CD8B2

Summary

CD8B2 (CD8B family member 2, HGNC:1708) is a protein-coding gene on chromosome 2q12.2, encoding T-cell surface glycoprotein CD8 beta-2 chain (A6NJW9). Identifies cytotoxic/suppressor T-cells that interact with MHC class I bearing targets.

Predicted to enable MHC class I protein binding activity and coreceptor activity. Predicted to be involved in adaptive immune response and regulation of immune response. Predicted to be located in plasma membrane. Predicted to be active in cell surface.

Source: NCBI Gene 927 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 8 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001349727

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1708
Approved symbol	CD8B2
Name	CD8B family member 2
Location	2q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000254126
Ensembl biotype	protein_coding
Entrez	927

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000416057, ENST00000643224

RefSeq mRNA: 2 — MANE Select: NM_001349727 NM_001349727, NM_001368307

CCDS: CCDS86870, CCDS92827

Canonical transcript exons

ENST00000643224 — 6 exons

Exon	Start	End
ENSE00001612726	106487364	106487469
ENSE00002511509	106502474	106502563
ENSE00003466094	106504289	106504325
ENSE00003511478	106496173	106496262
ENSE00003661055	106490874	106491233
ENSE00003822601	106506928	106511095

Expression profiles

Bgee: expression breadth broad, 78 present calls, max score 82.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3564 / max 50.5505, expressed in 60 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21833	0.2309	46
21834	0.0809	18
202328	0.0446	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	82.24	gold quality
prefrontal cortex	UBERON:0000451	64.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.30	gold quality
substantia nigra	UBERON:0002038	63.55	gold quality
islet of Langerhans	UBERON:0000006	63.11	gold quality
putamen	UBERON:0001874	60.70	gold quality
frontal cortex	UBERON:0001870	60.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	59.61	gold quality
lymph node	UBERON:0000029	59.15	gold quality
hypothalamus	UBERON:0001898	59.06	gold quality
caudate nucleus	UBERON:0001873	58.97	gold quality
Ammon’s horn	UBERON:0001954	58.88	gold quality
amygdala	UBERON:0001876	58.80	gold quality
temporal lobe	UBERON:0001871	58.79	gold quality
anterior cingulate cortex	UBERON:0009835	58.76	gold quality
cerebral cortex	UBERON:0000956	58.63	gold quality
pituitary gland	UBERON:0000007	57.73	gold quality
adenohypophysis	UBERON:0002196	57.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.37	gold quality
brain	UBERON:0000955	56.54	gold quality
right frontal lobe	UBERON:0002810	55.77	gold quality
superior frontal gyrus	UBERON:0002661	55.07	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	54.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	54.64	gold quality
vermiform appendix	UBERON:0001154	54.04	gold quality
nucleus accumbens	UBERON:0001882	53.84	gold quality
adult mammalian kidney	UBERON:0000082	52.13	gold quality
primary visual cortex	UBERON:0002436	51.14	gold quality
tonsil	UBERON:0002372	50.61	gold quality
duodenum	UBERON:0002114	49.22	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.42

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd8b	ENSDARG00000058682
mus_musculus	Cd8b1	ENSMUSG00000053044
rattus_norvegicus	Cd8b	ENSRNOG00000007129

Paralogs (1): CD8B (ENSG00000172116)

Protein

Protein identifiers

T-cell surface glycoprotein CD8 beta-2 chain — A6NJW9 (reviewed: A6NJW9)

Alternative names: CD8b pseudogene

All UniProt accessions (2): A6NJW9, A0A2R8Y6U7

UniProt curated annotations — full annotation on UniProt →

Function. Identifies cytotoxic/suppressor T-cells that interact with MHC class I bearing targets. CD8 is thought to play a role in the process of T-cell mediated killing.

Subunit / interactions. In general heterodimer of an alpha and a beta chain linked by two disulfide bonds.

Subcellular location. Cell membrane.

RefSeq proteins (2): NP_001336656, NP_001355236 (=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
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR042414	CD8B	Family

Pfam: PF07686

UniProt features (8 total): topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NJW9-F1	81.42	0.46

Functional residue map

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

Disulfide bonds (1): 41–116

Glycosylation sites (1): 102

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 10 (showing top): chr2q12, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GOMF_SIGNALING_RECEPTOR_BINDING, GOMF_MHC_CLASS_I_PROTEIN_BINDING, GOMF_CORECEPTOR_ACTIVITY, GOMF_MHC_PROTEIN_BINDING, GOBP_REGULATION_OF_IMMUNE_SYSTEM_PROCESS, GOMF_MOLECULAR_TRANSDUCER_ACTIVITY

GO Biological Process (3): adaptive immune response (GO:0002250), regulation of immune response (GO:0050776), immune system process (GO:0002376)

GO Molecular Function (2): coreceptor activity (GO:0015026), MHC class I protein binding (GO:0042288)

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	2
cellular anatomical structure	2
regulation of immune system process	1
regulation of response to stimulus	1
biological_process	1
signaling receptor activity	1
MHC protein binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

268 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD8B2	ARHGEF35	A5YM69	607
CD8B2	WDR27	A2RRH5	520
CD8B2	PATZ1	Q9HBE1	494
CD8B2	SATB1	Q01826	491
CD8B2	CD8A	P01732	453
CD8B2	PTPN20	Q4JDL3	433
CD8B2	FAM72C	H0Y354	429
CD8B2	FAM72B	Q86X60	414
CD8B2	BOLA2	Q9H3K6	407
CD8B2	ARHGEF5	Q12774	396
CD8B2	MAFIP	Q8WZ33	392
CD8B2	FAM72D	Q6L9T8	378
CD8B2	GTF2IRD2	Q86UP8	371
CD8B2	GNAO1	P09471	353
CD8B2	PDZK1	Q5T2W1	353
CD8B2	GPRIN2	O60269	353
CD8B2	ROCK1	Q13464	353

IntAct

0 interactions, top by confidence:

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: A0A1B0GX68, A6NJW9, P01735, P05541, P06321, P10300, P10966, P30434, P79336, Q9XSM7, A0A075B6L6, A0A075B6N1, A0A075B6N3, A0A075B6N4, A0A087WV62, A0A0A0MRZ8, A0A0A0MS03, A0A0A0MS05, A0A0A0MS06, A0A0A6YYD4, A0A0B4J1U6, A0A0B4J241, A0A0B4J274, A0A0B4J2E0, A0A0C4DH25, A0A0C4DH55, A0A0C4DH59, A0A0K0K1C0, A0A0K0K1G6, A0A1B0GX49, A0A1B0GX51, A0A1B0GX78, A0A1B0GXF2, A0A539, A0A576, A0A577, A0A578, A0A584, A0A589, A0A597

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	5
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
545240	NC_000002.12:g.(?106445028)(107839483_?)del	Likely pathogenic

SpliceAI

30 predictions. Top by Δscore:

Variant	Effect	Δscore
2:106487365:CCCA:C	donor_gain	0.9800
2:106487367:CAC:C	donor_loss	0.9300
2:106487368:A:T	donor_loss	0.9300
2:106487369:C:A	donor_loss	0.9300
2:106487364:AC:A	donor_gain	0.9200
2:106487365:CC:C	donor_gain	0.9200
2:106487364:A:AC	donor_gain	0.9100
2:106487365:C:CC	donor_gain	0.9100
2:106487368:A:AC	donor_gain	0.9000
2:106487368:AC:A	donor_gain	0.9000
2:106487369:C:CC	donor_gain	0.9000
2:106487369:CC:C	donor_gain	0.9000
2:106487370:C:T	donor_loss	0.8800
2:106487368:ACC:A	donor_gain	0.8400
2:106487369:CCC:C	donor_gain	0.8400
2:106487364:A:AG	donor_loss	0.5300
2:106487365:CCCAC:C	donor_loss	0.5300
2:106487366:C:G	donor_loss	0.5300
2:106487364:ACC:A	donor_gain	0.5100
2:106487365:CCC:C	donor_gain	0.5100
2:106487379:G:GT	donor_gain	0.4800
2:106487366:CCACC:C	donor_gain	0.4500
2:106487367:CACCC:C	donor_gain	0.4500
2:106487368:ACCCC:A	donor_gain	0.4500
2:106487369:CCCC:C	donor_gain	0.4400
2:106487370:C:G	donor_gain	0.4400
2:106487371:C:T	donor_loss	0.3900
2:106487370:C:CT	donor_loss	0.3300
2:106487371:C:A	donor_gain	0.3200
2:106487374:G:C	donor_gain	0.2500

AlphaMissense

1362 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:106491206:T:C	F126L	0.971
2:106491208:C:A	F126L	0.971
2:106491208:C:G	F126L	0.971
2:106490992:G:C	W54C	0.967
2:106490992:G:T	W54C	0.967
2:106491170:T:G	Y114D	0.962
2:106491176:T:A	C116S	0.947
2:106491177:G:C	C116S	0.947
2:106490998:A:C	R56S	0.945
2:106490998:A:T	R56S	0.945
2:106491132:T:C	L101P	0.931
2:106490990:T:A	W54R	0.930
2:106490990:T:C	W54R	0.930
2:106491035:T:C	F69L	0.930
2:106491037:C:A	F69L	0.930
2:106491037:C:G	F69L	0.930
2:106491171:A:G	Y114C	0.930
2:106491177:G:A	C116Y	0.930
2:106491173:T:C	F115L	0.927
2:106491175:C:A	F115L	0.927
2:106491175:C:G	F115L	0.927
2:106491138:T:C	L103P	0.926
2:106491176:T:C	C116R	0.926
2:106491178:C:G	C116W	0.925
2:106491165:G:T	G112V	0.918
2:106491225:T:C	L132P	0.914
2:106490997:G:C	R56T	0.912
2:106490994:T:C	L55P	0.903
2:106490951:T:A	C41S	0.901
2:106490952:G:C	C41S	0.901

dbSNP variants (sampled 300 via entrez): RS1000001071 (2:106533081 G>A,C), RS1000113624 (2:106502482 T>C), RS1000179797 (2:106528083 G>A), RS1000245833 (2:106543196 A>C,G,T), RS1000366047 (2:106508428 G>A), RS1000428933 (2:106513642 C>T), RS1000438075 (2:106526526 T>C), RS1000477837 (2:106495755 A>G), RS1000571972 (2:106542258 C>T), RS1000649835 (2:106518147 G>T), RS1000782801 (2:106489513 C>T), RS1000801321 (2:106536996 G>T), RS1000851816 (2:106530539 A>C), RS1000962111 (2:106496082 G>GCCA), RS1000966473 (2:106536184 G>A,C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:181500

GenCC curated gene-disease

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
beta-lapachone	decreases expression	1
Benzo(a)pyrene	affects methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety