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XRCC4 X-ray repair cross complementing 4 [ Homo sapiens (human) ]

Gene ID: 7518, updated on 24-Nov-2020

Summary

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Official Symbol
XRCC4provided by HGNC
Official Full Name
X-ray repair cross complementing 4provided by HGNC
Primary source
HGNC:HGNC:12831
See related
Ensembl:ENSG00000152422 MIM:194363
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
SSMED
Summary
The protein encoded by this gene functions together with DNA ligase IV and the DNA-dependent protein kinase in the repair of DNA double-strand breaks. This protein plays a role in both non-homologous end joining and the completion of V(D)J recombination. Mutations in this gene can cause short stature, microcephaly, and endocrine dysfunction (SSMED). Alternate transcript variants such as NM_022406 are unlikely to be expressed in some individuals due to a polymorphism (rs1805377) in the last splice acceptor site. [provided by RefSeq, Oct 2019]
Expression
Ubiquitous expression in testis (RPKM 2.7), lymph node (RPKM 2.1) and 25 other tissues See more
Orthologs
mouse all

Genomic context

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See XRCC4 in Genome Data Viewer
Location:
5q14.2
Exon count:
13
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 5 NC_000005.10 (83077534..83370333)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (82373317..82649579)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105379052 Neighboring gene transmembrane protein 167A Neighboring gene small Cajal body-specific RNA 18 Neighboring gene ribosomal protein L13 pseudogene 9 Neighboring gene coenzyme Q10B pseudogene 2 Neighboring gene uncharacterized LOC105379053 Neighboring gene ferritin heavy chain 1 pseudogene 9

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. Genotypic analysis of XRCC4 and susceptibility to cervical cancer. Gupta MK, et al. Br J Biomed Sci, 2020 Jan. PMID 31250713
  2. XRCC4 c.1394G>T Single Nucleotide Polymorphisms and Breast Cancer Risk among Filipinos Garcia JA, et al. Asian Pac J Cancer Prev, 2019 Apr 29. PMID 31030479, Free PMC Article
  3. Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy. Kitagawa M, et al. Strahlenther Onkol, 2019 Jul. PMID 30997540
  4. Silencing of XRCC4 increases radiosensitivity of triple-negative breast cancer cells. Wen Y, et al. Biosci Rep, 2019 Mar 29. PMID 30842344, Free PMC Article
  5. Exploring the deleterious SNPs in XRCC4 gene using computational approach and studying their association with breast cancer in the population of West India. Singh PK, et al. Gene, 2018 May 20. PMID 29452234

See all (248) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. Genotypic analysis of XRCC4 and susceptibility to cervical cancer.
    Title: Genotypic analysis of <i>XRCC4</i> and susceptibility to cervical cancer.
  3. XRCC4, which is inhibited by PFDA, regulates DNA damage repair and cell chemosensitivity.
    Title: XRCC4, which is inhibited by PFDA, regulates DNA damage repair and cell chemosensitivity.
  4. Findings suggest that X-ray repair cross complementing 4 DNA repair protein XRCC4 (XRCC4) knockdown sensitizes triple-negative breast cancer (TNBC) cells to ionizing radiation, and could be considered as a novel predictor of radiosensitivity and a promising target for TNBC.
    Title: Silencing of XRCC4 increases radiosensitivity of triple-negative breast cancer cells.
  5. The 40 patients with IBTR included 22 patients who developed TR and 18 who had NP. The 15-year overall survival rate was 85.9% for patients with NP and 95.5% for those with TR, while it was 96.5% for patients without IBTR. Patients with high XRCC4 expression in tumor cells had significantly higher IBTR rates than those with low XRCC4 expression (P< 0.001).
    Title: Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy.
  6. XRCC4 c.1394G>T Single Nucleotide Polymorphism is associated with Breast Cancer Risk.
    Title: XRCC4 c.1394G&gt;T Single Nucleotide Polymorphisms and Breast Cancer Risk among Filipinos
  7. Transcription factor ZEB1 was found to directly bind to the SBF2-AS1 promoter region to regulate SBF2-AS1 level and affected TMZ resistance in GBM cells. SBF2-AS1 functions as a ceRNA for miR-151a-3p, leading to the disinhibition of its endogenous target, X-ray repair cross complementing 4 (XRCC4), which enhances DSB repair in GBM cells.
    Title: Exosomal transfer of long non-coding RNA SBF2-AS1 enhances chemoresistance to temozolomide in glioblastoma.
  8. UHRF1-mediated XRCC4 upregulation under pathophysiological conditions triggered by RB1 gene inactivation may confer protection against endogenous DNA damages that arise during retinoblastoma development.
    Title: UHRF1 depletion sensitizes retinoblastoma cells to chemotherapeutic drugs via downregulation of XRCC4.
  9. The results suggest that XPD G751A, hOGG1 C326G and XRCC4 G1394T gene polymorphisms might play an important role in colorectal carcinogenesis and increase the risk of developing colorectal cancer in the Chinese Han population.
    Title: Impact of polymorphisms in DNA repair genes XPD, hOGG1 and XRCC4 on colorectal cancer risk in a Chinese Han Population.
  10. restriction fragment length polymorphism (RFLP) method was used for evaluating of XPD (-751), XRCC4 (-1394 and a variable number of tandem repeats in intron 3), and XRCC1 (-399) genes. A notable contrast was observed in patients with endometrial hyperplasia without atypia (the SH+CH group) and the NE group in terms of XRCC4 (VNTR intron 3) polymorphisms (P=0.026, P=0.018, respectively).
    Title: DNA Repair Gene (XPD, XRCC4, and XRCC1) Polymorphisms in Patients with Endometrial Hyperplasia: A Pilot Study.
Submit: New GeneRIF Correction See all GeneRIFs (136)

