CD8A

CD8 subunit alpha, the group of V-set domain containing|CD molecules

Basic information

Region (hg38): 2:86784610-86808396

Previous symbols: [ "CD8" ]

Links

ENSG00000153563

∙ NCBI:925 ∙ OMIM:186910 ∙ HGNC:1706 ∙ Uniprot:P01732 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

susceptibility to respiratory infections associated with CD8alpha chain mutation (Supportive), mode of inheritance: AR
susceptibility to respiratory infections associated with CD8alpha chain mutation (Limited), mode of inheritance: AR
susceptibility to respiratory infections associated with CD8alpha chain mutation (Strong), mode of inheritance: AR
susceptibility to respiratory infections associated with CD8alpha chain mutation (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 116	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	11435463; 17658607
Asymptomatic individuals have been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD8A gene.

Susceptibility_to_respiratory_infections_associated_with_CD8alpha_chain_mutation (177 variants)
not_provided (10 variants)
not_specified (10 variants)
CD8A-related_disorder (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD8A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001768.7. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				57 clinvar	3 clinvar	60
missense	1 clinvar		73 clinvar	2 clinvar	1 clinvar	77
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	77	59	4

Highest pathogenic variant AF is 0.00000123914

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD8A	protein_coding	protein_coding	ENST00000409511	6	23791

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000168	0.450	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.237	122	130	0.942	0.00000646	1455
Missense in Polyphen		40	39.169	1.0212		456
Synonymous	0.167	60	61.7	0.973	0.00000325	512
Loss of Function	0.469	8	9.56	0.836	4.18e-7	113

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000957	0.0000905
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000550	0.0000544
Finnish	0.000105	0.0000924
European (Non-Finnish)	0.0000621	0.0000615
Middle Eastern	0.0000550	0.0000544
South Asian	0.000197	0.000196
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). This mechanism enables CTLs to recognize and eliminate infected cells and tumor cells. In NK- cells, the presence of CD8A homodimers at the cell surface provides a survival mechanism allowing conjugation and lysis of multiple target cells. CD8A homodimer molecules also promote the survival and differentiation of activated lymphocytes into memory CD8 T-cells. {ECO:0000269|PubMed:16236125, ECO:0000269|PubMed:17678538, ECO:0000269|PubMed:23657257, ECO:0000269|PubMed:26082771}.;
Disease: DISEASE: CD8 deficiency, familial (CD8 deficiency) [MIM:608957]: An immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections. {ECO:0000269|PubMed:11435463}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Antigen processing and presentation - Homo sapiens (human);Primary immunodeficiency - Homo sapiens (human);Cell adhesion molecules (CAMs) - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);T-Cell Receptor and Co-stimulatory Signaling;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;T-Cell antigen Receptor (TCR) Signaling Pathway;TCR;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Downstream signaling in naïve CD8+ T cells;TCR signaling in naïve CD8+ T cells;IL12-mediated signaling events (Consensus)

Recessive Scores

pRec: 0.972

Intolerance Scores

loftool: 0.440
rvis_EVS: 0.01
rvis_percentile_EVS: 54.95

Haploinsufficiency Scores

pHI: 0.0844
hipred: Y
hipred_score: 0.560
ghis: 0.473

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.991

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cd8a
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); immune system phenotype; renal/urinary 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; hematopoietic system phenotype; endocrine/exocrine gland phenotype; cellular 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);

Gene ontology

Biological process: T cell mediated immunity;immune response;cell surface receptor signaling pathway;transmembrane receptor protein tyrosine kinase signaling pathway;antigen processing and presentation;T cell activation;cytotoxic T cell differentiation;regulation of immune response
Cellular component: extracellular region;plasma membrane;integral component of plasma membrane;external side of plasma membrane;T cell receptor complex;plasma membrane raft
Molecular function: protein binding;coreceptor activity;protein kinase binding;MHC class I protein binding