SLX4

Summary

SLX4 (SLX4 structure-specific endonuclease subunit, HGNC:23845) is a protein-coding gene on chromosome 16p13.3, encoding Structure-specific endonuclease subunit SLX4 (Q8IY92). Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. It is a selective cancer dependency (DepMap: 11.5% of cell lines).

This gene encodes a protein that functions as an assembly component of multiple structure-specific endonucleases. These endonuclease complexes are required for repair of specific types of DNA lesions and critical for cellular responses to replication fork failure. Mutations in this gene were found in patients with Fanconi anemia.

Source: NCBI Gene 84464 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Fanconi anemia complementation group P (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 2,650 total — 99 pathogenic, 40 likely-pathogenic
• Phenotypes (HPO): 119
• Cancer dependency (DepMap): dependent in 11.5% of screened cell lines
• MANE Select transcript: NM_032444

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23845
Approved symbol	SLX4
Name	SLX4 structure-specific endonuclease subunit
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1784, KIAA1987, FANCP
Ensembl gene	ENSG00000188827
Ensembl biotype	protein_coding
OMIM	613278
Entrez	84464

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 retained_intron, 1 protein_coding

ENST00000294008, ENST00000466154, ENST00000486524, ENST00000697858, ENST00000697859

RefSeq mRNA: 1 — MANE Select: NM_032444 NM_032444

CCDS: CCDS10506

Canonical transcript exons

ENST00000294008 — 15 exons

Exon	Start	End
ENSE00001062577	3592699	3592865
ENSE00001062580	3584769	3584871
ENSE00001062581	3589002	3591310
ENSE00001062582	3583097	3583510
ENSE00001226750	3581181	3582693
ENSE00001343635	3595605	3595693
ENSE00001490989	3594453	3594599
ENSE00001490991	3600979	3601191
ENSE00001490992	3602118	3602307
ENSE00001923972	3611560	3611606
ENSE00003458589	3608430	3609566
ENSE00003502891	3596153	3596393
ENSE00003592671	3606474	3606698
ENSE00003622763	3597797	3597999
ENSE00003644764	3597379	3597695

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 82.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2234 / max 53.6791, expressed in 1459 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156041	3.2234	1459

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	82.40	gold quality
cerebellar hemisphere	UBERON:0002245	82.03	gold quality
cerebellar cortex	UBERON:0002129	81.95	gold quality
pancreatic ductal cell	CL:0002079	81.89	silver quality
cerebellum	UBERON:0002037	80.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.75	gold quality
granulocyte	CL:0000094	77.90	gold quality
oviduct epithelium	UBERON:0004804	77.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.71	gold quality
right testis	UBERON:0004534	76.64	gold quality
left testis	UBERON:0004533	76.49	gold quality
testis	UBERON:0000473	76.03	gold quality
stromal cell of endometrium	CL:0002255	75.24	gold quality
ventricular zone	UBERON:0003053	75.19	gold quality
tibialis anterior	UBERON:0001385	74.42	silver quality
apex of heart	UBERON:0002098	74.26	gold quality
cortical plate	UBERON:0005343	74.03	gold quality
embryo	UBERON:0000922	73.63	gold quality
ganglionic eminence	UBERON:0004023	73.63	gold quality
right frontal lobe	UBERON:0002810	73.36	gold quality
sural nerve	UBERON:0015488	72.94	gold quality
prefrontal cortex	UBERON:0000451	71.58	gold quality
blood	UBERON:0000178	71.52	gold quality
vermiform appendix	UBERON:0001154	71.09	gold quality
upper arm skin	UBERON:0004263	70.86	gold quality
bone marrow cell	CL:0002092	70.58	silver quality
endothelial cell	CL:0000115	70.56	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.44	gold quality
parotid gland	UBERON:0001831	70.36	gold quality
leukocyte	CL:0000738	70.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.45
E-GEOD-110499	no	117.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

65 targeting SLX4, 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-4262	100.00	73.26	3931
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-4505	99.27	67.81	2678

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Genetic and biochemical evidence suggest that MUS312 and BTBD12 direct Holliday junction resolution by at least two distinct endonucleases in different recombination and repair contexts. (PMID:19595722)
• BTBD12/SLX4 was identified as the human ortholog of yeast DNA repair factor Slx4p and Drosophila MUS312; SLX4 assembles a modular toolkit for repair of specific types of DNA lesions and is critical for cellular responses to replication fork failure. (PMID:19596235)
• Study reports the identification of Slx4 orthologs in metazoa, including fly MUS312, essential for meiotic recombination, and human BTBD12, an ATM/ATR checkpoint kinase. (PMID:19596236)
• show that SLX4 binds the XPF(ERCC4) and MUS81 subunits of the XPF-ERCC1 and MUS81-EME1 endonucleases and is required for DNA interstrand crosslink repair. (PMID:19596236)
• biallelic mutations in SLX4 (renamed here as FANCP) cause a new subtype of Fanconi anemia, Fanconi anemia-P (PMID:21240275)
• SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype (PMID:21240277)
• there is no evidence for a major role of SLX4 coding variants in the inherited susceptibility towards breast cancer in German and Byelorussian patients. (PMID:21805310)
• Sequencing analysis of SLX4/FANCP gene in Italian familial breast cancer cases (PMID:22383991)
• Mutational analysis of SLX4 in Breast Cancer cases without mutations in BRCA1 or BRCA2 revealed extensive genetic variation. Twenty-nine novel single nucleotide variants were detected, however, none can be linked to alteration of the protein function. (PMID:22401137)
• The nuclease hSNM1B/Apollo is linked to the Fanconi anemia pathway via its interaction with FANCP/SLX4. (PMID:22907656)
• Data indicate that germline mutations in SLX4 are very rare and are unlikely to make a significant contribution to familial breast cancer. (PMID:22911665)
• SLX4-dependent XPF-ERCC1 activity is needed for interstrand cross-linking repair. MUS81-SLX4 interaction is critical for resistance to TOP1 inhibitors.SLX4 interacts with XPF-ERCC1, MUS81-EME1, & SLX1 via MLR, SAP, & SBD domains, respectively. (PMID:23093618)
• Data indicate that SLX4 mutation screening will have a very low impact (if any) in the genetic counseling of non-BRCA1/2 families. (PMID:23211700)
• Loss-of-function mutations in SLX4 may contribute to the development of breast cancer in very rare cases (PMID:23840564)
• Most, but not all, SLX4 foci localize to telomeres in a range of human cell lines irrespective of the mechanisms used to maintain telomere length. (PMID:23994477)
• SLX4 assembles an endonuclease toolkit that negatively regulates telomere length via SLX1-catalyzed nucleolytic resolution of telomere DNA structures. (PMID:24012755)
• 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)
• GEN1 activity cannot be substituted for the SLX4-associated nucleases, and one of the HJ resolvase activities, either of those associated with SLX4 or with GEN1, is required for cell viability, even in the presence of BLM. (PMID:24080495)
• Direct interaction of Vpr with SLX4 induced the recruitment of VPRBP and kinase-active PLK1, enhancing the cleavage of DNA by SLX4-associated MUS81-EME1 endonucleases and show that the SLX4com is involved in suppressing spontaneous and HIV-1-mediated induction of type 1 interferon and establishment of antiviral responses. (PMID:24412650)
• Data shed light on SLX4 recruitment, and they point to the existence of currently unidentified ubiquitylated ligands and E3 ligases that are crucial for ICL repair. (PMID:24794496)
• FANCP has versatile functions in genome maintenance, its mutations result in Fanconi anemia. (Review) (PMID:24938228)
• Identification and characterization of MUS81 point mutations that abolish interaction with the SLX4 scaffold protein. (PMID:25224045)
• Vpr recruits the SLX4 endonuclease complex and Vpr-induced inappropriate activation of this complex leads to cell cycle arrest at the G2 phase. (PMID:25496524)
