NHEJ1

Chr 2q35

non-homologous end joining factor 1

Aliases:: Cernunnos, XLF, FLJ12610
MANE:: ENST00000356853.10

OMIM: 611290 ↗NCBI: 79840 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

NHEJ1 · Q9H9Q4

v62025-08-01

Predicted Aligned Error matrix for NHEJ1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

81.8/ 100

Confident

299 residues

Confidence breakdown

Very high(≥ 90)65%
Confident(70–90)13%
Low(50–70)3%
Very low(< 50)19%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Cernunnos-XLF deficiency
0.80
T-B- severe combined immunodeficiency
0.46
T-B+ severe combined immunodeficiency
0.46
severe combined immunodeficiency
0.46
combined immunodeficiency
0.37
microphthalmia/coloboma 13
0.33
syndactyly type 1
0.33
isolated anophthalmia-microphthalmia syndrome
0.27
hereditary disease
0.19
hypothyroidism
0.18

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

Protein function (UniProt)

Non-homologous end-joining factor 1

DNA repair protein involved in DNA non-homologous end joining (NHEJ); it is required for double-strand break (DSB) repair and V(D)J recombination and is also involved in telomere maintenance (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781, PubMed:17717001, PubMed:18158905, PubMed:18644470, PubMed:20558749, PubMed:26100018, PubMed:28369633). Plays a key role in NHEJ by promoting the ligation of various mismatched and non-cohesive ends (PubMed:17470781, PubMed:17717001, PubMed:19056826). Together with PAXX, collaborates with DNA polymerase lambda (POLL) to promote joining of non-cohesive DNA ends (PubMed:25670504, PubMed:30250067). May act in concert with XRCC5-XRCC6 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are non-complementary or partially complementary (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781). In some studies, has been shown to associate with XRCC4 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:22228831, PubMed:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). Alternatively, it has also been shown that rather than forming filaments, a single NHEJ1 dimer interacts through both head domains with XRCC4 to promote the close alignment of DNA ends (By similarity). 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, PubMed:28500754). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Binds DNA in a length-dependent manner (PubMed:17317666, PubMed:18158905)