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
Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles.
GeneReviews: Not available
Meta-analysis identifies loci affecting levels of the potential osteoarthritis biomarkers sCOMP and uCTX-II with genome wide significance.
GeneReviews: Not available
Short stature, microcephaly, and endocrine dysfunction
MedGen: C4225288 OMIM: 616541 GeneReviews: Not available
Compare labs
Two-marker association tests yield new disease associations for coronary artery disease and hypertension.
GeneReviews: Not available

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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
NOT DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
NOT ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
protein C-terminus binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
DNA ligation involved in DNA repair IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
DNA ligation involved in DNA repair IDA
Inferred from Direct Assay
more info
 PubMed 
cellular response to lithium ion IEA
Inferred from Electronic Annotation
more info
  
double-strand break repair IDA
Inferred from Direct Assay
more info
 PubMed 
double-strand break repair via nonhomologous end joining IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
double-strand break repair via nonhomologous end joining IDA
Inferred from Direct Assay
more info
 PubMed 
double-strand break repair via nonhomologous end joining IMP
Inferred from Mutant Phenotype
more info
 PubMed 
double-strand break repair via nonhomologous end joining NAS
Non-traceable Author Statement
more info
 PubMed 
double-strand break repair via nonhomologous end joining TAS
Traceable Author Statement
more info
  
establishment of integrated proviral latency TAS
Traceable Author Statement
more info
  
immunoglobulin V(D)J recombination IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
positive regulation of ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
positive regulation of ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
response to X-ray IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
response to X-ray IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
DNA ligase IV complex IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
DNA ligase IV complex IDA
Inferred from Direct Assay
more info
 PubMed 
DNA-dependent protein kinase-DNA ligase 4 complex IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
DNA-dependent protein kinase-DNA ligase 4 complex IDA
Inferred from Direct Assay
more info
 PubMed 
NOT condensed chromosome IDA
Inferred from Direct Assay
more info
 PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
nonhomologous end joining complex IDA
Inferred from Direct Assay
more info
 PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
  
nucleoplasm TAS
Traceable Author Statement
more info
  
nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
nucleus NAS
Non-traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
DNA repair protein XRCC4
Names
X-ray repair complementing defective repair in Chinese hamster cells 4

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_047086.1 RefSeqGene

    Range
    5139..281379
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001318012.3 → NP_001304941.1  DNA repair protein XRCC4 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses alternate splice sites in the 5' UTR and in the 3' coding region compared to variant 1. The encoded isoform (2) is longer than isoform 1. Variants 2 and 4 encode the same isoform (2).
    Source sequence(s)
    BC010655, BC016314, DA067761
    Consensus CDS
    CCDS4059.1
    UniProtKB/Swiss-Prot
    Q13426
    UniProtKB/TrEMBL
    A0A024RAQ8, Q7Z763
    Related
    ENSP00000421491.1, ENST00000511817.1
    Conserved Domains (1) summary
    pfam06632
    Location:2 → 334
    XRCC4; DNA double-strand break repair and V(D)J recombination protein XRCC4

  2. NM_001318013.2 → NP_001304942.1  DNA repair protein XRCC4 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 3' coding region and 3' UTR compared to variant 1. The encoded isoform (3) has a distinct, shorter C-terminus than isoform 1.
    Source sequence(s)
    BC005259, DA067761
    UniProtKB/Swiss-Prot
    Q13426
    UniProtKB/TrEMBL
    A0A024RAP0
    Related
    ENST00000542685.5
    Conserved Domains (1) summary
    pfam06632
    Location:2 → 308
    XRCC4; DNA double-strand break repair and V(D)J recombination protein XRCC4

  3. NM_003401.5 → NP_003392.1  DNA repair protein XRCC4 isoform 1

    See identical proteins and their annotated locations for NP_003392.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1. Variants 1 and 3 encode the same isoform (1).
    Source sequence(s)
    BC010655, BC016314, BT007216, DA067761, U40622
    Consensus CDS
    CCDS4058.1
    UniProtKB/Swiss-Prot
    Q13426
    UniProtKB/TrEMBL
    A0A024RAL0, Q7Z763
    Related
    ENSP00000379344.4, ENST00000396027.8
    Conserved Domains (1) summary
    pfam06632
    Location:2 → 332
    XRCC4; DNA double-strand break repair and V(D)J recombination protein XRCC4

  4. NM_022406.5 → NP_071801.1  DNA repair protein XRCC4 isoform 2

    See identical proteins and their annotated locations for NP_071801.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. The encoded isoform (2) is longer than isoform 1. Variants 2 and 4 encode the same isoform (2).
    Source sequence(s)
    BC010655, BC016314, BT007216, DA067761
    Consensus CDS
    CCDS4059.1
    UniProtKB/Swiss-Prot
    Q13426
    UniProtKB/TrEMBL
    A0A024RAQ8, Q7Z763
    Related
    ENSP00000342011.6, ENST00000338635.10
    Conserved Domains (1) summary
    pfam06632
    Location:2 → 334
    XRCC4; DNA double-strand break repair and V(D)J recombination protein XRCC4

  5. NM_022550.4 → NP_072044.1  DNA repair protein XRCC4 isoform 1

    See identical proteins and their annotated locations for NP_072044.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1 and 3 encode the same isoform (1).
    Source sequence(s)
    BC010655, BC016314, DA067761, U40622
    Consensus CDS
    CCDS4058.1
    UniProtKB/Swiss-Prot
    Q13426
    UniProtKB/TrEMBL
    A0A024RAL0, Q7Z763
    Related
    ENSP00000282268.3, ENST00000282268.7
    Conserved Domains (1) summary
    pfam06632
    Location:2 → 332
    XRCC4; DNA double-strand break repair and V(D)J recombination protein XRCC4

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p13 Primary Assembly

    Range
    83077534..83370333
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017009827.2 → XP_016865316.1  DNA repair protein XRCC4 isoform X2

  2. XM_017009828.2 → XP_016865317.1  DNA repair protein XRCC4 isoform X3

  3. XM_017009829.2 → XP_016865318.1  DNA repair protein XRCC4 isoform X4

    Conserved Domains (1) summary
    pfam06632
    Location:2 → 252
    XRCC4; DNA double-strand break repair and V(D)J recombination protein XRCC4

  4. XM_011543626.1 → XP_011541928.1  DNA repair protein XRCC4 isoform X1

    See identical proteins and their annotated locations for XP_011541928.1

    UniProtKB/Swiss-Prot
    Q13426
    UniProtKB/TrEMBL
    A0A024RAQ8
    Conserved Domains (1) summary
    pfam06632
    Location:2 → 334
    XRCC4; DNA double-strand break repair and V(D)J recombination protein XRCC4
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13426.2 GenPept UniProtKB/Swiss-Prot:Q13426

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