SLX1B

Summary

SLX1B (structure-specific endonuclease subunit SLX1B, HGNC:28748) 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 telomeric copy. Alternative splicing results in multiple transcript variants. Read-through transcription also occurs between this gene and the downstream SULT1A4 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 4) gene.

Source: NCBI Gene 79008 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_024044

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28748
Approved symbol	SLX1B
Name	structure-specific endonuclease subunit SLX1B
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC5178
Ensembl gene	ENSG00000181625
Ensembl biotype	protein_coding
OMIM	615823
Entrez	79008

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000330181, ENST00000351581, ENST00000565219, ENST00000566424, ENST00000567248, ENST00000856228, ENST00000925429

RefSeq mRNA: 5 — MANE Select: NM_024044 NM_001400286, NM_001421660, NM_001421664, NM_024044, NM_178044

CCDS: CCDS10648, CCDS10649

Canonical transcript exons

ENST00000330181 — 6 exons

Exon	Start	End
ENSE00001720360	29458095	29458219
ENSE00001839442	29454533	29454930
ENSE00003488807	29457632	29457759
ENSE00003507209	29455398	29455449
ENSE00003525524	29457928	29458015
ENSE00003583186	29455544	29455885

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 88.11.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	88.11	gold quality
monocyte	CL:0000576	84.40	gold quality
leukocyte	CL:0000738	83.78	gold quality
vermiform appendix	UBERON:0001154	83.19	gold quality
placenta	UBERON:0001987	83.15	gold quality
cortical plate	UBERON:0005343	83.03	gold quality
ventricular zone	UBERON:0003053	82.43	gold quality
bone marrow cell	CL:0002092	82.32	gold quality
blood	UBERON:0000178	81.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.52	gold quality
ganglionic eminence	UBERON:0004023	81.36	gold quality
stromal cell of endometrium	CL:0002255	81.16	gold quality
bone marrow	UBERON:0002371	81.03	gold quality
cortex of kidney	UBERON:0001225	81.01	gold quality
popliteal artery	UBERON:0002250	80.32	gold quality
tibial artery	UBERON:0007610	80.30	gold quality
gastrocnemius	UBERON:0001388	79.82	gold quality
left coronary artery	UBERON:0001626	79.60	gold quality
superior frontal gyrus	UBERON:0002661	79.37	gold quality
descending thoracic aorta	UBERON:0002345	79.26	gold quality
thoracic aorta	UBERON:0001515	79.03	gold quality
ascending aorta	UBERON:0001496	78.92	gold quality
muscle of leg	UBERON:0001383	78.74	gold quality
primary visual cortex	UBERON:0002436	78.47	gold quality
mucosa of transverse colon	UBERON:0004991	77.59	gold quality
skeletal muscle tissue	UBERON:0001134	77.27	gold quality
mucosa of stomach	UBERON:0001199	76.95	gold quality
fundus of stomach	UBERON:0001160	76.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.83	gold quality
lymph node	UBERON:0000029	76.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	41.21
E-ANND-3	no	0.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting SLX1B, 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

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): SLX1A (ENSG00000132207)

Protein

Protein identifiers

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

Alternative names: GIY-YIG domain-containing protein 1

All UniProt accessions (2): Q9BQ83, H3BRR6

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_001387215, NP_001408589, NP_001408593, NP_076949, NP_835145 (=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: 75 (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, SHEPARD_BMYB_MORPHOLINO_DN, 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

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
SLX1B	SLX4	Q8IY92	999
SLX1B	MUS81	Q96NY9	998
SLX1B	EME1	Q96AY2	993
SLX1B	ERCC4	Q92889	992
SLX1B	ERCC1	P07992	980
SLX1B	SLX4IP	Q5VYV7	897
SLX1B	FANCD2	Q9BXW9	839
SLX1B	MSH3	P20585	830
SLX1B	GEN1	Q17RS7	816
SLX1B	TERF2IP	Q9NYB0	778
SLX1B	RMI1	Q9H9A7	767
SLX1B	TOP3A	Q13472	758
SLX1B	TOPBP1	Q92547	751
SLX1B	FANCM	Q8IYD8	735
SLX1B	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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

805 predictions. Top by Δscore:

Variant	Effect	Δscore
16:29457922:T:TA	acceptor_gain	1.0000
16:29457924:GTA:G	acceptor_loss	1.0000
16:29457925:TA:T	acceptor_loss	1.0000
16:29457926:A:AC	acceptor_loss	1.0000
16:29457926:A:AG	acceptor_gain	1.0000
16:29457926:AGCT:A	acceptor_gain	1.0000
16:29457927:G:GA	acceptor_gain	1.0000
16:29457927:GCT:G	acceptor_gain	1.0000
16:29457927:GCTG:G	acceptor_gain	1.0000
16:29455455:G:GT	donor_gain	0.9900
16:29457923:G:A	acceptor_gain	0.9900
16:29457927:GC:G	acceptor_gain	0.9900
16:29457927:GCTGT:G	acceptor_gain	0.9900
16:29454688:GACCC:G	donor_gain	0.9800
16:29455022:G:GT	donor_gain	0.9800
16:29455126:G:T	donor_gain	0.9800
16:29455447:CGGGT:C	donor_loss	0.9800
16:29455448:GGG:G	donor_loss	0.9800
16:29455449:GGTAA:G	donor_loss	0.9800
16:29455450:G:T	donor_loss	0.9800
16:29455451:TAA:T	donor_loss	0.9800
16:29457910:T:TA	acceptor_gain	0.9800
16:29455012:G:GT	donor_gain	0.9700
16:29455396:AG:A	acceptor_gain	0.9700
16:29455397:GG:G	acceptor_gain	0.9700
16:29454578:A:T	donor_gain	0.9600
16:29454920:C:T	donor_gain	0.9600
16:29454961:G:GT	donor_gain	0.9600
16:29455392:CCTCA:C	acceptor_loss	0.9600
16:29455393:CTCA:C	acceptor_loss	0.9600

AlphaMissense

1752 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1002602928 (16:29455497 C>T), RS1027321464 (16:29457636 A>T), RS1034049546 (16:29457550 C>T), RS1053924276 (16:29458102 G>A), RS1127227 (16:29457743 G>A,T), RS1158033941 (16:29458380 C>G), RS1159838096 (16:29458714 T>C), RS1160520613 (16:29458498 C>T), RS1160618003 (16:29458367 A>G), RS1164602375 (16:29457661 C>A,T), RS1166654672 (16:29457861 G>A,C), RS1167397675 (16:29458370 C>T), RS1167951088 (16:29458660 G>A), RS1168744832 (16:29457649 G>C), RS1170101700 (16:29458190 T>C)

Disease associations

OMIM: gene MIM:615823 | 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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance, increases expression	2
cobaltous chloride	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TP44	HAP1 SLX1B (-) 1	Cancer cell line	Male
CVCL_TP45	HAP1 SLX1B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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