CD3D

CD3 delta subunit of T-cell receptor complex, the group of CD molecules

Basic information

Region (hg38): 11:118339074-118342705

Previous symbols: [ "T3D" ]

Links

ENSG00000167286 ∙ NCBI:915 ∙ OMIM:186790 ∙ HGNC:1673 ∙ Uniprot:P04234 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 19 (Strong), mode of inheritance: AR
• T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta (Supportive), mode of inheritance: AR
• immunodeficiency 19 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 19	AR	Allergy/Immunology/Infectious	Individuals have been described with severe combined immunodeficiency, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported	Allergy/Immunology/Infectious	14602880; 15546002

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD3D gene.

• Immunodeficiency 19 (142 variants)
• not provided (13 variants)
• not specified (8 variants)
• Inborn genetic diseases (5 variants)
• Severe combined immunodeficiency disease (3 variants)
• CD3D-related condition (1 variants)
• Immunodeficiency 104 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD3D gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	25		28
missense			57	1		58
nonsense	4		2			6
start loss						0
frameshift	6					6
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3				3
splice region		1	6	9		16
non coding			7	20	10	37
Total	10	3	70	46	10

Highest pathogenic variant AF is 0.0000329

Variants in CD3D

This is a list of pathogenic ClinVar variants found in the CD3D region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-118339103-G-A		Immunodeficiency 19	Benign (Jan 13, 2018)
11-118339168-G-A		Immunodeficiency 19	Conflicting classifications of pathogenicity (Jan 08, 2024)
11-118339172-C-T		Immunodeficiency 19	Uncertain significance (Jul 19, 2022)
11-118339173-G-A		Immunodeficiency 19 • Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
11-118339187-C-G		Immunodeficiency 19	Uncertain significance (Feb 10, 2022)
11-118339192-G-A		Immunodeficiency 19	Likely benign (Dec 21, 2022)
11-118339193-T-A		Immunodeficiency 19	Uncertain significance (Jul 20, 2018)
11-118339198-G-A		Immunodeficiency 19	Likely benign (Jan 31, 2024)
11-118339201-C-T		Immunodeficiency 19	Likely benign (Dec 16, 2022)
11-118339213-T-G		Immunodeficiency 19	Likely benign (Feb 11, 2023)
11-118339215-G-A		Immunodeficiency 19	Uncertain significance (Nov 28, 2023)
11-118339217-T-C		Inborn genetic diseases	Uncertain significance (Nov 18, 2023)
11-118339220-C-T		Immunodeficiency 19	Uncertain significance (Jul 14, 2022)
11-118339221-G-A		Immunodeficiency 19	Uncertain significance (Jun 27, 2022)
11-118339221-G-C		Immunodeficiency 19	Uncertain significance (May 29, 2019)
11-118339223-A-G		Immunodeficiency 19	Uncertain significance (Dec 11, 2023)
11-118339223-AGG-A		not specified	Uncertain significance (Feb 05, 2024)
11-118339225-G-A		Immunodeficiency 19	Likely benign (Dec 02, 2023)
11-118339233-AGAG-A		Immunodeficiency 19	Likely benign (Dec 14, 2023)
11-118339234-G-C		Immunodeficiency 19	Likely benign (Dec 01, 2023)
11-118339235-A-G		Immunodeficiency 19	Likely benign (Jan 28, 2022)
11-118339236-G-A		Immunodeficiency 19	Likely benign (Oct 13, 2023)
11-118339239-G-A		Immunodeficiency 19	Likely benign (Aug 28, 2023)
11-118339242-G-A		Immunodeficiency 19	Likely benign (Jul 19, 2022)
11-118339245-A-C		Immunodeficiency 104 • Immunodeficiency 19 • not specified	Benign (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD3D	protein_coding	protein_coding	ENST00000300692	5	3791

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000859	0.558	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00952	92	92.3	0.997	0.00000531	1095
Missense in Polyphen		26	28.396	0.91563		364
Synonymous	0.0574	36	36.4	0.988	0.00000217	355
Loss of Function	0.602	7	8.94	0.783	5.54e-7	94

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000615	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 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 (PubMed:2470098). 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(PubMed:12215456). {ECO:0000269|PubMed:12215456, ECO:0000269|PubMed:12507424, ECO:0000269|PubMed:2470098}.
• Disease: DISEASE: Immunodeficiency 19 (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. {ECO:0000269|PubMed:14602880, ECO:0000269|PubMed:15546002, ECO:0000269|PubMed:21883749}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Primary immunodeficiency - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Measles - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;T-Cell antigen Receptor (TCR) Signaling Pathway;the co-stimulatory signal during t-cell activation;Vesicle-mediated transport;lck and fyn tyrosine kinases in initiation of tcr activation;role of mef2d in t-cell apoptosis;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;t cell receptor signaling pathway;Membrane Trafficking;Phosphorylation of CD3 and TCR zeta chains;Generation of second messenger molecules;Translocation of ZAP-70 to Immunological synapse;Downstream TCR signaling;TCR signaling;IL12 signaling mediated by STAT4;PD-1 signaling;Costimulation by the CD28 family;CD4 T cell receptor signaling-ERK cascade;TCR;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Clathrin-mediated endocytosis;CXCR4-mediated signaling events;Cargo recognition for clathrin-mediated endocytosis;Downstream signaling in naïve CD8+ T cells;TCR signaling in naïve CD8+ T cells;TCR signaling in naïve CD4+ T cells;IL12-mediated signaling events;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.382

Intolerance Scores

• loftool: 0.953
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• pHI: 0.0589
• hipred: N
• hipred_score: 0.464
• ghis: 0.513

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0142

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cd3d
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: adaptive immune response;cell surface receptor signaling pathway;T cell differentiation;positive thymic T cell selection;positive regulation of transcription by RNA polymerase II;regulation of immune response;T cell receptor signaling pathway;protein homooligomerization;membrane organization
• Cellular component: cytoplasm;plasma membrane;external side of plasma membrane;integral component of membrane;clathrin-coated vesicle membrane;T cell receptor complex;alpha-beta T cell receptor complex
• Molecular function: transcription coactivator activity;transmembrane signaling receptor activity;protein homodimerization activity;protein heterodimerization activity