XRCC4

Chr 5q14.2

X-ray repair cross complementing 4

Aliases:: hXRCC4
MANE:: ENST00000396027.9

OMIM: 194363 ↗NCBI: 7518 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

XRCC4 · Q13426

v62025-08-01

Predicted Aligned Error matrix for XRCC4 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

74.8/ 100

Confident

336 residues

Confidence breakdown

Very high(≥ 90)56%
Confident(70–90)5%
Low(50–70)7%
Very low(< 50)32%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
IUGR and IGF abnormalities
BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly
BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia
BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders
BIALLELIC, autosomal or pseudoautosomal
Monogenic short stature
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

microcephalic primordial dwarfism-insulin resistance syndrome
0.76
short stature, microcephaly, and endocrine dysfunction
0.73
neurodegenerative disease
0.53
isolated growth hormone deficiency type IA
0.46
HIV infectious disease
0.46
microcephalic primordial dwarfism
0.37
Fanconi anemia complementation group Q
0.37
Non-acquired isolated growth hormone deficiency
0.33
androgenetic alopecia
0.28
dyshidrosis
0.27

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

DNA repair protein XRCC4

DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:16412978, PubMed:17124166, PubMed:17290226, PubMed:22228831, PubMed:25597996, PubMed:25742519, PubMed:25934149, PubMed:26100018, PubMed:26774286, PubMed:8548796). Acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks (DSBs) (PubMed:15385968, PubMed:20852255, PubMed:26774286, PubMed:27437582). Associates with NHEJ1/XLF to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (PubMed:21768349, PubMed:21775435, PubMed:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (PubMed:27437582). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:19837014, PubMed:9242410). XRCC4 stabilizes LIG4, regulates its subcellular localization and enhances LIG4's joining activity (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:21982441, PubMed:22228831, PubMed:9242410). Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10757784, PubMed:10854421). Promotes displacement of PNKP from processed strand break termini (PubMed:20852255, PubMed:28453785)