CD3D

Summary

CD3D (CD3 delta subunit of T-cell receptor complex, HGNC:1673) is a protein-coding gene on chromosome 11q23.3, encoding T-cell surface glycoprotein CD3 delta chain (P04234). Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response.

The protein encoded by this gene is part of the T-cell receptor/CD3 complex (TCR/CD3 complex) and is involved in T-cell development and signal transduction. The encoded membrane protein represents the delta subunit of the CD3 complex, and along with four other CD3 subunits, binds either TCR alpha/beta or TCR gamma/delta to form the TCR/CD3 complex on the surface of T-cells. Defects in this gene are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (SCIDBNK). Two transcript variants encoding different isoforms have been found for this gene. Other variants may also exist, but the full-length natures of their transcripts has yet to be defined.

Source: NCBI Gene 915 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 19 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 232 total — 11 pathogenic, 5 likely-pathogenic
• GTEx eGene: eQTL in 3 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 33
• Drug target: yes — 16 via a complex or family
• Approved drugs acting on a complex or family including it: 10 — Blinatumomab, Catumaxomab, Elranatamab, +7 more (T cell surface glycoprotein CD3)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.32 (unconstrained)
• MANE Select transcript: NM_000732
• Interaction hub: 2,972 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1673
Approved symbol	CD3D
Name	CD3 delta subunit of T-cell receptor complex
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	CD3DELTA, CD3-DELTA
Ensembl gene	ENSG00000167286
Ensembl biotype	protein_coding
OMIM	186790
Entrez	915

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 4 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000300692

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3

ENST00000300692, ENST00000392884, ENST00000526561, ENST00000529594, ENST00000534687, ENST00000695666, ENST00000695667, ENST00000695668, ENST00001102243, ENST00001102244, ENST00001140190

RefSeq mRNA: 2 — MANE Select: NM_000732 NM_000732, NM_001040651

CCDS: CCDS41724, CCDS8394

Canonical transcript exons

ENST00000300692 — 5 exons

Exon	Start	End
ENSE00001111779	118339775	118339906
ENSE00002189483	118339075	118339227
ENSE00003619361	118339451	118339494
ENSE00003964668	118340375	118340593
ENSE00004796421	118342553	118342705

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 99.39.

FANTOM5 (CAGE): breadth broad, TPM avg 18.6406 / max 1352.3661, expressed in 289 samples.

Highest expression (Bgee): thymus, granulocyte, lymph node, vermiform appendix, blood.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CD3D is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 3 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

4 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Caudate basal ganglia	eqtl	1.3e-02	+0.36	11:117472677:G:A
Skin Sun Exposed Lower leg	sqtl	2.1e-02	-0.26	11:118035991:G:A
Pancreas	eqtl	2.6e-02	+1.06	11:118870939:C:G
Cells EBV-transformed lymphocytes	eqtl	3.4e-02	+0.50	11:119124615:T:C

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
122601	8.0280	196
122600	5.8575	224
122602	4.1248	139
206460	0.2873	102
122604	0.2490	64
122603	0.0941	38

