CD28

CD28 molecule, the group of V-set domain containing|CD molecules|Ig-like cell adhesion molecule family

Basic information

Region (hg38): 2:203706474-203738912

Links

ENSG00000178562 ∙ NCBI:940 ∙ OMIM:186760 ∙ HGNC:1653 ∙ Uniprot:P10747 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD28 gene.

• Inborn genetic diseases (5 variants)
• not specified (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD28 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	1
missense			4	1		5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	4	1	2

Variants in CD28

This is a list of pathogenic ClinVar variants found in the CD28 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-203706740-A-G		not specified	Uncertain significance (Feb 21, 2024)
2-203726685-G-A			Benign (Aug 23, 2018)
2-203726696-G-C		not specified	Uncertain significance (Jun 24, 2022)
2-203726857-G-A		not specified	Uncertain significance (Jan 09, 2024)
2-203726887-T-G		not specified	Uncertain significance (Apr 12, 2022)
2-203729683-C-T		not specified	Likely benign (Mar 28, 2023)
2-203729743-C-A		not specified	Uncertain significance (Jun 05, 2023)
2-203729789-T-C		not specified	Benign (Jan 24, 2024)
2-203734856-C-T		not specified	Uncertain significance (Mar 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD28	protein_coding	protein_coding	ENST00000324106	4	32438

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.358	0.631	125741	0	3	125744	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.797	103	128	0.802	0.00000722	1437
Missense in Polyphen		26	46.615	0.55777		503
Synonymous	-0.391	54	50.5	1.07	0.00000289	430
Loss of Function	2.13	2	8.85	0.226	3.72e-7	117

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival. Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation (PubMed:8617933). Isoform 3 enhances CD40L-mediated activation of NF-kappa-B and kinases MAPK8 and PAK2 in T-cells (PubMed:15067037). {ECO:0000269|PubMed:15067037, ECO:0000269|PubMed:8617933}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Type I diabetes mellitus - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Allograft rejection - Homo sapiens (human);Graft-versus-host disease - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Autoimmune thyroid disease - Homo sapiens (human);Measles - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Intestinal immune network for IgA production - Homo sapiens (human);Allograft Rejection;T-Cell Receptor and Co-stimulatory Signaling;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;Inflammatory Response Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;Disease;Signal Transduction;the co-stimulatory signal during t-cell activation;ras-independent pathway in nk cell-mediated cytotoxicity;Host Interactions of HIV factors;HIV Infection;IL12 signaling mediated by STAT4;CD28 dependent PI3K/Akt signaling;CD28 dependent Vav1 pathway;CD28 co-stimulation;Costimulation by the CD28 family;TCR;Infectious disease;Immune System;Adaptive Immune System;Nef mediated downregulation of CD28 cell surface expression;PIP3 activates AKT signaling;Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters;The role of Nef in HIV-1 replication and disease pathogenesis;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;Intracellular signaling by second messengers;Diseases of signal transduction;TCR signaling in naïve CD8+ T cells;TCR signaling in naïve CD4+ T cells;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.540

Intolerance Scores

• loftool: 0.254
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.12

Haploinsufficiency Scores

• pHI: 0.222
• hipred: Y
• hipred_score: 0.560
• ghis: 0.447

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.814

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cd28
• Phenotype: hematopoietic system phenotype; normal phenotype; neoplasm; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; digestive/alimentary 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); vision/eye 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; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: positive regulation of inflammatory response to antigenic stimulus;humoral immune response;cell surface receptor signaling pathway;positive regulation of gene expression;negative regulation of gene expression;positive regulation of phosphatidylinositol 3-kinase signaling;T cell costimulation;positive regulation of interleukin-10 production;positive regulation of interleukin-4 production;cytokine biosynthetic process;positive regulation of T cell proliferation;T cell activation;negative regulation of apoptotic process;negative thymic T cell selection;regulatory T cell differentiation;positive regulation of viral genome replication;positive regulation of interleukin-2 biosynthetic process;regulation of regulatory T cell differentiation;positive regulation of translation;positive regulation of mitotic nuclear division;positive regulation of transcription by RNA polymerase II;positive regulation of alpha-beta T cell proliferation;phosphatidylinositol phosphorylation;positive regulation of isotype switching to IgG isotypes;regulation of defense response to virus by virus;T cell receptor signaling pathway;positive regulation of protein kinase B signaling;apoptotic signaling pathway
• Cellular component: immunological synapse;cytosol;plasma membrane;integral component of plasma membrane;external side of plasma membrane;cell surface;protein complex involved in cell adhesion
• Molecular function: protease binding;SH3/SH2 adaptor activity;protein binding;coreceptor activity;protein kinase binding;identical protein binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity