CD3E

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

Basic information

Region (hg38): 11:118304730-118316175

Links

ENSG00000198851 ∙ NCBI:916 ∙ OMIM:186830 ∙ HGNC:1674 ∙ Uniprot:P07766 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 18 (Strong), mode of inheritance: AR
• T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta (Supportive), mode of inheritance: AR
• immunodeficiency 18 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 18	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	Allergy/Immunology/Infectious	8490660; 15546002

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD3E gene.

• Immunodeficiency 18 (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD3E 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			1	50	2	53
missense			48	2		50
nonsense	3	1				4
start loss						0
frameshift	3		1			4
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2	6	1		1	10
splice region			4	27	1	32
non coding			13	53	20	86
Total	8	7	66	105	23

Highest pathogenic variant AF is 0.00000657

Variants in CD3E

This is a list of pathogenic ClinVar variants found in the CD3E region.

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

Position	Type	Phenotype	Significance	ClinVar
11-118304763-T-C		Immunodeficiency 18	Uncertain significance (Jan 12, 2018)
11-118304825-A-G		not specified	Benign (Nov 12, 2023)
11-118304960-C-T		not specified • Immunodeficiency 18	Uncertain significance (Jun 27, 2022)
11-118304961-G-A		Immunodeficiency 18	Likely benign (Dec 26, 2023)
11-118304967-T-C		Immunodeficiency 18	Likely benign (Jan 16, 2024)
11-118304967-T-G		Immunodeficiency 18	Likely benign (Jan 02, 2024)
11-118304969-A-C		Immunodeficiency 18	Uncertain significance (Dec 07, 2023)
11-118304979-T-G		Immunodeficiency 18	Likely benign (Jan 29, 2024)
11-118304982-G-A		Immunodeficiency 18	Likely benign (Apr 01, 2022)
11-118304982-G-T		Immunodeficiency 18	Likely benign (Aug 18, 2023)
11-118304991-C-T		Immunodeficiency 18	Likely benign (Jan 14, 2023)
11-118304994-C-A			Likely benign (Mar 28, 2018)
11-118304994-C-T		Immunodeficiency 18	Likely benign (May 17, 2023)
11-118305002-G-A		Immunodeficiency 18	Pathogenic (Jun 28, 2023)
11-118305002-G-C		Immunodeficiency 18	Pathogenic (Dec 30, 2023)
11-118305004-G-A		Immunodeficiency 18 • not specified	Conflicting classifications of pathogenicity (Feb 19, 2024)
11-118305009-G-A		Immunodeficiency 18	Likely benign (Jun 02, 2023)
11-118305015-A-G		Immunodeficiency 18	Likely benign (Sep 14, 2023)
11-118305176-G-A			Likely benign (Dec 09, 2018)
11-118305192-G-A			Likely benign (Aug 06, 2019)
11-118307208-C-A			Likely benign (May 11, 2021)
11-118307271-T-C		Immunodeficiency 18	Likely benign (Nov 29, 2023)
11-118307275-AT-A		Immunodeficiency 18	Likely benign (Sep 19, 2023)
11-118307281-T-G		Immunodeficiency 18	Likely benign (Feb 03, 2022)
11-118307284-C-T		Immunodeficiency 18	Likely benign (Nov 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD3E	protein_coding	protein_coding	ENST00000361763	8	11631

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000345	0.955	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.304	101	110	0.918	0.00000554	1336
Missense in Polyphen		38	36.367	1.0449		457
Synonymous	1.19	31	40.7	0.762	0.00000225	381
Loss of Function	1.79	8	15.6	0.512	8.74e-7	171

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000351	0.000351
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000792	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

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, CD3E plays an essential role in correct T-cell development. Initiates the TCR-CD3 complex assembly by forming the two heterodimers CD3D/CD3E and CD3G/CD3E. Participates also in internalization and cell surface down- regulation of TCR-CD3 complexes via endocytosis sequences present in CD3E cytosolic region (PubMed:10384095, PubMed:26507128). {ECO:0000269|PubMed:10384095, ECO:0000269|PubMed:15294938, ECO:0000269|PubMed:15546002, ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:26507128, ECO:0000269|PubMed:8490660}.
• Disease: DISEASE: Immunodeficiency 18 (IMD18) [MIM:615615]: An autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell- positive, natural killer (NK) cell-positive phenotype, whereas T- cell development is not impaired in the mild form of IMD18. {ECO:0000269|PubMed:15546002, ECO:0000269|PubMed:8490660}. 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) Signaling Pathway;the co-stimulatory signal during t-cell activation;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;Prolactin;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;CXCR4-mediated signaling events;IL23-mediated signaling events;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: 0.0410

Intolerance Scores

• loftool: 0.693
• rvis_EVS: 0.37
• rvis_percentile_EVS: 75.12

Haploinsufficiency Scores

• pHI: 0.0167
• hipred: Y
• hipred_score: 0.546
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.406

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cd3e
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; neoplasm; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; cellular phenotype

Gene ontology

• Biological process: positive regulation of cell-matrix adhesion;adaptive immune response;positive regulation of T cell anergy;cell surface receptor signaling pathway;transmembrane receptor protein tyrosine kinase signaling pathway;signal complex assembly;G protein-coupled receptor signaling pathway;response to nutrient;positive regulation of gene expression;negative regulation of gene expression;dendrite development;cerebellum development;T cell differentiation;T cell costimulation;positive regulation of interferon-gamma production;positive regulation of interleukin-4 production;positive regulation of cell-cell adhesion mediated by integrin;positive regulation of T cell proliferation;T cell activation;regulation of apoptotic process;positive thymic T cell selection;negative thymic T cell selection;positive regulation of interleukin-2 biosynthetic process;negative regulation of smoothened signaling pathway;positive regulation of alpha-beta T cell proliferation;positive regulation of peptidyl-tyrosine phosphorylation;regulation of immune response;positive regulation of calcium-mediated signaling;T cell receptor signaling pathway;protein homooligomerization;protein-containing complex assembly;apoptotic signaling pathway
• Cellular component: immunological synapse;plasma membrane;integral component of plasma membrane;cell-cell junction;external side of plasma membrane;T cell receptor complex;alpha-beta T cell receptor complex;dendritic spine;cell body
• Molecular function: transmembrane signaling receptor activity;protein binding;SH3 domain binding;protein kinase binding;receptor signaling complex scaffold activity;T cell receptor binding;protein homodimerization activity;protein heterodimerization activity