CD8A

Summary

CD8A (CD8 subunit alpha, HGNC:1706) is a protein-coding gene on chromosome 2p11.2, encoding T-cell surface glycoprotein CD8 alpha chain (P01732). Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses.

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 acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class I MHC molecules. The coreceptor functions as either a homodimer composed of two alpha chains or as 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 alpha chain. Multiple transcript variants encoding different isoforms have been found for this gene. The major protein isoforms of this gene differ by the presence or absence of a transmembrane domain and thus differ in being a membrane-anchored or secreted protein.

Source: NCBI Gene 925 — RefSeq curated summary.

At a glance

• Gene–disease (curated): susceptibility to respiratory infections associated with CD8alpha chain mutation (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 222 total — 2 pathogenic
• Phenotypes (HPO): 7
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001768

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1706
Approved symbol	CD8A
Name	CD8 subunit alpha
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	p32, CD8alpha
Ensembl gene	ENSG00000153563
Ensembl biotype	protein_coding
OMIM	186910
Entrez	925

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000283635, ENST00000352580, ENST00000409511, ENST00000409781, ENST00000699436, ENST00000699437, ENST00000699438, ENST00000699439

RefSeq mRNA: 4 — MANE Select: NM_001768 NM_001145873, NM_001382698, NM_001768, NM_171827

CCDS: CCDS1992, CCDS1993

Canonical transcript exons

ENST00000283635 — 6 exons

Exon	Start	End
ENSE00001011445	86788530	86788560
ENSE00001011446	86789640	86789750
ENSE00001011450	86789323	86789433
ENSE00001220182	86790328	86790681
ENSE00001843887	86784610	86785971
ENSE00001897263	86790777	86790913

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 99.01.

FANTOM5 (CAGE): breadth broad, TPM avg 10.0625 / max 1364.5695, expressed in 325 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29565	8.4630	218
29566	0.5380	69
29564	0.3895	53
29573	0.2261	111
29570	0.1777	9
29563	0.0758	24
29562	0.0657	25
29572	0.0324	13
29567	0.0312	16
29561	0.0251	16

Top tissues by expression

276 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	99.01	gold quality
spleen	UBERON:0002106	96.58	gold quality
granulocyte	CL:0000094	94.34	gold quality
blood	UBERON:0000178	92.48	gold quality
superficial temporal artery	UBERON:0001614	89.28	silver quality
lymph node	UBERON:0000029	88.47	gold quality
jejunal mucosa	UBERON:0000399	87.90	gold quality
vermiform appendix	UBERON:0001154	86.91	gold quality
bone marrow	UBERON:0002371	83.12	gold quality
bone marrow cell	CL:0002092	82.83	gold quality
caecum	UBERON:0001153	82.04	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.79	gold quality
ileal mucosa	UBERON:0000331	81.24	gold quality
small intestine	UBERON:0002108	80.44	gold quality
gall bladder	UBERON:0002110	80.13	gold quality
palpebral conjunctiva	UBERON:0001812	79.72	gold quality
right uterine tube	UBERON:0001302	79.60	gold quality
colonic epithelium	UBERON:0000397	78.54	gold quality
duodenum	UBERON:0002114	78.50	gold quality
epithelium of nasopharynx	UBERON:0001951	77.90	silver quality
nasopharynx	UBERON:0001728	77.88	silver quality
cervix squamous epithelium	UBERON:0006922	77.57	silver quality
upper lobe of left lung	UBERON:0008952	77.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.36	gold quality
upper lobe of lung	UBERON:0008948	76.88	gold quality
body of stomach	UBERON:0001161	76.74	gold quality
rectum	UBERON:0001052	75.73	gold quality
oviduct epithelium	UBERON:0004804	75.50	gold quality
trabecular bone tissue	UBERON:0002483	75.19	gold quality
jejunum	UBERON:0002115	75.05	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-CURD-120	yes	1761.63
E-CURD-79	yes	1489.15
E-CURD-84	yes	1378.48
E-CURD-55	yes	1139.21
E-CURD-122	yes	1067.81
E-MTAB-8410	yes	1039.20
E-CURD-95	yes	924.03
E-GEOD-149689	yes	894.15
E-GEOD-139324	yes	887.77
E-CURD-77	yes	882.54
E-MTAB-6505	yes	797.62
E-HCAD-36	yes	756.95
E-CURD-46	yes	743.47
E-HCAD-4	yes	560.45
E-CURD-88	yes	61.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BATF3, BATF, BCL11B, BCL6, BCL6B, CREM, CUX1, DNMT1, EGR2, EGR3, ELF4, EOMES, ETS1, FLCN, FOXP4, GATA3, GFI1, HES1, ID1, ID2, ID3, MAF, MYB, MYC, NOTCH1, PATZ1, PRDM1, RBPJ, REL, RELA, RELB, RUNX1, RUNX3, SATB1, SP1, STAT1, STAT4, STAT5A, TBX21

miRNA regulators (miRDB)

64 targeting CD8A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-372-5P	99.41	69.11	2299

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Four new weak but tissue-specific DNase I hypersensitivity sites have been mapped 0-0.8 kb upstream of the first exon of CD8A, in the promoter region. (PMID:11937547)
• Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation. (PMID:12594841)
• examined the folding and solution structures of ternary CD4-Lck-Zn2+ and CD8alpha-Lck-Zn2+ complexes;coreceptor tails and the Lck N-terminus are unstructured in isolation but assemble in the presence of zinc to form compactly folded heterodimeric domains (PMID:14500983)
• expression of the HMG box protein TOX is sufficient to induce changes in coreceptor gene expression associated with beta-selection, including CD8 gene demethylation (PMID:15078895)
• Establishment of a permanent CD8+ cell line from a patient with leukemic phase of acute lymphoblastic lymphoma. (PMID:15927673)
• p32 recruits ganciclovir kinase to redistribute the nuclear lamina. (PMID:15975922)
• Introduction of CD8 alpha down-regulates the production of major T helper (Th) type 2 cytokines and may induce differentiation of tumor-specific Th1 cells to improve the clinical potential of T cell receptor (TCR) gene transfer to treat melanoma. (PMID:16818755)
• The results reported in this study demonstrate the activation of both gammadelta- and alphabeta-T cell responses in healthy elderly after influenza vaccination. (PMID:16821115)
• The results indicate that p.Gly111Ser is confined to the Spanish Gypsy population, where it occurs at a carrier rate of 0.4%. (PMID:17658607)
• human monocytes express CD8 alpha; co-engagement of CD8 alpha and FcR enhances monocyte TNF release, suggesting FcR may be a novel partner receptor for CD8 alpha on innate immune cells (PMID:17678538)
• Results indicate that CD8(+) T cells actively contribute to macrophage accumulation and the development of irritant-induced airspace enlargement in a mouse model of COPD. (PMID:17950725)
• CD8+FOXP3+ T cells play an important role in unresponsiveness related to upregulated interleukin receptors on dendritic cells. (PMID:18089323)
• there is an enrichment of both IL-17+CD4+ and CD8+ T cells in active multiple sclerosis lesions (PMID:18156204)
• Data suggest that Bim-mediated attrition of HBV-specific CD8(+) T cells contributes to the inability of these cell populations to persist and control viral replication. (PMID:18398508)
• The alloreactivity of expanded cells was negatively correlated with cell expansion and positively correlated with CD4/CD8 ratio and CD8 expression level. (PMID:18418773)
• tumor-induced TGF-beta may actively subvert the CD8+ arm of the immune system into directly promoting tumor growth by an IL-17-dependent mechanism (PMID:18483277)
• Data suggest that a decrease in CD8+CD28- T cells may reflect impaired T-cell suppression and accordingly, increased T cell help to autoreactive B cells in patients with systemic lupus erythematosus. (PMID:18625635)
• analysis of an interaction between B7-H3 and TLT-2 that preferentially enhances CD8(+) T cell activation (PMID:18650384)
• polarized CD8 T cells within the HBV-infected liver may impede proliferative antiviral effector function, while contributing to the proinflammatory cytokine environment (PMID:18695005)
• in patients with melanoma, who underwent a peptide-based vaccination, homodimer may represent a marker of antigen-specific T-cell memory (PMID:18833003)
• An important finding was the difference in the results on targeting the CD8 antigen by using two different commercially available monoclonal antibodies. (PMID:18956469)
• results indicate that CD4(+)CD8(+) FOXP3(+) thymocytes are more susceptible to apoptosis than mature CD4(+) FOXP3(+) Treg cells. (PMID:19751272)
• self-class I MHC molecules support CD8 T cell survival, but that these interactions also attenuate naive T cell sensitivity by dynamic tuning of CD8 levels. (PMID:19752186)
• Data show that CD8+LAP+ cells produce IFN-gamma, and these cells suppress EAE that is dependent on both TGF-beta and IFN-gamma. (PMID:19768696)
• Binding of the CD8 coreceptor to class I histocompatibility molecules significantly enhances the amount of calcium released from intracellular stores, triggered by a weaker ESO1 peptide agonist. (PMID:20053942)
• The study shows that impaired Epstein-Barr virus-specific CD8+ T-cell function in X-linked lymphoproliferative disease is restricted to SLAM family-positive B-cell targets. (PMID:20644117)
• PD-L1 and PD-L2 knockdown dendritic cells showed superior potential to expand minor histocompatibility antigen-specific CD8(+) effector and memory T cells from leukemia patients early after donor lymphocyte infusion and later during relapse. (PMID:20682852)
• The positive rate of CD8 in primary lung cancer tissue was significantly higher than that in normal lung tissue. (PMID:20704820)
• Studies indicate that The thymus leukemia (TL) antigen and CD8alphaalpha are interacting surface molecules that are expressed at the frontline of the mucosal immune system. (PMID:20850477)
• Radiation-induced CD8 T-lymphocytes and, for the first time, B-lymphocytes apoptosis can predict differences in late toxicity in cervical cancer patients (PMID:21142701)
• In the setting of HIV-induced lymphopenia, naive CD4-expressing T cells are recruited mainly into the proliferating pool in response to CD4 T cell depletion, whereas naive CD8-positive T cell proliferation is driven mainly by levels of HIV RNA. (PMID:21257970)
• anti-TIM3 requires IFN-gamma producing CD8(+) T cells and CD4(+) T cells, and a higher ratio of tumor infiltrating CD8(+):CD4(+) T cells correlating with therapeutic success (PMID:21430066)
• the presence of IL-1 and/or IL-6 during activation of human CD8 T cells attenuates Fas-mediated AICD, whereas IL-12 increases the susceptibility of activated CD8 T cells to this form of cell death (PMID:21518761)
• we present the complex structures of human CD8alphaalpha bound to HLA-A*2402 (PMID:21645925)
• These results suggest that the elevated frequency of PD-1(+) CD8(+) T cells could be associated with leukemic relapse in pediatric umbilical cord blood transplantation recipients. (PMID:21813446)
• The aim was to determine if SPARC, FOXP3, CD8 and CD45RO expression levels are associated with colorectal cancer (CRC) stage, disease outcome and long-term cancer-specific survival (PMID:21818290)
• Lymphoid tissue (LT)-resident CD8alpha-positive dendritic cells (DCs) and non(LT)-derived CD103-positive DCs express transgenic XCR1 and are characterized by a unique transcriptional fingerprint, irrespective of their tissue of origin. (PMID:21948982)
• Coreceptor CD8alphabeta contributes to the antigen-recognition process by binding to a largely invariant region of the MHC class I molecule and by promoting intracellular signaling. (PMID:21954283)
• Multiple sclerosis is characterized by a dysregulation of CD8+CD56-perforin+ T cells that may play a role in the development of disability. (PMID:22001684)
• Nef-mediated down-modulation of CD8alphabeta is a fundamental property of primate lentiviruses. (PMID:22013062)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd8a	ENSDARG00000044797
mus_musculus	Cd8a	ENSMUSG00000053977
rattus_norvegicus	Cd8a	ENSRNOG00000007178

Protein

Protein identifiers

T-cell surface glycoprotein CD8 alpha chain — P01732 (reviewed: P01732)

Alternative names: T-lymphocyte differentiation antigen T8/Leu-2

All UniProt accessions (2): P01732, B8ZZZ4

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Forms disulfide-linked heterodimers with CD8B at the cell surface. Also forms homodimers in several cell types including NK-cells or peripheral blood T-lymphocytes. Interacts with the MHC class I HLA-A/B2M dimer. One HLA-A molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop). Interacts with LCK in a zinc-dependent manner. Interacts with HLA-G; this interaction is direct and might down-regulate T cell receptor signaling.

Subcellular location. Cell membrane Secreted.

Tissue specificity. CD8 on thymus-derived T-cells usually consists of a disulfide-linked alpha/CD8A and a beta/CD8B chain. Less frequently, CD8 can be expressed as a CD8A homodimer. A subset of natural killer cells, memory T-cells, intraepithelial lymphocytes, monocytes and dendritic cells expresses CD8A homodimers. Expressed at the cell surface of plasmacytoid dendritic cells upon herpes simplex virus-1 stimulation.

Post-translational modifications. Palmitoylated, but association with CD8B seems to be more important for the enrichment of CD8A in lipid rafts. O-glycosylated. Phosphorylated in cytotoxic T-lymphocytes (CTLs) following activation.

Disease relevance. Immunodeficiency 116 (IMD116) [MIM:608957] An autosomal recessive immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
P01732-1	1, membrane, mCD8alpha	yes
P01732-2	2, secreted, sCD8alpha
P01732-3	3

RefSeq proteins (4): NP_001139345, NP_001369627, NP_001759, NP_741969 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015468	CD8_asu	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07686

UniProt features (25 total): strand 10, mutagenesis site 2, topological domain 2, splice variant 2, signal peptide 1, chain 1, sequence variant 1, turn 1, helix 1, transmembrane region 1, domain 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8EW6	X-RAY DIFFRACTION	1.9
2HP4	X-RAY DIFFRACTION	2.1
7UMG	X-RAY DIFFRACTION	2.4
1CD8	X-RAY DIFFRACTION	2.6
7UVF	X-RAY DIFFRACTION	2.6
1AKJ	X-RAY DIFFRACTION	2.65
3QZW	X-RAY DIFFRACTION	2.8
1Q69	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01732-F1	79.03	0.49

Antibody-complex structures (SAbDab): 2 — 7UVF, 8EW6

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 206

Disulfide bonds (1): 43–115

Mutagenesis-validated functional residues (2):

Position	Phenotype
111	prevents cd8 expression.
206	complete loss of palmitoylation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 304 (showing top): MORF_ITGA2, WALLACE_PROSTATE_CANCER_RACE_UP, BENPORATH_ES_WITH_H3K27ME3, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_255, MODULE_45, MODULE_64, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, MODULE_317, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, MORF_RAD51L3, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN

GO Biological Process (10): adaptive immune response (GO:0002250), T cell mediated immunity (GO:0002456), immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), antigen processing and presentation (GO:0019882), T cell activation (GO:0042110), cytotoxic T cell differentiation (GO:0045065), T cell receptor signaling pathway (GO:0050852), immune system process (GO:0002376)

GO Molecular Function (4): coreceptor activity (GO:0015026), MHC class I protein complex binding (GO:0023024), MHC class I protein binding (GO:0042288), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), T cell receptor complex (GO:0042101), signaling receptor complex (GO:0043235), plasma membrane raft (GO:0044853), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune system process	2
cellular anatomical structure	2
plasma membrane	2
immune response	1
lymphocyte mediated immunity	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
response to stimulus	1
signal transduction	1
enzyme-linked receptor protein signaling pathway	1
lymphocyte activation	1
T cell differentiation	1
antigen receptor-mediated signaling pathway	1
biological_process	1
signaling receptor activity	1
MHC protein complex binding	1
MHC protein binding	1
binding	1
membrane	1
cell periphery	1
cell surface	1
side of membrane	1
plasma membrane signaling receptor complex	1
protein-containing complex	1
membrane raft	1
plasma membrane region	1

Protein interactions and networks

STRING

6570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD8A	LCK	P06239	998
CD8A	CD2	P06729	995
CD8A	CD4	P01730	993
CD8A	IFNG	P01579	987
CD8A	HLA-E	P13747	986
CD8A	IL2	P01585	971
CD8A	HLA-A	P01891	966
CD8A	CD81	P18582	961
CD8A	HLA-G	P17693	961
CD8A	FYN	P06241	960
CD8A	CD80	P33681	959
CD8A	TNF	P01375	957
CD8A	CD28	P10747	956
CD8A	IL10	P22301	956
CD8A	IL4	P05112	947
CD8A	CD5	P06127	947

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CD8A	CDK1	psi-mi:“MI:0915”(physical association)	0.490
CDK1	CD8A	psi-mi:“MI:0915”(physical association)	0.490
CEACAM5	CD8A	psi-mi:“MI:0407”(direct interaction)	0.440
HLA-C		psi-mi:“MI:0915”(physical association)	0.400
HLA-B		psi-mi:“MI:0915”(physical association)	0.400
HLA-G		psi-mi:“MI:0915”(physical association)	0.400
CALR	CD8A	psi-mi:“MI:0915”(physical association)	0.400
CACYBP	CD8A	psi-mi:“MI:0915”(physical association)	0.370
SLF1	CD8A	psi-mi:“MI:0914”(association)	0.350
CD8A	HSPA5	psi-mi:“MI:0914”(association)	0.350
CD8A		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): COPA (Affinity Capture-Western), CD8A (Affinity Capture-Luminescence), CD8B (Co-localization), CD8A (Co-localization), CD8A (Co-crystal Structure), CD8A (Reconstituted Complex), CD8A (Reconstituted Complex), CD8A (Reconstituted Complex), CD8A (Reconstituted Complex), CD8A (Reconstituted Complex), CD8A (Co-crystal Structure), CD8A (FRET), CD8A (Affinity Capture-Western), CD8A (FRET), CD8A (Negative Genetic)

ESM2 similar proteins: A6NJW9, O02757, P01730, P01731, P01732, P05541, P07725, P09793, P0DSE1, P10300, P10747, P10966, P15530, P16003, P16004, P16410, P30433, P30434, P31041, P31042, P31043, P31783, P33705, P33706, P40259, P41688, P42069, P42072, P50283, P79184, P79336, Q08338, Q08340, Q28071, Q2YFS1, Q2YFS2, Q2YFS3, Q3LRV9, Q495A1, Q5JXA9

Diamond homologs: P01731, P01732, P07725, P30433, P31783, P33706, P41688, A0A075B6I4, A0A075B6J9, A0A0C4DH55, P01652, P01680, P01704, P01714, P04210, P04433, A0A075B6H7, A0A075B6S4, A0A075B6S5, A0A075B6S9, A0A087WSY6, A0A0A0MRZ8, A0A0B4J2D9, A0A0C4DH25, A0A0C4DH67, A0A0C4DH69, A0A0C4DH72, A0A0C4DH73, P01597, P01599, P01601, P01602, P01611, P01619, P01624, P01637, P01638, P01650, P01651, P01653

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ETS1	“up-regulates quantity by expression”	CD8A	“transcriptional regulation”
GATA3	“up-regulates quantity by expression”	CD8A	“transcriptional regulation”
“Class I MHC:Antigen”	“up-regulates activity”	CD8A	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

222 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	94
Likely benign	104
Benign	9

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
12742	NM_001768.7(CD8A):c.331G>A (p.Gly111Ser)	Pathogenic
60182	GRCh38/hg38 2p11.2(chr2:86395172-86859284)x1	Pathogenic

SpliceAI

1224 predictions. Top by Δscore:

Variant	Effect	Δscore
2:86785967:CAGGC:C	acceptor_gain	1.0000
2:86785968:AGGCC:A	acceptor_loss	1.0000
2:86785970:GCCT:G	acceptor_loss	1.0000
2:86785971:CCTGA:C	acceptor_loss	1.0000
2:86785972:CTGAA:C	acceptor_loss	1.0000
2:86785973:T:C	acceptor_loss	1.0000
2:86788559:CC:C	acceptor_gain	1.0000
2:86788559:CCCTG:C	acceptor_loss	1.0000
2:86788560:CC:C	acceptor_gain	1.0000
2:86788561:C:CC	acceptor_gain	1.0000
2:86789634:CCTCA:C	donor_loss	1.0000
2:86789635:CTCA:C	donor_loss	1.0000
2:86789636:TCAC:T	donor_loss	1.0000
2:86789637:CACCT:C	donor_loss	1.0000
2:86789638:A:T	donor_loss	1.0000
2:86789746:CTTCG:C	acceptor_gain	1.0000
2:86789747:TTCG:T	acceptor_gain	1.0000
2:86789749:CG:C	acceptor_gain	1.0000
2:86789751:C:CC	acceptor_gain	1.0000
2:86785969:GGC:G	acceptor_gain	0.9900
2:86785970:GC:G	acceptor_gain	0.9900
2:86785971:CC:C	acceptor_gain	0.9900
2:86785972:C:CC	acceptor_gain	0.9900
2:86788523:GACTC:G	donor_loss	0.9900
2:86788524:ACT:A	donor_loss	0.9900
2:86788527:CACCG:C	donor_loss	0.9900
2:86788528:A:AC	donor_gain	0.9900
2:86788528:ACCG:A	donor_loss	0.9900
2:86788529:C:CC	donor_gain	0.9900
2:86788557:TTCC:T	acceptor_gain	0.9900

