NEIL3 belongs to a class of DNA glycosylases homologous to the bacterial Fpg/Nei family. These glycosylases initiate the first step in base excision repair by cleaving bases damaged by reactive oxygen species and introducing a DNA strand break via the associated lyase reaction (Bandaru et al., 2002 [PubMed 12509226]).[supplied by OMIM, Mar 2008] See more...

Aliases for NEIL3 Gene

Aliases for NEIL3 Gene

  • Nei Like DNA Glycosylase 3 2 3 5
  • Zinc Finger, GRF-Type Containing 3 2 3
  • DNA Glycosylase/AP Lyase Neil3 3 4
  • Endonuclease VIII-Like 3 3 4
  • Endonuclease 8-Like 3 3 4
  • DNA Glycosylase FPG2 3 4
  • Nei-Like Protein 3 3 4
  • ZGRF3 2 3
  • HFPG2 2 3
  • HNEI3 2 3
  • FPG2 2 3
  • Nei Endonuclease VIII-Like 3 (E. Coli) 2
  • Nei Endonuclease VIII-Like 3 3
  • DNA Glycosylase HFPG2 3
  • EC 4.2.99.18 4
  • EC 3.2.2.- 4
  • FLJ10858 2
  • NEIL3 5
  • FGP2 3
  • NEI3 3

External Ids for NEIL3 Gene

Previous GeneCards Identifiers for NEIL3 Gene

  • GC04P178607
  • GC04P178468
  • GC04P178230
  • GC04P173981

Summaries for NEIL3 Gene

Entrez Gene Summary for NEIL3 Gene

  • NEIL3 belongs to a class of DNA glycosylases homologous to the bacterial Fpg/Nei family. These glycosylases initiate the first step in base excision repair by cleaving bases damaged by reactive oxygen species and introducing a DNA strand break via the associated lyase reaction (Bandaru et al., 2002 [PubMed 12509226]).[supplied by OMIM, Mar 2008]

GeneCards Summary for NEIL3 Gene

NEIL3 (Nei Like DNA Glycosylase 3) is a Protein Coding gene. Diseases associated with NEIL3 include Fanconi Anemia, Complementation Group A. Among its related pathways are Telomere C-strand (Lagging Strand) Synthesis. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and single-stranded DNA binding. An important paralog of this gene is NEIL2.

UniProtKB/Swiss-Prot Summary for NEIL3 Gene

  • DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA) (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). Mediates interstrand cross-link repair in response to replication stress: acts by mediating DNA glycosylase activity, cleaving one of the two N-glycosyl bonds comprising the interstrand cross-link, which avoids the formation of a double-strand break but generates an abasic site that is bypassed by translesion synthesis polymerases (By similarity). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). No activity on 8-oxoG detected (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NEIL3 Gene

Genomics for NEIL3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NEIL3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J177308 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 250.7 0.0 -13 3.5 SP1 MYC POLR2A NFIC ZIC2 MXD4 CEBPB KLF11 SMAD5 SIN3A HSALNG0038744 NEIL3 VEGFC
GH04J177339 Enhancer 0.9 Ensembl ENCODE dbSUPER 11.3 +30.0 29997 0.5 ZNF654 REST TRIM22 CTCF NR2C1 RAD21 SMC3 EGR1 NR2F1 NR2F6 ENSG00000249008 NEIL3 HSALNG0038745 LOC105377558 AGA
GH04J177281 Enhancer 0.6 Ensembl ENCODE 12.4 -28.4 -28370 1.8 GATA2 ZNF384 CEBPB NR2F2 NEIL3 ENSG00000287544 LOC105377557 ENSG00000249008 HSALNG0038743 VEGFC
GH04J177270 Enhancer 0.5 ENCODE 11.6 -38.1 -38074 1.8 ZNF316 ATF4 MAFK REST CBFA2T3 EMSY NEIL3 ENSG00000249008 HSALNG0038743 ENSG00000287544 LOC105377557 VEGFC
GH04J177265 Enhancer 0.5 ENCODE 11 -43.5 -43506 1.8 CEBPA SMAD4 BHLHE40 HNF4A NFIL3 HLF GABPA NEIL3 HSALNG0038743 LOC105377557 ENSG00000249008 ENSG00000287544 VEGFC
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NEIL3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NEIL3

Top Transcription factor binding sites by QIAGEN in the NEIL3 gene promoter:
  • CUTL1
  • Evi-1
  • GATA-1
  • HNF-3beta
  • IRF-2
  • Nkx6-1
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)
  • RSRFC4

Genomic Locations for NEIL3 Gene

Latest Assembly
chr4:177,309,871-177,362,936
(GRCh38/hg38)
Size:
53,066 bases
Orientation:
Plus strand

Previous Assembly
chr4:178,231,028-178,284,090
(GRCh37/hg19 by Entrez Gene)
Size:
53,063 bases
Orientation:
Plus strand

chr4:178,230,990-178,284,097
(GRCh37/hg19 by Ensembl)
Size:
53,108 bases
Orientation:
Plus strand

Genomic View for NEIL3 Gene

Genes around NEIL3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NEIL3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NEIL3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NEIL3 Gene

Proteins for NEIL3 Gene

  • Protein details for NEIL3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TAT5-NEIL3_HUMAN
    Recommended name:
    Endonuclease 8-like 3
    Protein Accession:
    Q8TAT5
    Secondary Accessions:
    • Q2PPJ3
    • Q8NG51
    • Q9NV95

    Protein attributes for NEIL3 Gene

    Size:
    605 amino acids
    Molecular mass:
    67769 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for NEIL3 Gene

neXtProt entry for NEIL3 Gene

Post-translational modifications for NEIL3 Gene

  • Ubiquitination at Lys13, Lys110, Lys195, Lys316, Lys372, Lys398, Lys558, Lys574, and Lys585
  • Modification sites at PhosphoSitePlus

Other Protein References for NEIL3 Gene

No data available for DME Specific Peptides for NEIL3 Gene

Domains & Families for NEIL3 Gene

Gene Families for NEIL3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for NEIL3 Gene

GenScript: Design optimal peptide antigens:
  • Nei-like protein 3 (NEIL3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8TAT5

UniProtKB/Swiss-Prot:

NEIL3_HUMAN :
  • The N-terminal region (2-281) contains the glycosylase and lyase activities.
  • Belongs to the FPG family.
Domain:
  • The N-terminal region (2-281) contains the glycosylase and lyase activities.
  • The RanBP2-type zinc-finger, also named NZF zinc finger, recognizes and binds ubiquitinated CMG helicase complex. The GRF-type zinc-fingers recognize single-stranded DNA (ssDNA), possibly on the lagging strand template.
Family:
  • Belongs to the FPG family.
genes like me logo Genes that share domains with NEIL3: view

Function for NEIL3 Gene

Molecular function for NEIL3 Gene

UniProtKB/Swiss-Prot Function:
DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA) (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). Mediates interstrand cross-link repair in response to replication stress: acts by mediating DNA glycosylase activity, cleaving one of the two N-glycosyl bonds comprising the interstrand cross-link, which avoids the formation of a double-strand break but generates an abasic site that is bypassed by translesion synthesis polymerases (By similarity). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). No activity on 8-oxoG detected (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.; EC=4.2.99.18; Evidence={ECO:0000255|PROSITE-ProRule:PRU00392, ECO:0000269|PubMed:22569481};.

Enzyme Numbers (IUBMB) for NEIL3 Gene

Phenotypes From GWAS Catalog for NEIL3 Gene

Gene Ontology (GO) - Molecular Function for NEIL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000405 bubble DNA binding IEA,ISS --
GO:0003676 nucleic acid binding IEA --
GO:0003677 DNA binding IEA --
GO:0003684 damaged DNA binding ISS --
GO:0003690 double-stranded DNA binding IEA,ISS --
genes like me logo Genes that share ontologies with NEIL3: view
genes like me logo Genes that share phenotypes with NEIL3: view

Animal Models for NEIL3 Gene

MGI Knock Outs for NEIL3:

miRNA for NEIL3 Gene

miRTarBase miRNAs that target NEIL3

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NEIL3

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NEIL3 Gene

Localization for NEIL3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NEIL3 Gene

Nucleus. Chromosome. Note=Recruited to replication stress sites via interaction with ubiquitinated CMG helicase. {ECO:0000250 UniProtKB:A0A1L8HU22}.

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 NEIL3 gene
Compartment Confidence
nucleus 5
mitochondrion 2
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NEIL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 12433996
GO:0005654 nucleoplasm IDA --
GO:0005694 chromosome IEA --
genes like me logo Genes that share ontologies with NEIL3: view

Pathways & Interactions for NEIL3 Gene

PathCards logo

SuperPathways for NEIL3 Gene

genes like me logo Genes that share pathways with NEIL3: view

Pathways by source for NEIL3 Gene

1 KEGG pathway for NEIL3 Gene

Gene Ontology (GO) - Biological Process for NEIL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006281 DNA repair IEA --
GO:0006284 base-excision repair IDA,ISS --
GO:0006289 nucleotide-excision repair IEA --
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0008152 metabolic process IEA --
genes like me logo Genes that share ontologies with NEIL3: view

No data available for SIGNOR curated interactions for NEIL3 Gene

Drugs & Compounds for NEIL3 Gene

No Compound Related Data Available

Transcripts for NEIL3 Gene

mRNA/cDNA for NEIL3 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NEIL3

Alternative Splicing Database (ASD) splice patterns (SP) for NEIL3 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11
SP1: -
SP2:
SP3: -

Relevant External Links for NEIL3 Gene

GeneLoc Exon Structure for
NEIL3

Expression for NEIL3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NEIL3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NEIL3 Gene

This gene is overexpressed in Esophagus - Mucosa (x5.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NEIL3 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NEIL3

SOURCE GeneReport for Unigene cluster for NEIL3 Gene:

Hs.405467

mRNA Expression by UniProt/SwissProt for NEIL3 Gene:

Q8TAT5-NEIL3_HUMAN
Tissue specificity: Expressed in keratinocytes and embryonic fibroblasts (at protein level). Also detected in thymus, testis and fetal lung primary fibroblasts.

Evidence on tissue expression from TISSUES for NEIL3 Gene

  • Skin(4.2)
genes like me logo Genes that share expression patterns with NEIL3: view

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for NEIL3 Gene

Orthologs for NEIL3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NEIL3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NEIL3 29 30
  • 99.01 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NEIL3 29 30
  • 85.26 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NEIL3 29 30
  • 83.8 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Neil3 29 16 30
  • 80.5 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Neil3 29
  • 80 (n)
Oppossum
(Monodelphis domestica)
Mammalia NEIL3 30
  • 62 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NEIL3 29 30
  • 64.82 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NEIL3 30
  • 55 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia neil3 29
  • 62.25 (n)
Str.6541 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.10504 29
Zebrafish
(Danio rerio)
Actinopterygii neil3 29 30
  • 59.16 (n)
OneToMany
Dr.17827 29
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.3316 29
Species where no ortholog for NEIL3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • Platypus (Ornithorhynchus anatinus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (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 NEIL3 Gene

ENSEMBL:
Gene Tree for NEIL3 (if available)
TreeFam:
Gene Tree for NEIL3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NEIL3: view image
Alliance of Genome Resources:
Additional Orthologs for NEIL3

Paralogs for NEIL3 Gene

Paralogs for NEIL3 Gene

genes like me logo Genes that share paralogs with NEIL3: view

Variants for NEIL3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NEIL3 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
rs141063624 Likely Benign: not provided 177,310,022(+) G/A
NM_018248.3(NEIL3):c.69G>A (p.Ala23=)
SYNONYMOUS
rs13112358 -- p.Pro443Leu
rs13112390 -- p.Gln471His
rs17064658 -- p.Gln172His
rs17064676 -- p.Ile346Val

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NEIL3 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for NEIL3 Gene

Variant ID Type Subtype PubMed ID
esv2728772 CNV deletion 23290073
esv2759304 CNV gain 17122850
esv34846 CNV gain 17911159
esv3569839 CNV loss 25503493
esv3603300 CNV gain 21293372
esv3894076 CNV loss 25118596
nsv508336 CNV deletion 20534489
nsv822852 CNV gain 20364138

Variation tolerance for NEIL3 Gene

Residual Variation Intolerance Score: 93.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.35; 85.37% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NEIL3 Gene

Human Gene Mutation Database (HGMD)
NEIL3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NEIL3
Leiden Open Variation Database (LOVD)
NEIL3

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NEIL3 Gene

Disorders for NEIL3 Gene

MalaCards: The human disease database

(1) MalaCards diseases for NEIL3 Gene - From: COP

Disorder Aliases PubMed IDs
fanconi anemia, complementation group a
  • fanca
- elite association - COSMIC cancer census association via MalaCards
Search NEIL3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for NEIL3

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with NEIL3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NEIL3 Gene

Publications for NEIL3 Gene

  1. Human Nei-like protein NEIL3 has AP lyase activity specific for single-stranded DNA and confers oxidative stress resistance in Escherichia coli mutant. (PMID: 19170771) Takao M … Zhang QM (Genes to cells : devoted to molecular & cellular mechanisms 2009) 2 3 4 22
  2. Human NEIL3 is mainly a monofunctional DNA glycosylase removing spiroimindiohydantoin and guanidinohydantoin. (PMID: 23755964) Krokeide SZ … Bjørås M (DNA repair 2013) 2 3 4
  3. Expression and purification of NEIL3, a human DNA glycosylase homolog. (PMID: 19121397) Krokeide SZ … Luna L (Protein expression and purification 2009) 3 4 22
  4. The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death. (PMID: 12713815) Rosenquist TA … Grollman AP (DNA repair 2003) 2 3 22
  5. Human DNA glycosylases of the bacterial Fpg/MutM superfamily: an alternative pathway for the repair of 8-oxoguanine and other oxidation products in DNA. (PMID: 12433996) Morland I … Seeberg E (Nucleic acids research 2002) 3 4 22

Products for NEIL3 Gene

Sources for NEIL3 Gene