DCLRE1C

Chr 10

DNA cross-link repair 1C

Also known as: A-SCID, DCLREC1C, RS-SCID, SCIDA, SNM1C

NCBI Gene: 64421 ENSG00000152457 UniProt: Q96SD1

This protein functions as a nuclease essential for DNA non-homologous end joining (NHEJ) and V(D)J recombination, exhibiting single-strand specific 5'-3' exonuclease activity and endonuclease activity on hairpins and overhangs when complexed with PRKDC. Autosomal recessive mutations cause Athabascan-type severe combined immunodeficiency (SCIDA) and Omenn syndrome through impaired V(D)J recombination required for proper immune system development. The pathogenic mechanism involves loss of function, preventing proper assembly of immunoglobulin and T-cell receptor genes from individual V, D, and J segments.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The encoded protein has single-strand-specific 5'-3' exonuclease activity; it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins. The protein also functions in the regulation of the cell cycle in response to DNA damage. Mutations in this gene can cause Athabascan-type severe combined immunodeficiency (SCIDA) and Omenn syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSevere combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation

UniProtSevere combined immunodeficiency Athabaskan type

UniProtOmenn syndrome

Clinical highlights

Gene-disease validity (ClinGen)

severe combined immunodeficiency due to DCLRE1C deficiency · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.71

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — DCLRE1C

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.71LOEUF

pLI 0.000

Z-score 2.92

OE 0.47 (0.32–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.68Z-score

OE missense 1.10 (1.01–1.20)

391 obs / 355.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.47 (0.32–0.71)

0≤0.351.4

Missense OE?1.10 (1.01–1.20)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 17 / 35.9Missense obs/exp: 391 / 355.1Syn Z: -2.14

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DCLRE1C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — DCLRE1C

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Pancreatic Cancer

Multicenter Study of Circulating Tumor DNA in Patients With Pancreatic Cancer Using a Personalized Panel

RECRUITING

NCT06043921Invitae CorporationStarted 2022-11-01

No intervention

Artemis (DCLRE1C ) Deficient Severe Combined Immunodeficiency

Safety and Efficacy Study of Transplantation of Autologous CD34+ Cells Transduced With the G2ARTE Lentiviral Vector Expressing the DCLRE1C cDNA in Artemis (DCLRE1C) Deficient Severe Combined Immunodeficiency Patients (ARTEGENE)

RECRUITING

NCT05071222Phase PHASE1, PHASE2Assistance Publique - Hôpitaux de ParisStarted 2023-07-19

ARTEGENE drug product

Neovascular Age-Related Macular Degeneration (nAMD)Wet AMD

Efficacy and Safety Study of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-Related Macular Degeneration

ACTIVE NOT RECRUITING

NCT06856577Phase PHASE3Adverum Biotechnologies, Inc.Started 2025-02-28

Ixo-vecAflibercept

Catecholaminergic Polymorphic Ventricular Tachycardia

A Study of SGT-501 Gene Therapy in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

RECRUITING

NCT07148089Phase PHASE1Solid Biosciences Inc.Started 2026-02-23