XRCC4 (X-ray repair cross complementing 4)

Gene

• Entrez ID: 7518
• Gene name: X-ray repair cross complementing 4
• Gene symbol: XRCC4
• Synonyms: SSMED
• Chromosome: 5
• Chromosome location: 5q14.2
• 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587779351	T>C	Pathogenic	Coding sequence variant, missense variant
rs768825050	C>T	Pathogenic	Coding sequence variant, stop gained
rs779773463	C>T	Pathogenic	Coding sequence variant, stop gained
rs797045016	C>T	Pathogenic	Coding sequence variant, genic downstream transcript variant, stop gained
rs797045017	G>A,T	Pathogenic	Coding sequence variant, missense variant
rs869320677	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs869320678	G>T	Pathogenic	Splice acceptor variant
rs879255258	T>A,G	Pathogenic	Coding sequence variant, missense variant
rs879255259	G>-	Pathogenic	Coding sequence variant, genic downstream transcript variant, frameshift variant
rs991596636	A>T	Likely-pathogenic	Stop gained, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000793	Component	Condensed chromosome	IDA	12589063
GO:0003677	Function	DNA binding	IDA	9259561
GO:0005515	Function	Protein binding	IPI	9809069, 11702069, 15380105, 16275660, 16439205, 16713569, 17124166, 17353262, 17389648, 17396150, 18064046, 21349273, 21637298, 21768349, 22529269, 23178593, 23219551, 24095731, 25416956, 25910212, 26496610, 28514442, 29997244, 31515488, 31548606, 32296183
GO:0005634	Component	Nucleus	IDA	9259561, 12589063
GO:0005634	Component	Nucleus	NAS	16439205
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005829	Component	Cytosol	IDA	9259561
GO:0005958	Component	DNA-dependent protein kinase-DNA ligase 4 complex	IBA	21873635
GO:0005958	Component	DNA-dependent protein kinase-DNA ligase 4 complex	IDA	15194694
GO:0006302	Process	Double-strand break repair	IDA	9242410
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IBA	21873635
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IDA	12517771
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IMP	9809069
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	NAS	16439205
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	TAS
GO:0008022	Function	Protein C-terminus binding	IPI	9259561
GO:0010165	Process	Response to X-ray	IBA	21873635
GO:0010165	Process	Response to X-ray	IDA	9242410
GO:0016874	Function	Ligase activity	IDA	9242410
GO:0032807	Component	DNA ligase IV complex	IBA	21873635
GO:0032807	Component	DNA ligase IV complex	IDA	9242410
GO:0033152	Process	Immunoglobulin V(D)J recombination	IBA	21873635
GO:0035861	Component	Site of double-strand break	IDA	31548606
GO:0042802	Function	Identical protein binding	IPI	16169070, 21768349, 25416956, 31515488, 32296183
GO:0051103	Process	DNA ligation involved in DNA repair	IBA	21873635
GO:0051103	Process	DNA ligation involved in DNA repair	IDA	12517771
GO:0051351	Process	Positive regulation of ligase activity	IBA	21873635
GO:0051351	Process	Positive regulation of ligase activity	IDA	9242410
GO:0070419	Component	Nonhomologous end joining complex	IDA	20383123, 25941166
GO:0071285	Process	Cellular response to lithium ion	IEA
GO:0075713	Process	Establishment of integrated proviral latency	TAS
GO:1990166	Process	Protein localization to site of double-strand break	IDA	31548606

Other IDs

• MIM: 194363
• HGNC: 12831
• e!Ensembl: ENSG00000152422

Protein

• UniProt ID: Q13426
• Protein name: DNA repair protein XRCC4 (X-ray repair cross-complementing protein 4)
• Protein function: Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. Binds to DNA and to DNA ligase IV (LIG4). The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.
• PDB: 1FU1, 1IK9, 3II6, 3MUD, 3Q4F, 3RWR, 3SR2, 3W03, 4XA4, 5CHX, 5CJ0, 5CJ4, 5E50, 5WJ7, 5WLZ, 6ABO
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF06632	XRCC4	1 → 334	DNA double-strand break repair and V(D)J recombination protein XRCC4	Family

• Sequence:

  MERKISRIHLVSEPSITHFLQVSWEKTLESGFVITLTDGHSAWTGTVSESEISQEADDMA
  MEKGKYVGELRKALLSGAGPADVYTFNFSKESCYFFFEKNLKDVSFRLGSFNLEKVENPA
  EVIRELICYCLDTIAENQAKNEHLQKENERLLRDWNDVQGRFEKCVSAKEALETDLYKRF
  ILVLNEKKTKIRSLHNKLLNAAQEREKDIKQEGETAICSEMTADRDPVYDESTDEESENQ
  TDLSGLASAAVSKDDSIISSLDVTDIAPSRKRRQRMQRNLGTEPKMAPQENQLQEKENSR
  PDSSLPETSKKEHISAENMSLETLRNSSPEDLFDEI

• Sequence length: 336