CD247

CD247 molecule, the group of CD molecules

Basic information

Region (hg38): 1:167425026-167518640

Previous symbols: [ "CD3Z" ]

Links

ENSG00000198821 ∙ NCBI:919 ∙ OMIM:186780 ∙ HGNC:1677 ∙ Uniprot:P20963 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 25 (Limited), mode of inheritance: AR
• immunodeficiency 25 (Strong), mode of inheritance: AR
• T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta (Supportive), mode of inheritance: AR
• immunodeficiency 25 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency due to defect in CD3-Zeta	AR	Allergy/Immunology/Infectious	Individuals may present with a variety of infectious manifestations, including oral, pulmonary, and skin infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; The use of G-CSF has been reported, as has BMT	Allergy/Immunology/Infectious; Gastrointestinal	3262828; 16672702

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD247 gene.

• Immunodeficiency 25 (125 variants)
• not provided (31 variants)
• not specified (7 variants)
• Inborn genetic diseases (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD247 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			2	17	4	23
missense			44	1		45
nonsense		1	1			2
start loss			1			1
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			7	7	2	16
non coding	1		5	36	19	61
Total	2	1	54	54	23

Highest pathogenic variant AF is 0.00000657

Variants in CD247

This is a list of pathogenic ClinVar variants found in the CD247 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-167431429-TACCTGCACC-T			Likely benign (Aug 10, 2018)
1-167431681-T-G		Immunodeficiency 25	Uncertain significance (Jul 08, 2020)
1-167431685-C-T		Immunodeficiency 25	Uncertain significance (Jul 19, 2022)
1-167431686-G-A		Immunodeficiency 25	Uncertain significance (May 12, 2022)
1-167431688-G-C		Immunodeficiency 25	Uncertain significance (Mar 19, 2022)
1-167431690-G-A		Immunodeficiency 25	Benign (Jan 03, 2024)
1-167431713-C-T		Immunodeficiency 25	Uncertain significance (Jun 30, 2019)
1-167431714-G-A		Immunodeficiency 25	Likely benign (Dec 19, 2017)
1-167431729-G-A		Immunodeficiency 25	Likely benign (Dec 27, 2022)
1-167431732-G-A		Immunodeficiency 25	Likely benign (Nov 08, 2022)
1-167431751-C-T		Immunodeficiency 25	Likely benign (Jun 03, 2023)
1-167431752-G-A		Immunodeficiency 25	Likely benign (Nov 04, 2023)
1-167431752-G-T		Immunodeficiency 25	Uncertain significance (Mar 20, 2022)
1-167431758-G-C		Immunodeficiency 25	Likely benign (Jan 14, 2022)
1-167431764-C-T		Immunodeficiency 25	Benign (Sep 04, 2023)
1-167431874-A-T			Likely benign (Sep 04, 2018)
1-167431887-C-T			Likely benign (Sep 04, 2018)
1-167432017-C-T			Benign (Jul 02, 2018)
1-167432746-G-A			Benign (Jul 02, 2018)
1-167433005-G-A		Immunodeficiency 25	Likely benign (Jul 06, 2022)
1-167433008-C-T		Immunodeficiency 25	Likely benign (Dec 06, 2022)
1-167433009-G-A		Immunodeficiency 25	Likely benign (Jan 08, 2024)
1-167433011-C-T		Immunodeficiency 25	Likely benign (Dec 28, 2021)
1-167433012-G-A		Immunodeficiency 25	Likely benign (Jan 06, 2024)
1-167433026-G-A		Immunodeficiency 25	Uncertain significance (Oct 20, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD247	protein_coding	protein_coding	ENST00000362089	8	87971

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0167	0.962	125673	1	74	125748	0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.307	104	95.5	1.09	0.00000620	1070
Missense in Polyphen		38	37.652	1.0092		459
Synonymous	0.651	33	38.1	0.866	0.00000257	302
Loss of Function	2.01	5	12.8	0.392	6.68e-7	140

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	0.000741	0.000739
European (Non-Finnish)	0.000362	0.000360
Middle Eastern	0.00	0.00
South Asian	0.000196	0.000196
Other	0.000326	0.000326

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, PubMed:7509083). CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (PubMed:7509083). Plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN) (By similarity). {ECO:0000250|UniProtKB:P24161, ECO:0000269|PubMed:16027224, ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:28465009, ECO:0000269|PubMed:7509083}.
• Disease: DISEASE: Immunodeficiency 25 (IMD25) [MIM:610163]: An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens. {ECO:0000269|PubMed:16672702}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: T cell receptor signaling pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);T-Cell antigen Receptor (TCR) Signaling Pathway;Disease;the co-stimulatory signal during t-cell activation;stathmin and breast cancer resistance to antimicrotubule agents;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;Phosphorylation of CD3 and TCR zeta chains;Generation of second messenger molecules;Host Interactions of HIV factors;HIV Infection;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;Infectious disease;Innate Immune System;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Nef and signal transduction;CXCR4-mediated signaling events;The role of Nef in HIV-1 replication and disease pathogenesis;Regulation of actin dynamics for phagocytic cup formation;HIV-1 Nef: Negative effector of Fas and TNF-alpha;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)

Intolerance Scores

• loftool: 0.130
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.462
• hipred: Y
• hipred_score: 0.534
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.633

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cd247
• Phenotype: immune system phenotype; 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); hematopoietic system phenotype; reproductive system phenotype; 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); normal phenotype; embryo phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: adaptive immune response;interleukin-2 production;Fc-gamma receptor signaling pathway involved in phagocytosis;regulation of defense response to virus by virus;regulation of immune response;T cell receptor signaling pathway;protein homotetramerization;protein homotrimerization;positive regulation of protein localization to cell surface
• Cellular component: cytoplasm;plasma membrane;integral component of membrane;T cell receptor complex;alpha-beta T cell receptor complex
• Molecular function: transmembrane signaling receptor activity;protein binding;identical protein binding;protein homodimerization activity;protein tyrosine kinase binding