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. [provided by RefSeq, Sep 2016] See more...

Aliases for SLX4 Gene

Aliases for SLX4 Gene

  • SLX4 Structure-Specific Endonuclease Subunit 2 3 5
  • Structure-Specific Endonuclease Subunit SLX4 3 4
  • BTB/POZ Domain-Containing Protein 12 3 4
  • BTBD12 3 4
  • SLX4 Structure-Specific Endonuclease Subunit Homolog (S. Cerevisiae) 2
  • Fanconi Anemia, Complementation Group P 2
  • BTB (POZ) Domain Containing 12 2
  • KIAA1784 4
  • KIAA1987 4
  • MUS312 3
  • FANCP 3

External Ids for SLX4 Gene

Previous HGNC Symbols for SLX4 Gene

  • BTBD12

Previous GeneCards Identifiers for SLX4 Gene

  • GC16M003632

Summaries for SLX4 Gene

Entrez Gene Summary for SLX4 Gene

  • 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. [provided by RefSeq, Sep 2016]

GeneCards Summary for SLX4 Gene

SLX4 (SLX4 Structure-Specific Endonuclease Subunit) is a Protein Coding gene. Diseases associated with SLX4 include Fanconi Anemia, Complementation Group P and Fanconi Anemia, Complementation Group A. Among its related pathways are Resolution of D-loop Structures through Holliday Junction Intermediates and Homologous DNA Pairing and Strand Exchange. Gene Ontology (GO) annotations related to this gene include enzyme activator activity and 5'-flap endonuclease activity.

UniProtKB/Swiss-Prot Summary for SLX4 Gene

  • 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.

Additional gene information for SLX4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SLX4 Gene

Genomics for SLX4 Gene

GeneHancer (GH) Regulatory Elements for SLX4 Gene

Promoters and enhancers for SLX4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SLX4 on UCSC Golden Path with GeneCards custom track

Genomic Locations for SLX4 Gene

Genomic Locations for SLX4 Gene
chr16:3,581,165-3,611,606
(GRCh38/hg38)
Size:
30,442 bases
Orientation:
Minus strand
chr16:3,631,182-3,661,599
(GRCh37/hg19)
Size:
30,418 bases
Orientation:
Minus strand

Genomic View for SLX4 Gene

Genes around SLX4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLX4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLX4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLX4 Gene

Proteins for SLX4 Gene

  • Protein details for SLX4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IY92-SLX4_HUMAN
    Recommended name:
    Structure-specific endonuclease subunit SLX4
    Protein Accession:
    Q8IY92
    Secondary Accessions:
    • Q69YT8
    • Q8TF15
    • Q96JP1

    Protein attributes for SLX4 Gene

    Size:
    1834 amino acids
    Molecular mass:
    200012 Da
    Quaternary structure:
    • Forms a heterodimer with SLX1A/GIYD1. Interacts with ERCC4; 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.

    Three dimensional structures from OCA and Proteopedia for SLX4 Gene

    Alternative splice isoforms for SLX4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SLX4 Gene

Post-translational modifications for SLX4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SLX4 Gene

No data available for DME Specific Peptides for SLX4 Gene

Domains & Families for SLX4 Gene

Gene Families for SLX4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for SLX4 Gene

Suggested Antigen Peptide Sequences for SLX4 Gene

GenScript: Design optimal peptide antigens:
  • BTB/POZ domain-containing protein 12 (SLX4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8IY92

UniProtKB/Swiss-Prot:

SLX4_HUMAN :
  • Belongs to the SLX4 family.
Family:
  • Belongs to the SLX4 family.
genes like me logo Genes that share domains with SLX4: view

Function for SLX4 Gene

Molecular function for SLX4 Gene

UniProtKB/Swiss-Prot 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.

Phenotypes From GWAS Catalog for SLX4 Gene

Gene Ontology (GO) - Molecular Function for SLX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 19595721
GO:0008047 enzyme activator activity IDA 19596235
GO:0008821 contributes_to crossover junction endodeoxyribonuclease activity IDA 19595721
GO:0017108 contributes_to 5'-flap endonuclease activity IDA,IBA 19595721
GO:0048257 contributes_to 3'-flap endonuclease activity IDA,IBA 19595721
genes like me logo Genes that share ontologies with SLX4: view
genes like me logo Genes that share phenotypes with SLX4: view

Human Phenotype Ontology for SLX4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SLX4 Gene

MGI Knock Outs for SLX4:
  • Slx4 Slx4<tm1a(EUCOMM)Wtsi>
  • Slx4 Slx4<tm1.2Jrou>
  • Slx4 Slx4<tm1Jrou>

Animal Model Products

CRISPR Products

miRNA for SLX4 Gene

miRTarBase miRNAs that target SLX4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SLX4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SLX4 Gene

Localization for SLX4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLX4 Gene

Nucleus. Note=Localizes to sites of DNA damage.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SLX4 gene
Compartment Confidence
nucleus 5
cytosol 5

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (3)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SLX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000781 chromosome, telomeric region IDA 24012755
GO:0000784 colocalizes_with nuclear chromosome, telomeric region IDA 19596235
GO:0000790 colocalizes_with nuclear chromatin IDA 19596235
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm TAS --
genes like me logo Genes that share ontologies with SLX4: view

Pathways & Interactions for SLX4 Gene

genes like me logo Genes that share pathways with SLX4: view

SIGNOR curated interactions for SLX4 Gene

Activates:

Gene Ontology (GO) - Biological Process for SLX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000706 meiotic DNA double-strand break processing IBA 21873635
GO:0000712 resolution of meiotic recombination intermediates IBA 21873635
GO:0000724 double-strand break repair via homologous recombination IMP 19595721
GO:0006260 DNA replication IEA --
GO:0006281 DNA repair IMP 19595722
genes like me logo Genes that share ontologies with SLX4: view

Drugs & Compounds for SLX4 Gene

No Compound Related Data Available

Transcripts for SLX4 Gene

mRNA/cDNA for SLX4 Gene

(1) REFSEQ mRNAs :
(17) Additional mRNA sequences :
(67) Selected AceView cDNA sequences:
(3) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SLX4

Alternative Splicing Database (ASD) splice patterns (SP) for SLX4 Gene

No ASD Table

Relevant External Links for SLX4 Gene

GeneLoc Exon Structure for
SLX4
ECgene alternative splicing isoforms for
SLX4

Expression for SLX4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SLX4 Gene

mRNA differential expression in normal tissues according to GTEx for SLX4 Gene

This gene is overexpressed in Brain - Cerebellum (x4.3).

Protein differential expression in normal tissues from HIPED for SLX4 Gene

This gene is overexpressed in Nasal epithelium (51.6) and Cervix (12.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SLX4 Gene



NURSA nuclear receptor signaling pathways regulating expression of SLX4 Gene:

SLX4

SOURCE GeneReport for Unigene cluster for SLX4 Gene:

Hs.143681

Evidence on tissue expression from TISSUES for SLX4 Gene

  • Nervous system(4.2)
  • Liver(4.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SLX4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • lymphatic
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
  • neck
  • nose
  • outer ear
  • pituitary gland
  • skull
Thorax:
  • breast
  • esophagus
  • heart
  • lung
  • rib
  • rib cage
Abdomen:
  • intestine
  • kidney
  • large intestine
  • liver
  • stomach
Pelvis:
  • anus
  • ovary
  • pelvis
  • penis
  • prostate
  • rectum
  • testicle
  • ureter
  • uterus
  • vagina
  • vulva
Limb:
  • arm
  • digit
  • finger
  • forearm
  • hand
  • radius
  • upper limb
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • hair
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal column
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with SLX4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for SLX4 Gene

Orthologs for SLX4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for SLX4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SLX4 33 32
  • 99.04 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SLX4 33 32
  • 74.36 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SLX4 33 32
  • 73.2 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Slx4 32
  • 71.11 (n)
mouse
(Mus musculus)
Mammalia Slx4 17 33 32
  • 70.59 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SLX4 33
  • 50 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SLX4 33
  • 45 (a)
OneToOne
chicken
(Gallus gallus)
Aves SLX4 33 32
  • 52.58 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SLX4 33
  • 52 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.16284 32
zebrafish
(Danio rerio)
Actinopterygii SLX4 (2 of 2) 33
  • 42 (a)
OneToMany
slx4 33
  • 26 (a)
OneToMany
Species where no ortholog for SLX4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SLX4 Gene

ENSEMBL:
Gene Tree for SLX4 (if available)
TreeFam:
Gene Tree for SLX4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SLX4: view image

Paralogs for SLX4 Gene

No data available for Paralogs for SLX4 Gene

Variants for SLX4 Gene

Sequence variations from dbSNP and Humsavar for SLX4 Gene

SNP ID Clin Chr 16 pos Variation AA Info Type
rs1003342051 uncertain-significance, Fanconi anemia 3,608,607(-) T/C coding_sequence_variant, genic_upstream_transcript_variant, missense_variant
rs1041739465 uncertain-significance, Fanconi anemia 3,594,575(-) C/G coding_sequence_variant, missense_variant
rs1056085 uncertain-significance, benign-likely-benign, likely-benign, Fanconi anemia, not specified 3,596,179(-) C/A/G/T coding_sequence_variant, missense_variant
rs1060501792 uncertain-significance, Fanconi anemia 3,590,276(-) G/A/T coding_sequence_variant, missense_variant
rs1060501793 uncertain-significance, Fanconi anemia 3,589,559(-) T/A coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for SLX4 Gene

Variant ID Type Subtype PubMed ID
nsv1111122 CNV tandem duplication 24896259
nsv517451 CNV loss 19592680
nsv518509 CNV gain 19592680
nsv571255 CNV gain 21841781
nsv833128 CNV loss 17160897

Variation tolerance for SLX4 Gene

Residual Variation Intolerance Score: 98.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.53; 91.14% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SLX4 Gene

Human Gene Mutation Database (HGMD)
SLX4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SLX4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLX4 Gene

Disorders for SLX4 Gene

MalaCards: The human disease database

(6) MalaCards diseases for SLX4 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search SLX4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SLX4_HUMAN
  • 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. {ECO:0000269 PubMed:21240275, ECO:0000269 PubMed:21240277}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for SLX4

genes like me logo Genes that share disorders with SLX4: view

No data available for Genatlas for SLX4 Gene

Publications for SLX4 Gene

  1. Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair. (PMID: 19595721) Muñoz IM … Rouse J (Molecular cell 2009) 2 3 4 56
  2. Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PMID: 11347906) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 2001) 2 3 4 56
  3. Analysis of the novel fanconi anemia gene SLX4/FANCP in familial breast cancer cases. (PMID: 22911665) Bakker JL … Waisfisz Q (Human mutation 2013) 3 4 56
  4. Mutations of the SLX4 gene in Fanconi anemia. (PMID: 21240275) Kim Y … Smogorzewska A (Nature genetics 2011) 3 4 56
  5. SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype. (PMID: 21240277) Stoepker C … de Winter JP (Nature genetics 2011) 3 4 56

Products for SLX4 Gene

Sources for SLX4 Gene