DCLRE1C

Chr 10AR

DNA cross-link repair 1C

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

NCBI Gene: 64421UniProt: 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.

Summary from RefSeq, OMIM, UniProt, Mechanism
Research Assistant →

Primary Disease Associations & Inheritance

Omenn syndromeMIM #603554
AR
Severe combined immunodeficiency, Athabascan typeMIM #602450
AR
8
Active trials
14
Pubs (1 yr)
156
P/LP submissions
9%
P/LP missense
0.71
LOEUF
LOF
Mechanism· G2P
Clinical Summary— DCLRE1C
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Gene-Disease Validity (ClinGen)
severe combined immunodeficiency due to DCLRE1C deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
104 unique Pathogenic / Likely Pathogenic· 196 VUS of 500 total submissions
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Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — DCLRE1C
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

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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 OE0.47 (0.32–0.71)
0≤0.351.4
Missense OE1.10 (1.01–1.20)
0≤0.61.4
Synonymous OE1.24
0≤1.21.6
LoF obs/exp: 17 / 35.9Missense obs/exp: 391 / 355.1Syn Z: -2.14
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDCLRE1C-related Omenn syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6647th %ile
GOF
0.4776th %ile
LOF
0.3453th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic53
VUS196
Likely Benign180
Benign10
Conflicting8
51
Pathogenic
53
Likely Pathogenic
196
VUS
180
Likely Benign
10
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
34
0
51
Likely Pathogenic
32
9
12
0
53
VUS
3
172
19
2
196
Likely Benign
1
3
57
119
180
Benign
0
0
9
1
10
Conflicting
—8
Total53184131122498

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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

RECRUITING
NCT06856577Phase PHASE3Adverum Biotechnologies, Inc.Started 2025-02-28
Ixo-vecAflibercept
Spinal Muscular AtrophyFragile X SyndromeFragile X - Premutation

Early Check: Expanded Screening in Newborns

ENROLLING BY INVITATION
NCT03655223RTI InternationalStarted 2018-10-15
Confirmatory Testing
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
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
Gastrointestinal Tolerance of Probiotics in Infants

Evaluating the Impact of Synbiotic Supplementation on Infants and Toddlers

ACTIVE NOT RECRUITING
NCT06746285Phase NAPersephone BiosciencesStarted 2025-01-01
Synbiotic SupplementLactose (inactive placebo)
Stimulant UseHuman Immunodeficiency Virus (HIV)Depression

Project neuroARTEMIS

RECRUITING
NCT06814275Phase NAWake Forest University Health SciencesStarted 2025-04-29
ARTEMISContingency management for Antiretroviral (ARV) adherence
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
SGT-501
Severe Combined Immunodeficiency

Autologous Gene Therapy for Artemis-Deficient SCID

RECRUITING
NCT03538899Phase PHASE1, PHASE2University of California, San FranciscoStarted 2018-05-31
AProArt-CD34CliniMACS® CD34 Reagent System cell sorter deviceBusulfan
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
[Analysis of a child with severe combined immunodeficiency due to variants of DCLRE1C gene].
Xu X et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2022
Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene
Ghadimi S et al.·Allergy Asthma Clin Immunol
2023Cohort
Effect of ARTEMIS (DCLRE1C) deficiency and microinjection timing on editing efficiency during somatic cell nuclear transfer and in vitro fertilization using the CRISPR/Cas9 system.
Li Y et al.·Theriogenology
2021
CRISPR-Cas9-based gene editing as a proof-of-concept approach in an inborn error of immunity caused by a DCLRE1C variant.
Duran T et al.·Immunol Res
2026
Case report: Rubella virus-induced cutaneous granulomas in a girl with atypical SCID caused by DCLRE1C gene mutations
Deng S et al.·Front Genet
2023Case report
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Lentiviral Gene Therapy for Artemis-Deficient SCID.
Cowan MJ et al.·N Engl J Med
2022Clinical trial
Variable clinical presentation of hypomorphic DCLRE1C deficiency from childhood to adulthood.
Hazar E et al.·Pediatr Allergy Immunol
2024
Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency.
Felgentreff K et al.·J Allergy Clin Immunol
2015Functional
Compound heterozygous DCLRE1C mutations lead to clinically typical Severe Combined Immunodeficiency presenting with Graft Versus Host Disease.
Mou W et al.·Immunogenetics
2021
A Novel Non-Coding Variant in DCLRE1C Results in Deregulated Splicing and Induces SCID Through the Generation of a Truncated ARTEMIS Protein That Fails to Support V(D)J Recombination and DNA Damage Repair.
Strubbe S et al.·Front Immunol
2021Case report
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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