CD3G

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

Basic information

Region (hg38): 11:118344343-118355161

Links

ENSG00000160654 ∙ NCBI:917 ∙ OMIM:186740 ∙ HGNC:1675 ∙ Uniprot:P09693 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined immunodeficiency due to CD3gamma deficiency (Strong), mode of inheritance: AR
• combined immunodeficiency due to CD3gamma deficiency (Supportive), mode of inheritance: AR
• combined immunodeficiency due to CD3gamma deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 17	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	1709425; 1635567

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD3G gene.

• Combined immunodeficiency due to CD3gamma deficiency (130 variants)
• not provided (7 variants)
• Severe combined immunodeficiency disease (5 variants)
• not specified (4 variants)
• Inborn genetic diseases (4 variants)
• Immunodeficiency due to defect in CD3-gamma (4 variants)
• CD3G-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD3G 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				18	1	19
missense			42		3	45
nonsense	6	1				7
start loss						0
frameshift	1	1	1			3
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region		1	2	4	1	8
non coding			23	23	3	49
Total	7	3	66	41	7

Highest pathogenic variant AF is 0.0000462

Variants in CD3G

This is a list of pathogenic ClinVar variants found in the CD3G region.

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

Position	Type	Phenotype	Significance	ClinVar
11-118344360-AGGCT-A		Immunodeficiency due to defect in CD3-gamma • Severe combined immunodeficiency disease	Benign/Likely benign (Jun 14, 2016)
11-118344407-G-T		Combined immunodeficiency due to CD3gamma deficiency	Uncertain significance (Jan 12, 2018)
11-118344424-A-G		Combined immunodeficiency due to CD3gamma deficiency	Pathogenic (Aug 20, 1992)
11-118344434-G-T		Combined immunodeficiency due to CD3gamma deficiency	Uncertain significance (Apr 09, 2019)
11-118344435-G-A		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Nov 25, 2022)
11-118344436-A-T		Combined immunodeficiency due to CD3gamma deficiency	Pathogenic (Mar 25, 2021)
11-118344439-G-C		Combined immunodeficiency due to CD3gamma deficiency	Uncertain significance (Jun 05, 2021)
11-118344455-T-C		Combined immunodeficiency due to CD3gamma deficiency	Uncertain significance (Oct 13, 2022)
11-118344456-C-G		Combined immunodeficiency due to CD3gamma deficiency	Uncertain significance (Oct 13, 2022)
11-118344459-G-A		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Jan 31, 2024)
11-118344460-G-A		Combined immunodeficiency due to CD3gamma deficiency	Uncertain significance (Nov 22, 2022)
11-118344461-C-T		Combined immunodeficiency due to CD3gamma deficiency	Uncertain significance (May 27, 2020)
11-118344463-A-G		Combined immunodeficiency due to CD3gamma deficiency • CD3G-related disorder	Uncertain significance (Feb 13, 2023)
11-118344464-T-A		Combined immunodeficiency due to CD3gamma deficiency	Uncertain significance (Jul 19, 2022)
11-118344486-C-T		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Oct 24, 2022)
11-118344489-A-G		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Aug 23, 2022)
11-118344489-ACTAGGGGTCTGG-GGCTATCATTCTTCTTCAAGGTAAGGGCCTTC		Combined immunodeficiency due to CD3gamma deficiency	Uncertain significance (Aug 26, 2022)
11-118344490-C-G		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Aug 23, 2022)
11-118344492-A-G		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Oct 13, 2023)
11-118344493-G-A		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Aug 23, 2022)
11-118344494-G-A		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Oct 29, 2020)
11-118344497-T-C		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Aug 23, 2022)
11-118349010-C-A		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Oct 17, 2023)
11-118349010-C-T		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Dec 03, 2020)
11-118349022-T-C		Combined immunodeficiency due to CD3gamma deficiency	Likely benign (Oct 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD3G	protein_coding	protein_coding	ENST00000532917	6	10818

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000171	0.692	125706	1	41	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0765	89	91.1	0.977	0.00000477	1184
Missense in Polyphen		20	29.045	0.6886		408
Synonymous	0.184	33	34.4	0.960	0.00000192	329
Loss of Function	1.00	9	12.9	0.699	7.01e-7	146

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000260	0.000260
Ashkenazi Jewish	0.00	0.00
East Asian	0.000598	0.000598
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000264
Middle Eastern	0.000598	0.000598
South Asian	0.00108	0.000523
Other	0.000652	0.000489

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 to this role of signal transduction in T-cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface (PubMed:8187769). Indeed, constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3G. {ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:8187769, ECO:0000269|PubMed:8636209}.
• Disease: DISEASE: Immunodeficiency 17 (IMD17) [MIM:615607]: An autosomal recessive primary immunodeficiency characterized by highly variable clinical severity. Some patients have onset of severe recurrent infections in early infancy that may be lethal, whereas others may be only mildly affected or essentially asymptomatic into young adulthood. More severely affected patients may have evidence of autoimmune disease or enteropathy. The immunologic pattern is similar among patients, showing partial T-cell lymphopenia, decreased amounts of the CD3 complex, and impaired proliferative responses to T-cell receptor dependent stimuli. The phenotype in some patients is reminiscent of severe combined immunodeficiency. {ECO:0000269|PubMed:1635567, ECO:0000269|PubMed:17277165}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: 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;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;FCGR activation;CD4 T cell receptor signaling-ERK cascade;Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;TCR;Innate Immune System;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Clathrin-mediated endocytosis;CXCR4-mediated signaling events;Regulation of actin dynamics for phagocytic cup formation;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: 0.207

Intolerance Scores

• loftool: 0.823
• rvis_EVS: 0.53
• rvis_percentile_EVS: 80.58

Haploinsufficiency Scores

• pHI: 0.0653
• hipred: N
• hipred_score: 0.294

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.746

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cd3g
• Phenotype: hematopoietic system phenotype; immune system phenotype; endocrine/exocrine gland phenotype; cellular phenotype

Gene ontology

• Biological process: adaptive immune response;establishment or maintenance of cell polarity;cell surface receptor signaling pathway;protein transport;T cell differentiation;Fc-gamma receptor signaling pathway involved in phagocytosis;T cell activation;positive thymic T cell selection;regulation of immune response;T cell receptor signaling pathway;protein homooligomerization;membrane organization;protein-containing complex assembly;regulation of lymphocyte apoptotic process
• Cellular component: plasma membrane;integral component of plasma membrane;external side of plasma membrane;clathrin-coated vesicle membrane;T cell receptor complex;alpha-beta T cell receptor complex
• Molecular function: transmembrane signaling receptor activity;receptor signaling complex scaffold activity;T cell receptor binding;protein homodimerization activity;protein heterodimerization activity