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	99.39	gold quality
granulocyte	CL:0000094	98.67	gold quality
lymph node	UBERON:0000029	97.71	gold quality
vermiform appendix	UBERON:0001154	96.45	gold quality
blood	UBERON:0000178	95.33	gold quality
spleen	UBERON:0002106	93.94	gold quality
epithelium of nasopharynx	UBERON:0001951	93.55	gold quality
caecum	UBERON:0001153	93.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.15	gold quality
ileal mucosa	UBERON:0000331	90.83	gold quality
bone marrow	UBERON:0002371	90.64	gold quality
superficial temporal artery	UBERON:0001614	89.71	gold quality
bone marrow cell	CL:0002092	89.48	gold quality
tonsil	UBERON:0002372	89.01	gold quality
rectum	UBERON:0001052	88.72	gold quality
jejunal mucosa	UBERON:0000399	88.61	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.62	gold quality
gall bladder	UBERON:0002110	86.89	gold quality
mucosa of transverse colon	UBERON:0004991	86.78	gold quality
palpebral conjunctiva	UBERON:0001812	86.40	gold quality
colonic epithelium	UBERON:0000397	85.91	gold quality
small intestine	UBERON:0002108	85.83	gold quality
periodontal ligament	UBERON:0008266	85.69	gold quality
duodenum	UBERON:0002114	84.55	gold quality
amniotic fluid	UBERON:0000173	84.37	gold quality
nasal cavity epithelium	UBERON:0005384	84.17	gold quality
buccal mucosa cell	CL:0002336	83.30	gold quality
trabecular bone tissue	UBERON:0002483	82.80	gold quality
pylorus	UBERON:0001166	82.56	gold quality
oral cavity	UBERON:0000167	82.03	gold quality
jejunum	UBERON:0002115	81.12	gold quality
colonic mucosa	UBERON:0000317	80.93	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.68	gold quality
nasal cavity mucosa	UBERON:0001826	79.64	gold quality
cervix epithelium	UBERON:0004801	79.41	gold quality
upper lobe of left lung	UBERON:0008952	78.93	gold quality
mammalian vulva	UBERON:0000997	78.46	gold quality
upper lobe of lung	UBERON:0008948	78.10	gold quality
decidua	UBERON:0002450	77.85	gold quality
trachea	UBERON:0003126	77.59	gold quality
calcaneal tendon	UBERON:0003701	77.49	gold quality
bronchus	UBERON:0002185	77.31	gold quality
epithelium of bronchus	UBERON:0002031	77.11	gold quality
parietal pleura	UBERON:0002400	76.91	gold quality
lung	UBERON:0002048	76.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	76.40	silver quality
urinary bladder	UBERON:0001255	76.28	gold quality
intestine	UBERON:0000160	76.23	gold quality
cardia of stomach	UBERON:0001162	76.18	gold quality
mammary duct	UBERON:0001765	76.00	gold quality
pleura	UBERON:0000977	75.99	gold quality
body of stomach	UBERON:0001161	75.93	gold quality
transverse colon	UBERON:0001157	75.92	gold quality
fundus of stomach	UBERON:0001160	75.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.83	gold quality
cervix squamous epithelium	UBERON:0006922	75.80	silver quality
epithelium of mammary gland	UBERON:0003244	75.61	gold quality
right uterine tube	UBERON:0001302	75.46	gold quality
bronchial epithelial cell	CL:0002328	75.35	gold quality
esophagus squamous epithelium	UBERON:0006920	74.76	gold quality
stomach	UBERON:0000945	74.65	gold quality
epithelial cell of pancreas	CL:0000083	74.60	silver quality
right coronary artery	UBERON:0001625	74.52	gold quality
oviduct epithelium	UBERON:0004804	74.46	gold quality
superior surface of tongue	UBERON:0007371	74.42	gold quality
peritoneum	UBERON:0002358	74.16	gold quality
omental fat pad	UBERON:0010414	74.16	gold quality
epithelium of esophagus	UBERON:0001976	74.14	silver quality
adipose tissue of abdominal region	UBERON:0007808	74.08	gold quality
mucosa of paranasal sinus	UBERON:0005030	73.98	silver quality
lower esophagus mucosa	UBERON:0035834	73.87	gold quality
right lung	UBERON:0002167	73.76	gold quality
mucosa of urinary bladder	UBERON:0001259	73.51	gold quality
pharyngeal mucosa	UBERON:0000355	73.49	gold quality
large intestine	UBERON:0000059	73.46	gold quality
triceps brachii	UBERON:0001509	73.44	gold quality
smooth muscle tissue	UBERON:0001135	73.29	gold quality
squamous epithelium	UBERON:0006914	73.25	silver quality
vena cava	UBERON:0004087	73.06	silver quality
skin of hip	UBERON:0001554	73.02	gold quality
fallopian tube	UBERON:0003889	72.98	gold quality
biceps brachii	UBERON:0001507	72.88	silver quality
gluteal muscle	UBERON:0002000	72.79	gold quality
visceral pleura	UBERON:0002401	72.79	gold quality
colon	UBERON:0001155	72.75	gold quality
tendon	UBERON:0000043	72.72	gold quality
esophagus mucosa	UBERON:0002469	72.68	gold quality
upper leg skin	UBERON:0004262	72.48	gold quality
vagina	UBERON:0000996	72.32	gold quality
gingiva	UBERON:0001828	72.15	silver quality
thoracic mammary gland	UBERON:0005200	71.84	gold quality
mammary gland	UBERON:0001911	71.82	gold quality
penis	UBERON:0000989	71.77	gold quality
nipple	UBERON:0002030	71.62	gold quality
uterine cervix	UBERON:0000002	71.42	gold quality
liver	UBERON:0002107	71.16	gold quality
endothelial cell	CL:0000115	71.06	silver quality
tongue	UBERON:0001723	70.81	gold quality
gingival epithelium	UBERON:0001949	70.65	silver quality
lower lobe of lung	UBERON:0008949	70.51	silver quality

Single-cell (SCXA)

Detected in 47 experiment(s), a significant marker in 38.

Experiment	Marker?	Max mean expression
E-GEOD-139324	yes	2905.58
E-MTAB-8410	yes	2084.80
E-GEOD-111727	yes	1958.14
E-MTAB-6653	yes	1727.63
E-HCAD-1	yes	1612.25
E-MTAB-6308	yes	1323.92
E-MTAB-9906	yes	1318.37
E-HCAD-15	yes	1262.78
E-MTAB-8322	yes	1241.33
E-MTAB-8221	yes	1201.05
E-HCAD-4	yes	1163.17
E-CURD-46	yes	1128.20
E-MTAB-10042	yes	1108.02
E-HCAD-36	yes	1075.20
E-CURD-122	yes	1061.87

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 72 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	809.4	medium
Lymph node	tissue	184.8	not detected
Tonsil	tissue	139.6	medium
Appendix	tissue	63.9	not detected
Spleen	tissue	50.5	not detected
Bone marrow	tissue	24.6	not detected
Urinary bladder	tissue	23.6	not detected
Small intestine	tissue	23.4	low
Stomach 1	tissue	20.7	low
Rectum	tissue	18.2	not detected
Lung	tissue	17.9	not detected
Duodenum	tissue	17.8	not detected
Colon	tissue	15.9	not detected
Gallbladder	tissue	13.1	not detected
Breast	tissue	8.6	not detected
Salivary gland	tissue	6.9	not detected
Olfactory bulb	tissue	6.9
Liver	tissue	6.8	not detected
Esophagus	tissue	6.3	not detected
Cerebral cortex	tissue	5.6	not detected
Occipital cortex	tissue	5.6
Cerebellum	tissue	5.4	not detected
Insular cortex	tissue	5.4
Epididymis	tissue	5.1	not detected
Prostate	tissue	5.0	not detected
Temporal cortex	tissue	5.0
Cervix	tissue	4.9	not detected
Retrosplenial cortex	tissue	4.9
Amygdala	tissue	4.8
Corpus callosum	tissue	4.8
Retrosplenial and cingulate cortex	tissue	4.8
Basal ganglia	tissue	4.7	not detected
Hippocampal formation	tissue	4.6
Entorhinal cortex	tissue	4.6
Prefrontal cortex	tissue	4.5
Vagina	tissue	4.4	not detected
Spinal cord	tissue	4.4
Somatosensory cortex	tissue	4.3
Periaqueductal gray	tissue	4.2
Ventral forebrain	tissue	4.1
Motor cortex	tissue	3.9
Fallopian tube	tissue	3.9	not detected
Septum	tissue	3.9
Putamen	tissue	3.8
Substantia nigra	tissue	3.8
Medulla oblongata	tissue	3.7
Hypothalamus	tissue	3.7
Adipose tissue	tissue	3.6	not detected
Smooth muscle	tissue	3.2	not detected
Thalamus	tissue	3.2
Skin 1	tissue	3.1	not detected
Midbrain	tissue	3.1
Superior colliculi	tissue	3.0
Heart muscle	tissue	2.9	not detected
Endometrium 1	tissue	2.9	not detected
Seminal vesicle	tissue	2.8	not detected
Adrenal gland	tissue	2.8	not detected
Pons	tissue	2.7
Ovary	tissue	2.5	not detected
Thyroid gland	tissue	2.5	not detected

Brain sub-regions (HPA Brain Atlas): detected in 114; highest nTPM — White matter (4.8), Dorsal spinal cord (4.4), Ventral hippocampus (4.2), Subiculum (3.9), Ventral spinal cord (3.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, ELF1, ELF2, ETS1, IKZF1, YY1

Functional genomics

gnomAD constraint: pLI 1.94e-07, LOEUF 1.32, missense Z 0.449 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000300692 — one region, missense o/e 0.97. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 30)

• CD3 epsilon undergoes a conformational change after dimerization with CD3 gamma or CD3 delta (PMID:12410792)
• defect in CD3delta gene in severe combined immunodeficiency is characterized by the absence of T cells but normal B cells (PMID:14602880)
• crystal structure at 1.9-A resolution of a complex between a CD3-epsilon/delta ectodomain heterodimer and a single-chain fragment of the UCHT1 antibody (PMID:15534202)
• SCID is caused by a CD3D deficiency. (PMID:15546002)
• a single, membrane-distal YxxO motif in CD3delta could mediate approximately 75% of receptor internalization, whereas its removal only reduced internalization by approximately 20% (PMID:15778375)
• A human CD3 transgene that encodes full length CD3delta and a truncated but functional form of CD3epsilon restored the defective preTCR function in not only CD3epsilon- but CD3gamma- and CD3gammadelta-deficient mice as well. (PMID:16412509)
• CD3delta and CD3gamma play a different role in humans and mice in pre-TCR and TCR function during alphabeta T-cell development (PMID:16888097)
• analysis of TCRalpha-CD3deltaepsilon and TCRbeta-CD3gammaepsilon dimers and the role of the membrane-proximal tetracysteine motif (PMID:17023417)
• The CD3 delta immune recognition receptor cytoplasmic domain binds to acidic and mixed phospholipid vesicles with a binding strength that correlates with the protein net charge and the presence of clustered basic amino acid residues. (PMID:17176095)
• In CD3gamma-deficient patients there can be substitution of CD3gamma by the CD3delta chain and which can then support gammadelta T cell development. (PMID:17923503)
• Enumeration of NK cells and of T lymphocytes expressing TCR alpha/beta in human body effusions is not helpful in attempting to distinguish between benign and malignant effusions. (PMID:18803280)
• Stage-dependent molecular changes in Notch signaling that are critical for normal human T-cell development. (PMID:19056690)
• Data show CD3 epsilon pairs with CD3 gamma or with CD3 delta, forming CD3 epsilon gamma and CD3 epsilon delta heterodimers, which provide insight into our understanding of the molecular assembly of the CD3 molecular complex. (PMID:19724882)
• When compared with other human T cell subsets, T cell receptor/CD3-activated Vgamma9Vdelta2-expressing T cells display an unusually delayed and sustained intracellular calcium mobilization, dramatically quickened and shortened on costimulation by NKG2D. (PMID:20511557)
• Protein sequence comparison indicates that the CD3elta and CD3gamma subunits evolved with highly homologous heterodimeric interfaces and membrane proximal segments for efficient and specific signaling transfer when paired with CD3epsilon. (PMID:20660709)
• Data show that the expression pattern of the four CD3 chains was epsilon>zeta>delta>gamma in peripheral blood mononuclear cells from MM, while a gamma>epsilon>zeta>delta expression pattern was found in healthy controls. (PMID:21669053)
• Study characterized the expression pattern of CD3-gamma, -delta, -epsilon and -zeta chain genes from placenta, which contributes to further understanding of the features of T-cell immune status in placenta. (PMID:21669059)
• A combination of trastuzumab antibody and phosphoantigen-stimulated gammadelta T-lymphocytes increases the efficacy of trastuzumab alone against HER-2-positive breast carcinoma cell lines in vivo and mammary carcinoma xenografts in mice. (PMID:21670311)
• report 2 unrelated cases of SCID with a selective block in alphabeta but not in gammadelta T cell development, associated with a new splicing mutation in the CD3D gene (PMID:21926461)
• A transgenic T cell receptor gammadelta-low expressing subset of T cells accumulates in mouse ear keratinocytes after IL-23 injections. (PMID:21984702)
• Altered expression of the TCR signaling related genes CD3 and FcepsilonRIgamma in patients with aplastic anemia. (PMID:22401598)
• The surface TCR expression of primary alphabeta and gammadelta T cells from healthy donors carrying a single null or leaky mutation in CD3G (gamma+/-) or CD3D (delta+/-, delta+/leaky) with that of normal controls, were compared. (PMID:23336327)
• Two cases of SCID with CD3delta gene mutation in Mexican Mennonite infants are described. (PMID:24288697)
• analysis of the molecular organization of the TCR-CD3 complex (PMID:25422432)
• The docking site for CD3 subunits on the T Cell receptor beta chain has been identified by solution NMR. (PMID:26109064)
• A FOXP3(+)CD3(+)CD56(+)-expressed T-cell population with immunosuppressive function and reduced patient survival has been identified in cancer tissues of human hepatocellular carcinoma. (PMID:26437631)
• PCR and transcriptome analysis suggest that the genes CD3D and PKRCQ together can be used as a model for differentiating between B-cell and T-cell acute lymphoblastic leukemia. (PMID:27494091)
• we demonstrate that the incorporation of a 2A self-processing peptide derived from foot-and-mouth disease virus conveying co-translational cleavage into a two-chain anti-CD3 x anti-CEA diabody gene enables near-equimolar expression of diabody chains 1 and 2, and thus increases the final amount of assembled diabody. (PMID:28075428)
• Comprehensive analysis reveals a prognostic and therapeutic biomarker CD3D in the breast carcinoma microenvironment. (PMID:33350431)
• Hypomethylation of CD3D promoter induces immune cell infiltration and supports malignant phenotypes in uveal melanoma. (PMID:37651092)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd3d	ENSMUSG00000032094
rattus_norvegicus	Cd3d	ENSRNOG00000015994

Paralogs (2): CD3G (ENSG00000160654), CD3E (ENSG00000198851)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88331) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
arrested T cell differentiation	1
decreased CD4-positive, alpha-beta T cell number	1
decreased CD8-positive, alpha-beta T cell number	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q95LI8	94.2%	Diamond
Ovis aries	P18439	87.7%	Diamond
Bos taurus	Q28074	87.7%	Diamond
Sus scrofa	Q5PXD3	72.9%	Diamond
Gallus gallus	Q98910	42.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TTC36-AS1	ncRNA	101929089
ATP5MG	protein-coding	10632
TTC36	protein-coding	143941
KMT2A	protein-coding	4297
CD3G	protein-coding	917
UBE4A	protein-coding	9354
JAML	protein-coding	120425
MPZL3	protein-coding	196264
CD3E	protein-coding	916
MPZL2	protein-coding	10205

Protein

Protein identifiers

T-cell surface glycoprotein CD3 delta chain — P04234 (reviewed: P04234)

Alternative names: T-cell receptor T3 delta chain

All UniProt accessions (3): B0YIY4, E9PMT5, P04234

UniProt curated annotations — full annotation on UniProt →

Function. Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD247/CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways. In addition of this role of signal transduction in T-cell activation, CD3D plays an essential role in thymocyte differentiation. Indeed, participates in correct intracellular TCR-CD3 complex assembly and surface expression. In absence of a functional TCR-CD3 complex, thymocytes are unable to differentiate properly. Interacts with CD4 and CD8 and thus serves to establish a functional link between the TCR and coreceptors CD4 and CD8, which is needed for activation and positive selection of CD4 or CD8 T-cells.

Subunit / interactions. The TCR-CD3 complex is composed of a CD3D-CD3E and a CD3G-CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha-CD3E-CD3G and TCRbeta/CD3G-CD3E trimers. In turn, the hexamer interacts with CD247/CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta. Interacts with coreceptors CD4 and CD8.

Subcellular location. Cell membrane.

Tissue specificity. CD3D is mostly present on T-lymphocytes with its TCR-CD3 partners. Present also in fetal NK-cells.

Post-translational modifications. Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8.

Disease relevance. Immunodeficiency 19, severe combined (IMD19) [MIM:615617] An autosomal recessive form of severe combined immunodeficiency characterized by onset in early infancy of recurrent bacterial, viral, and fungal infections. Patients usually have chronic diarrhea, recurrent respiratory infections, and failure to thrive. Immunologic work-up shows a T-cell negative, B-cell positive, NK-cell positive phenotype. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
P04234-1	1	yes
P04234-2	2

RefSeq proteins (2): NP_000723, NP_001035741 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003110	Phos_immunorcpt_sig_ITAM	Repeat
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015484	CD3_esu/gsu/dsu	Family
IPR032052	Ig_4	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF02189, PF16680

UniProt features (27 total): strand 9, helix 5, topological domain 2, modified residue 2, glycosylation site 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1, sequence variant 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

showing 30 of 31 structures by resolution:

PDB	Title	Method	Resolution (Å)
1XIW	Crystal structure of human CD3-e/d dimer in complex with a UCHT1 single-chain antibody …	X-RAY DIFFRACTION	1.9
8ES8	CryoEM structure of PN45545 TCR-CD3 in complex with HLA-A2 MAGEA4 (230-239)	ELECTRON MICROSCOPY	2.65
7FJE	Cryo-EM structure of a membrane protein(LL)	ELECTRON MICROSCOPY	3
9CI8	T cell receptor complex	ELECTRON MICROSCOPY	3.01
8ES7	CryoEM structure of PN45545 TCR-CD3 complex	ELECTRON MICROSCOPY	3.04
7PHR	Structure of a fully assembled T-cell receptor engaging a tumor-associated peptide-MHC I	ELECTRON MICROSCOPY	3.08
9JY1	delta epsilon/delta epsilon Fab-TCR tetramer	ELECTRON MICROSCOPY	3.08
7FJF	Cryo-EM structure of a membrane protein(CS)	ELECTRON MICROSCOPY	3.1
8TW6	TCR in nanodisc ND-II	ELECTRON MICROSCOPY	3.1
9IRU	Cryo-em structure of TCR-4B1 complex	ELECTRON MICROSCOPY	3.14
9IRS	Cryo-EM structure of the TCR-OKT3 complex	ELECTRON MICROSCOPY	3.18
7FJD	Cryo-EM structure of a membrane protein(WT)	ELECTRON MICROSCOPY	3.2
9JY2	Fab-CD3-delta epsilon-TCR complex	ELECTRON MICROSCOPY	3.24
8ES9	CryoEM structure of PN45428 TCR-CD3 in complex with HLA-A2 MAGEA4	ELECTRON MICROSCOPY	3.25
9CQ4	G115 gamma delta TCR/CD3 complex bound by OKT3 Fab	ELECTRON MICROSCOPY	3.27
9JY4	gamma epsilon/gamma epsilon Fab-TCR tetramer	ELECTRON MICROSCOPY	3.29
8TW4	TCR in nanodisc ND-I	ELECTRON MICROSCOPY	3.3
9BBC	TCR GDN detergent micelle	ELECTRON MICROSCOPY	3.3
9JXZ	V gamma9 V delta2 TCR and CD3 complex	ELECTRON MICROSCOPY	3.31
9JY3	delta epsilon/gamma epsilon Fab-TCR tetramer	ELECTRON MICROSCOPY	3.35
9CIA	T cell receptor complex	ELECTRON MICROSCOPY	3.39
8JC0	V gamma9 V delta2 TCR and CD3 complex in LMNG	ELECTRON MICROSCOPY	3.4
8ZA6	Cryo-EM structure of the gdTCR-CD3 complex	ELECTRON MICROSCOPY	3.43
9C3E	TCR - CD3 complex bound to HLA	ELECTRON MICROSCOPY	3.5
9JY0	Fab-CD3-gamma epsilon-TCR complex	ELECTRON MICROSCOPY	3.69
6JXR	Structure of human T cell receptor-CD3 complex	ELECTRON MICROSCOPY	3.7
8WY0	T cell receptor delta 2 gamma 9 with F283A, F290A, and F291A	ELECTRON MICROSCOPY	3.8
8WYI	T cell receptor delta 2 gamma 9 with TCRD TM domain chimera of TRAC	ELECTRON MICROSCOPY	3.9
8WXE	Vgamma5Vdelta1 EH TCR-CD3 complex	ELECTRON MICROSCOPY	4
8YC0	T cell receptor V delta2 V gamma9 in GDN	ELECTRON MICROSCOPY	4.12

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04234-F1	77.57	0.39

Antibody-complex structures (SAbDab)

7 antibodies co-crystallized with this protein: 1XIW, 9CIA, 9CQ4, 9JY0, 9JY1, 9JY2, BLONTUVETMAB

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, FDA approved drug targets, Biotech drugs, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): endoplasmic reticulum; vesicles

Antibody reliability (HPA): IH enhanced · IF uncertain

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 (2)

Type	Positions
Phosphotyrosine	149, 160

Disulfide bonds (1)

Type	Positions
Disulfide bond	37–73

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	38, 74

Function

Pathways and Gene Ontology

Reactome pathways

8 curated (TAS) of 14; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

14 pathways:

ID	Pathway	Evidence
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-389948	Co-inhibition by PD-1	curated
R-HSA-202424	Downstream TCR signaling	curated
R-HSA-202433	Generation of second messenger molecules	curated
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	curated
R-HSA-202427	Phosphorylation of CD3 and TCR zeta chains	curated
R-HSA-202430	Translocation of ZAP-70 to Immunological synapse	curated
R-HSA-1280218	Adaptive Immune System	—
R-HSA-168256	Immune System	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-388841	Regulation of T cell activation by CD28 family	—
R-HSA-202403	TCR signaling	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 363 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, WALLACE_PROSTATE_CANCER_RACE_UP, MODULE_169, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, BIOCARTA_TCRA_PATHWAY, GOBP_THYMIC_T_CELL_SELECTION, MODULE_45, MODULE_64, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, REACTOME_MEMBRANE_TRAFFICKING, WIELAND_UP_BY_HBV_INFECTION, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP, MODULE_118

GO Biological Process (6): adaptive immune response (GO:0002250), cell surface receptor signaling pathway (GO:0007166), positive thymic T cell selection (GO:0045059), alpha-beta T cell activation (GO:0046631), T cell receptor signaling pathway (GO:0050852), immune system process (GO:0002376)

GO Molecular Function (4): transmembrane signaling receptor activity (GO:0004888), identical protein binding (GO:0042802), protein binding (GO:0005515), MHC class II receptor activity (GO:0032395)

GO Cellular Component (7): cytoplasm (GO:0005737), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), clathrin-coated endocytic vesicle membrane (GO:0030669), T cell receptor complex (GO:0042101), alpha-beta T cell receptor complex (GO:0042105), membrane (GO:0016020)

Reactome top-level categories

7 top-level categories:

Category	Pathways
TCR signaling	4
Adaptive Immune System	3
Regulation of T cell activation by CD28 family	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Immune System	1
Vesicle-mediated transport	1

GO top-level categories

25 GO namespaces:

Category	Terms
cellular anatomical structure	2
immune response	1
signal transduction	1
positive T cell selection	1
thymic T cell selection	1
T cell activation	1
antigen receptor-mediated signaling pathway	1
biological_process	1
signaling receptor activity	1
protein binding	1
binding	1
transmembrane signaling receptor activity	1
MHC class II protein binding	1
immune receptor activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
clathrin-coated vesicle membrane	1
endocytic vesicle membrane	1
clathrin-coated endocytic vesicle	1
plasma membrane signaling receptor complex	1
T cell receptor complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
T cell receptor signaling pathway	BP	direct assay
T cell receptor complex	CC	direct assay
alpha-beta T cell receptor complex	CC	direct assay
plasma membrane	CC	direct assay
identical protein binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,972 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD3D	CD3E	P07766	974
CD3D	CD247	P20963	870
CD3D	CD79A	P11912	836
CD3D	MS4A1	P08984	836
CD3D	NKG7	Q16617	816
CD3D	CD3G	P09693	810
CD3D	HMBS	P08396	756
CD3D	MS4A2	Q01362	751
CD3D	E9PD41	E9PD41	737
CD3D	THY1	P04216	732
CD3D	ZAP70	P43403	708
CD3D	CD8A	P01732	700
CD3D	LCK	P06239	700
CD3D	UBXN4	Q92575	690
CD3D	PTPRC	P08575	677

IntAct

Human interaction partners of CD3D in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
SGTB	physical association	0.560	3
CANX	proximity	0.480	1
AMFR	physical association	0.400	1
FYN	physical association	0.400	1
NR3C1	physical association	0.400	1
CD3E	association	0.350	1
CLGN	association	0.350	1
ITGB8	association	0.350	1
TAP2	association	0.350	1

BioGRID (88 interactions; top human partners by supporting records): CANX (Co-localization; 3 records), SYVN1 (Affinity Capture-Western; 3 records), AMFR (Affinity Capture-Western; 2 records), CD8A (FRET; 2 records), VCP (Affinity Capture-Western; 2 records), ZAP70 (Affinity Capture-Western; 2 records), ABCB6 (Affinity Capture-MS), ACAD10 (Affinity Capture-MS), ADCK2 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), ATP7A (Affinity Capture-MS), ATP8B2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), BCKDHB (Affinity Capture-MS)

SIGNOR signaling

4 signaling interactions:

A	Effect	B	Mechanism
CD3D	“form complex”	CD3	binding
TRIM13	“down-regulates quantity by destabilization”	CD3D	polyubiquitination
AMFR	“down-regulates quantity by destabilization”	CD3D	polyubiquitination
LCK	“up-regulates activity”	CD3D	phosphorylation

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ TCR-CD3 complex	6	CD247, CD3D, CD3E, CD3G, TRA, TRB
★ CD3-LAG3-TCR complex	6	CD3D, CD3E, CD3G, LAG3, TRA, TRB

Disease & clinical

Genetic variants

Variant evidence for CD3D: 232 ClinVar records (16 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	5
Uncertain significance	84
Likely benign	107
Benign	12

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 16 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
12747	NM_000732.6(CD3D):c.202C>T (p.Arg68Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
12748	NM_000732.6(CD3D):c.279C>A (p.Cys93Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1468778	NM_000732.6(CD3D):c.407-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
643120	NM_000732.6(CD3D):c.128G>A (p.Trp43Ter)	Pathogenic	criteria provided, single submitter	1
1075708	NM_000732.6(CD3D):c.51_52del (p.Gln18fs)	Pathogenic	criteria provided, single submitter	1
2691273	NM_000732.6(CD3D):c.107del (p.Asn36fs)	Pathogenic	criteria provided, single submitter	1
2697867	NM_000732.6(CD3D):c.9_10del (p.His3fs)	Pathogenic	criteria provided, single submitter	1
2754021	NM_000732.6(CD3D):c.237C>G (p.Tyr79Ter)	Pathogenic	criteria provided, single submitter	1
2766936	NM_000732.6(CD3D):c.15del (p.Leu7fs)	Pathogenic	criteria provided, single submitter	1
2772341	NM_000732.6(CD3D):c.40_41dup (p.Leu15fs)	Pathogenic	criteria provided, single submitter	1
2869561	NM_000732.6(CD3D):c.271C>T (p.Arg91Ter)	Pathogenic	criteria provided, single submitter	1
1508408	NM_000732.6(CD3D):c.407-1G>A	Likely pathogenic	criteria provided, single submitter	1
2759883	NM_000732.6(CD3D):c.274+2T>C	Likely pathogenic	criteria provided, single submitter	1
2810710	NM_000732.6(CD3D):c.406+1G>T	Likely pathogenic	criteria provided, single submitter	1
3599120	NM_000732.6(CD3D):c.450+1G>A	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CD3D’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 330):

Position(s)	Effect	Δscore	Sites
11:118339228–118339229	acceptor_loss	1.0000	2
11:118339449–118339450	donor_loss	1.0000	5
11:118339495	acceptor_loss	1.0000
11:118339773–118339774	donor_loss	1.0000	4
11:118339788–118339789	donor_gain	1.0000	2
11:118339820	donor_gain	1.0000
11:118339907–118339908	acceptor_loss	1.0000	6
11:118342551–118342552	donor_loss	1.0000	5
11:118339228–118339229	acceptor_loss	0.9900	4
11:118339495–118339496	acceptor_loss	0.9900	5

AlphaMissense

176 missense substitutions predicted likely pathogenic (of 1,098 scored), across 61 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D66	8	0.783	0.863
C73	7	0.920	0.975
C37	7	0.911	0.951
C93	7	0.896	0.950
C96	7	0.873	0.912
P67	6	0.823	0.896
Y71	5	0.878	0.968
G61	5	0.825	0.906
G69	5	0.810	0.886
F125	5	0.792	0.867
Y160	5	0.708	0.804
Y149	5	0.675	0.757
D111	5	0.635	0.721
S161	4	0.745	0.796
G121	3	0.929	0.941
L118	3	0.879	0.938
L117	3	0.812	0.889
F22	3	0.800	0.800
L60	3	0.796	0.842
M92	3	0.782	0.782

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	0.000109
Breast Invasive Carcinoma (TCGA)	favorable	0.000336

Disease associations

OMIM: gene MIM:186790 | disease phenotypes: MIM:615617

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
immunodeficiency 19	Strong	Autosomal recessive
T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
immunodeficiency 19	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
COVID-19 research	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (3): immunodeficiency 19 (MONDO:0014280), severe combined immunodeficiency (MONDO:0015974), T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta (MONDO:0015703)

Orphanet (1): Severe combined immunodeficiency (Orphanet:183660)

HPO phenotypes

33 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000388	Otitis media
HP:0000403	Recurrent otitis media
HP:0001019	Erythroderma
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001880	Increased total eosinophil count
HP:0001888	Decreased total lymphocyte count
HP:0001945	Fever
HP:0002014	Diarrhea
HP:0002028	Chronic diarrhea
HP:0002039	Anorexia
HP:0002090	Pneumonia
HP:0002205	Recurrent respiratory infections
HP:0002719	Recurrent infections
HP:0002722	Recurrent abscess formation
HP:0002846	Abnormal B cell morphology
HP:0003460	Chronic decreased circulating IgA concentration
HP:0003593	Infantile onset
HP:0004315	Decreased circulating IgG concentration
HP:0004385	Protracted diarrhea
HP:0004430	Severe combined immunodeficiency
HP:0005353	Recurrent herpes
HP:0005401	Recurrent Candida infection
HP:0005403	Decreased total T cell count
HP:0006532	Recurrent pneumonia
HP:0008866	Failure to thrive secondary to recurrent infections
HP:0009098	Recurrent oral thrush
HP:0010702	Increased circulating immunoglobulin concentration
HP:0012115	Hepatitis
HP:0012176	Abnormal natural killer cell morphology
HP:0031381	Decreased mitogen-induced T-cell proliferation
HP:0031691	Severe viral infection

GWAS associations

1 associations:

Study	Trait	p-value
GCST007096_147	Pulse pressure	3e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364168 (PROTEIN COMPLEX)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes CD3D — the drug acts on the assembly or class, not necessarily on this subunit alone.

16 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
BLINATUMOMAB	T cell surface glycoprotein CD3	3	4
CATUMAXOMAB	T cell surface glycoprotein CD3	3	4
ELRANATAMAB	T cell surface glycoprotein CD3	3	4
EPCORITAMAB	T cell surface glycoprotein CD3	3	4
GLOFITAMAB	T cell surface glycoprotein CD3	3	4
MOSUNETUZUMAB	T cell surface glycoprotein CD3	3	4
MUROMONAB-CD3	T cell surface glycoprotein CD3	3	4
TALQUETAMAB	T cell surface glycoprotein CD3	3	4
TARLATAMAB	T cell surface glycoprotein CD3	3	4
TECLISTAMAB	T cell surface glycoprotein CD3	3	4
ODRONEXTAMAB	T cell surface glycoprotein CD3	3	3
FLOTETUZUMAB	T cell surface glycoprotein CD3	3	2
FORALUMAB	T cell surface glycoprotein CD3	3	2
SOLITOMAB	T cell surface glycoprotein CD3	3	2
FBT-A05	T cell surface glycoprotein CD3	3	1
IMC-GP100	T cell surface glycoprotein CD3	3	—

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	4
Aflatoxin B1	affects expression, increases expression, increases methylation	4
(+)-JQ1 compound	decreases expression	3
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	decreases methylation, increases expression	2
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
nabiximols	increases expression	1
Acetaminophen	increases expression	1
Benzene	increases expression	1
Cadmium	decreases expression	1
Calcifediol	increases reaction, decreases reaction, affects binding, affects cotreatment, increases expression	1
Calcitriol	decreases reaction, affects binding, affects cotreatment, increases expression, increases reaction (+1 more)	1
Diuron	decreases expression	1
Hydroxychloroquine	affects cotreatment, decreases expression	1
Ketoconazole	increases expression, increases reaction, increases abundance, affects binding, affects cotreatment (+1 more)	1
Methamphetamine	affects reaction, increases expression	1
Methotrexate	decreases expression, affects cotreatment	1
N-Nitrosopyrrolidine	increases expression	1
Nickel	increases expression	1
Quercetin	increases expression	1
Sulfasalazine	affects cotreatment, decreases expression	1
Dronabinol	increases methylation	1
Tretinoin	decreases expression	1
Isotretinoin	increases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E4AD	Genomeditech HEK-293 H_CD3	Transformed cell line	Female
CVCL_E4IL	Genomeditech CHO-K1 H_CD3	Spontaneously immortalized cell line	Female
CVCL_E8IP	Jurkat-NFAT-Luc2-CD3D-CD3E-KO-1C4	Cancer cell line	Male
CVCL_E8IQ	Jurkat-NFAT-Luc2-CD3D-CD3E-KO-2A3	Cancer cell line	Male
CVCL_E8IY	Jurkat-NFAT-Luc2-CD3D-KO-1B1	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

44 trials:

NCT	Phase	Status	Title
NCT00220766	Phase 3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	Phase 3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	Phase 3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT00000603	Phase 2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	Phase 2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	Phase 2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	Phase 2	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	Phase 2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	Phase 2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	Phase 2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00008450	Phase 1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	Phase 1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	Phase 1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	Phase 1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT01019876	Phase 2/3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	Phase 1/2	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	Phase 1/2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	Phase 1/2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	Phase 1/2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	Phase 1/2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	Phase 1/2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	Phase 1/2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03538899	Phase 1/2	RECRUITING	Autologous Gene Therapy for Artemis-Deficient SCID
NCT03597594	Phase 1/2	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
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