DCLRE1C Gene

The DCLRE1C gene (DCLRE1C stands for "DNA Cross-Link Repair 1C") is a protein-coding gene located on chromosome 10p13. The gene encodes a nuclear protein, a nuclease involved in V(D)J recombination. It is required for the repair of double-strand breaks.

The enzyme has single-strand-specific 5'-3' exonuclease activity; it also shows endonuclease activity at 5' and 3' overhangs and hairpins. Furthermore, it plays a role in cell cycle regulation in response to DNA damage.

Mutations in this gene can cause severe combined Athabascan-type immunodeficiency (Athabascan-type disease is more common in individuals of Apache and Navajo descent) and Omenn syndrome (Volk T et al. 2015). Patients with these diseases suffer from frequent infections, diarrhea, and failure to thrive in infancy. Other clinical features include impaired immunity, decreased numbers of polyclonal T and B cells, and sensitivity to ionizing radiation. Without successful bone marrow transplantation, affected individuals usually die within the first 6 months of life.

1. Mou W et al (2021) Compound heterozygous DCLRE1C mutations lead to clinically typical Severe Combined Immunodeficiency presenting with Graft Versus Host Disease. Immunogenetics 73:425-434.
2. Volk T et al. (2015) DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency. Hum Mol Genet 24:7361-7372.