AlphaMissense

1477 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:86790400:C:A	G111C	0.997
2:86790563:C:A	W56C	0.997
2:86790563:C:G	W56C	0.997
2:86790353:G:C	S126R	0.995
2:86790353:G:T	S126R	0.995
2:86790355:T:G	S126R	0.995
2:86790603:C:G	C43S	0.995
2:86790604:A:T	C43S	0.995
2:86790389:G:C	F114L	0.994
2:86790389:G:T	F114L	0.994
2:86790391:A:G	F114L	0.994
2:86790399:C:A	G111V	0.994
2:86790400:C:G	G111R	0.994
2:86790565:A:G	W56R	0.994
2:86790565:A:T	W56R	0.994
2:86790387:C:G	C115S	0.993
2:86790388:A:T	C115S	0.993
2:86790394:A:C	Y113D	0.993
2:86790524:G:C	F69L	0.993
2:86790524:G:T	F69L	0.993
2:86790526:A:G	F69L	0.993
2:86790417:A:C	F105C	0.992
2:86790387:C:T	C115Y	0.991
2:86790354:C:A	S126I	0.989
2:86790432:A:G	L100P	0.989
2:86790386:G:C	C115W	0.988
2:86790388:A:G	C115R	0.987
2:86790525:A:C	F69C	0.987
2:86790604:A:G	C43R	0.987
2:86790399:C:T	G111D	0.984

dbSNP variants (sampled 300 via entrez): RS1000105034 (2:86802769 C>A), RS1000311966 (2:86808742 C>G), RS1000359308 (2:86810347 T>G), RS1000737409 (2:86784957 A>G), RS1000790467 (2:86791535 C>T), RS1000805811 (2:86806002 T>G), RS1000900251 (2:86798500 C>T), RS1001001800 (2:86804866 G>A), RS1001043171 (2:86785349 C>T), RS1001076275 (2:86798901 T>C), RS1001193560 (2:86807404 A>G), RS1001238999 (2:86790875 G>A), RS1001343474 (2:86798158 T>C), RS1001467824 (2:86787333 A>G), RS1001624426 (2:86793483 T>A)

Disease associations

OMIM: gene MIM:186910 | disease phenotypes: MIM:608957

GenCC curated gene-disease

Disease	Classification	Inheritance
susceptibility to respiratory infections associated with CD8alpha chain mutation	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
susceptibility to respiratory infections associated with CD8alpha chain mutation	Limited	AR

Mondo (1): susceptibility to respiratory infections associated with CD8alpha chain mutation (MONDO:0012161)

Orphanet (1): Susceptibility to respiratory infections associated with CD8alpha chain mutation (Orphanet:169085)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002718	Recurrent bacterial infections
HP:0003577	Congenital onset
HP:0004429	Recurrent viral infections
HP:0005422	Absence of CD8-positive T cells

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_1578	Blood protein levels	7.000000e-73

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563824	CD8 Deficiency, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression	2
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
nickel sulfate	increases expression	1
pentanal	increases expression	1
monomethylpropion	increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
jinfukang	decreases expression, affects cotreatment	1
Fingolimod Hydrochloride	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Aldehydes	increases expression	1
Allergens	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Aspirin	decreases expression	1
Vehicle Emissions	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Cycloheximide	affects cotreatment, increases expression	1
Cytarabine	increases expression	1
Fonofos	increases methylation	1
Fluorouracil	affects reaction, decreases expression	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Parathion	increases methylation	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1

Cellosaurus cell lines

7 cell lines: 4 spontaneously immortalized cell line, 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1D87	HeLa-T8+	Cancer cell line	Female
CVCL_A6ID	FRT-U10	Spontaneously immortalized cell line	Sex unspecified
CVCL_B8DB	Abcam HCT 116 CD8A KO	Cancer cell line	Male
CVCL_B9FI	Abcam A-549 CD8A KO	Cancer cell line	Male
CVCL_ZV47	MDCK-A3-15	Spontaneously immortalized cell line	Female
CVCL_ZW00	MDCK-A3-10	Spontaneously immortalized cell line	Female
CVCL_ZW01	MDCK-A3-14	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.