NHEJ1

Summary

NHEJ1 (non-homologous end joining factor 1, HGNC:25737) is a protein-coding gene on chromosome 2q35, encoding Non-homologous end-joining factor 1 (Q9H9Q4). 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.

Double-strand breaks in DNA result from genotoxic stresses and are among the most damaging of DNA lesions. This gene encodes a DNA repair factor essential for the nonhomologous end-joining pathway, which preferentially mediates repair of double-stranded breaks. Mutations in this gene cause different kinds of severe combined immunodeficiency disorders.

Source: NCBI Gene 79840 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Cernunnos-XLF deficiency (Definitive, ClinGen)
• GWAS associations: 9
• Clinical variants (ClinVar): 244 total — 26 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 95
• MANE Select transcript: NM_024782

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25737
Approved symbol	NHEJ1
Name	non-homologous end joining factor 1
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	Cernunnos, XLF, FLJ12610
Ensembl gene	ENSG00000187736
Ensembl biotype	protein_coding
OMIM	611290
Entrez	79840

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 14 protein_coding, 6 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000356853, ENST00000409720, ENST00000418099, ENST00000426304, ENST00000450447, ENST00000457600, ENST00000481764, ENST00000483627, ENST00000491159, ENST00000494211, ENST00000698174, ENST00000698175, ENST00000698176, ENST00000698202, ENST00000698203, ENST00000698210, ENST00000881108, ENST00000881109, ENST00000929432, ENST00000929433, ENST00000929434, ENST00000929435, ENST00000929436, ENST00000929437, ENST00000929438, ENST00000941811

RefSeq mRNA: 3 — MANE Select: NM_024782 NM_001377498, NM_001377499, NM_024782

CCDS: CCDS2432, CCDS92945

Canonical transcript exons

ENST00000356853 — 8 exons

Exon	Start	End
ENSE00001781266	219069357	219076455
ENSE00001869065	219160720	219160815
ENSE00003484115	219146680	219146738
ENSE00003525879	219078089	219078206
ENSE00003529426	219157472	219157684
ENSE00003531330	219077246	219077364
ENSE00003661705	219147657	219147795
ENSE00003756107	219158186	219158362

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 92.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4577 / max 40.5868, expressed in 1747 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34021	4.5813	1697
34022	1.3764	959
34020	0.5000	261

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	92.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.45	gold quality
mucosa of transverse colon	UBERON:0004991	89.47	gold quality
kidney epithelium	UBERON:0004819	87.21	silver quality
monocyte	CL:0000576	86.91	gold quality
transverse colon	UBERON:0001157	86.86	gold quality
leukocyte	CL:0000738	86.81	gold quality
gastrocnemius	UBERON:0001388	85.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.42	gold quality
left testis	UBERON:0004533	85.21	gold quality
smooth muscle tissue	UBERON:0001135	85.17	gold quality
muscle of leg	UBERON:0001383	85.13	gold quality
right testis	UBERON:0004534	84.68	gold quality
calcaneal tendon	UBERON:0003701	84.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.32	gold quality
islet of Langerhans	UBERON:0000006	84.05	gold quality
metanephros cortex	UBERON:0010533	83.98	gold quality
testis	UBERON:0000473	83.90	gold quality
small intestine	UBERON:0002108	83.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.71	gold quality
adult mammalian kidney	UBERON:0000082	83.63	gold quality
cortex of kidney	UBERON:0001225	83.54	gold quality
colon	UBERON:0001155	83.22	gold quality
intestine	UBERON:0000160	83.21	gold quality
large intestine	UBERON:0000059	83.00	gold quality
tendon	UBERON:0000043	82.96	gold quality
granulocyte	CL:0000094	82.64	gold quality
left ventricle myocardium	UBERON:0006566	82.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	82.58	gold quality
popliteal artery	UBERON:0002250	82.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting NHEJ1, 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-12118	100.00	65.88	1270
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4761-5P	99.51	66.69	804

Literature-anchored findings (GeneRIF, showing 40)

• Cernunnos-XLF is a new Non-homologous End Joining pathway protein, which if mutated results in several conditions -immunodeficiency and developmental anomalies and other conditions, which likely result from inability to repair spontaneous DNA damage. (PMID:16439204)
• Studies on the binding of XLF and its role in DNA repair. (PMID:16439205)
• The XLF-encoded protein (XRRC4 like factor, FLJ12610) is involved in DNA double-strand break repair via nonhomologous end-joining and associates with the Ligase IV-XRCC4 complex. XLF is mutated in a number of radiosensitive and immuno-deficient patients. (PMID:16439205)
• Cernunnos physically interacts with the XRCC4 x DNA-ligase IV complex (PMID:16571728)
• DNA repair protein involved in lymphocyte activation and cell division. (PMID:16828027)
• Results show that a truncated transcript of NHEJ1 is expressed in the polymicrogyric patient cells, suggesting a potential dominant negative effect possibly leading to a different phenotype. (PMID:17191205)
• mutant protein retained its ability to stimulate XRCC4.DNA ligase IV but failed to translocate to the nucleus, and this appears to be the basis for the non-homologous DNA end joining defect in this patient (PMID:17317666)
• Cernunnos/XRCC4-like factor promotes a mismatched end (MEnd) DNA ligase activity to facilitate joining and to preserve DNA sequence. (PMID:17470781)
• Review focuses on the proteins involved in the NHEJ pathway, the major pathway for repair of DNA double-strand breaks, which can become molecular targets in the treatment of cancer. (PMID:17504121)
• Data shows that an intact XRCC4/ligase IV complex is necessary for Cernunnos-XLF mobilization to damaged chromatin. (PMID:17720816)
• The XLF dimer adopts a similar overall structure to that of the XRCC4 dimer, supporting the contention that these two factors are related in function and have arisen from a common evolutionary ancestor. (PMID:18046455)
• Mutational analysis of XLF and XRCC4 reveals a potential interaction interface, suggesting a mechanism for how XLF stimulates the ligation of mismatched ends. (PMID:18158905)
• REVIEW: Role and regulation of XLF (PMID:18335491)
• The major phosphorylation sites in XLF, serine 245 is phosphorylated by DNA-PK, while serine 251 is phosphorylated by Ataxia-Telangiectasia Mutated (ATM), in vivo. (PMID:18644470)
• Results implicate XLF as a C-NHEJ factor but also indicate that developing mouse lymphocytes harbor cell-type-specific factors/pathways that compensate for the absence of XLF function during V(D)J recombination. (PMID:18775323)
• the heads and coiled-coil regions of Cernunnos and X4 are not interchangeable, and they suggest specific roles for each in NHEJ (PMID:19103754)
• role of Cernunnos/XLF in repair of DSBs and maintenance of genomic stability under replication stress conditions (PMID:19223975)
• Recombinant Cernunnos protein restored gap filling and end joining of partially complementary overhangs, and stimulated joining of cohesive ends more than twentyfold. (PMID:19420065)
• a natural mutator variant of human DNA polymerase lambda promotes chromosomal instability by compromising NHEJ (PMID:19806195)
• identified three amino acids (Arg(64), Leu(65), and Leu(115)) essential for the interaction with X4 and the proper function of Cernunnos (PMID:20558749)
• Patients with NBS-like phenotypes may have mutations in the NHEJ1 gene including multiexon deletions, and show that considerable clinical variability could be observed even within the same family. (PMID:20597108)
• NHEJ in human embryonic stem cells is largely independent of ATM, DNA-PKcs, and PARP but dependent on XRCC4 with repair fidelity several-fold greater than in astrocytes. (PMID:20844317)
• Data show that the heterodimeric domain of Ku was sufficient for the recruitment of XLF to DSBs and for the interaction of Ku with XLF. (PMID:21349273)
• Regulation of Double Strand Break repair by EGFR involves both the NHEJ and HR pathway, and appears to occur in most tumor cell lines regardless of p53 and K-Ras mutation status. (PMID:21665306)
• X-ray structure reveals a filament arrangement for XRCC4(1-157) and Cernunnos(1-224) homodimers mediated by repeated interactions through their N-terminal head domains. (PMID:21768349)
• molecular mechanism for XLF-XRCC4 stimulation of DNA ligation. (PMID:21775435)
• Data show that XLF and XRCC4 dimers interact through their head domains and form an alternating left-handed helical structure with polypeptide coiled coils and pseudo-dyads of individual XLF and XRCC4 dimers at right angles to the helical axis. (PMID:21936820)
• Multiple truncations of the XLF and XRCC4 proteins were cocrystallized, but yielded low-resolution diffraction (~20 A) (PMID:22102241)
• Evidence for how XRCC4-XLF complexes robustly bridge DNA molecules. (PMID:22287571)
• A suggested link between defects in the Cernunnos-dependent nonhomologous end-joining pathway and aberrant class switch recombination or switch translocations during the development of B cell malignancies. (PMID:22312109)
• Cernunnos deficiency results in chronic activation of the DNA damage response, P53-driven upregulation of proapoptotic factors, leading to decreased thymocyte viability and a qualitative alteration of the T cell repertoire in both humans and mice. (PMID:23207905)
• XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair. (Review) (PMID:23442139)
• Data indicate that Ku70/Ku80 facilitates the cooperative binding of multiple XRCC4/Ligase IV (XL) and XLF molecules to DNA. (PMID:23620595)
• An induced pluripotent stem cell (iPSC) model of XLF deficiency, which accurately replicates the double-strand break repair deficiency observed in XLF syndrome patients, is reported. (PMID:23818183)
• Human XLF is a non-essential, but critical, classic non-homologous end-joining -repair factor. (PMID:24461734)
• Werner syndrome protein positively regulates XRCC4-like factor transcription. (PMID:24626809)
• PC4 protects esophageal squamous cell carcinoma cells from IR-induced death by enhancing the nonhomologous end joining-promoting activity of XLF. (PMID:25321468)
• Phosphorylation of XLF impairs non-homologous end-joining DNA repair. (PMID:25661488)
• The data suggest that XLF has multiple functions in DNA repair, and they offer potential explanations for the pleiotropic phenotypes associated with XLF deficiency. (PMID:26100018)
• XLF has an important role during V(D)J recombination. (PMID:27281794)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nhej1	ENSDARG00000058893
mus_musculus	Nhej1	ENSMUSG00000026162
rattus_norvegicus	Nhej1	ENSRNOG00000018162

Protein

Protein identifiers

Non-homologous end-joining factor 1 — Q9H9Q4 (reviewed: Q9H9Q4)

Alternative names: Protein cernunnos, XRCC4-like factor

All UniProt accessions (6): A0A8V8TMZ4, C9JWV4, F8WEB8, G5E9Q8, H7C0G7, Q9H9Q4

UniProt curated annotations — full annotation on UniProt →

Function. 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. Plays a key role in NHEJ by promoting the ligation of various mismatched and non-cohesive ends. Together with PAXX, collaborates with DNA polymerase lambda (POLL) to promote joining of non-cohesive DNA ends. 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. 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. 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. 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. The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors. Binds DNA in a length-dependent manner.

Subunit / interactions. Homodimer; mainly exists as a homodimer when not associated with XRCC4. Interacts with XRCC4; the interaction is direct and is mediated via a head-to-head interaction between N-terminal head regions. Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Additional component of the NHEJ complex includes PAXX. Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Interacts with POLL (DNA polymerase lambda); promoting POLL recruitment to double-strand breaks (DSBs) and stimulation of the end-filling activity of POLL.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated by PRKDC at the C-terminus in response to DNA damage. Phosphorylations by PRKDC at the C-terminus of XRCC4 and NHEJ1/XLF are highly redundant and regulate ability of the XRCC4-NHEJ1/XLF subcomplex to bridge DNA. Phosphorylation does not prevent interaction with XRCC4 but disrupts ability to bridge DNA and promotes detachment from DNA.

Disease relevance. Immunodeficiency 124, severe combined (IMD124) [MIM:611291] A form of severe combined immunodeficiency (SCID), 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 with SCID 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. IMD124 is characterized by a profound T- and B- lymphocytopenia associated with increased cellular sensitivity to ionizing radiation, shortened telomeres and premature senescence of hematopoietic stem cells, microcephaly and growth retardation. Some patients may manifest SCID with sensitivity to ionizing radiation without microcephaly and mild growth retardation, probably due to hypomorphic NHEJ1 variants. The disease is caused by variants affecting the gene represented in this entry. Microphthalmia/coloboma 13 (MCOPCB13) [MIM:620968] A form of colobomatous microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like coloboma, opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). MCOPCB13 is an autosomal recessive form characterized by variable ocular anomalies, even between eyes within the same patient. Patients may also exhibit high myopia, strabismus, nystagmus, and/or retinal pigmentary changes and atrophy. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by a homozygous NHEJ1 intronic variant that disrupts a conserved enhancer of IHH expression (i8), a gene known to be involved in eye development in mice. A chromosomal aberration involving NHEJ1 is found in a patient with polymicrogyria. Translocation t(2;7)(q35;p22).

Domain organisation. The coiled-coil region mediates homodimerization. The Leu-lock (Leu-115) site inserts into a hydrophobic pocket in XRCC4. The XLM motif (also called the KBM motif or KBMX motif) and the interior region of the C-terminal tail preceding the XLM motif are essential for DNA end joining. The sequence of the C-terminal tail is not critical for its role in end joining but it must be sufficiently long to interact with XRCC4 and to stabilize the interaction of XRCC4 with LIG4. A single XLM motif and C-terminal tail is sufficient to promote end joining.

Miscellaneous. Was named ‘Cernunnos’ after the enigmatic Celtic god of hunting, the underworld and fertility.

Similarity. Belongs to the XRCC4-XLF family. XLF subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H9Q4-1	1	yes
Q9H9Q4-2	2

RefSeq proteins (3): NP_001364427, NP_001364428, NP_079058* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015381	XLF-like_N	Domain
IPR038051	XRCC4-like_N_sf	Homologous_superfamily
IPR052287	NHEJ_factor	Family
IPR053829	XLF-like_CC	Domain

Pfam: PF09302, PF21928

UniProt features (92 total): mutagenesis site 48, helix 10, sequence variant 9, modified residue 7, strand 7, region of interest 3, compositionally biased region 2, chain 1, splice variant 1, coiled-coil region 1, short sequence motif 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
2QM4	X-RAY DIFFRACTION	2.3
2R9A	X-RAY DIFFRACTION	2.5
7ZYG	ELECTRON MICROSCOPY	2.68
6ERH	X-RAY DIFFRACTION	2.8
9CQ3	ELECTRON MICROSCOPY	2.8
9N81	ELECTRON MICROSCOPY	2.8
6ERG	X-RAY DIFFRACTION	2.9
9CQ6	ELECTRON MICROSCOPY	3.1
9N83	ELECTRON MICROSCOPY	3.1
9N82	ELECTRON MICROSCOPY	3.3
9CQC	ELECTRON MICROSCOPY	3.4
9IOL	ELECTRON MICROSCOPY	3.46
3RWR	X-RAY DIFFRACTION	3.94
9IAX	ELECTRON MICROSCOPY	3.97
3SR2	X-RAY DIFFRACTION	3.97
7NFC	ELECTRON MICROSCOPY	4.14
7NFE	ELECTRON MICROSCOPY	4.29
8EZA	ELECTRON MICROSCOPY	4.39
8BHV	ELECTRON MICROSCOPY	4.51
7LT3	ELECTRON MICROSCOPY	4.6
8BHY	ELECTRON MICROSCOPY	5.33
3Q4F	X-RAY DIFFRACTION	5.5
8BOT	ELECTRON MICROSCOPY	7.76
7LSY	ELECTRON MICROSCOPY	8.4
3W03	X-RAY DIFFRACTION	8.49
8EZB	ELECTRON MICROSCOPY	8.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H9Q4-F1	82.66	0.66

Functional residue map

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

Catalytic / active sites (1): 115 (leu-lock)

Post-translational modifications (7): 203, 245, 251, 263, 266, 287, 132

Mutagenesis-validated functional residues (48):

Position	Phenotype
11	does not affect ability to participate in v(d)j recombination.
13	does not affect ability to participate in v(d)j recombination.
15	does not affect ability to participate in v(d)j recombination.
24	does not affect ability to participate in v(d)j recombination.
26	abolished ability to participate in v(d)j recombination.
37	does not affect ability to participate in v(d)j recombination.
40	does not affect ability to participate in v(d)j recombination.
41	does not affect ability to participate in v(d)j recombination.
43	does not affect ability to participate in v(d)j recombination.
61	does not affect ability to participate in v(d)j recombination.
64–65	abolished interaction with xrcc4.
64	abolished ability to repair double-strand breaks (dsbs). abolished interaction with xrcc4. abolished ability to particip
64	does not affect ability to participate in v(d)j recombination.
65	abolished ability to repair double-strand breaks (dsbs). abolished ability to participate in v(d)j recombination. decrea
105	does not affect ability to repair double-strand breaks (dsbs). does not affect interaction with xrcc4.
111	does not affect ability to repair double-strand breaks (dsbs). does not affect interaction with xrcc4.
111	does not affect interaction with xrcc4.
115	impaired ability to repair double-strand breaks (dsbs). abolished ability to bridge dna. some studies show lack of inter
115	impaired ability to repair double-strand breaks (dsbs). abolished ability to bridge dna. abolished ability to participat
116	does not affect ability to participate in v(d)j recombination.
117	does not affect ability to participate in v(d)j recombination.
117	abolished ability to participate in v(d)j recombination.
118	does not affect ability to participate in v(d)j recombination.
119	abolished ability to participate in v(d)j recombination.
132	in 6a mutant; abolished phosphorylation; does not affect ability to repair double-strand breaks (dsbs), possibly because

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 325 (showing top): MORF_ITGA2, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_B_CELL_ACTIVATION, GOBP_TELOMERE_ORGANIZATION, MORF_RAD51L3, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, MORF_CTSB, GOBP_IMMUNOGLOBULIN_PRODUCTION, MORF_IL4, MORF_PRKCA, GOBP_DNA_DAMAGE_RESPONSE, GOBP_SOMATIC_DIVERSIFICATION_OF_IMMUNE_RECEPTORS, GOBP_RESPONSE_TO_RADIATION

GO Biological Process (11): telomere maintenance (GO:0000723), double-strand break repair via nonhomologous end joining (GO:0006303), central nervous system development (GO:0007417), response to ionizing radiation (GO:0010212), B cell differentiation (GO:0030183), T cell differentiation (GO:0030217), immunoglobulin V(D)J recombination (GO:0033152), positive regulation of ligase activity (GO:0051351), DNA repair (GO:0006281), double-strand break repair (GO:0006302), DNA damage response (GO:0006974)

GO Molecular Function (4): DNA binding (GO:0003677), DNA end binding (GO:0045027), DNA polymerase binding (GO:0070182), protein binding (GO:0005515)

GO Cellular Component (8): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), DNA-dependent protein kinase-DNA ligase 4 complex (GO:0005958), DNA ligase IV complex (GO:0032807), site of double-strand break (GO:0035861), nonhomologous end joining complex (GO:0070419), chromosome (GO:0005694)

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	2
lymphocyte differentiation	2
cellular anatomical structure	2
nonhomologous end joining complex	2
nuclear protein-containing complex	2
telomere organization	1
double-strand break repair	1
nervous system development	1
system development	1
response to radiation	1
B cell activation	1
T cell activation	1
somatic recombination of immunoglobulin gene segments	1
V(D)J recombination	1
ligase activity	1
positive regulation of catalytic activity	1
DNA damage response	1
DNA repair	1
cellular response to stress	1
nucleic acid binding	1
DNA binding	1
enzyme binding	1
binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
site of DNA damage	1
intracellular protein-containing complex	1
DNA repair complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NHEJ1	LIG4	P49917	999
NHEJ1	XRCC4	Q13426	999
NHEJ1	PRKDC	P78527	997
NHEJ1	PAXX	Q9BUH6	997
NHEJ1	XRCC6	P12956	994
NHEJ1	XRCC5	P13010	987
NHEJ1	DCLRE1C	Q96SD1	924
NHEJ1	APLF	Q8IW19	879
NHEJ1	TP53BP1	Q12888	809
NHEJ1	RBBP8	Q99708	793
NHEJ1	APTX	Q7Z2E3	788
NHEJ1	ATM	Q13315	775
NHEJ1	H2AX	P16104	740
NHEJ1	PNKP	Q96T60	734
NHEJ1	MDC1	Q14676	722

IntAct

21 interactions, top by confidence:

A	B	Type	Score
XRCC4	NHEJ1	psi-mi:“MI:2364”(proximity)	0.870
NHEJ1	XRCC4	psi-mi:“MI:0915”(physical association)	0.870
XRCC4	NHEJ1	psi-mi:“MI:0915”(physical association)	0.870
NHEJ1	XRCC5	psi-mi:“MI:0914”(association)	0.710
NHEJ1	XRCC5	psi-mi:“MI:0915”(physical association)	0.710
NHEJ1	LIG4	psi-mi:“MI:0915”(physical association)	0.690
LIG4	NHEJ1	psi-mi:“MI:0915”(physical association)	0.690
NHEJ1	NHEJ1	psi-mi:“MI:0915”(physical association)	0.400
FOXB1	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
	XRCC6	psi-mi:“MI:0914”(association)	0.350
NHEJ1	H2AX	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (27): NHEJ1 (Synthetic Growth Defect), NHEJ1 (Affinity Capture-MS), NHEJ1 (Affinity Capture-MS), NHEJ1 (Affinity Capture-MS), NHEJ1 (Two-hybrid), XRCC4 (Two-hybrid), NHEJ1 (Affinity Capture-Western), LIG4 (Affinity Capture-Western), NHEJ1 (Affinity Capture-Western), NHEJ1 (Affinity Capture-Western), NHEJ1 (Affinity Capture-Western), NHEJ1 (FRET), XRCC4 (FRET), XRCC4 (Affinity Capture-Western), NHEJ1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8ENT6, A2BGP7, A2CJ06, B1H1W9, F6RRD7, O00124, O55036, P54274, Q1LV50, Q1LWH4, Q1T7B8, Q28HU3, Q3KNJ2, Q3U1D0, Q3US16, Q4KLN8, Q4V832, Q5I0E6, Q5I2W8, Q5NVA9, Q5RA37, Q5RET9, Q5XI46, Q5ZIN2, Q6AYI4, Q6DRL4, Q6IQ49, Q6IRN0, Q6NV18, Q6P1H6, Q7Z2Z1, Q7Z4M0, Q8BJW7, Q8BKT3, Q8BMG1, Q8BMI4, Q8BQ33, Q8IXW5, Q8K1J5, Q8VC34

Diamond homologs: A0A1L8ENT6, Q3KNJ2, Q6AYI4, Q6NV18, Q9H9Q4

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ATM	unknown	NHEJ1	phosphorylation
PRKDC	unknown	NHEJ1	phosphorylation
AKT1	“down-regulates quantity by destabilization”	NHEJ1	phosphorylation
SCF-betaTRCP	“down-regulates quantity by destabilization”	NHEJ1	ubiquitination
NHEJ1	“up-regulates activity”	“Lig4-Xrcc4 complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	13
Uncertain significance	84
Likely benign	77
Benign	29

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1453461	NM_024782.3(NHEJ1):c.670_671del (p.Gln224fs)	Pathogenic
1458287	NM_024782.3(NHEJ1):c.569_570insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCTGTCCTCGTGATACGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGAAAATTCCTTCTT (p.Leu190fs)	Pathogenic
1705616	NM_024782.3(NHEJ1):c.134G>A (p.Trp45Ter)	Pathogenic
2030418	NM_024782.3(NHEJ1):c.94C>T (p.Gln32Ter)	Pathogenic
2122980	NM_024782.3(NHEJ1):c.75_78dup (p.Val27fs)	Pathogenic
2734397	NM_024782.3(NHEJ1):c.526C>T (p.Arg176Ter)	Pathogenic
280838	NM_024782.3(NHEJ1):c.324dup (p.Arg109fs)	Pathogenic
2968501	NM_024782.3(NHEJ1):c.546del (p.Glu182fs)	Pathogenic
3021248	NM_024782.3(NHEJ1):c.75del (p.Lys26fs)	Pathogenic
3247343	NC_000002.11:g.(?220011382)(220011480_?)del	Pathogenic
3336660	NM_024782.3(NHEJ1):c.169C>T (p.Arg57Ter)	Pathogenic
3336661	NM_024782.3(NHEJ1):c.236T>C (p.Leu79Pro)	Pathogenic
3336662	NM_024782.3(NHEJ1):c.233dup (p.Asn78fs)	Pathogenic
3720410	NM_024782.3(NHEJ1):c.501C>A (p.Tyr167Ter)	Pathogenic
418719	NM_024782.3(NHEJ1):c.570_573dup (p.Gln192fs)	Pathogenic
419273	NM_024782.3(NHEJ1):c.530-2A>T	Pathogenic
424561	NM_024782.3(NHEJ1):c.350del (p.Phe117fs)	Pathogenic
4735399	NM_024782.3(NHEJ1):c.31C>T (p.Gln11Ter)	Pathogenic
4766092	NM_024782.3(NHEJ1):c.489_490del (p.Glu163fs)	Pathogenic
536739	NM_024782.3(NHEJ1):c.643C>T (p.Gln215Ter)	Pathogenic
845632	NM_024782.3(NHEJ1):c.369C>A (p.Cys123Ter)	Pathogenic
982	NM_024782.3(NHEJ1):c.367T>C (p.Cys123Arg)	Pathogenic
983	NM_024782.3(NHEJ1):c.532C>T (p.Arg178Ter)	Pathogenic
984	NM_024782.3(NHEJ1):c.177+1_177+3delinsTT	Pathogenic
984380	NC_000002.12:g.219102933_219134970dup	Pathogenic
985	NM_024782.3(NHEJ1):c.11dup (p.Glu5fs)	Pathogenic
1466691	NM_024782.3(NHEJ1):c.530-1G>A	Likely pathogenic
1484040	NM_024782.3(NHEJ1):c.529+1G>A	Likely pathogenic
1809806	NM_024782.3(NHEJ1):c.588+18131A>G	Likely pathogenic
2030417	NM_024782.3(NHEJ1):c.390+1G>A	Likely pathogenic

SpliceAI

1765 predictions. Top by Δscore:

Variant	Effect	Δscore
2:219076454:CC:C	acceptor_gain	1.0000
2:219076455:CC:C	acceptor_gain	1.0000
2:219076456:C:CC	acceptor_gain	1.0000
2:219076456:CT:C	acceptor_loss	1.0000
2:219077240:ACT:A	donor_loss	1.0000
2:219077241:CTC:C	donor_loss	1.0000
2:219077242:TCA:T	donor_loss	1.0000
2:219077242:TCAC:T	donor_loss	1.0000
2:219077243:CA:C	donor_loss	1.0000
2:219077244:A:AC	donor_gain	1.0000
2:219077244:A:C	donor_loss	1.0000
2:219077245:C:CC	donor_gain	1.0000
2:219077362:CTC:C	acceptor_gain	1.0000
2:219077363:TC:T	acceptor_gain	1.0000
2:219077363:TCC:T	acceptor_loss	1.0000
2:219077364:CC:C	acceptor_gain	1.0000
2:219077365:C:A	acceptor_loss	1.0000
2:219077365:C:CC	acceptor_gain	1.0000
2:219077365:C:CG	acceptor_loss	1.0000
2:219077366:T:C	acceptor_loss	1.0000
2:219077372:C:CT	acceptor_gain	1.0000
2:219077373:A:T	acceptor_gain	1.0000
2:219078087:A:AC	donor_gain	1.0000
2:219078088:C:CC	donor_gain	1.0000
2:219078115:TGG:T	donor_gain	1.0000
2:219078202:AGTTT:A	acceptor_gain	1.0000
2:219078203:GTTT:G	acceptor_gain	1.0000
2:219078204:TTT:T	acceptor_gain	1.0000
2:219078205:TT:T	acceptor_gain	1.0000
2:219078206:TCTG:T	acceptor_loss	1.0000

AlphaMissense

1947 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:219157507:A:G	W119R	0.992
2:219157507:A:T	W119R	0.992
2:219158326:A:G	W13R	0.991
2:219158326:A:T	W13R	0.991
2:219147707:T:A	K160I	0.981
2:219147706:T:A	K160N	0.980
2:219147706:T:G	K160N	0.980
2:219157676:G:C	N62K	0.980
2:219157676:G:T	N62K	0.980
2:219158193:C:G	R57P	0.980
2:219158324:C:A	W13C	0.979
2:219158324:C:G	W13C	0.979
2:219147757:A:C	S143R	0.978
2:219147757:A:T	S143R	0.978
2:219147759:T:G	S143R	0.978
2:219078133:A:T	V221D	0.975
2:219157500:A:G	F121S	0.975
2:219158285:C:A	K26N	0.975
2:219158285:C:G	K26N	0.975
2:219146716:A:C	F184L	0.972
2:219146716:A:T	F184L	0.972
2:219146718:A:G	F184L	0.972
2:219158202:A:T	V54D	0.972
2:219157505:C:A	W119C	0.969
2:219157505:C:G	W119C	0.969
2:219157512:A:G	F117S	0.969
2:219158191:C:G	A58P	0.968
2:219157532:A:C	S110R	0.967
2:219157532:A:T	S110R	0.967
2:219157534:T:G	S110R	0.967

dbSNP variants (sampled 300 via entrez): RS1000036236 (2:219161146 C>T), RS1000060614 (2:219125789 C>T), RS1000119008 (2:219159935 G>C), RS1000120795 (2:219072736 C>A,T), RS1000124953 (2:219081216 C>T), RS1000158890 (2:219145715 C>T), RS1000183463 (2:219155139 C>T), RS1000210163 (2:219111597 A>C,G), RS1000215900 (2:219155386 G>C), RS1000273285 (2:219104486 C>T), RS1000283917 (2:219152734 T>C), RS1000298178 (2:219094311 T>A,C), RS1000304347 (2:219104190 T>C), RS1000318000 (2:219107370 G>A), RS1000323513 (2:219073786 G>A)

Disease associations

OMIM: gene MIM:611290 | disease phenotypes: MIM:611291, MIM:620968, MIM:185900

GenCC curated gene-disease

Disease	Classification	Inheritance
Cernunnos-XLF deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Cernunnos-XLF deficiency	Definitive	AR

Mondo (5): Cernunnos-XLF deficiency (MONDO:0012650), isolated anophthalmia-microphthalmia syndrome (MONDO:0016764), microphthalmia/coloboma 13 (MONDO:0975809), syndactyly type 1 (MONDO:0008512), severe combined immunodeficiency (MONDO:0015974)

Orphanet (4): Cernunnos-XLF deficiency (Orphanet:169079), Isolated microphthalmia-anophthalmia-coloboma (Orphanet:2542), Syndactyly type 1 (Orphanet:93402), Severe combined immunodeficiency (Orphanet:183660)

HPO phenotypes

95 total (30 of 95 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000246	Sinusitis
HP:0000252	Microcephaly
HP:0000320	Bird-like facies
HP:0000340	Sloping forehead
HP:0000414	Bulbous nose
HP:0000444	Convex nasal ridge
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000508	Ptosis
HP:0000528	Anophthalmia
HP:0000533	Chorioretinal atrophy
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000565	Esotropia
HP:0000568	Microphthalmia
HP:0000588	Optic disc coloboma
HP:0000589	Coloboma
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0001105	Retinal atrophy
HP:0001263	Global developmental delay
HP:0001433	Hepatosplenomegaly
HP:0001488	Bilateral ptosis
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001744	Splenomegaly

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002647_82	Height	5.000000e-17
GCST002702_35	Height	1.000000e-23
GCST008839_512	Height	2.000000e-45
GCST010313_7	Serum polyunsaturated fatty acid concentration x sex interaction in metabolic syndrome	9.000000e-06
GCST010653_64	Thyroid stimulating hormone levels	7.000000e-09
GCST012226_195	Waist circumference adjusted for body mass index	5.000000e-08
GCST012226_197	Waist circumference adjusted for body mass index	2.000000e-10
GCST90000025_874	Appendicular lean mass	4.000000e-15
GCST90020028_715	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007761	docosahexaenoic acid measurement
EFO:0008343	sex interaction measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

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
C566970	Severe Combined Immunodeficiency with Microcephaly, Growth Retardation, and Sensitivity to Ionizing Radiation (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects binding, increases reaction, decreases expression (+1 more)	3
Valproic Acid	affects expression, decreases expression	3
bisphenol A	affects cotreatment, increases methylation, increases expression, increases reaction	2
Benzo(a)pyrene	affects methylation, decreases expression	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
beta-lapachone	decreases expression	1
nickel chloride	affects expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Melatonin	increases expression, increases reaction	1
T-2 Toxin	increases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

10 cell lines: 5 cancer cell line, 3 finite cell line, 1 telomerase immortalized cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_8087	2BN	Finite cell line	Female
CVCL_8088	2BNneo	Finite cell line	Female
CVCL_8089	2BNhTERT	Telomerase immortalized cell line	Female
CVCL_HD85	HCT 116 NHEJ1(+/-)	Cancer cell line	Male
CVCL_HD86	HCT 116 NHEJ1(-/-)	Cancer cell line	Male
CVCL_KU24	HeLa SilenciX XLF	Cancer cell line	Female
CVCL_TA72	HAP1 NHEJ1 (-) 1	Cancer cell line	Male
CVCL_TA73	HAP1 NHEJ1 (-) 2	Cancer cell line	Male
CVCL_WX38	F07/402	Finite cell line	Male
CVCL_WX39	F07/402-iPSC	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

44 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
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
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
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
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
NCT04246840	Not specified	COMPLETED	Study Through Imaging of Visceral Lymphoid Organs in Patients With SCID Who Have Recieved Bone Marrow Allograft
NCT04331483	Not specified	WITHDRAWN	A Study to Assess a Physical Activity Program in Children, Adolescents and Young Adults Requiring Hematopoietic Stem Cell Allografts