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NHEJ1 non-homologous end joining factor 1 [ Homo sapiens (human) ]

Gene ID: 79840, updated on 7-Apr-2024

Summary

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Official Symbol
NHEJ1provided by HGNC
Official Full Name
non-homologous end joining factor 1provided by HGNC
Primary source
HGNC:HGNC:25737
See related
Ensembl:ENSG00000187736 MIM:611290; AllianceGenome:HGNC:25737
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
XLF
Summary
Double-strand breaks in DNA result from genotoxic stresses and are among the most damaging of DNA lesions. This gene encodes a DNA repair factor essential for the nonhomologous end-joining pathway, which preferentially mediates repair of double-stranded breaks. Mutations in this gene cause different kinds of severe combined immunodeficiency disorders. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in testis (RPKM 11.1), colon (RPKM 7.7) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
2q35
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (219069357..219160815, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (219557705..219649239, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (219934079..220025537, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107985987 Neighboring gene uncharacterized LOC124906120 Neighboring gene microRNA 3131 Neighboring gene Indian hedgehog signaling molecule Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:219941606-219942805 Neighboring gene RNA, 7SL, cytoplasmic 764, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12340 Neighboring gene solute carrier family 23 member 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17139 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17140 Neighboring gene Sharpr-MPRA regulatory region 9830 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12342 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12343 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:220042692-220043192 Neighboring gene cyclin Pas1/PHO80 domain containing 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The canonical non-homologous end joining factor XLF promotes chromosomal deletion rearrangements in human cells. Bhargava R, et al. J Biol Chem, 2020 Jan 3. PMID 31753920, Free PMC Article
  2. Combined Immunodeficiency, Hemolytic Anemia, and Growth Retardation Secondary to a Homozygous Mutation in the NHEJ1 Gene. Al-Marhoobi R, et al. J Pediatr Hematol Oncol, 2020 May. PMID 31259832
  3. Extreme Phenotypes With Identical Mutations: Two Patients With Same Non-sense NHEJ1 Homozygous Mutation. Recio MJ, et al. Front Immunol, 2018. PMID 30666249, Free PMC Article
  4. XLF/Cernunnos: An important but puzzling participant in the nonhomologous end joining DNA repair pathway. Menon V, et al. DNA Repair (Amst), 2017 Oct. PMID 28846869, Free PMC Article
  5. Loss of NHEJ1 Protein Due to a Novel Splice Site Mutation in a Family Presenting with Combined Immunodeficiency, Microcephaly, and Growth Retardation and Literature Review. Sheikh F, et al. J Clin Immunol, 2017 Aug. PMID 28741180

See all (90) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. PAXX binding to the NHEJ machinery explains functional redundancy with XLF.
    Title: PAXX binding to the NHEJ machinery explains functional redundancy with XLF.
  2. X-ray scattering reveals disordered linkers and dynamic interfaces in complexes and mechanisms for DNA double-strand break repair impacting cell and cancer biology.
    Title: X-ray scattering reveals disordered linkers and dynamic interfaces in complexes and mechanisms for DNA double-strand break repair impacting cell and cancer biology.
  3. The conserved Tpk1 regulates non-homologous end joining double-strand break repair by phosphorylation of Nej1, a homolog of the human XLF.
    Title: The conserved Tpk1 regulates non-homologous end joining double-strand break repair by phosphorylation of Nej1, a homolog of the human XLF.
  4. Cryo-EM of NHEJ supercomplexes provides insights into DNA repair.
    Title: Cryo-EM of NHEJ supercomplexes provides insights into DNA repair.
  5. Combined Immunodeficiency, Hemolytic Anemia, and Growth Retardation Secondary to a Homozygous Mutation in the NHEJ1 Gene.
    Title: Combined Immunodeficiency, Hemolytic Anemia, and Growth Retardation Secondary to a Homozygous Mutation in the NHEJ1 Gene.
  6. Absence of XRCC4 and its paralogs in human cells reveal differences in outcomes for DNA repair and V(D)J recombination.
    Title: Absence of XRCC4 and its paralogs in human cells reveal differences in outcomes for DNA repair and V(D)J recombination.
  7. The canonical non-homologous end joining factor XLF promotes chromosomal deletion rearrangements in human cells.
    Title: The canonical non-homologous end joining factor XLF promotes chromosomal deletion rearrangements in human cells.
  8. Description of two unrelated cases with Cernunnos/XLF deficiency and with the same non-sense mutation in the NHEJ1 gene showing significant differences in clinical presentation and immunological profile but a similar DNA repair defect.
    Title: Extreme Phenotypes With Identical Mutations: Two Patients With Same Non-sense NHEJ1 Homozygous Mutation.
  9. The crystal structures of the Ku-binding motifs (KBM) of the non-homologous end joining (NHEJ) proteins APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex are discussed.
    Title: XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining.
  10. PC4 expression correlated with radiosensitivity and was an independent prognostic factor of progression-free survival (PFS) in patients with NSCLC.
    Title: Inhibition of PC4 radiosensitizes non-small cell lung cancer by transcriptionally suppressing XLF.
Submit: New GeneRIF Correction See all GeneRIFs (61)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Cernunnos-XLF deficiency
MedGen: C1969799 OMIM: 611291 GeneReviews: Not available
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EBI GWAS Catalog

Description
A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci.
EBI GWAS Catalog
Genome-wide association analysis identifies 20 loci that influence adult height.
EBI GWAS Catalog
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ12610

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA end binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables DNA end binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables DNA polymerase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in B cell differentiation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in DNA ligation involved in DNA repair IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in T cell differentiation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in central nervous system development NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in double-strand break repair via nonhomologous end joining IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in double-strand break repair via nonhomologous end joining IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in double-strand break repair via nonhomologous end joining IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in immunoglobulin V(D)J recombination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of ligase activity NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in response to ionizing radiation IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
part_of DNA ligase IV complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of DNA-dependent protein kinase-DNA ligase 4 complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in fibrillar center IDA
Inferred from Direct Assay
more info
  
part_of nonhomologous end joining complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in site of double-strand break IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
non-homologous end-joining factor 1
Names
XRCC4-like factor
nonhomologous end-joining factor 1
protein cernunnos

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007880.1 RefSeqGene

    Range
    5001..90542
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_90

mRNA and Protein(s)

  1. NM_001377498.1 → NP_001364427.1  non-homologous end-joining factor 1 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC068946, AC097468
    Consensus CDS
    CCDS2432.1
    UniProtKB/Swiss-Prot
    B8ZZA4, Q4ZFW7, Q6IA64, Q96JS9, Q9H9Q4
    Related
    ENSP00000407201.2, ENST00000457600.3
    Conserved Domains (1) summary
    pfam09302
    Location:12 → 174
    XLF; XLF-Cernunnos, XRcc4-like factor, NHEJ component

  2. NM_001377499.1 → NP_001364428.1  non-homologous end-joining factor 1 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC068946, AC097468
    Consensus CDS
    CCDS92945.1
    UniProtKB/TrEMBL
    H7C0G7
    Related
    ENSP00000394896.2, ENST00000426304.6
    Conserved Domains (1) summary
    pfam09302
    Location:12 → 174
    XLF; XLF-Cernunnos, XRcc4-like factor, NHEJ component

  3. NM_024782.3 → NP_079058.1  non-homologous end-joining factor 1 isoform 1

    See identical proteins and their annotated locations for NP_079058.1

    Status: REVIEWED

    Source sequence(s)
    AC097468, AJ972687, DB124934
    Consensus CDS
    CCDS2432.1
    UniProtKB/Swiss-Prot
    B8ZZA4, Q4ZFW7, Q6IA64, Q96JS9, Q9H9Q4
    Related
    ENSP00000349313.5, ENST00000356853.10
    Conserved Domains (1) summary
    pfam09302
    Location:12 → 174
    XLF; XLF-Cernunnos, XRcc4-like factor, NHEJ component

RNA

  1. NR_165304.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC020575, AC068946, AC097468

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    219069357..219160815 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    219557705..219649239 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9H9Q4.1 GenPept UniProtKB/Swiss-Prot:Q9H9Q4

Gene LinkOut

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