• The interactions of SLX4 with SUMO and ubiquitin increase its affinity for factors recognizing different DNA lesions or telomeres, helping to direct the SLX4 complex in distinct functional contexts. (PMID:25533185)
• The SLX4 complex is a SUMO E3 ligase that SUMOylates SLX4 itself and the XPF subunit of the DNA repair/recombination XPF-ERCC1 endonuclease. (PMID:25533188)
• SUMOylation and PARylation cooperate to recruit and stabilize SLX4 at DNA damage sites. (PMID:25722289)
• SLX4 (FANCP) and XPF (FANCQ) proteins interact with each other and play a vital role in the Fanconi anemia (FA) DNA repair pathway. Study has revealed that the global minor allele, SLX4(Y546C), is defective in this interaction. (PMID:26453996)
• Results identified homozygous mutations in FANCA and FANCP/SLX4 genes, both located on chromosome 16, were the affected recessive FA genes in three and one family respectively. Genotyping with short tandem repeat markers and SNP arrays revealed uniparental disomy of the entire mutation-carrying chromosome 16 in all four patients. (PMID:26841305)
• The functioning of SLX4 is dependent on its dimerization via an oligomerization motif called the BTB domain. (PMID:27131364)
• SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr). (PMID:27354282)
• These data also indicate that HIV-1 and HIV-2 Vpr activate the DNA damage response through an SLX4-independent mechanism that remains uncharacterized. (PMID:27624129)
• Data suggest that dimeric GEN1 binds with high affinity/selectivity to Holliday junctions, introducing two symmetrical hydrolytic cleavages of phosphodiester backbone; at present, less is known about SLX1-SLX4-MUS81-EME1 resolving enzyme complex. (GEN1 = Holliday junction 5’ flap endonuclease; SLX = structure-specific endonuclease subunit; MUS81 = MUS81 endonuclease; EME1 = essential meiotic endonuclease 1) [REVIEW] (PMID:27990631)
• Using RNAi or FA-P cells complemented with SLX4 mutants that abrogate interaction with MUS81 or SLX1, we show that SLX4 cooperates with MUS81 to introduce DSBs after replication stress but also counteracts pathological targeting of demised forks by GEN1. (PMID:28290553)
• The BLM-TOP3A-RMI (BTR) dissolvase complex is required for Alternative lengthening of telomeres-mediated telomere synthesis. BLM and SLX4 play opposing roles in recombination-dependent replication at human telomeres. (PMID:28877996)
• Findings propose a risk variant with high penetrance on the haplotype spanning SLX4/FANCP to be functionally associated to BC predisposition via decreased repair capacity and suggest this variant is carried by a fraction of these haplotypes that is enriched in early onset BC cases. (PMID:29044504)
• observed aberrant bands of CSMD1 in one case of CRCs and SRPK1 in two cases of colorectal cancers (PMID:29258766)
• This review aims at providing an up-to-date and comprehensive view on the key functions that SLX4 fulfills to maintain genome stability as well as to highlight and discuss areas of uncertainty and emerging concepts. [review] (PMID:30284473)
• RAD52 and SLX4 mediate distinct postreplicative DNA repair processes that maintain ALT telomere stability and cancer cell viability (PMID:30692206)
• The binding of SLX4IP to both SLX4 and XPF-ERCC1 not only is vital for maintaining the stability of SLX4IP protein, but also promotes the interaction between SLX4 and XPF-ERCC1, especially after DNA damage. Collectively, these results demonstrate a new regulatory role for SLX4IP in maintaining an efficient SLX4-XPF-ERCC1 complex in interstrand crosslinks (ICLs) repair. (PMID:31495888)
• SLX4 interacts with RTEL1 to prevent transcription-mediated DNA replication perturbations. (PMID:32398829)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slx4	ENSDARG00000061414
danio_rerio	si:dkey-44g23.2	ENSDARG00000092927
mus_musculus	Slx4	ENSMUSG00000039738
rattus_norvegicus	Slx4	ENSRNOG00000024445
caenorhabditis_elegans		WBGENE00011415

Protein

Protein identifiers

Structure-specific endonuclease subunit SLX4 — Q8IY92 (reviewed: Q8IY92)

Alternative names: BTB/POZ domain-containing protein 12

All UniProt accessions (1): Q8IY92

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component 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. Interacts with the structure-specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81-EME1 endonuclease and promotes the cleavage of 3’-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks.

Subunit / interactions. Forms a heterodimer with SLX1A/GIYD1. Interacts with ERCC4/XPF; catalytic subunit of the ERCC4-ERCC1 endonuclease. Interacts with MUS81; catalytic subunit of the MUS81-EME1 endonuclease. Interacts with MSH2; component of the MSH2-MSH3 mismatch repair complex. Interacts with TERF2-TERF2IP. Interacts with PLK1 and SLX4IP.

Subcellular location. Nucleus.

Disease relevance. Fanconi anemia complementation group P (FANCP) [MIM:613951] A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. Some individuals affected by Fanconi anemia of complementation group P have skeletal anomalies. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SLX4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IY92-1	1	yes
Q8IY92-2	2

RefSeq proteins (1): NP_115820* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR006642	Rad18_UBZ4	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR018574	Slx4_HTH	Domain

Pfam: PF00651, PF09494

UniProt features (145 total): sequence variant 41, compositionally biased region 23, cross-link 19, region of interest 14, helix 11, modified residue 11, strand 8, binding site 8, turn 3, zinc finger region 2, splice variant 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7BU5	X-RAY DIFFRACTION	1.8
4UYI	X-RAY DIFFRACTION	1.86
4M7C	X-RAY DIFFRACTION	2.05
4ZOU	X-RAY DIFFRACTION	2.15
9QED	ELECTRON MICROSCOPY	3.2
9QEE	ELECTRON MICROSCOPY	3.4
7TUJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IY92-F1	47.20	0.10

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 (8): 296; 299; 314; 318; 336; 339; 352; 356

Post-translational modifications (30): 169, 287, 1028, 1044, 1070, 1121, 1135, 1185, 1464, 1469, 1610, 68, 291, 347, 359, 412, 458, 835, 902, 970 …

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: 372 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, 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_NUCLEOTIDE_EXCISION_REPAIR, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ORGANELLE_FISSION, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_DNA_DAMAGE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_TELOMERE_MAINTENANCE

GO Biological Process (14): resolution of meiotic recombination intermediates (GO:0000712), double-strand break repair via homologous recombination (GO:0000724), DNA replication (GO:0006260), DNA repair (GO:0006281), nucleotide-excision repair (GO:0006289), DNA double-strand break processing involved in repair via single-strand annealing (GO:0010792), positive regulation of telomere maintenance (GO:0032206), telomeric D-loop disassembly (GO:0061820), response to intra-S DNA damage checkpoint signaling (GO:0072429), 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)

GO Molecular Function (5): DNA binding (GO:0003677), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleoplasm (GO:0005654), Slx1-Slx4 complex (GO:0033557), nucleus (GO:0005634), Holliday junction resolvase complex (GO:0048476), ERCC4-ERCC1 complex (GO:0070522)

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	3
cellular anatomical structure	2
reciprocal meiotic recombination	1
meiosis I cell cycle process	1
recombinational repair	1
double-strand break repair	1
DNA biosynthetic process	1
DNA damage response	1
DNA repair	1
DNA double-strand break processing	1
double-strand break repair via single-strand annealing	1
telomere maintenance	1
regulation of telomere maintenance	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
telomeric loop disassembly	1
response to DNA damage checkpoint signaling	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
nucleic acid binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
transition metal ion binding	1
binding	1
cation binding	1
chromosomal region	1
chromosome	1
nuclear lumen	1
nuclear chromosome	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2179 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLX4	SLX1A	Q9BQ83	999
SLX4	MUS81	Q96NY9	999
SLX4	ERCC1	P07992	998
SLX4	EME1	Q96AY2	998
SLX4	ERCC4	Q92889	996
SLX4	FANCD2	Q9BXW9	972
SLX4	SLX4IP	Q5VYV7	960
SLX4	MSH3	P20585	955
SLX4	TOPBP1	Q92547	950
SLX4	FANCI	Q9NVI1	935
SLX4	MSH2	P43246	900
SLX4	RTEL1	Q9NZ71	898
SLX4	FANCA	O15360	870
SLX4	DCLRE1B	Q9H816	851
SLX4	FANCM	Q8IYD8	835

IntAct

88 interactions, top by confidence:

A	B	Type	Score
MUS81	SLX4	psi-mi:“MI:0915”(physical association)	0.880
SLX4	MUS81	psi-mi:“MI:0915”(physical association)	0.880
MUS81	SLX4	psi-mi:“MI:0403”(colocalization)	0.880
ERCC4	SLX4	psi-mi:“MI:0915”(physical association)	0.790
SLX4	ERCC4	psi-mi:“MI:0915”(physical association)	0.790
PLK1	SLX4	psi-mi:“MI:0915”(physical association)	0.780
SLX4	PLK1	psi-mi:“MI:0915”(physical association)	0.780
PLK1	SLX4	psi-mi:“MI:0914”(association)	0.780
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	TERF2	psi-mi:“MI:0914”(association)	0.660
SLX4	TERF2	psi-mi:“MI:0915”(physical association)	0.660
SLX4	ERCC1	psi-mi:“MI:0914”(association)	0.640
ERCC1	SLX4	psi-mi:“MI:0915”(physical association)	0.640
ERCC1	SLX4	psi-mi:“MI:0403”(colocalization)	0.640

BioGRID (855): SLX4 (Two-hybrid), SLX4 (Reconstituted Complex), SLX4 (Affinity Capture-MS), SLX4 (Affinity Capture-MS), TOPBP1 (Affinity Capture-Western), SLX4 (Two-hybrid), SLX4 (Affinity Capture-MS), SLX4 (Affinity Capture-MS), SLX4 (Affinity Capture-MS), SLX4 (Two-hybrid), SLX4 (Affinity Capture-Western), MUS81 (Affinity Capture-Western), SLX4 (Reconstituted Complex), SLX4 (Affinity Capture-Western), SUMO2 (Affinity Capture-Western)

ESM2 similar proteins: A0A0A6YY25, A6NGG8, A6X8Z5, B2RQL2, B2RXH4, D3ZMK9, D3ZUE1, E9Q7F2, O08696, O14513, P59598, P97691, Q05860, Q05AH6, Q08050, Q0GGX2, Q0VET5, Q13029, Q2M1Z3, Q3U0P1, Q571I4, Q5PSV9, Q5SSG4, Q5U2M8, Q5VV67, Q63755, Q66H04, Q68DA7, Q69ZL1, Q6DIA7, Q6JPI3, Q6P1D7, Q6PAC4, Q6PG16, Q71F56, Q76N32, Q811R2, Q86YN6, Q86YV5, Q8BJS7

Diamond homologs: A0JMG1, B3DIV9, E7F6F9, F1LZF0, O43791, O95198, P0DMR5, P0DMR6, P34371, P34568, Q04652, Q0IHH9, Q0VCW1, Q2M2N2, Q2WGJ6, Q5BL35, Q5NVK7, Q5U504, Q6DBN1, Q6EJ98, Q6GR09, Q6IQ16, Q6P8B3, Q6TDP3, Q6TDP4, Q6YCH1, Q6YCH2, Q6ZWS8, Q717B2, Q717B4, Q7KRI2, Q7T330, Q7ZX06, Q8BSF5, Q8IY92, Q8JZP3, Q8K430, Q94420, Q9CR40, Q9LQ95

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SLX4	up-regulates	ERCC4	binding
SLX4	up-regulates	ERCC4/ERCC1	binding
DNA_damage	up-regulates	SLX4

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Fanconi Anemia Pathway	5	27.9×	2e-04
DNA Repair	7	13.8×	2e-04
mRNA Splicing	5	11.0×	3e-03
mRNA Polyadenylation	6	10.5×	1e-03
Processing of Capped Intron-Containing Pre-mRNA	6	9.9×	1e-03
mRNA Splicing - Major Pathway	8	8.7×	4e-04
Dengue Virus-Host Interactions	8	7.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair	7	24.1×	3e-06
DNA repair	9	9.7×	5e-05
mRNA splicing, via spliceosome	6	9.3×	2e-03
RNA splicing	5	7.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2650 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	99
Likely pathogenic	40
Uncertain significance	1474
Likely benign	768
Benign	68

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012390	NM_032444.4(SLX4):c.3916C>T (p.Gln1306Ter)	Pathogenic
1070617	NC_000016.9:g.(?3658425)(3658971_?)del	Pathogenic
1072456	NM_032444.4(SLX4):c.4798C>T (p.Gln1600Ter)	Pathogenic
1073415	NM_032444.4(SLX4):c.3282del (p.Glu1094fs)	Pathogenic
1073979	NM_032444.4(SLX4):c.4381_4391del (p.Ala1461fs)	Pathogenic
1319472	NM_032444.4(SLX4):c.4910C>G (p.Ser1637Ter)	Pathogenic
1323619	NM_032444.4(SLX4):c.4625T>A (p.Leu1542Ter)	Pathogenic
1359745	NM_032444.4(SLX4):c.4258_4259dup (p.Ile1421fs)	Pathogenic
1384595	NM_032444.4(SLX4):c.86_89del (p.Arg29fs)	Pathogenic
1412283	NM_032444.4(SLX4):c.4764del (p.Lys1588fs)	Pathogenic
1451413	NM_032444.4(SLX4):c.3239C>G (p.Ser1080Ter)	Pathogenic
1451487	NM_032444.4(SLX4):c.3983_4115del (p.Val1328fs)	Pathogenic
1453866	NM_032444.4(SLX4):c.5055_5058dup (p.Pro1687fs)	Pathogenic
1454910	NM_032444.4(SLX4):c.2635_2636insA (p.Trp879Ter)	Pathogenic
1455275	NM_032444.4(SLX4):c.383G>A (p.Trp128Ter)	Pathogenic
1456873	NM_032444.4(SLX4):c.2974_2977del (p.Gly992fs)	Pathogenic
1458487	NC_000016.9:g.(?3634760)(3634882_?)del	Pathogenic
1459393	NC_000016.9:g.(?3632343)(3658965_?)del	Pathogenic
1460209	NM_032444.4(SLX4):c.3724G>T (p.Glu1242Ter)	Pathogenic
1913866	NM_032444.4(SLX4):c.4336_4340del (p.Thr1446fs)	Pathogenic
1928491	NM_032444.4(SLX4):c.1552C>T (p.Gln518Ter)	Pathogenic
1935301	NM_032444.4(SLX4):c.1912G>T (p.Glu638Ter)	Pathogenic
1936637	NM_032444.4(SLX4):c.2800del (p.Gln934fs)	Pathogenic
1947544	NM_032444.4(SLX4):c.4668del (p.Val1558fs)	Pathogenic
1958549	NM_032444.4(SLX4):c.3529G>T (p.Glu1177Ter)	Pathogenic
1981127	NM_032444.4(SLX4):c.4435C>T (p.Arg1479Ter)	Pathogenic
1982304	NM_032444.4(SLX4):c.619_623dup (p.Leu208fs)	Pathogenic
2002224	NM_032444.4(SLX4):c.4850C>G (p.Ser1617Ter)	Pathogenic
2020404	NM_032444.4(SLX4):c.1816C>T (p.Gln606Ter)	Pathogenic
2020867	NM_032444.4(SLX4):c.1255G>T (p.Glu419Ter)	Pathogenic

SpliceAI

2903 predictions. Top by Δscore:

Variant	Effect	Δscore
16:3584720:A:AC	donor_gain	1.0000
16:3584771:A:AC	donor_gain	1.0000
16:3584771:AT:A	donor_gain	1.0000
16:3584772:T:C	donor_gain	1.0000
16:3584778:T:TA	donor_gain	1.0000
16:3584782:T:TA	donor_gain	1.0000
16:3584869:CTT:C	acceptor_gain	1.0000
16:3584872:C:CC	acceptor_gain	1.0000
16:3584876:G:C	acceptor_gain	1.0000
16:3592718:G:C	donor_gain	1.0000
16:3594447:A:AC	donor_gain	1.0000
16:3594448:C:CC	donor_gain	1.0000
16:3594448:CTTA:C	donor_gain	1.0000
16:3594451:A:AC	donor_gain	1.0000
16:3594452:C:CA	donor_gain	1.0000
16:3594452:CA:C	donor_gain	1.0000
16:3594452:CAT:C	donor_gain	1.0000
16:3594452:CATA:C	donor_gain	1.0000
16:3594455:A:AC	donor_gain	1.0000
16:3594456:C:CC	donor_gain	1.0000
16:3594597:GAG:G	acceptor_gain	1.0000
16:3594600:C:CC	acceptor_gain	1.0000
16:3594606:C:CT	acceptor_gain	1.0000
16:3595599:TCTTA:T	donor_loss	1.0000
16:3595600:CTTA:C	donor_loss	1.0000
16:3595601:TTACC:T	donor_loss	1.0000
16:3595602:TACCA:T	donor_loss	1.0000
16:3595603:A:AT	donor_loss	1.0000
16:3595604:C:CG	donor_loss	1.0000
16:3597530:T:TA	donor_gain	1.0000

AlphaMissense

11950 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:3591067:A:C	F857L	0.999
16:3591067:A:T	F857L	0.999
16:3591069:A:G	F857L	0.999
16:3601136:A:G	C336R	0.999
16:3583466:A:G	L1595P	0.998
16:3591068:A:C	F857C	0.998
16:3591068:A:G	F857S	0.998
16:3591063:C:G	A859P	0.997
16:3602182:A:G	C296R	0.997
16:3601135:C:G	C336S	0.996
16:3601136:A:T	C336S	0.996
16:3601076:A:G	C356R	0.995
16:3583468:C:A	K1594N	0.994
16:3583468:C:G	K1594N	0.994
16:3584775:A:G	L1578P	0.994
16:3601072:G:T	A357D	0.994
16:3601127:A:G	C339R	0.994
16:3601190:A:G	C318R	0.994
16:3583507:A:C	F1581L	0.993
16:3583507:A:T	F1581L	0.993
16:3583509:A:G	F1581L	0.993
16:3601075:C:G	C356S	0.993
16:3601076:A:T	C356S	0.993
16:3601134:G:C	C336W	0.993
16:3602135:C:A	R311S	0.993
16:3602135:C:G	R311S	0.993
16:3602173:A:G	C299R	0.993
16:3583457:A:T	I1598K	0.992
16:3591077:A:C	I854S	0.992
16:3594529:A:G	F695S	0.992

dbSNP variants (sampled 300 via entrez): RS1000009415 (16:3591802 G>A), RS1000061609 (16:3611076 G>C), RS1000171088 (16:3605478 C>A), RS1000541496 (16:3607102 T>C), RS1000593180 (16:3601555 G>A,C), RS1000606511 (16:3605758 T>C), RS1000613717 (16:3598541 A>G,T), RS1000666621 (16:3601850 G>A), RS1000822449 (16:3596647 G>C), RS1000889934 (16:3595736 C>A,T), RS1000993005 (16:3592473 G>A), RS1000999401 (16:3609048 T>A,C), RS1001100797 (16:3603506 T>C), RS1001242696 (16:3611368 C>T), RS1001371476 (16:3608731 CTT>C,CT)

Disease associations

OMIM: gene MIM:613278 | disease phenotypes: MIM:227650, MIM:613951, MIM:114480

GenCC curated gene-disease

Disease	Classification	Inheritance
Fanconi anemia complementation group P	Definitive	Autosomal recessive
Fanconi anemia	Supportive	Autosomal recessive
familial ovarian cancer	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hereditary breast carcinoma	Refuted	AD
Fanconi anemia complementation group P	Definitive	AR
familial ovarian cancer	No Known Disease Relationship	AD

Mondo (12): Fanconi anemia (MONDO:0019391), Fanconi anemia complementation group P (MONDO:0013499), Fanconi anemia complementation group A (MONDO:0009215), hepatoblastoma (MONDO:0018666), hereditary neoplastic syndrome (MONDO:0015356), intellectual disability (MONDO:0001071), breast cancer (MONDO:0007254), hereditary breast ovarian cancer syndrome (MONDO:0003582), hereditary breast carcinoma (MONDO:0016419), microcephaly (MONDO:0001149), pituitary stalk interruption syndrome (MONDO:0019828), familial ovarian cancer (MONDO:0016248)

Orphanet (7): Fanconi anemia (Orphanet:84), Hepatoblastoma (Orphanet:449), Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Hereditary breast cancer (Orphanet:227535), Pituitary stalk interruption syndrome (Orphanet:95496), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

119 total (30 of 119 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000035	Abnormal testis morphology
HP:0000047	Hypospadias
HP:0000072	Hydroureter
HP:0000079	Abnormality of the urinary system
HP:0000083	Renal insufficiency
HP:0000085	Horseshoe kidney
HP:0000125	Pelvic kidney
HP:0000130	Abnormality of the uterus
HP:0000135	Hypogonadism
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000364	Hearing abnormality
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000414	Bulbous nose
HP:0000453	Choanal atresia
HP:0000478	Abnormality of the eye
HP:0000483	Astigmatism

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010118_55	Type 2 diabetes	3.000000e-09

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D005199	Fanconi Anemia	C15.378.050.085.080.280; C15.378.190.223.500.500.280; C16.320.077.280; C18.452.284.280
D018197	Hepatoblastoma	C04.557.435.380
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
bisphenol S	increases methylation, affects cotreatment, decreases expression	2
Cadmium Chloride	increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CPG-oligonucleotide	decreases expression	1
abrine	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Arsenic	increases expression, affects cotreatment, decreases expression, increases abundance	1
Asbestos	affects response to substance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TP46	HAP1 SLX4 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT06519786	PHASE3	UNKNOWN	Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia
NCT03017326	PHASE3	ACTIVE_NOT_RECRUITING	Paediatric Hepatic International Tumour Trial
NCT03533582	PHASE3	ACTIVE_NOT_RECRUITING	Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
NCT04478292	PHASE3	RECRUITING	A Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00001749	PHASE2	COMPLETED	Medical Treatment for Diamond Blackfan Anemia
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT00053989	PHASE2	COMPLETED	NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
NCT00084695	PHASE2	UNKNOWN	Umbilical Cord Blood for Stem Cell Transplantation in Treating Young Patients With Malignant or Nonmalignant Diseases
NCT00258427	PHASE2	COMPLETED	Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
NCT00453388	PHASE2	COMPLETED	Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
NCT01071239	PHASE2	COMPLETED	Hematopoietic Stem Cell Transplant for Fanconi Anemia
NCT02143830	PHASE2	RECRUITING	HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy
NCT02931071	PHASE2	COMPLETED	Clinical Phase II Trial to Evaluate CD34+ Cells Mobilization and Collection in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene. FANCOSTEM-1
NCT03206086	PHASE2	ACTIVE_NOT_RECRUITING	Eltrombopag for People With Fanconi Anemia
NCT03398824	PHASE2	COMPLETED	Pilot Study of Metformin for Patients With Fanconi Anemia
NCT03476330	PHASE2	COMPLETED	Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia
NCT03579875	PHASE2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT03600909	PHASE2	TERMINATED	A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia
NCT04232085	PHASE2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT06045052	PHASE2	COMPLETED	Eltrombopag for Treatment of Fanconi Anemia
NCT04069533	PHASE2	ACTIVE_NOT_RECRUITING	Lentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A
NCT04248439	PHASE2	ACTIVE_NOT_RECRUITING	Gene Therapy for Fanconi Anemia, Complementation Group A
NCT01154816	PHASE2	COMPLETED	Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
NCT02011126	PHASE2	WITHDRAWN	Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial