DCLRE1C

Summary

DCLRE1C (DNA cross-link repair 1C, HGNC:17642) is a protein-coding gene on chromosome 10p13, encoding Protein artemis (Q96SD1). Nuclease involved in DNA non-homologous end joining (NHEJ); required for double-strand break repair and V(D)J recombination.

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.

Source: NCBI Gene 64421 — RefSeq curated summary.

At a glance

• Gene–disease (curated): severe combined immunodeficiency due to DCLRE1C deficiency (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 1,274 total — 102 pathogenic, 100 likely-pathogenic
• Phenotypes (HPO): 124
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001033855

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17642
Approved symbol	DCLRE1C
Name	DNA cross-link repair 1C
Location	10p13
Locus type	gene with protein product
Status	Approved
Aliases	ARTEMIS, FLJ11360, SNM1C, A-SCID
Ensembl gene	ENSG00000152457
Ensembl biotype	protein_coding
OMIM	605988
Entrez	64421

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 26 nonsense_mediated_decay, 11 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000357717, ENST00000378241, ENST00000378242, ENST00000378246, ENST00000378249, ENST00000378254, ENST00000378255, ENST00000378258, ENST00000378278, ENST00000378289, ENST00000396817, ENST00000418843, ENST00000456122, ENST00000489161, ENST00000492201, ENST00000697047, ENST00000697070, ENST00000697071, ENST00000697072, ENST00000697073, ENST00000697074, ENST00000697075, ENST00000697076, ENST00000697077, ENST00000697078, ENST00000697079, ENST00000697080, ENST00000697081, ENST00000697082, ENST00000697083, ENST00000697084, ENST00000697085, ENST00000697086, ENST00000697087, ENST00000697088, ENST00000697089, ENST00000697090, ENST00000697091, ENST00000873030, ENST00000873031, ENST00000913370, ENST00000948506, ENST00000948507

RefSeq mRNA: 11 — MANE Select: NM_001033855 NM_001033855, NM_001033857, NM_001033858, NM_001289076, NM_001289077, NM_001289078, NM_001289079, NM_001350965, NM_001350966, NM_001350967, NM_022487

CCDS: CCDS31149, CCDS91218

Canonical transcript exons

ENST00000378278 — 14 exons

Exon	Start	End
ENSE00001005308	14928016	14928152
ENSE00001005311	14934703	14934775
ENSE00001005314	14932854	14932955
ENSE00001681824	14934380	14934520
ENSE00001689880	14935463	14935564
ENSE00003512956	14939810	14939869
ENSE00003550344	14936538	14936593
ENSE00003589880	14926843	14926897
ENSE00003590261	14945105	14945189
ENSE00003606976	14919738	14919832
ENSE00003622044	14953902	14954096
ENSE00003628934	14949036	14949087
ENSE00003641731	14922981	14923069
ENSE00003845006	14904613	14909330

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2676 / max 63.2175, expressed in 1715 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108403	3.6611	1466
108402	3.4378	1440
108404	0.1688	76

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.07	gold quality
tendon of biceps brachii	UBERON:0008188	95.15	gold quality
epithelium of nasopharynx	UBERON:0001951	93.15	gold quality
sperm	CL:0000019	91.22	gold quality
nipple	UBERON:0002030	91.14	gold quality
pylorus	UBERON:0001166	91.12	gold quality
cardia of stomach	UBERON:0001162	90.54	gold quality
superior surface of tongue	UBERON:0007371	90.52	gold quality
endothelial cell	CL:0000115	90.35	silver quality
cervix squamous epithelium	UBERON:0006922	90.29	gold quality
male germ cell	CL:0000015	90.06	gold quality
amniotic fluid	UBERON:0000173	89.55	gold quality
renal medulla	UBERON:0000362	89.24	gold quality
corpus callosum	UBERON:0002336	89.06	gold quality
trabecular bone tissue	UBERON:0002483	89.04	gold quality
ventral tegmental area	UBERON:0002691	88.87	gold quality
inferior vagus X ganglion	UBERON:0005363	88.87	gold quality
pharyngeal mucosa	UBERON:0000355	88.84	gold quality
trigeminal ganglion	UBERON:0001675	88.71	gold quality
trachea	UBERON:0003126	88.42	gold quality
pancreatic ductal cell	CL:0002079	88.34	gold quality
tendon	UBERON:0000043	87.57	gold quality
pericardium	UBERON:0002407	87.51	gold quality
dorsal root ganglion	UBERON:0000044	87.35	gold quality
tonsil	UBERON:0002372	87.07	gold quality
tongue	UBERON:0001723	87.04	gold quality
tibia	UBERON:0000979	86.99	gold quality
lymph node	UBERON:0000029	86.79	gold quality
visceral pleura	UBERON:0002401	86.63	gold quality
medulla oblongata	UBERON:0001896	86.60	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, STAT1

miRNA regulators (miRDB)

126 targeting DCLRE1C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-5582-3P	99.86	72.48	4221

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• DNA-PKcs regulates Artemis by both phosphorylation and complex formation to permit enzymatic activities that are critical for the hairpin-opening step of V(D)J recombination and for the 5’ and 3’ overhang processing in nonhomologous DNA end joining. (PMID:11955432)
• A nonsense founder mutation discovered in exon 8 of Artemis results in the truncation of the deduced protein product and indicates that the SNM1-like gene (Artemis) is the gene responsible for SCID in Athabascan-speaking Native Americans. (PMID:12055248)
• deletions and missense mutations in the Artemis gene can cause radiosensitive-SCID with defective coding joint formation and lead to an early and complete B-cell differentiation block (PMID:12406895)
• Artemis has a role in T and B lymphocyte immunodeficiency and in predisposition to lymphoma through the NHEJ pathway of DNA repair (PMID:12569164)
• the genomic exon 3 deletion is unique to Japan and may be considered as a founder haplotype. (PMID:12592555)
• Properties of the Artemis proteins are integrated into the processes of V(D)J recombination and non-homologous end-joining factors. (PMID:14628082)
• Artemis uses one or two Zn(II) ions to exert its catalytic activity, like bacterial class B beta-Lact enzymes hydrolyzing beta-lactam compounds. (PMID:14744996)
• The hairpin-opening activity of ARTEMIS and/or its overhang endonucleolytic activity are necessary but its exonuclease activity is not sufficient for the process of V(D)J recombination. (PMID:15071507)
• Data show that Artemis interacts with cell cycle checkpoint proteins and is a phosphorylation target of the checkpoint kinases ATM or ATR after exposure of cells to IR or UV irradiation, respectively. (PMID:15456891)
• Atemis is an effector of dna repair that can be phosphorylated by ataxia-telangiectasia-mutated kinase (ATM) and possibly by DNA-dependent protein kinase catalytic subunit and ATM-and Rad3-related kinase depending on the type of DNA damage. (PMID:15468306)
• ATM, Artemis, and proteins locating to gamma-H2AX foci have roles in double-strand break rejoining (PMID:15574327)
• our finding places Artemis at the signaling crossroads downstream of DNA-PKcs and ATM in IR-induced DSB repair. (PMID:15723659)
• report on a first patient with clinical and immunologic features of OS caused by hypomorphic ARTEMIS mutations. Sequencing of the ARTEMIS gene revealed a compound heterozygosity in this nonhomologous end-joining (NHEJ) factor (PMID:15731174)
• Artemis:DNA-PKcs nuclease may be important in removing secondary structures that hinder processing of DNA ends during nonhomologous DNA end joining . (PMID:15936993)
• The uncharacterized C-terminal domain of Artemis has important regulatory roles; results lead to a model for how DNA-PKcs activates Artemis by phosphorylation (PMID:16093244)
• characterization of six DNA-PK phosphorylation sites on Artemis whose phosphorylation shows dependence on its association with DNA-PK catalytic subunit and is induced by double-stranded DNA damage (PMID:16600297)
• Ku-mediated assembly of DNA-PK on DNA ends is responsible for a dissociation of the DNA-PKcs.Artemis complex. (PMID:16857680)
• DNA-PK autophosphorylation regulates Artemis access to DNA ends, providing insight into the mechanism of Artemis mediated DNA end processing. (PMID:16874298)
• Artemis efficiently trims long 3’-phosphoglycate-terminated overhangs induced in DNA by radiation and other radical-based toxins. (PMID:17121861)
• analyzed the phenotype of cells derived from SCID patients with different mutations in the Artemis gene (PMID:17169382)
• ATM regulates G(2)/M checkpoint recovery through inhibitory phosphorylations of Artemis that occur soon after DNA damage, thus setting a molecular switch that, hours later upon completion of DNA repair, allows activation of the Cdk1-cyclin B complex. (PMID:17242184)
• There is some sequence-dependent variation in the efficiency and position of hairpin opening by Artemis:DNA-PKcs; providing more clarity on the extent to which the hairpin opening position contributes to junctional diversity in V(D)J recombination. (PMID:17932067)
• The Artemis C terminus is essential for V(D)J recombination at the normal Artemis expression level. (PMID:18034425)
• H254 plays a key role in the Artemis function, as it is critical for its full activity in vitro. (PMID:19022407)
• Results link Artemis to the predominant nonhomologous end-joining pathway during immunoglobulin class switch recombination. (PMID:19075292)
• Results identify the first human RS-SCID patient with a DNA-PKcs missense mutation, which also affects Artemis activation and function. (PMID:19075392)
• Artemis and DNA-PKcs participate in a new, signaling pathway to modulate p53 function in response to oxidative stress produced by mitochondrial respiration. (PMID:19398950)
• recovery from the S phase checkpoint in that in response to replication stress phosphorylation of Artemis by ATR enhances its interaction with Fbw7, which in turn promotes ubiquitylation and the ultimate degradation of cyclin E (PMID:19423708)
• Mutations in Artemis leads to reduced immunoglobulin class switch recombination. (PMID:19692705)
• ATM and DNA cross-link repair 1C (PSO2 homolog S. cerevisiae) are required for efficient formation of single-stranded DNA and Rad51 foci at radiation-induced double-strand breaks in G2 phase. (PMID:19779458)
• Functional analyses on patients’ fibroblasts demonstrated that the corresponding alleles carry null mutations of the DCLRE1C gene. (PMID:19953608)
• Plays role in the 3’-processing reaction and protection of the ends of viral DNA (HIV-1) after reverse transcription. Involved in multiple steps including integration and pre-integration steps during retroviral replication. (PMID:20003485)
• Studies indicate that codon-based models of gene evolution yielded statistical support for the recurrent positive selection of five NHEJ genes during primate evolution: XRCC4, NBS1, Artemis, POLlambda, and CtIP. (PMID:20975951)
• antisense oligonucleotide (AON) covering the intronic mutation restored WT Artemis transcript levels and non-homologous end-joining pathway activity in the patient fibroblasts (PMID:21390052)
• Restoration of chemo/radioresistance by wild-type, but not D165N Artemis suggests that the lack of endonucleolytic trimming of DNA ends is the principal cause of sensitivity to double-strand cleaving agents in Artemis-deficient cells. (PMID:21531702)
• Artemis is required for the repair of DNA double strand breaks that arise endogenously or following oxidative stress. (PMID:21596788)
• The dominant negative mutant Artemis fragment (D37N-413aa) enhanced tumor cell radiosensitivity through blocking activity of endogenous Artemis and DNA repair. (PMID:21641068)
• analysis of differences in sensitivity to DNA-damaging Agents between XRCC4- and Artemis-deficient human cells (PMID:21785230)
• Regulation of p27 by Artemis and DDB2 is important for cell cycle progression in normally proliferating cells. (PMID:22134138)
• study identified a new SCID mutation in a consanguineous Israeli Arab family; sequencing identified an 8 bp insertion in exon 14 (1306ins8) of DCLRE1C in all affected patients; this causes an alteration in amino acid 330 of the protein from cysteine to a stop codon (p.C330X) (PMID:22527898)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dclre1c	ENSDARG00000045704
mus_musculus	Dclre1c	ENSMUSG00000026648
rattus_norvegicus	Dclre1c	ENSRNOG00000015980

Paralogs (2): DCLRE1B (ENSG00000118655), DCLRE1A (ENSG00000198924)

Protein

Protein identifiers

Protein artemis — Q96SD1 (reviewed: Q96SD1)

Alternative names: DNA cross-link repair 1C protein, Protein A-SCID, SNM1 homolog C, SNM1-like protein

All UniProt accessions (12): Q96SD1, A0A8V8TKH3, A0A8V8TKM3, A0A8V8TKM6, A0A8V8TKN9, A0A8V8TKP5, A0A8V8TL07, A0A8V8TLW6, A0A8V8TLX1, A0A8V8TM57, A0A9S7JGJ5, A0A9S7JK93

UniProt curated annotations — full annotation on UniProt →

Function. Nuclease involved in DNA non-homologous end joining (NHEJ); required for double-strand break repair and V(D)J recombination. Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5’-3’ exonuclease activity in isolation and acquires endonucleolytic activity on 5’ and 3’ hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. Also required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ.

Subunit / interactions. Interacts with LIG4; the interaction is direct. Interacts with ATM. Interacts with BRCA1. Interacts with PRKDC. Interacts with TP53BP1. Also exhibits ATM- and phosphorylation-dependent interaction with the MRN complex, composed of MRE11, RAD50, and NBN.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed, with highest levels in the kidney, lung, pancreas and placenta (at the mRNA level). Expression is not increased in thymus or bone marrow, sites of V(D)J recombination.

Post-translational modifications. Phosphorylation on undefined residues by PRKDC may stimulate endonucleolytic activity on 5’ and 3’ hairpins and overhangs. PRKDC must remain present, even after phosphorylation, for efficient hairpin opening. Also phosphorylated by ATM in response to ionizing radiation (IR) and by ATR in response to ultraviolet (UV) radiation.

Disease relevance. Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:602450] A form of severe combined immunodeficiency, a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity. The disease is caused by variants affecting the gene represented in this entry. Severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:602450] A variety of SCID with sensitivity to ionizing radiation. A founder mutation has been detected in Athabascan-speaking native Americans, being inherited as an autosomal recessive trait. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID. The disease is caused by variants affecting the gene represented in this entry. Omenn syndrome (OS) [MIM:603554] Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96SD1-1	1	yes
Q96SD1-2	2, SCIDA
Q96SD1-3	3
Q96SD1-4	4

RefSeq proteins (11): NP_001029027, NP_001029029, NP_001029030, NP_001276005, NP_001276006, NP_001276007, NP_001276008, NP_001337894, NP_001337895, NP_001337896, NP_071932 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011084	DRMBL	Domain
IPR036866	RibonucZ/Hydroxyglut_hydro	Homologous_superfamily

Pfam: PF07522

UniProt features (86 total): strand 24, helix 18, mutagenesis site 16, sequence variant 9, splice variant 5, compositionally biased region 4, turn 3, modified residue 3, region of interest 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
6TT5	X-RAY DIFFRACTION	1.5
7AFU	X-RAY DIFFRACTION	1.56
7AF1	X-RAY DIFFRACTION	1.7
7AFS	X-RAY DIFFRACTION	1.7
7AGI	X-RAY DIFFRACTION	1.7
7APV	X-RAY DIFFRACTION	1.95
6WO0	X-RAY DIFFRACTION	1.97
7ABS	X-RAY DIFFRACTION	1.97
4HTP	X-RAY DIFFRACTION	2.25
6WNL	X-RAY DIFFRACTION	2.37
3W1B	X-RAY DIFFRACTION	2.4
3W1G	X-RAY DIFFRACTION	2.55
7SGL	ELECTRON MICROSCOPY	3
7TYR	ELECTRON MICROSCOPY	3.33

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96SD1-F1	70.10	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 380, 385, 645

Mutagenesis-validated functional residues (16):

Position	Phenotype
17	abolishes prkdc-dependent endonuclease activity and v(d)j recombination.
33	abolishes prkdc-dependent endonuclease activity and v(d)j recombination.
35	abolishes prkdc-dependent endonuclease activity and v(d)j recombination.
37	abolishes prkdc-dependent endonuclease activity and v(d)j recombination.
38	reduces prkdc-dependent endonuclease activity, although v(d)j recombination is largely normal.
115	abolishes prkdc-dependent endonuclease activity and v(d)j recombination.
136	abolishes prkdc-dependent endonuclease activity and v(d)j recombination.
165	abolishes prkdc-dependent endonuclease activity and v(d)j recombination.
319	abolishes prkdc-dependent endonuclease activity and v(d)j recombination.
516	reduced ir induced phosphorylation; when associated with a-534; a-538; a-548; a-553; a-561 and a-562.
534	reduced ir induced phosphorylation; when associated with a-516; a-538; a-548; a-553; a-561 and a-562.
538	reduced ir induced phosphorylation; when associated with a-516; a-534; a-548; a-553; a-561 and a-562.
548	reduced ir induced phosphorylation; when associated with a-516; a-534; a-538; a-553; a-561 and a-562.
553	reduced ir induced phosphorylation; when associated with a-516; a-534; a-538; a-548; a-561 and a-562.
561	reduced ir induced phosphorylation; when associated with a-516; a-534; a-538; a-548; a-553 and a-562.
562	reduced ir induced phosphorylation; when associated with a-516; a-534; a-538; a-548; a-553 and a-561.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)

MSigDB gene sets: 357 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MODULE_97, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOMF_ENDONUCLEASE_ACTIVITY, GOBP_B_CELL_ACTIVATION, GOMF_NUCLEASE_ACTIVITY, GOBP_TELOMERE_ORGANIZATION, MODULE_182, KAUFFMANN_DNA_REPAIR_GENES, chr10p13, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, FISCHER_G2_M_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE, GOBP_SOMATIC_DIVERSIFICATION_OF_IMMUNE_RECEPTORS

GO Biological Process (14): telomere maintenance (GO:0000723), adaptive immune response (GO:0002250), double-strand break repair via nonhomologous end joining (GO:0006303), response to ionizing radiation (GO:0010212), B cell differentiation (GO:0030183), V(D)J recombination (GO:0033151), interstrand cross-link repair (GO:0036297), immune system process (GO:0002376), DNA metabolic process (GO:0006259), DNA repair (GO:0006281), double-strand break repair (GO:0006302), DNA recombination (GO:0006310), DNA damage response (GO:0006974), chromosome organization (GO:0051276)

GO Molecular Function (9): single-stranded DNA endonuclease activity (GO:0000014), damaged DNA binding (GO:0003684), endonuclease activity (GO:0004519), 5’-3’ exonuclease activity (GO:0008409), 5’-3’ DNA exonuclease activity (GO:0035312), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), nonhomologous end joining complex (GO:0070419)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DNA Double-Strand Break Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
DNA repair	2
hydrolase activity, acting on ester bonds	2
nuclease activity	2
intracellular membrane-bounded organelle	2
telomere organization	1
immune response	1
double-strand break repair	1
response to radiation	1
lymphocyte differentiation	1
B cell activation	1
somatic diversification of immune receptors via germline recombination within a single locus	1
biological_process	1
nucleic acid metabolic process	1
DNA damage response	1
cellular response to stress	1
organelle organization	1
DNA endonuclease activity	1
DNA binding	1
exonuclease activity	1
5’-3’ exonuclease activity	1
DNA exonuclease activity, producing 5’-phosphomonoesters	1
catalytic activity, acting on a nucleic acid	1
binding	1
catalytic activity	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular protein-containing complex	1
DNA repair complex	1

Protein interactions and networks

STRING

1630 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCLRE1C	PRKDC	P78527	978
DCLRE1C	LIG4	P49917	929
DCLRE1C	NHEJ1	Q9H9Q4	924
DCLRE1C	RAG1	P15918	831
DCLRE1C	RAG2	P55895	814
DCLRE1C	XRCC4	Q13426	782
DCLRE1C	BTK	Q06187	734
DCLRE1C	XRCC5	P13010	733
DCLRE1C	XRCC6	P12956	722
DCLRE1C	IL2RG	P31785	672
DCLRE1C	IGLL1	P15814	583
DCLRE1C	AK2	P54819	532
DCLRE1C	EXO1	Q9UQ84	518
DCLRE1C	CHEK2	O96017	502
DCLRE1C	FANCA	O15360	501

IntAct

23 interactions, top by confidence:

A	B	Type	Score
LIG4	XRCC4	psi-mi:“MI:0914”(association)	0.970
LIG4	DCLRE1C	psi-mi:“MI:0407”(direct interaction)	0.790
DCLRE1C	LIG4	psi-mi:“MI:0914”(association)	0.790
DCLRE1C	LIG4	psi-mi:“MI:0915”(physical association)	0.790
LIG4	DCLRE1C	psi-mi:“MI:0915”(physical association)	0.790
DCLRE1C	LIG4	psi-mi:“MI:0407”(direct interaction)	0.790
DCLRE1C	PRKDC	psi-mi:“MI:0915”(physical association)	0.700
LIG4	PRKDC	psi-mi:“MI:0914”(association)	0.350
CHEK2	EPB41	psi-mi:“MI:0914”(association)	0.350
CHTF18	ALDOB	psi-mi:“MI:0914”(association)	0.350
DCLRE1C	PRKAG1	psi-mi:“MI:0914”(association)	0.350
DCLRE1C	USP9Y	psi-mi:“MI:0914”(association)	0.350

BioGRID (103): CDKN1B (Reconstituted Complex), AKAP11 (Affinity Capture-MS), ANKRD52 (Affinity Capture-MS), ZSWIM8 (Affinity Capture-MS), PRKAG2 (Affinity Capture-MS), PRKAG1 (Affinity Capture-MS), PPP6R2 (Affinity Capture-MS), PRKAB1 (Affinity Capture-MS), PRKAB2 (Affinity Capture-MS), TRIM26 (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKAA1 (Affinity Capture-MS), PRKAA2 (Affinity Capture-MS), PASK (Affinity Capture-MS), ANKRD28 (Affinity Capture-MS)

ESM2 similar proteins: A4FV61, A8MYV0, D3ZR10, G9CGD6, M0R2J8, O54828, O60543, O70302, O75916, O88974, P17863, P28715, P35689, P49805, P55265, P55266, Q02040, Q15047, Q3B7M3, Q3UY96, Q5DU00, Q5EAN7, Q5F3L9, Q5R6F3, Q5T848, Q5VT97, Q642B6, Q68D51, Q69Z99, Q6P3Z3, Q6P9P8, Q7TPQ3, Q8C4S8, Q8K0Q5, Q8N392, Q8NE31, Q8TEW8, Q8WY91, Q91VL8, Q95JV5

Diamond homologs: B0V2S2, D2H8V8, F4HPZ9, Q38961, Q4KLY6, Q55470, Q5QJC3, Q5QJC4, Q5R6Z9, Q5XIX3, Q6PJP8, Q86KS1, Q8C7W7, Q8K4J0, Q96SD1, Q9H816, Q9JIC3, P30620, Q5QJC2, Q5RGE5, Q10264, Q58633, B1ZZL9

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PRKDC	up-regulates	DCLRE1C	phosphorylation
ATM	up-regulates	DCLRE1C	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1274 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	102
Likely pathogenic	100
Uncertain significance	437
Likely benign	521
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070011	NC_000010.10:g.(?14953179)(14961841_?)del	Pathogenic
1070012	NC_000010.10:g.(?14946600)(14951339_?)del	Pathogenic
1070013	NC_000010.10:g.(?14981789)(14996029_?)del	Pathogenic
1071047	NM_001033855.3(DCLRE1C):c.1299_1306dup (p.Cys436Ter)	Pathogenic
1071845	NM_001033855.3(DCLRE1C):c.629del (p.Tyr210fs)	Pathogenic
1074072	NM_001033855.3(DCLRE1C):c.1316_1317del (p.Glu439fs)	Pathogenic
1075444	NM_001033855.3(DCLRE1C):c.511_512delinsTG (p.Pro171Ter)	Pathogenic
1322192	NM_001033855.3(DCLRE1C):c.571C>T (p.Arg191Ter)	Pathogenic
1370296	NM_001033855.3(DCLRE1C):c.1313_1317del (p.Ala438fs)	Pathogenic
1375314	NM_001033855.3(DCLRE1C):c.1467G>A (p.Trp489Ter)	Pathogenic
1378789	NM_001033855.3(DCLRE1C):c.1543G>T (p.Gly515Ter)	Pathogenic
1386133	NM_001033855.3(DCLRE1C):c.1507_1508del (p.Ser503fs)	Pathogenic
1406894	NC_000010.10:g.(?14977452)(14978602_?)del	Pathogenic
1440557	NM_001033855.3(DCLRE1C):c.1558_1559del (p.Lys520fs)	Pathogenic
1451198	NM_001033855.3(DCLRE1C):c.1502_1503dup (p.Glu502fs)	Pathogenic
1452422	NM_001033855.3(DCLRE1C):c.1221C>G (p.Tyr407Ter)	Pathogenic
1452686	NC_000010.10:g.(?14978527)(14978602_?)del	Pathogenic
1453056	NM_001033855.3(DCLRE1C):c.1545dup (p.Ser516fs)	Pathogenic
1453759	NM_001033855.3(DCLRE1C):c.801G>A (p.Trp267Ter)	Pathogenic
1455217	NC_000010.10:g.(?14995891)(14996441_?)del	Pathogenic
1455220	NC_000010.10:g.(?14989514)(14996441_?)del	Pathogenic
1460007	NC_000010.10:g.(?14977452)(14996009_?)del	Pathogenic
1703605	GRCh37/hg19 10p13(chr10:14983910-15065646)	Pathogenic
1708141	NM_001033855.3(DCLRE1C):c.1147C>T (p.Arg383Ter)	Pathogenic
1708489	Single allele	Pathogenic
1713266	NC_000010.10:g.14983601_15065700del	Pathogenic
1722324	NM_001033855.3(DCLRE1C):c.161+2T>G	Pathogenic
1946287	NM_001033855.3(DCLRE1C):c.1636C>T (p.Gln546Ter)	Pathogenic
2016139	NM_001033855.3(DCLRE1C):c.822del (p.Thr275fs)	Pathogenic
2027073	NM_001033855.3(DCLRE1C):c.484_487dup (p.Tyr163fs)	Pathogenic

SpliceAI

2867 predictions. Top by Δscore:

Variant	Effect	Δscore
10:14899537:A:AG	acceptor_gain	1.0000
10:14899537:AG:A	acceptor_gain	1.0000
10:14899538:G:GT	acceptor_gain	1.0000
10:14899538:GG:G	acceptor_gain	1.0000
10:14899538:GGT:G	acceptor_gain	1.0000
10:14899538:GGTA:G	acceptor_gain	1.0000
10:14899614:GACTA:G	donor_gain	1.0000
10:14899658:C:T	donor_gain	1.0000
10:14899682:CAGC:C	donor_gain	1.0000
10:14899683:AGC:A	donor_gain	1.0000
10:14899684:GC:G	donor_gain	1.0000
10:14899684:GCG:G	donor_gain	1.0000
10:14899686:G:GG	donor_gain	1.0000
10:14899693:GACA:G	donor_gain	1.0000
10:14899696:A:AG	donor_gain	1.0000
10:14899696:A:G	donor_gain	1.0000
10:14899700:G:GG	donor_gain	1.0000
10:14901131:A:AG	acceptor_gain	1.0000
10:14901131:AGTGT:A	acceptor_gain	1.0000
10:14901132:G:GA	acceptor_gain	1.0000
10:14901132:GT:G	acceptor_gain	1.0000
10:14901132:GTGT:G	acceptor_gain	1.0000
10:14901132:GTGTG:G	acceptor_gain	1.0000
10:14901258:GAAAG:G	donor_gain	1.0000
10:14901259:AAAGG:A	donor_loss	1.0000
10:14901261:AGG:A	donor_loss	1.0000
10:14901262:GGTAT:G	donor_loss	1.0000
10:14901263:G:T	donor_loss	1.0000
10:14901264:T:G	donor_loss	1.0000
10:14902395:T:A	acceptor_gain	1.0000

AlphaMissense

4554 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:14926860:G:C	H319D	1.000
10:14935514:C:G	R138T	1.000
10:14935520:T:A	D136V	1.000
10:14926858:G:C	H319Q	0.999
10:14926858:G:T	H319Q	0.999
10:14926874:G:T	A314D	0.999
10:14928051:A:C	F294L	0.999
10:14928051:A:T	F294L	0.999
10:14928053:A:G	F294L	0.999
10:14934426:C:A	G211V	0.999
10:14934426:C:T	G211D	0.999
10:14934427:C:G	G211R	0.999
10:14934736:G:C	F168L	0.999
10:14934736:G:T	F168L	0.999
10:14934738:A:G	F168L	0.999
10:14934746:T:A	D165V	0.999
10:14934746:T:G	D165A	0.999
10:14935513:T:A	R138S	0.999
10:14935513:T:G	R138S	0.999
10:14935514:C:A	R138I	0.999
10:14935519:G:C	D136E	0.999
10:14935519:G:T	D136E	0.999
10:14935520:T:C	D136G	0.999
10:14935520:T:G	D136A	0.999
10:14935521:C:G	D136H	0.999
10:14935523:C:A	G135V	0.999
10:14935523:C:T	G135E	0.999
10:14935532:A:G	L132P	0.999
10:14936547:C:T	G118E	0.999
10:14936548:C:G	G118R	0.999

dbSNP variants (sampled 300 via entrez): RS1000053246 (10:14902331 A>G,T), RS1000091100 (10:14951701 T>C), RS1000091507 (10:14950054 C>CA), RS1000147156 (10:14953027 G>A,C,T), RS1000252455 (10:14914927 G>T), RS1000260897 (10:14920695 A>G,T), RS1000264838 (10:14952009 T>C), RS1000362251 (10:14915520 AAATT>A), RS1000394689 (10:14915743 A>G), RS1000464585 (10:14938281 C>T), RS1000496158 (10:14935301 C>T), RS1000513871 (10:14901580 C>A), RS1000524740 (10:14910297 T>C,G), RS1000529495 (10:14913572 A>G), RS1000583194 (10:14913758 T>A,G)

Disease associations

OMIM: gene MIM:605988 | disease phenotypes: MIM:602450, MIM:603554, MIM:225750, MIM:225400

GenCC curated gene-disease

Disease	Classification	Inheritance
severe combined immunodeficiency due to DCLRE1C deficiency	Definitive	Autosomal recessive
Omenn syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
severe combined immunodeficiency due to DCLRE1C deficiency	Definitive	AR

Mondo (5): severe combined immunodeficiency due to DCLRE1C deficiency (MONDO:0011225), Omenn syndrome (MONDO:0011338), severe combined immunodeficiency (MONDO:0015974), Aicardi-Goutieres syndrome 1 (MONDO:0009165), Ehlers-Danlos syndrome, kyphoscoliotic type 1 (MONDO:0016002)

Orphanet (5): Severe combined immunodeficiency due to DCLRE1C deficiency (Orphanet:275), Severe combined immunodeficiency (Orphanet:183660), Omenn syndrome (Orphanet:39041), Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency (Orphanet:1900), Aicardi-Goutières syndrome (Orphanet:51)

HPO phenotypes

124 total (30 of 124 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000100	Nephrotic syndrome
HP:0000155	Oral ulcer
HP:0000388	Otitis media
HP:0000561	Absent eyelashes
HP:0000778	Hypoplasia of the thymus
HP:0000821	Hypothyroidism
HP:0000872	Hashimoto thyroiditis
HP:0000944	Abnormal metaphysis morphology
HP:0000958	Dry skin
HP:0000962	Hyperkeratosis
HP:0000964	Eczematoid dermatitis
HP:0000969	Edema
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001036	Parakeratosis
HP:0001045	Vitiligo
HP:0001072	Thickened skin
HP:0001250	Seizure
HP:0001287	Meningitis
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001581	Recurrent skin infections
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001831	Short toe
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001880	Increased total eosinophil count

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008359_6	Response to cognitive-behavioural therapy in anxiety disorder	4.000000e-06
GCST90002388_236	Lymphocyte count	1.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy
EFO:0004587	lymphocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750
C536198	Ehlers-Danlos syndrome type 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

84 measured of 103 human assays (133 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
6-bromanyl-2-(furan-2-yl)quinoline-4-carboxylic acid	IC50	23 nM
2-[2-oxidanylidene-2-[2-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]hydrazinyl]ethoxy]-N’’-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]benzohydrazide	IC50	1070 nM
3-methyl-N-[4-methyl-5-(phenylcarbamoyl)-1,3-thiazol-2-yl]-1-phenylthieno[2,3-c]pyrazole-5-carboxamide	IC50	1220 nM
SMR000147121	IC50	1680 nM
6-Methoxy-1,3-dimethyl-1H-benzo[de]cinnoline	EC50	2010 nM
SMR000125251	IC50	2090 nM
(6E)-6-[[2-[4-(3,5-dimethylpyrazol-1-yl)-6-phenylazanyl-1,3,5-triazin-2-yl]hydrazinyl]methylidene]-4-methoxy-cyclohexa-2,4-dien-1-one	IC50	2230 nM
cid_5334418	IC50	2650 nM
4-methoxy-N-(4-pyrrolidin-1-ylphenyl)benzamide	IC50	3440 nM
SMR000038583	IC50	3620 nM
7-[2-pyridinyl(2-pyridinylamino)methyl]-8-quinolinol	EC50	3990 nM
1-[4-(2-pyridin-2-ylpyrimidin-4-yl)phenyl]benzimidazole	IC50	4000 nM
MLS000540808	IC50	4170 nM
3-[[2-(3,5-dimethyl-1-pyrazolyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]amino]-1-propanol	EC50	4280 nM
MLS000098300	IC50	4400 nM
2-[4-[(4-chlorophenyl)methoxy]phenyl]-5-[3-(1-imidazolyl)propylamino]-4-oxazolecarbonitrile	IC50	4520 nM
MLS000533785	IC50	4720 nM
3-(4-methoxyphenyl)-N-[3-(2-oxidanylidenepropyl)-1,2,4-thiadiazol-5-yl]-1-phenyl-pyrazole-4-carboxamide	EC50	5320 nM
MLS000071484	IC50	6410 nM
2,2-Diphenyl-N-(4-pyrrolidin-1-yl-phenyl)-acetamide	IC50	7090 nM
cid_2211247	IC50	7470 nM
1-[[2-(3,5-dimethyl-1-pyrazolyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]amino]-2-propanol	EC50	7790 nM
4-(4-phenyl-1-piperazinyl)-2-(2-pyridinyl)quinazoline	IC50	8630 nM
(E)-[1-[4-(2,4-dichlorobenzyl)oxyphenyl]-2,5-dimethyl-pyrrol-3-yl]methylene-(1,2,4-triazol-4-yl)amine	EC50	9470 nM
3-(4-methoxyphenyl)-1-phenyl-N-1,3-thiazol-2-yl-1H-pyrazole-4-carboxamide	IC50	9490 nM
2-(1-benzotriazolyl)-3-(4-morpholinyl)naphthalene-1,4-dione	EC50	10500 nM
2,3-bis(2-furanyl)-N-[3-(trifluoromethyl)phenyl]-6-quinoxalinecarboxamide	EC50	10900 nM
1-Pyridin-2-yl-decan-1-one oxime	IC50	11000 nM
N-[5-(4-chlorophenyl)-7-(4-methoxyphenyl)-1,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl]furan-2-carboxamide	IC50	11800 nM
2-(3,5-dimethyl-1-pyrazolyl)-N-(2-methoxyethyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-amine	EC50	13300 nM
2-pyridin-2-yl-3H-benzo[e]benzimidazole	IC50	14400 nM
2-amino-N-cyclopentyl-1-(2-oxolanylmethyl)-3-pyrrolo[3,2-b]quinoxalinecarboxamide	EC50	14700 nM
MLS000541069	IC50	15500 nM
N-(5-ethyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-2-yl)-3,3-diphenylpropanamide	EC50	15600 nM
SMR000012310	IC50	16300 nM
cid_542828	IC50	16700 nM
1-(2-furanylmethyl)-2-imino-N-[(4-methylphenyl)methyl]-5-oxo-3-dipyrido[1,2-d:3’,4’-f]pyrimidinecarboxamide	IC50	17300 nM
2-(4-Bromo-phenyl)-6,7,8,9-tetrahydro-benzo[e]imidazo[1,2-b][1,2,4]triazine	IC50	17400 nM
cid_625142	IC50	17500 nM
2-N,4-N-ditert-butyl-6-hydrazinyl-1,3,5-triazine-2,4-diamine	IC50	17900 nM
SMR000045256	IC50	18500 nM
N-[5-(4-chlorophenyl)-7-phenyl-1,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl]-2-furancarboxamide	IC50	18700 nM
4-{(5-hydroxy-3-methyl-1H-pyrazol-4-yl)[1-(1-naphthylmethyl)-1H-indol-3-yl]methyl}-3-methyl-1H-pyrazol-5-ol	IC50	19300 nM
4-(1-azepanyl)-2-(2-pyridinyl)quinazoline	EC50	19800 nM
SMR000162513	IC50	19900 nM
cid_624478	IC50	20000 nM
SMR000045139	IC50	20000 nM
N-(1-butyl-3-cyano-10-methyl-5-oxo-2-dipyrido[3,4-c:1’,2’-f]pyrimidinylidene)-1,3-benzodioxole-5-carboxamide	IC50	20000 nM
3-phenyl-6-(4,5,6,7-tetrahydro-1-benzothiophen-3-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole	IC50	20000 nM
N-(6-methoxy-1,3-benzothiazol-2-yl)-1-thiophen-2-ylsulfonyl-3-piperidinecarboxamide	IC50	20000 nM

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
monomethylarsonous acid	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression	2
Cisplatin	decreases response to substance, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
selenocystine	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
titanium dioxide	decreases expression	1
potassium nitrate	increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Hydroxyurea	increases response to substance	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
2,4-Dichlorophenoxyacetic Acid	increases expression	1
Cyclosporine	increases expression	1

Cellosaurus cell lines

14 cell lines: 7 cancer cell line, 6 telomerase immortalized cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E3FS	NB1-Tert Artemis clone 1	Telomerase immortalized cell line	Male
CVCL_E3FT	NB1-Tert Artemis clone 2	Telomerase immortalized cell line	Male
CVCL_E3FU	NB1-Tert Artemis clone 3	Telomerase immortalized cell line	Male
CVCL_E3FV	NB1-Tert Artemis clone 4	Telomerase immortalized cell line	Male
CVCL_E3FW	NB1-Tert Artemis clone 5	Telomerase immortalized cell line	Male
CVCL_E3FX	NB1-Tert Artemis clone 6	Telomerase immortalized cell line	Male
CVCL_HE04	NALM-6 DCLRE1C(-/-)	Cancer cell line	Male
CVCL_KT33	HeLa SilenciX Artemis	Cancer cell line	Female
CVCL_SK48	HAP1 DCLRE1C (-) 1	Cancer cell line	Male
CVCL_SK49	HAP1 DCLRE1C (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

46 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	PHASE2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	PHASE2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	PHASE2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	PHASE1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	PHASE1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	PHASE1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	PHASE1/PHASE2	COMPLETED	IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency
NCT00579137	PHASE1/PHASE2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	PHASE1/PHASE2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	PHASE1/PHASE2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	PHASE1/PHASE2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03538899	PHASE1/PHASE2	RECRUITING	Autologous Gene Therapy for Artemis-Deficient SCID
NCT03597594	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)
NCT00001255	Not specified	COMPLETED	Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006335	Not specified	COMPLETED	Influences on Female Adolescents’ Decisions Regarding Testing for Carrier Status of XSCID
NCT00055172	Not specified	RECRUITING	Genetic Basis of Immunodeficiency
NCT00695279	Not specified	COMPLETED	Long Term Follow Up Of Patients Who Have Received Gene Therapy Or Gene Marked Products
NCT00845416	Not specified	COMPLETED	Newborn Screening for Severe Combined Immunodeficiency (SCID) in a High-Risk Population
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01953016	Not specified	COMPLETED	Participation in a Research Registry for Immune Disorders
NCT02231983	Not specified	UNKNOWN	Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China
NCT02590328	Not specified	COMPLETED	Neonatal Screening of Severe Combined Immunodeficiencies
NCT04049084	Not specified	ENROLLING_BY_INVITATION	An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID
NCT04172181	Not specified	UNKNOWN	Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID