BST2

Summary

BST2 (bone marrow stromal cell antigen 2, HGNC:1119) is a protein-coding gene on chromosome 19p13.11, encoding Bone marrow stromal antigen 2 (Q10589). IFN-induced antiviral host restriction factor which efficiently blocks the release of diverse mammalian enveloped viruses by directly tethering nascent virions to the membranes of infected cells.

Bone marrow stromal cells are involved in the growth and development of B-cells. The specific function of the protein encoded by the bone marrow stromal cell antigen 2 is undetermined; however, this protein may play a role in pre-B-cell growth and in rheumatoid arthritis.

Source: NCBI Gene 684 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• Druggable target: yes
• MANE Select transcript: NM_004335

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1119
Approved symbol	BST2
Name	bone marrow stromal cell antigen 2
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	CD317, tetherin, BST-2, HM1.24
Ensembl gene	ENSG00000130303
Ensembl biotype	protein_coding
OMIM	600534
Entrez	684

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000252593, ENST00000527220, ENST00000533098, ENST00000860181, ENST00000860182, ENST00000860183, ENST00000860184, ENST00000860185, ENST00000860186

RefSeq mRNA: 1 — MANE Select: NM_004335 NM_004335

CCDS: CCDS12358

Canonical transcript exons

ENST00000252593 — 5 exons

Exon	Start	End
ENSE00000665591	17404371	17404437
ENSE00001257451	17402939	17403326
ENSE00001728588	17405291	17405630
ENSE00003635845	17403680	17403824
ENSE00003655252	17404129	17404189

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.4462 / max 439.6829, expressed in 1137 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179864	13.3254	1107
179865	0.5942	323
179863	0.3707	192
208723	0.1559	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	99.52	gold quality
right adrenal gland cortex	UBERON:0035827	99.51	gold quality
left adrenal gland	UBERON:0001234	99.49	gold quality
left adrenal gland cortex	UBERON:0035825	99.49	gold quality
left ovary	UBERON:0002119	99.47	gold quality
adrenal cortex	UBERON:0001235	99.45	gold quality
right ovary	UBERON:0002118	99.44	gold quality
adrenal gland	UBERON:0002369	98.93	gold quality
left uterine tube	UBERON:0001303	98.89	gold quality
monocyte	CL:0000576	98.74	gold quality
granulocyte	CL:0000094	98.62	gold quality
spleen	UBERON:0002106	98.49	gold quality
right uterine tube	UBERON:0001302	98.48	gold quality
peritoneum	UBERON:0002358	98.44	gold quality
omental fat pad	UBERON:0010414	98.44	gold quality
leukocyte	CL:0000738	98.35	gold quality
mononuclear cell	CL:0000842	98.35	gold quality
gall bladder	UBERON:0002110	98.07	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.05	gold quality
apex of heart	UBERON:0002098	98.02	gold quality
right lobe of liver	UBERON:0001114	97.79	gold quality
pericardium	UBERON:0002407	97.69	gold quality
mucosa of stomach	UBERON:0001199	97.63	gold quality
lymph node	UBERON:0000029	97.43	gold quality
right lung	UBERON:0002167	97.32	gold quality
ovary	UBERON:0000992	97.21	gold quality
upper lobe of left lung	UBERON:0008952	97.05	gold quality
descending thoracic aorta	UBERON:0002345	97.03	gold quality
thoracic aorta	UBERON:0001515	96.50	gold quality
ascending aorta	UBERON:0001496	96.47	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 27.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	3321.36
E-GEOD-124472	yes	3199.59
E-HCAD-10	yes	2837.65
E-HCAD-24	yes	1563.71
E-ENAD-20	yes	1004.43
E-MTAB-8559	yes	845.71
E-HCAD-13	yes	418.66
E-HCAD-6	yes	403.04
E-MTAB-10018	yes	274.59
E-MTAB-10290	yes	215.14
E-MTAB-6701	yes	97.79
E-HCAD-4	yes	79.55
E-MTAB-10287	yes	71.79
E-MTAB-10553	yes	59.14
E-HCAD-1	yes	54.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ERCC6, GATA1, STAT1, STAT2, STAT3, TFAP2A

miRNA regulators (miRDB)

6 targeting BST2, 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-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-1266-5P	97.71	66.92	1052

Literature-anchored findings (GeneRIF, showing 40)

• CD317 expression correlated with, and induced, a requirement for Vpu during HIV-1 and murine leukaemia virus particle release (PMID:18200009)
• CD317, a tetherin, is associated with antiviral activity; tetherin expression correlates with a requirement for the antiviral antagonist Vpu during HIV-1 virus particle release. (PMID:18200009)
• Interferon-alpha enhances BST2 expression and the antitumor activity of anti-CD317 monoclonal antibody in renal cell carcinoma xenogfraft models. (PMID:19032371)
• Tetherin inhibits the release of Lassa and Marburg virus from host cells. (PMID:19091864)
• Thus, CD317 provides a physical link between lipid rafts and the apical actin network in polarized epithelial cells and is crucial for the maintenance of microvilli in such cells. (PMID:19273615)
• HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells. (PMID:19286137)
• Results provide novel data indicating the BST2 protein expression is associated with the formation of bone metastases in human breast cancer and that BST2 may be a potential biomarker in breast cancer with bone metastasis. (PMID:19338666)
• Clathrin-dependent endocytosis of human CD317 from the cell surface lipid rafts is mediated by direct interaction with alpha-adaptin. (PMID:19359243)
• findings show that SIV Nef overcomes restriction by rhesus macaque & sooty mangabey tetherin, but not human tetherin; HIV-1 Vpu counteracts restriction by human tetherin, but is ineffective against macaque or mangabey tetherin (PMID:19436700)
• study provides evidence that tetherin is important in protecting against viral infection, and that the HIV-1 Vpu-mediated countermeasure is specifically adapted to act against human tetherin (PMID:19461879)
• Vpu antagonizes human BST-2 through interacting with the transmembrane domain of BST-2. (PMID:19474106)
• Vpu co-opts the beta-TrCP/SCF E3 ubiquitin ligase complex to induce endosomal trafficking events that remove BST-2 from its site of action as a virion-tethering factor. (PMID:19478868)
• hBST-2 has potential to suppress the release of Vpu-deficient HIV-1. hBST-2 can tether HIV-1 particles without the need of additional co-factor(s) that may be expressed exclusively in primates. (PMID:19490609)
• Vpu appears to interact with BST-2 in the trans-Golgi network or in early endosomes, leading to lysosomal degradation of BST-2. (PMID:19515779)
• Data show that BST2 directly binds to purified ILT7, initiates signaling via the ILT7-FcepsilonRIgamma complex, and regulates TLR7/9 responses in plasmacytoid dendritic cells. (PMID:19564354)
• KSHV release is decreased in the absence of K5 in a BST2-dependent manner, suggesting that K5 contributes to the evasion of intracellular antiviral defense programs (PMID:19605472)
• Analysis of single, double, or triple cysteine mutants revealed that any one of three cysteine residues present in the BST-2 extracellular domain was sufficient for BST-2 dimerization, for inhibition of virus release, and sensitivity to Vpu. (PMID:19737401)
• HIV-2 envelope glycoprotein antagonism by intracellular sequestration (PMID:19740980)
• tetherin retains progeny virions on the cell surface by a mechanism other than dimerization (PMID:19742323)
• Results show that HIV-1 Vpu physically interacts with BST-2 through their mutual transmembrane domains and leads to the degradation of this host factor via a lysosomal, not proteasomal, pathway. (PMID:19837671)
• These observations emphasize the importance of tetherin in protecting mammals against viral infection and suggest that HIV-1 Vpu inhibitors may select active envelope mutants. (PMID:19864625)
• Study demonstrates, through mutational analyses and domain replacement experiments, that tetherin configuration rather than primary sequence is critical for antiviral activity. (PMID:19879838)
• Data show that human tetherin, recently described as an antiviral protein able to inhibit the release of enveloped viruses, and its porcine homologue can inhibit PERV release from producer cells. (PMID:20015985)
• BCA2 is a co-factor or enhancer for the tetherin-dependent restriction of HIV-1 release from infected cells. (PMID:20019814)
• The authors show that mutation of serine 52 to alanine (S52A) entirely disrupts Vpu-mediated degradation of CD4 and strongly impairs its ability to antagonize tetherin. (PMID:20078884)
• Data show that tetherin restricts particle release and does not require CAML for this effect. (PMID:20126395)
• tetherin is the physical tether linking HIV-1 virions and the plasma membrane. (PMID:20140192)
• CD317 localizes to the plasma membrane, to early and recycling endosomes, and to the trans-Golgi network and largely relocates to endosomes upon HIV-1 infection (PMID:20147389)
• These data show that HIV-1 Vpu can efficiently antagonize virion tethering in the absence of CD317 degradation. (PMID:20147395)
• incorporation of BST-2 into viral envelopes underlies its broad restrictive activity, whereas its relative exclusion from virions and sites of viral assembly by proteins such as HIV-1 Vpu may provide viral antagonism of restriction (PMID:20221443)
• Tetherin inhibits virus shedding during HIV1 infection. (PMID:20329562)
• The authors propose that the irregular coiled coil provides conformational flexibility, ensuring that BST-2/tetherin anchoring both in the plasma membrane and in the newly formed virus membrane is maintained during virus budding. (PMID:20399176)
• These findings suggest that Ebola virus GP uses a novel mechanism to circumvent tetherin restriction. (PMID:20444895)
• Combined evolutionary and functional studies have allowed reconstruction of the host-pathogen interactions that have shaped Tetherin and its lentivirus-encoded antagonists, including Vpu and Nef. (PMID:20444900)
• viral proteins such as HIV-1 Vpu, simian immunodeficiency virus Nef, and KSHV K5 counteract BST-2, thereby allowing mature virions to readily escape from infected cells (PMID:20485522)
• Both HIV-1 Vpu and HIV-2 Env redirect tetherin away from the cell surface and sequester the protein in a perinuclear compartment, which likely blocks the action of this cellular restriction factor. (PMID:20529266)
• Tetherin restricts productive HIV-1 cell-to-cell transmission. (PMID:20585562)
• TLR3 acativation by polyI:C resulted in inhibition of HIV infections in macrophages via induction of type 1 interferon antiviral factors, tetherin and APOBEC3G. (PMID:20636339)
• Elevated cellular levels of BST-2 inhibited the release of virus-like particles consisting of the matrix proteins of multiple highly virulent NIAID Priority Pathogens (PMID:20686043)
• siRNA-mediated knockdown of CD317 relieved a virion release restriction and markedly enhanced the egress of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) in rat cells, including primary macrophages. (PMID:20702620)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bst2	ENSMUSG00000046718
rattus_norvegicus	Bst2	ENSRNOG00000059900

Protein

Protein identifiers

Bone marrow stromal antigen 2 — Q10589 (reviewed: Q10589)

Alternative names: HM1.24 antigen, Tetherin

All UniProt accessions (3): Q10589, A0A024R7H5, A0A7P0T9F9

UniProt curated annotations — full annotation on UniProt →

Function. IFN-induced antiviral host restriction factor which efficiently blocks the release of diverse mammalian enveloped viruses by directly tethering nascent virions to the membranes of infected cells. Acts as a direct physical tether, holding virions to the cell membrane and linking virions to each other. The tethered virions can be internalized by endocytosis and subsequently degraded or they can remain on the cell surface. In either case, their spread as cell-free virions is restricted. Its target viruses belong to diverse families, including retroviridae: human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency viruses (SIVs), equine infectious anemia virus (EIAV), feline immunodeficiency virus (FIV), prototype foamy virus (PFV), Mason-Pfizer monkey virus (MPMV), human T-cell leukemia virus type 1 (HTLV-1), Rous sarcoma virus (RSV) and murine leukemia virus (MLV), flavivirideae: hepatitis C virus (HCV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), arenaviridae: lassa virus (LASV) and machupo virus (MACV), herpesviridae: kaposis sarcoma-associated herpesvirus (KSHV), rhabdoviridae: vesicular stomatitis virus (VSV), orthomyxoviridae: influenza A virus, paramyxoviridae: nipah virus, and coronaviridae: SARS-CoV. Can inhibit cell surface proteolytic activity of MMP14 causing decreased activation of MMP15 which results in inhibition of cell growth and migration. Can stimulate signaling by LILRA4/ILT7 and consequently provide negative feedback to the production of IFN by plasmacytoid dendritic cells in response to viral infection. Plays a role in the organization of the subapical actin cytoskeleton in polarized epithelial cells. Isoform 1 and isoform 2 are both effective viral restriction factors but have differing antiviral and signaling activities. Isoform 2 is resistant to HIV-1 Vpu-mediated degradation and restricts HIV-1 viral budding in the presence of Vpu. Isoform 1 acts as an activator of NF-kappa-B and this activity is inhibited by isoform 2.

Subunit / interactions. Parallel homodimer; disulfide-linked. May form homotetramers under reducing conditions. Isoform 1 and isoform 2 form homodimers and also heterodimers with each other. Dimerization is essential for its antiviral activity. Interacts (via cytoplasmic domain) with ARHGAP44. Interacts with MMP14 (via C-terminal cytoplasmic tail). Interacts with LILRA4/ILT7. Interacts with RNF115. (Microbial infection) Interacts with ebola GP protein. (Microbial infection) Interacts (via transmembrane domain) with HIV-1 VPU (via transmembrane domain). (Microbial infection) Interacts with HIV-2 ENV. (Microbial infection) Interacts with SARS-CoV ORF7a protein. (Microbial infection) Interacts with rabies virus protein G.

Subcellular location. Golgi apparatus. trans-Golgi network. Cell membrane. Membrane raft. Cytoplasm. Apical cell membrane Golgi apparatus. Late endosome.

Tissue specificity. Predominantly expressed in liver, lung, heart and placenta. Lower levels in pancreas, kidney, skeletal muscle and brain. Overexpressed in multiple myeloma cells. Highly expressed during B-cell development, from pro-B precursors to plasma cells. Highly expressed on T-cells, monocytes, NK cells and dendritic cells (at protein level).

Post-translational modifications. Monoubiquitinated by KSHV E3 ubiquitin-protein ligase K5, leading to its targeting to late endosomes and degradation. The GPI anchor is essential for its antiviral activity. Heavily glycosylated.

Domain organisation. The extracellular coiled coil domain forms an extended 170 A long semi-flexible rod-like structure important for virion retention at the cell surface and prevention of virus spreading.

Induction. By type I interferons. (Microbial infection) Down-regulated by HIV-1 VPU protein. Antagonizes its function by targeting it to the trans-Golgi network, sequestering it away from virus assembly sites on the cell membrane. VPU also acts as an adapter molecule linking it to BTRC, a substrate recognition subunit of the Skp1/Cullin/F-box protein E3 ubiquitin ligase, inducing its ubiquitination and subsequent proteasomal degradation. (Microbial infection) Down-regulated by HIV-2 ENV protein. Antagonizes its function by targeting it to the trans-Golgi network, sequestering it away from virus assembly sites on the cell membrane. (Microbial infection) Down-regulated by KSHV K5 protein. K5 ubiquitinates it leading to its targeting to late endosomes and degradation. (Microbial infection) Down-regulated by ebola virus GP protein. (Microbial infection) Made inactive by SARS-CoV ORF7a protein through impairing proper glycosylation. May be down-regulated by SARS-CoV Spike protein through lysosomal degradation pathway.

Miscellaneous. Tetherin shows evidence of positive (adaptive) selection, presumably as a result of evolutionary pressure applied by antagonistic viral proteins that counteract its inhibitiory activity and this has led to the species-specific tetherin sensitivity to viral countermeasures. For example, Tantalus monkey tetherin cannot be abrogated by HIV-1 VPU due to variation in the tetherin transmembrane region. Similarly, SIV Nefs are able to overcome simian tetherins, but not human tetherin, due to a unique 5-amino-acid deletion in the cytoplasmic tail domain of human tetherin. Produced by alternative initiation at Met-13 of isoform 1.

Similarity. Belongs to the tetherin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q10589-1	1, l-Tetherin	yes
Q10589-2	2, s-Tetherin

RefSeq proteins (1): NP_004326* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024886	BST2	Family

Pfam: PF16716

UniProt features (29 total): mutagenesis site 10, disulfide bond 3, topological domain 2, strand 2, glycosylation site 2, chain 1, propeptide 1, cross-link 1, splice variant 1, sequence variant 1, sequence conflict 1, helix 1, transmembrane region 1, coiled-coil region 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
7Q9A	X-RAY DIFFRACTION	2.1
3MQ7	X-RAY DIFFRACTION	2.28
3NWH	X-RAY DIFFRACTION	2.6
2X7A	X-RAY DIFFRACTION	2.77
3MQ9	X-RAY DIFFRACTION	2.8
3MQC	X-RAY DIFFRACTION	2.8
4P6Z	X-RAY DIFFRACTION	3
3MQB	X-RAY DIFFRACTION	3.2
2XG7	X-RAY DIFFRACTION	3.45
6CM9	ELECTRON MICROSCOPY	3.73
6DFF	ELECTRON MICROSCOPY	3.9
6D83	ELECTRON MICROSCOPY	4.27
6D84	ELECTRON MICROSCOPY	6.72
6CRI	ELECTRON MICROSCOPY	6.8
2LK9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q10589-F1	85.63	0.69

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 (2): 18, 161

Disulfide bonds (3): 63, 91, 53

Glycosylation sites (2): 65, 92

Mutagenesis-validated functional residues (10):

Position	Phenotype
3–5	partial resistance to vpu.
6	partial resistance to vpu and significantly reduced activation of nf-kb; when associated with a-8.
8	partial resistance to vpu and significantly reduced activation of nf-kb; when associated with a-6.
18	abolishes redistribution to late endosomes in cells expressing ksh virus e3 ubiquitin-protein ligase k5.
21	no effect on redistribution to late endosomes in cells expressing ksh virus e3 ubiquitin-protein ligase k5.
53	prevents homodimerization and inhibition of sars-cov, hcov-229e, and hiv-1 viral particles production ex vivo; when asso
63	prevents homodimerization and inhibition of sars-cov, hcov-229e, and hiv-1 viral particles production ex vivo; when asso
65	loss of glycosylation site.
91	prevents homodimerization and inhibition of sars-cov, hcov-229e, and hiv-1 viral particles production ex vivo; when asso
92	loss of glycosylation site. impairs anti-viral activity.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-5663205	Infectious disease
R-HSA-913531	Interferon Signaling
R-HSA-9678108	SARS-CoV-1 Infection
R-HSA-9679506	SARS-CoV Infections
R-HSA-9692914	SARS-CoV-1-host interactions
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 431 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, MODULE_92, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, MODULE_151, BECKER_TAMOXIFEN_RESISTANCE_UP, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, MODULE_64

GO Biological Process (16): negative regulation of plasmacytoid dendritic cell cytokine production (GO:0002737), response to virus (GO:0009615), negative regulation of cell growth (GO:0030308), negative regulation of cell migration (GO:0030336), regulation of actin cytoskeleton organization (GO:0032956), response to type II interferon (GO:0034341), response to interferon-alpha (GO:0035455), response to interferon-beta (GO:0035456), B cell activation (GO:0042113), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of viral genome replication (GO:0045071), innate immune response (GO:0045087), defense response to virus (GO:0051607), positive regulation of leukocyte proliferation (GO:0070665), negative regulation of intracellular transport of viral material (GO:1901253), immune system process (GO:0002376)

GO Molecular Function (5): RNA binding (GO:0003723), metalloendopeptidase inhibitor activity (GO:0008191), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (13): multivesicular body (GO:0005771), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), apical plasma membrane (GO:0016324), azurophil granule membrane (GO:0035577), membrane raft (GO:0045121), extracellular exosome (GO:0070062), side of membrane (GO:0098552), cytoplasm (GO:0005737), endosome (GO:0005768), late endosome (GO:0005770)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Immune System	2
Innate Immune System	1
Interferon Signaling	1
SARS-CoV-1-host interactions	1
Disease	1
Cytokine Signaling in Immune system	1
SARS-CoV Infections	1
Viral Infection Pathways	1
SARS-CoV-1 Infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
response to cytokine	3
endomembrane system	2
membrane	2
plasmacytoid dendritic cell cytokine production	1
negative regulation of dendritic cell cytokine production	1
regulation of plasmacytoid dendritic cell cytokine production	1
response to other organism	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
innate immune response	1
lymphocyte activation	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
immune response	1
defense response to symbiont	1
defense response	1
response to virus	1
positive regulation of cell population proliferation	1
leukocyte proliferation	1
regulation of leukocyte proliferation	1
intracellular transport of virus	1
regulation of intracellular transport of viral material	1
negative regulation of viral life cycle	1
biological_process	1
nucleic acid binding	1
metalloendopeptidase activity	1
endopeptidase inhibitor activity	1

