

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20922
Approved symbol	SLX1A
Name	structure-specific endonuclease subunit SLX1A
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000132207
Ensembl biotype	protein_coding
OMIM	615822
Entrez	548593

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000251303, ENST00000345535, ENST00000563616, ENST00000563995, ENST00000564268, ENST00000565081, ENST00000889733, ENST00000889734, ENST00000941761, ENST00000941762

RefSeq mRNA: 5 — MANE Select: NM_001014999 NM_001014999, NM_001015000, NM_001400287, NM_001421660, NM_001421664

CCDS: CCDS32431, CCDS32432

Canonical transcript exons

ENST00000251303 — 6 exons

Exon	Start	End
ENSE00001866597	30193875	30194272
ENSE00003460673	30194740	30194791
ENSE00003542268	30196974	30197101
ENSE00003562829	30194886	30195227
ENSE00003654915	30197270	30197357
ENSE00003903820	30197437	30197561

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.86.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.86	gold quality
duodenum	UBERON:0002114	96.75	gold quality
mucosa of transverse colon	UBERON:0004991	96.45	gold quality
monocyte	CL:0000576	96.21	gold quality
leukocyte	CL:0000738	96.01	gold quality
metanephros cortex	UBERON:0010533	95.49	gold quality
right lobe of liver	UBERON:0001114	95.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.08	gold quality
spleen	UBERON:0002106	94.96	gold quality
blood	UBERON:0000178	94.71	gold quality
small intestine	UBERON:0002108	94.45	gold quality
transverse colon	UBERON:0001157	93.32	gold quality
minor salivary gland	UBERON:0001830	93.20	gold quality
body of stomach	UBERON:0001161	93.03	gold quality
lower esophagus mucosa	UBERON:0035834	92.91	gold quality
right lung	UBERON:0002167	92.77	gold quality
apex of heart	UBERON:0002098	92.68	gold quality
saliva-secreting gland	UBERON:0001044	92.66	gold quality
right lobe of thyroid gland	UBERON:0001119	92.64	gold quality
left lobe of thyroid gland	UBERON:0001120	92.27	gold quality
right adrenal gland	UBERON:0001233	92.27	gold quality
liver	UBERON:0002107	92.17	gold quality
left adrenal gland cortex	UBERON:0035825	91.93	gold quality
esophagus mucosa	UBERON:0002469	91.88	gold quality
body of pancreas	UBERON:0001150	91.82	gold quality
right adrenal gland cortex	UBERON:0035827	91.78	gold quality
left adrenal gland	UBERON:0001234	91.75	gold quality
gastrocnemius	UBERON:0001388	91.66	gold quality
omental fat pad	UBERON:0010414	91.64	gold quality
pituitary gland	UBERON:0000007	91.60	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-4850	yes	134.72
E-MTAB-6379	no	242.45
E-CURD-88	no	3.63
E-ANND-3	no	1.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting SLX1A, 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-4500	99.99	72.72	2367
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-499B-5P	98.35	68.39	988
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-6865-5P	96.05	65.58	675

Literature-anchored findings (GeneRIF, showing 3)

• Data show that three structure-selective endonucleases, SLX1-SLX4, MUS81-EME1, and GEN1, define two pathways of Holliday junctions (HJs) resolution in HeLa cells. (PMID:24076221)
• SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr). (PMID:27354282)
• Folate stress induces SLX1- and RAD51-dependent mitotic DNA synthesis at the fragile X locus in human cells. (PMID:32601218)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slx1b	ENSDARG00000098605
mus_musculus	Slx1b	ENSMUSG00000059772
rattus_norvegicus	Slx1b	ENSRNOG00000019369
drosophila_melanogaster	slx1	FBGN0037263
caenorhabditis_elegans	slx-1	WBGENE00018909

Paralogs (1): SLX1B (ENSG00000181625)

Protein

Protein identifiers

Structure-specific endonuclease subunit SLX1 — Q9BQ83 (reviewed: Q9BQ83)

Alternative names: GIY-YIG domain-containing protein 1

All UniProt accessions (2): Q9BQ83, H3BPC3

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5’-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products.

Subunit / interactions. Forms a heterodimer with SLX4.

Subcellular location. Nucleus.

Similarity. Belongs to the SLX1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BQ83-1	1	yes
Q9BQ83-2	2

RefSeq proteins (5): NP_001014999, NP_001015000, NP_001387216, NP_001408589, NP_001408593 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000305	GIY-YIG_endonuc	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR027520	Slx1	Family
IPR035901	GIY-YIG_endonuc_sf	Homologous_superfamily
IPR048749	SLX1_C	Domain
IPR050381	SLX1_endonuclease	Family

Pfam: PF01541, PF21202

UniProt features (8 total): mutagenesis site 2, chain 1, domain 1, zinc finger region 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQ83-F1	83.82	0.71

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
41	abolishes endonucleolytic activity.
82	abolishes endonucleolytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-6783310	Fanconi Anemia Pathway
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693532	DNA Double-Strand Break Repair
R-HSA-5693537	Resolution of D-Loop Structures
R-HSA-5693538	Homology Directed Repair
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)
R-HSA-73894	DNA Repair

MSigDB gene sets: 71 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, chr16p11, GOBP_DNA_DAMAGE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_TELOMERE_MAINTENANCE

GO Biological Process (11): double-strand break repair via homologous recombination (GO:0000724), DNA repair (GO:0006281), DNA double-strand break processing involved in repair via single-strand annealing (GO:0010792), telomere maintenance via telomere lengthening (GO:0010833), telomeric D-loop disassembly (GO:0061820), t-circle formation (GO:0090656), negative regulation of telomere maintenance via telomere lengthening (GO:1904357), positive regulation of t-circle formation (GO:1904431), DNA recombination (GO:0006310), DNA damage response (GO:0006974), regulation of telomere maintenance (GO:0032204)

GO Molecular Function (8): zinc ion binding (GO:0008270), crossover junction DNA endonuclease activity (GO:0008821), 5’-flap endonuclease activity (GO:0017108), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleoplasm (GO:0005654), Slx1-Slx4 complex (GO:0033557), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
DNA Repair	2
Resolution of D-Loop Structures	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
HDR through Homologous Recombination (HRR)	1
DNA Double-Strand Break Repair	1
Homology Directed Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
telomere maintenance	2
recombinational repair	1
double-strand break repair	1
DNA damage response	1
DNA double-strand break processing	1
double-strand break repair via single-strand annealing	1
telomeric loop disassembly	1
formation of extrachromosomal circular DNA	1
telomere maintenance via telomere trimming	1
telomere maintenance via telomere lengthening	1
negative regulation of telomere maintenance	1
regulation of telomere maintenance via telomere lengthening	1
positive regulation of telomere maintenance	1
positive regulation of cellular component biogenesis	1
t-circle formation	1
regulation of t-circle formation	1
cellular response to stress	1
regulation of chromosome organization	1
regulation of DNA metabolic process	1
transition metal ion binding	1
DNA endonuclease activity, producing 3’-phosphomonoesters	1
DNA endonuclease activity, producing 5’-phosphomonoesters	1
flap endonuclease activity	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
nuclear chromosome	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

882 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLX1A	SLX4	Q8IY92	999
SLX1A	MUS81	Q96NY9	998
SLX1A	EME1	Q96AY2	993
SLX1A	ERCC4	Q92889	992
SLX1A	ERCC1	P07992	980
SLX1A	SLX4IP	Q5VYV7	897
SLX1A	FANCD2	Q9BXW9	839
SLX1A	MSH3	P20585	830
SLX1A	GEN1	Q17RS7	816
SLX1A	TERF2IP	Q9NYB0	778
SLX1A	RMI1	Q9H9A7	767
SLX1A	TOP3A	Q13472	758
SLX1A	TOPBP1	Q92547	751
SLX1A	FANCM	Q8IYD8	735
SLX1A	EXO1	Q9UQ84	716

IntAct

26 interactions, top by confidence:

A	B	Type	Score
SLX1A	SLX4	psi-mi:“MI:0915”(physical association)	0.710
SLX4	SLX1A	psi-mi:“MI:0915”(physical association)	0.710
SLX1A	SLX4	psi-mi:“MI:0914”(association)	0.710
SLX1A	SLX4	psi-mi:“MI:0403”(colocalization)	0.710
SLX4	ERCC1	psi-mi:“MI:0914”(association)	0.640
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
SLX1A	BACH1	psi-mi:“MI:0914”(association)	0.530
THAP11	SLX1A	psi-mi:“MI:0915”(physical association)	0.370
TUBA1B	SLX1A	psi-mi:“MI:0915”(physical association)	0.370
DUSP10	SLX1A	psi-mi:“MI:0915”(physical association)	0.370
GRB2	SLX1A	psi-mi:“MI:0915”(physical association)	0.370
ERCC1	SLX4IP	psi-mi:“MI:0914”(association)	0.350
SLX4	DDX39A	psi-mi:“MI:0914”(association)	0.350
SLX4	SMAP	psi-mi:“MI:0914”(association)	0.350
SLX1A	PSMD11	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
	SLX1A	psi-mi:“MI:0915”(physical association)	0.000
pog	SLX1A	psi-mi:“MI:0915”(physical association)	0.000
SLX1A	b0025	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (106): SLX1B (Affinity Capture-MS), GPBP1 (Affinity Capture-MS), BACH1 (Affinity Capture-MS), HMMR (Affinity Capture-MS), PSME4 (Affinity Capture-MS), KIAA1804 (Affinity Capture-MS), NCOA1 (Affinity Capture-MS), CDKN2C (Affinity Capture-MS), USP4 (Affinity Capture-MS), HDAC6 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), EAPP (Affinity Capture-MS), ARNT (Affinity Capture-MS), SLX1B (Affinity Capture-MS), UBR7 (Affinity Capture-MS)

ESM2 similar proteins: C9JLR9, D3YZZ2, E1BDF2, E7ERA6, O00110, P0DH78, P29590, P51172, P70225, Q01113, Q02833, Q0VCS0, Q13477, Q13505, Q14626, Q32KV8, Q3UIW8, Q3UV31, Q4R7H0, Q4VA45, Q5R866, Q5RF19, Q5U4P2, Q5VTJ3, Q64385, Q6BAA4, Q6ISU1, Q6ZVT0, Q70EL4, Q7L591, Q86UR1, Q8IYG6, Q8N1F8, Q8N554, Q8NFT6, Q969Z4, Q96G42, Q96HA4, Q96IQ9, Q99640

Diamond homologs: A1C4Z4, A1CZX3, A2QUJ2, A4I1H7, A5DFX7, A6RYJ8, A6ZLG6, A7STV9, A8B2Z8, A8PV03, A8PWH1, A8WJ66, A9V196, B0Y2U0, B2B674, B2WM34, B3LMT5, B3M0F3, B3P230, B4GEU1, B4I3R2, B4JGW7, B4KBJ0, B5DXG8, B5VEH8, B6HK90, B6QFH5, B8MDD1, B9WGW9, C0NTM8, C0S8C7, C1GJU5, C1H0K4, P0CN80, P0CN81, P38324, P91351, Q0CE14, Q0UAL6, Q2GWJ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

797 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30197264:T:TA	acceptor_gain	1.0000
16:30197266:GTA:G	acceptor_loss	1.0000
16:30197267:TA:T	acceptor_loss	1.0000
16:30197268:A:AC	acceptor_loss	1.0000
16:30197268:A:AG	acceptor_gain	1.0000
16:30197268:AGCT:A	acceptor_gain	1.0000
16:30197269:G:GT	acceptor_gain	1.0000
16:30197269:GCT:G	acceptor_gain	1.0000
16:30197269:GCTG:G	acceptor_gain	1.0000
16:30194364:G:GT	donor_gain	0.9900
16:30194468:G:T	donor_gain	0.9900
16:30194797:G:GT	donor_gain	0.9900
16:30197265:G:A	acceptor_gain	0.9900
16:30197269:GC:G	acceptor_gain	0.9900
16:30197269:GCTGT:G	acceptor_gain	0.9900
16:30194030:GACCC:G	donor_gain	0.9800
16:30194734:CCTCA:C	acceptor_loss	0.9800
16:30194735:CTCAG:C	acceptor_loss	0.9800
16:30194736:TCAGG:T	acceptor_loss	0.9800
16:30194737:CAGG:C	acceptor_loss	0.9800
16:30194738:A:AG	acceptor_gain	0.9800
16:30194738:AG:A	acceptor_gain	0.9800
16:30194738:AGGG:A	acceptor_loss	0.9800
16:30194739:G:GG	acceptor_gain	0.9800
16:30194739:G:T	acceptor_loss	0.9800
16:30194739:GG:G	acceptor_gain	0.9800
16:30194791:GGTAA:G	donor_loss	0.9800
16:30194792:G:C	donor_loss	0.9800
16:30194793:T:A	donor_loss	0.9800
16:30197252:T:TA	acceptor_gain	0.9800

AlphaMissense

1752 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30194184:T:C	F34L	0.994
16:30194186:C:A	F34L	0.994
16:30194186:C:G	F34L	0.994
16:30194765:T:C	F72L	0.992
16:30194767:C:A	F72L	0.992
16:30194767:C:G	F72L	0.992
16:30194766:T:C	F72S	0.991
16:30194886:T:C	F81L	0.990
16:30194888:T:A	F81L	0.990
16:30194888:T:G	F81L	0.990
16:30194891:G:C	E82D	0.987
16:30194891:G:T	E82D	0.987
16:30194766:T:G	F72C	0.982
16:30197291:G:C	W244C	0.982
16:30197291:G:T	W244C	0.982
16:30194898:T:A	W85R	0.981
16:30194898:T:C	W85R	0.981
16:30197289:T:A	W244R	0.978
16:30197289:T:C	W244R	0.978
16:30194887:T:C	F81S	0.975
16:30194890:A:T	E82V	0.974
16:30194784:C:A	A78D	0.969
16:30194894:G:C	W83C	0.969
16:30194894:G:T	W83C	0.969
16:30194886:T:A	F81I	0.967
16:30195039:T:A	W132R	0.967
16:30195039:T:C	W132R	0.967
16:30194765:T:G	F72V	0.966
16:30194970:T:C	F109L	0.965
16:30194972:C:A	F109L	0.965

dbSNP variants (sampled 300 via entrez): RS1003660683 (16:30194786 C>T), RS1005284345 (16:30197850 C>G), RS1012475256 (16:30197522 A>G), RS1012919487 (16:30194823 G>A,T), RS1014971225 (16:30197882 G>A), RS1015002392 (16:30194881 C>A,G,T), RS1027624502 (16:30194827 G>A), RS1049757961 (16:30197657 A>C), RS1056525105 (16:30197453 T>G), RS112165087 (16:30196456 A>T), RS1158214601 (16:30194904 C>T), RS1159511580 (16:30194479 C>G), RS1159665083 (16:30194800 G>A), RS1160221756 (16:30195147 G>A), RS1162414009 (16:30194840 G>A,T)

Disease associations

OMIM: gene MIM:615822 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_269	Brain morphology (MOSTest)	4.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	decreases expression, affects cotreatment	1
beta-lapachone	decreases expression	1
butyraldehyde	increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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