CD8B

protein-coding

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

Gene summary

The CD8 antigen is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. The CD8 antigen, acting as a coreceptor, and the T-cell receptor on the T lymphocyte recognize antigens displayed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional coreceptor is either a homodimer composed of two alpha chains, or a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains. This gene encodes the CD8 beta chain isoforms. Multiple alternatively spliced transcript variants encoding distinct membrane associated or secreted isoforms have been described. A pseudogene, also located on chromosome 2, has been identified. [provided by RefSeq, May 2010]

Previous symbols:

CD8B1

MANE transcript

NM_004931.5

Inheritance

—

ClinVar variants

U:28B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr2:86,815,339-86,861,924

External References & Databases

Ensembl (ENSG00000172116)

Transcript & Mutation Effects

hg38 • Region Span ~46.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CD8B variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 29

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004931.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			28 clinvar	3 clinvar		31
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	28	3	0	31

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004931.5	RefSeq	NP_004922.1	6	MANE Select
ENST00000390655.12	Ensembl	ENSP00000375070.6	6	MANE Select
NM_001178100.2	RefSeq	NP_001171571.1	4	Standard
NM_172101.5	RefSeq	NP_742099.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

adaptive immune response
immune response
transmembrane receptor protein tyrosine kinase signaling pathway
T cell activation
regulation of defense response to virus by virus

Molecular Function

protein binding
coreceptor activity
MHC class I protein binding

Cellular Component

extracellular region
plasma membrane
integral component of plasma membrane
early endosome membrane
T cell receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000331469
Coding exons: 6
Length: 46586
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.523	112	129	0.870	0.00000759	1528
Missense (PolyPhen)		25	35.961	0.69519		474
Synonymous	0.689	46	52.3	0.879	0.00000317	495
Loss of Function	0.723	6	8.24	0.728	3.49e-7	112

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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. A palmitoylation site in the cytoplasmic tail of CD8B chain contributes to partitioning of CD8 into the plasma membrane lipid rafts where signaling proteins are enriched. Once LCK recruited, it initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). Additionally, plays a critical role in thymic selection of CD8+ T-cells. {ECO:0000250|UniProtKB:P10300, ECO:0000269|PubMed:10925291, ECO:0000269|PubMed:11714755, ECO:0000269|PubMed:17145893}.;

Recessive Scores

pRec: 0.201

Intolerance Scores

LoFtool: 0.207
RVIS EVS: 1.55
RVIS percentile EVS: 95.6

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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