Protein interactions and networks

STRING

1810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BST2	LILRA4	P59901	993
BST2	D6RGC4	D6RGC4	971
BST2	APOBEC3G	Q9HC16	939
BST2	AGRN	O00468	884
BST2	TRIM5	Q9C035	842
BST2	SAMHD1	Q9Y3Z3	791
BST2	CD4	P01730	784
BST2	PLVAP	Q9BX97	747
BST2	CAMLG	P49069	728
BST2	RIGI	O95786	715
BST2	MX2	P20592	703
BST2	ISG15	P05161	679
BST2	ARHGAP44	Q17R89	679
BST2	RSAD2	Q8WXG1	667
BST2	IFNA13	P01562	666

IntAct

54 interactions, top by confidence:

A	B	Type	Score
BST2	BST2	psi-mi:“MI:0408”(disulfide bond)	0.830
BST2	BST2	psi-mi:“MI:0407”(direct interaction)	0.830
BST2	BST2	psi-mi:“MI:0195”(covalent binding)	0.830
BST2	BST2	psi-mi:“MI:0915”(physical association)	0.830
LILRA4	BST2	psi-mi:“MI:0407”(direct interaction)	0.680
LILRA4	BST2	psi-mi:“MI:0915”(physical association)	0.680
vpu	BST2	psi-mi:“MI:0915”(physical association)	0.630
BST2	vpu	psi-mi:“MI:0407”(direct interaction)	0.630
vpu	BST2	psi-mi:“MI:0403”(colocalization)	0.630
CD81	BST2	psi-mi:“MI:0915”(physical association)	0.560
	BST2	psi-mi:“MI:0407”(direct interaction)	0.540
BST2	Ap1m1	psi-mi:“MI:0407”(direct interaction)	0.530
Ap1m1	BST2	psi-mi:“MI:0915”(physical association)	0.530
BST2	GP	psi-mi:“MI:0915”(physical association)	0.520
BST2	vpu	psi-mi:“MI:0915”(physical association)	0.460
BST2	vpu	psi-mi:“MI:0403”(colocalization)	0.460
BST2	RPL14	psi-mi:“MI:0915”(physical association)	0.400
BST2	RBBP5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (75): BST2 (Affinity Capture-MS), BST2 (Affinity Capture-MS), BST2 (Affinity Capture-MS), BST2 (Affinity Capture-MS), BST2 (Affinity Capture-MS), BST2 (Affinity Capture-MS), BST2 (Affinity Capture-RNA), BST2 (Affinity Capture-MS), BST2 (Affinity Capture-MS), VDAC3 (Co-fractionation), BST2 (Co-fractionation), BST2 (Co-fractionation), BST2 (Co-fractionation), BST2 (Co-fractionation), BST2 (Affinity Capture-MS)

ESM2 similar proteins: A2VE00, A5PK14, F1QEA1, O75324, P0DKX4, P20826, P21581, P21583, P58550, P59773, P61807, P61808, P79169, P79368, Q06220, Q09108, Q10589, Q15053, Q17Q87, Q28132, Q28C41, Q28GJ0, Q29030, Q2T9X8, Q3UQS2, Q5PQQ9, Q5RBY6, Q5RKG1, Q5U3Z6, Q640L3, Q6AY06, Q6DF94, Q6IQY5, Q6NRX3, Q811A2, Q86YF9, Q8BIS8, Q8BMD2, Q8C804, Q8N0Z3

Diamond homologs: Q10589, Q6WRU0, Q811A2, Q8R2Q8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

467 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17403685:T:TA	donor_gain	1.0000
19:17403697:A:AC	donor_gain	1.0000
19:17403698:C:CC	donor_gain	1.0000
19:17403820:CTCTT:C	acceptor_gain	1.0000
19:17403822:CTT:C	acceptor_gain	1.0000
19:17403823:TT:T	acceptor_gain	1.0000
19:17403824:TCT:T	acceptor_loss	1.0000
19:17403825:C:CC	acceptor_gain	1.0000
19:17405286:CTTAC:C	donor_loss	1.0000
19:17405288:TA:T	donor_loss	1.0000
19:17405289:A:AC	donor_gain	1.0000
19:17405289:AC:A	donor_gain	1.0000
19:17405289:ACCAC:A	donor_loss	1.0000
19:17405290:C:CC	donor_gain	1.0000
19:17405290:CC:C	donor_gain	1.0000
19:17405290:CCA:C	donor_gain	1.0000
19:17405290:CCACA:C	donor_gain	1.0000
19:17405328:T:TA	donor_gain	1.0000
19:17403669:T:TA	donor_gain	0.9900
19:17403674:A:AC	donor_gain	0.9900
19:17403675:C:CC	donor_gain	0.9900
19:17403679:CCAG:C	donor_gain	0.9900
19:17403698:CTG:C	donor_gain	0.9900
19:17403826:T:A	acceptor_loss	0.9900
19:17403829:G:T	acceptor_gain	0.9900
19:17403830:G:GC	acceptor_gain	0.9900
19:17404190:C:CC	acceptor_gain	0.9900
19:17404193:G:C	acceptor_gain	0.9900
19:17404193:G:GC	acceptor_gain	0.9900
19:17404198:G:C	acceptor_gain	0.9900

AlphaMissense

1160 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17404162:A:G	L127P	0.986
19:17404154:C:G	A130P	0.974
19:17404132:A:G	L137P	0.972
19:17405355:A:G	L74P	0.965
19:17404376:A:G	L116P	0.963
19:17404430:A:G	L98P	0.946
19:17404183:A:G	I120T	0.942
19:17405464:C:G	G38R	0.938
19:17405464:C:T	G38R	0.938
19:17405347:C:G	A77P	0.935
19:17404183:A:C	I120S	0.928
19:17405376:G:A	T67I	0.925
19:17404174:A:G	L123S	0.920
19:17404135:C:G	R136P	0.906
19:17404151:A:G	S131P	0.904
19:17404422:A:G	S101P	0.903
19:17405401:C:G	A59P	0.900
19:17404162:A:T	L127H	0.894
19:17405444:G:C	F44L	0.893
19:17405444:G:T	F44L	0.893
19:17405446:A:G	F44L	0.893
19:17405367:A:G	L70P	0.889
19:17405333:A:C	F81L	0.888
19:17405333:A:T	F81L	0.888
19:17405335:A:G	F81L	0.888
19:17404148:C:G	A132P	0.885
19:17404413:C:G	A104P	0.882
19:17405410:C:G	G56R	0.878
19:17404376:A:T	L116H	0.871
19:17404418:A:G	L102P	0.853

dbSNP variants (sampled 300 via entrez): RS1000906895 (19:17406000 C>G,T), RS1000937391 (19:17406221 C>G,T), RS1001694957 (19:17406924 G>T), RS1002035142 (19:17405696 G>C), RS1002947281 (19:17404930 C>T), RS1003830786 (19:17402712 C>T), RS1004079821 (19:17404153 G>A), RS1004828258 (19:17406931 C>A), RS1005933084 (19:17406608 C>A,T), RS1006178016 (19:17403967 C>T), RS1006335908 (19:17403591 CCTCT>C,CCT,CCTCTCT), RS1006726225 (19:17404832 C>G,T), RS1007228969 (19:17407493 G>A), RS1008794952 (19:17404700 T>C), RS1008872741 (19:17406036 G>A,C)

Disease associations

OMIM: gene MIM:600534 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067079 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.67	Kd	215.9	nM	CHEMBL3752910
6.67	ED50	215.9	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147961: Binding affinity to human BST2 incubated for 45 mins by Kinobead based pull down assay	kd	0.2159	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, decreases expression, increases expression	5
sodium arsenite	decreases expression, increases expression	4
Estradiol	affects cotreatment, increases expression, decreases expression	4
Tretinoin	affects expression, affects cotreatment, increases expression, decreases expression	4
(+)-JQ1 compound	decreases expression	3
Tetrachlorodibenzodioxin	increases expression, decreases expression, affects cotreatment	3
Cyclosporine	decreases expression, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Resveratrol	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	increases methylation, decreases expression	2
Methotrexate	affects response to substance, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
GSK-J4	decreases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects expression	1
kojic acid	decreases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel chloride	affects cotreatment, increases expression	1
chloroquine diphosphate	decreases expression	1
nickel sulfate	increases expression	1
hydroquinone	decreases expression	1
pentanal	increases expression	1
tamibarotene	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651003	Binding	Binding affinity to human BST2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1BT	Abcam A-431 BST2 KO	Cancer cell line	Female
CVCL_D9AC	Ubigene HEK293 BST2 KO	Transformed cell line	Female
CVCL_SF88	HAP1 BST2 (-) 1	Cancer cell line	Male
CVCL_SF89	HAP1 BST2 (-) 2	Cancer cell line	Male
CVCL_WL54	Teth-CRFK	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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