VSIR

gene
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Also known as SISP1GI24B7-H5B7H5VISTAPD-1HDies1

Summary

VSIR (V-set immunoregulatory receptor, HGNC:30085) is a protein-coding gene on chromosome 10q22.1, encoding V-type immunoglobulin domain-containing suppressor of T-cell activation (Q9H7M9). Immunoregulatory receptor which inhibits the T-cell response.

Enables endopeptidase activator activity; enzyme binding activity; and identical protein binding activity. Involved in several processes, including negative regulation of cytokine production; positive regulation of metabolic process; and regulation of T cell activation. Located in plasma membrane.

Source: NCBI Gene 64115 — RefSeq curated summary.

At a glance

  • GWAS associations: 16
  • Clinical variants (ClinVar): 1 total
  • Druggable target: yes
  • MANE Select transcript: NM_022153

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:30085
Approved symbolVSIR
NameV-set immunoregulatory receptor
Location10q22.1
Locus typegene with protein product
StatusApproved
AliasesSISP1, GI24, B7-H5, B7H5, VISTA, PD-1H, Dies1
Ensembl geneENSG00000107738
Ensembl biotypeprotein_coding
OMIM615608
Entrez64115

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000394957, ENST00000470317, ENST00000481568, ENST00000866267, ENST00000866268, ENST00000866269, ENST00000866270, ENST00000866271, ENST00000866272, ENST00000954601, ENST00000954602

RefSeq mRNA: 1 — MANE Select: NM_022153 NM_022153

CCDS: CCDS31218

Canonical transcript exons

ENST00000394957 — 7 exons

ExonStartEnd
ENSE000008343947176159871762026
ENSE000011853507174755671751290
ENSE000012408677176086871760924
ENSE000017963777177335871773520
ENSE000032365717175166871751861
ENSE000032568097175535971755466
ENSE000032774347175297571753002

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 99.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.5478 / max 2760.7204, expressed in 1425 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
10989238.31701410
1098931.3026742
1098940.7367471
1098880.191496

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
granulocyteCL:000009499.32gold quality
leukocyteCL:000073899.07gold quality
monocyteCL:000057699.05gold quality
bloodUBERON:000017898.93gold quality
bone marrow cellCL:000209298.24gold quality
spleenUBERON:000210698.13gold quality
vermiform appendixUBERON:000115497.97gold quality
right lungUBERON:000216797.68gold quality
tibial nerveUBERON:000132397.37gold quality
apex of heartUBERON:000209897.12gold quality
omental fat padUBERON:001041497.11gold quality
peritoneumUBERON:000235897.07gold quality
left uterine tubeUBERON:000130397.02gold quality
upper lobe of left lungUBERON:000895296.97gold quality
adipose tissue of abdominal regionUBERON:000780896.80gold quality
right coronary arteryUBERON:000162596.69gold quality
caecumUBERON:000115396.63gold quality
upper lobe of lungUBERON:000894896.46gold quality
lymph nodeUBERON:000002996.12gold quality
ileal mucosaUBERON:000033196.05gold quality
mucosa of stomachUBERON:000119995.58gold quality
nasal cavity epitheliumUBERON:000538495.53gold quality
gall bladderUBERON:000211095.51gold quality
coronary arteryUBERON:000162195.50gold quality
left coronary arteryUBERON:000162695.46gold quality
bone marrowUBERON:000237195.24gold quality
body of uterusUBERON:000985395.21gold quality
small intestine Peyer’s patchUBERON:000345495.13gold quality
subcutaneous adipose tissueUBERON:000219095.12gold quality
heart left ventricleUBERON:000208495.11gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 15.

ExperimentMarker?Max mean expression
E-GEOD-106540yes1444.47
E-HCAD-4yes177.48
E-CURD-122yes74.26
E-MTAB-10553yes33.81
E-HCAD-10yes30.91
E-MTAB-6701yes28.92
E-MTAB-6678yes28.08
E-CURD-112yes27.15
E-GEOD-134144yes26.52
E-MTAB-9221yes26.04
E-HCAD-9yes21.30
E-ANND-3yes20.23
E-MTAB-9467yes18.19
E-MTAB-8498yes10.44
E-MTAB-9801yes9.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4692100.0067.322066
HSA-MIR-451499.9967.101870
HSA-MIR-6721-5P99.9368.922981
HSA-MIR-497-5P99.9271.832674
HSA-MIR-498-3P99.9171.271114
HSA-MIR-15A-5P99.9072.802787
HSA-MIR-15B-5P99.9072.782798
HSA-MIR-16-5P99.9072.802780
HSA-MIR-195-5P99.9072.812805
HSA-MIR-424-5P99.8971.902641
HSA-MIR-6838-5P99.8971.942690
HSA-MIR-4731-5P99.8967.232537
HSA-MIR-449699.8868.892236
HSA-MIR-449299.8768.253611
HSA-MIR-3065-3P99.8770.251407
HSA-MIR-4728-5P99.8569.394718
HSA-MIR-130B-5P99.8368.501888
HSA-MIR-6785-5P99.8268.684428
HSA-MIR-205299.7969.372031
HSA-MIR-1273H-5P99.7766.322471
HSA-MIR-431999.7669.832586
HSA-MIR-6764-5P99.7567.892304
HSA-MIR-149-3P99.7268.223963
HSA-MIR-378G99.7164.901106
HSA-MIR-120099.7170.421838
HSA-MIR-3059-5P99.7069.932491
HSA-MIR-6883-5P99.6968.053785
HSA-MIR-453099.6966.471509
HSA-MIR-366099.6867.331149
HSA-MIR-6892-3P99.6866.401178

Literature-anchored findings (GeneRIF, showing 40)

  • Results suggest that GI24 contributes to tumor-invasive growth in the collagen matrix by augmenting cell surface MT1-MMP. (PMID:20666777)
  • overexpression of the newly described co-stimulatory molecule, PD1 homologue (PD-1H) in human monocyte/macrophages is sufficient to induce spontaneous secretion of multiple cytokines. (PMID:25279955)
  • p53-induced expression of DD1alpha prevents persistence of cell corpses and ensures efficient generation of precise immune responses in mice. (PMID:26228159)
  • Taken together, the results indicated that the VISTA high and CD8 low group, as an immunosuppressive subgroup, might be associated with a poor prognosis in primary OSCC. These findings indicated that VISTA might be a potential immunotherapeutic target in OSCC treatment. (PMID:28236118)
  • this review describes the functions of VISTA in the context of cancer immunotherapy (PMID:28258694)
  • This study is the first to describe the expression of VISTA-expressing lymphocytes in melanoma samples and in the context of acquired resistance to immune checkpoint inhibitors (PMID:28776578)
  • The immunomodulatory role of VISTA in human NSCLC. (PMID:29203588)
  • VISTA expression supports immune-complex inflammation in collagen antibody-induced arthritis and VISTA is expressed in human synovium (PMID:29216931)
  • VISTA protein expression in hepatocellular carcinoma showed cell specific and displayed different prognosis (PMID:29720116)
  • High VISTA expression is associated with primary cutaneous melanoma. (PMID:29737375)
  • Data indicate that VISTA is predominantly expressed and up-regulated in the high-density infiltrated immune cells but minimal in pancreatic cancerous cells. (PMID:29771768)
  • EGFR may be involved in immune evasion, possibly through regulation of B7H5 expression in nonsmall cell lung carcinoma. (PMID:30106102)
  • High VISTA expression is associated with colorectal carcinoma. (PMID:30128738)
  • this study shows that VSIG-3 as a ligand of VISTA inhibits human T-cell function (PMID:30220083)
  • This study is the first to demonstrate that in the CNS, VISTA is expressed by microglia, and that VISTA is differentially expressed in CNS pathologies. (PMID:30306644)
  • The data suggest that VISTA is a novel immunosuppressive factor within the tumour microenvironment, as well as a new target for cancer immunotherapy. (PMID:30382166)
  • VISTA may be a relevant immunotherapy target for effective treatment of patients with pancreatic cancer. (PMID:30635425)
  • Hypoxia-Induced VISTA Promotes the Suppressive Function of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment. (PMID:31088847)
  • Expression of V-set immunoregulatory receptor in malignant mesothelioma. (PMID:31363159)
  • Structure and Functional Binding Epitope of V-domain Ig Suppressor of T Cell Activation. (PMID:31484064)
  • V-domain Ig-containing suppressor of T-cell activation (VISTA), a potentially targetable immune checkpoint molecule, is highly expressed in epithelioid malignant pleural mesothelioma. (PMID:31537897)
  • findings identify a mechanism by which VISTA may engender resistance to anti-tumour immune responses, as well as an unexpectedly determinative role for pH in immune co-receptor engagement (PMID:31645726)
  • VISTA was detected in 51.4% of all samples and 46.6% of PD-L1-negative samples in patients with high-grade serous ovarian cancer. Furthermore, VISTA expression was associated with pathologic type and PD-L1 expression. Moreover, VISTA expression in tumor cells, but not in immune cells, was associated with prolonged progression-free and overall survival in patients with high-grade serous ovarian cancer. (PMID:31781843)
  • Overexpression of B7H5/CD28H is associated with worse survival in human gastric cancer. (PMID:31883303)
  • VISTA protein (B7-H5) is a ligand for transmembrane and immunoglobulin domain containing 2 protein (CD28H) and is widely expressed in tumor cells. B7-H5 expression is closely related to the prognosis of the tumor [Review]. (PMID:31901178)
  • FOXD3 Regulates VISTA Expression in Melanoma. (PMID:31940493)
  • VISTA is therefore a distinctive negative checkpoint regulator of naive T cells that is critical for steady-state maintenance of quiescence and peripheral tolerance. (PMID:31949051)
  • Prognostic value of VISTA in solid tumours: a systematic review and meta-analysis. (PMID:32060343)
  • Expression of TIM3/VISTA checkpoints and the CD68 macrophage-associated marker correlates with anti-PD1/PDL1 resistance: implications of immunogram heterogeneity. (PMID:32117584)
  • Galectin-9 and VISTA Expression Define Terminally Exhausted T Cells in HIV-1 Infection. (PMID:32205423)
  • Low VISTA expression is associated with breast cancer. (PMID:32266446)
  • VISTA: an immune regulatory protein checking tumor and immune cells in cancer immunotherapy. (PMID:32600443)
  • The prognostic significance of VISTA and CD33-positive myeloid cells in cutaneous melanoma and their relationship with PD-1 expression. (PMID:32873829)
  • High VISTA Expression Correlates With a Favorable Prognosis in Patients With Colorectal Cancer. (PMID:33086339)
  • VISTA Re-programs Macrophage Biology Through the Combined Regulation of Tolerance and Anti-inflammatory Pathways. (PMID:33178206)
  • The Expression Pattern and Clinical Significance of the Immune Checkpoint Regulator VISTA in Human Breast Cancer. (PMID:33250890)
  • Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity. (PMID:33329552)
  • LAG-3, TIM-3 and VISTA Expression on Tumor-Infiltrating Lymphocytes in Oropharyngeal Squamous Cell Carcinoma-Potential Biomarkers for Targeted Therapy Concepts. (PMID:33396515)
  • Expression of VISTA on tumor-infiltrating immune cells correlated with short intravesical recurrence in non-muscle-invasive bladder cancer. (PMID:33770210)
  • VISTA and PD-L1 synergistically predict poor prognosis in patients with extranodal natural killer/T-cell lymphoma. (PMID:33889438)

Cross-species orthologs

7 orthologs

OrganismSymbolGene ID
danio_reriovsig8bENSDARG00000013685
danio_reriojam2aENSDARG00000058996
danio_reriojam2bENSDARG00000079071
danio_reriosi:dkey-22i16.9ENSDARG00000095949
danio_rerioENSDARG00000116487
danio_rerioENSDARG00000116937
mus_musculusVsirENSMUSG00000020101

Paralogs (14): VSIG2 (ENSG00000019102), VSIG1 (ENSG00000101842), GPA33 (ENSG00000143167), IGSF11 (ENSG00000144847), ESAM (ENSG00000149564), CXADR (ENSG00000154639), JAM2 (ENSG00000154721), F11R (ENSG00000158769), MXRA8 (ENSG00000162576), JAM3 (ENSG00000166086), CLMP (ENSG00000166250), MUC15 (ENSG00000169550), VSTM2B (ENSG00000187135), VSIG8 (ENSG00000243284)

Protein

Protein identifiers

V-type immunoglobulin domain-containing suppressor of T-cell activationQ9H7M9 (reviewed: Q9H7M9)

Alternative names: Platelet receptor Gi24, Stress-induced secreted protein-1, V-set domain-containing immunoregulatory receptor, V-set immunoregulatory receptor

All UniProt accessions (1): Q9H7M9

UniProt curated annotations — full annotation on UniProt →

Function. Immunoregulatory receptor which inhibits the T-cell response. May promote differentiation of embryonic stem cells, by inhibiting BMP4 signaling. May stimulate MMP14-mediated MMP2 activation.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in spleen. Detected on a number of myeloid cells including CD11b monocytes, CD66b+ neutrophils, at low levels on CD4+ and CD8+ T-cells, and in a subset of NK cells. Not detected on B cells (at protein level). Expressed at high levels in placenta, spleen, plasma blood leukocytes, and lung. Expressed at moderate levels in lymph node, bone marrow, fat, uterus, and trachea. Has low expression levels in other tissues.

Post-translational modifications. At the cell surface, may be cleaved by MMP14. N-glycosylated.

RefSeq proteins (1): NP_071436* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR003599Ig_subDomain
IPR007110Ig-like_domDomain
IPR013106Ig_V-setDomain
IPR013783Ig-like_foldHomologous_superfamily
IPR036179Ig-like_dom_sfHomologous_superfamily
IPR042473VISTAFamily

Pfam: PF07686

UniProt features (33 total): strand 13, glycosylation site 3, sequence conflict 2, topological domain 2, turn 2, helix 2, modified residue 2, signal peptide 1, chain 1, disulfide bond 1, sequence variant 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDBMethodResolution (Å)
6MVLX-RAY DIFFRACTION1.61
6OILX-RAY DIFFRACTION1.85
6U6VX-RAY DIFFRACTION1.9
8TBQX-RAY DIFFRACTION2.59

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9H7M9-F173.890.33

Antibody-complex structures (SAbDab): 26MVL, 8TBQ

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): 235, 248

Disulfide bonds (1): 54–146

Glycosylation sites (3): 91, 128, 49

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 272 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, PEREZ_TP63_TARGETS, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, RODRIGUES_NTN1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY

GO Biological Process (14): positive regulation of gene expression (GO:0010628), positive regulation of endopeptidase activity (GO:0010950), positive regulation of cell migration (GO:0030335), zymogen activation (GO:0031638), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-10 production (GO:0032693), negative regulation of interleukin-17 production (GO:0032700), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of regulatory T cell differentiation (GO:0045591), negative regulation of alpha-beta T cell activation (GO:0046636), regulation of immune response (GO:0050776), positive regulation of collagen catabolic process (GO:0120158), negative regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000562), negative regulation of CD8-positive, alpha-beta T cell proliferation (GO:2000565)

GO Molecular Function (4): enzyme binding (GO:0019899), identical protein binding (GO:0042802), endopeptidase activator activity (GO:0061133), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
negative regulation of cytokine production3
endopeptidase activity2
negative regulation of alpha-beta T cell proliferation2
protein binding2
gene expression1
regulation of gene expression1
positive regulation of macromolecule biosynthetic process1
positive regulation of peptidase activity1
regulation of endopeptidase activity1
cell migration1
regulation of cell migration1
positive regulation of cell motility1
protein processing1
type II interferon production1
regulation of type II interferon production1
interleukin-10 production1
regulation of interleukin-10 production1
interleukin-17 production1
regulation of interleukin-17 production1
tumor necrosis factor production1
regulation of tumor necrosis factor production1
negative regulation of tumor necrosis factor superfamily cytokine production1
regulatory T cell differentiation1
positive regulation of T cell differentiation1
regulation of regulatory T cell differentiation1
alpha-beta T cell activation1
regulation of alpha-beta T cell activation1
negative regulation of T cell activation1
regulation of immune system process1
immune response1
regulation of response to stimulus1
positive regulation of catabolic process1
regulation of collagen catabolic process1
positive regulation of collagen metabolic process1
collagen catabolic process1
CD4-positive, alpha-beta T cell proliferation1
negative regulation of CD4-positive, alpha-beta T cell activation1
regulation of CD4-positive, alpha-beta T cell proliferation1
CD8-positive, alpha-beta T cell proliferation1
regulation of CD8-positive, alpha-beta T cell proliferation1

Protein interactions and networks

STRING

1054 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
VSIRBTLAQ7Z6A9794
VSIRIGSF11Q5DX21740
VSIRLGALS9O00182735
VSIRTMIGD2Q96BF3728
VSIRLAG3P18627713
VSIRHAVCR2Q8TDQ0697
VSIRCD28P10747680
VSIRTIGITQ495A1670
VSIRCD274Q9NZQ7667
VSIRCTLA4P16410661
VSIRLGALS9BQ3B8N2650
VSIRLGALS9CQ6DKI2650
VSIRVTCN1Q7Z7D3645
VSIRPDCD1Q15116621
VSIRCD40P25942613

IntAct

83 interactions, top by confidence:

ABTypeScore
VSIRVSIRpsi-mi:“MI:0407”(direct interaction)0.610
VSIRVSIRpsi-mi:“MI:0915”(physical association)0.610
TSPAN2VSIRpsi-mi:“MI:0915”(physical association)0.560
TMEM14CVSIRpsi-mi:“MI:0915”(physical association)0.560
PLPP6VSIRpsi-mi:“MI:0915”(physical association)0.560
TMEM97VSIRpsi-mi:“MI:0915”(physical association)0.560
CLRN2VSIRpsi-mi:“MI:0915”(physical association)0.560
SLC35B1VSIRpsi-mi:“MI:0915”(physical association)0.560
VSIRSMCO4psi-mi:“MI:0915”(physical association)0.560
VAMP3VSIRpsi-mi:“MI:0915”(physical association)0.560
SLC35B4VSIRpsi-mi:“MI:0915”(physical association)0.560
TMEM218VSIRpsi-mi:“MI:0915”(physical association)0.560
BMP10VSIRpsi-mi:“MI:0915”(physical association)0.560
TNFVSIRpsi-mi:“MI:0915”(physical association)0.560
CCL4L1VSIRpsi-mi:“MI:0915”(physical association)0.560
NRACVSIRpsi-mi:“MI:0915”(physical association)0.560
PLPPR2VSIRpsi-mi:“MI:0915”(physical association)0.560
VSIRTMEM14Cpsi-mi:“MI:0915”(physical association)0.560
TMEM229BVSIRpsi-mi:“MI:0915”(physical association)0.560
TSPO2VSIRpsi-mi:“MI:0915”(physical association)0.560
APODVSIRpsi-mi:“MI:0915”(physical association)0.560
ASGR1VSIRpsi-mi:“MI:0915”(physical association)0.560
CNIH3VSIRpsi-mi:“MI:0915”(physical association)0.560
CLEC7AVSIRpsi-mi:“MI:0915”(physical association)0.560

BioGRID (29): C10orf54 (Two-hybrid), C10orf54 (Two-hybrid), C10orf54 (Two-hybrid), TMEM97 (Two-hybrid), TMEM14C (Two-hybrid), TSPO2 (Two-hybrid), SLC35B1 (Two-hybrid), TSPAN2 (Two-hybrid), ASGR1 (Two-hybrid), CNIH3 (Two-hybrid), TMEM218 (Two-hybrid), BMP10 (Two-hybrid), SMCO4 (Two-hybrid), TMEM100 (Two-hybrid), CLEC7A (Two-hybrid)

ESM2 similar proteins: A0A1B0GU29, A6NLX4, A6QNY1, A9CBA0, B7ZWI3, O14669, O88472, P14784, P16297, P25918, P26896, Q0VFL4, Q13651, Q32M26, Q38J84, Q38J85, Q3SYS8, Q58CT8, Q5BK39, Q5EAA5, Q5HZE8, Q5NCP0, Q5RCL0, Q64322, Q68DV7, Q6AXS2, Q6AXU5, Q6NUJ2, Q6UWV7, Q86UW2, Q8BHB3, Q8BLR5, Q8BSU2, Q8C353, Q8C708, Q8K1T1, Q8MII8, Q8N6P7, Q8NET5, Q8R182

Diamond homologs: Q9D659, Q9H7M9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance1
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1275 predictions. Top by Δscore:

VariantEffectΔscore
10:71755357:A:ACdonor_gain1.0000
10:71755358:C:CCdonor_gain1.0000
10:71755358:CGG:Cdonor_gain1.0000
10:71760866:A:ACdonor_gain1.0000
10:71760867:C:CCdonor_gain1.0000
10:71760925:C:CCacceptor_gain1.0000
10:71761593:CTCAC:Cdonor_loss1.0000
10:71761594:TCACC:Tdonor_loss1.0000
10:71761596:ACCTG:Adonor_loss1.0000
10:71761597:C:CTdonor_loss1.0000
10:71761597:CCTGT:Cdonor_gain1.0000
10:71773352:CCTTA:Cdonor_loss1.0000
10:71773353:CTTA:Cdonor_loss1.0000
10:71773354:TTA:Tdonor_loss1.0000
10:71773355:TA:Tdonor_loss1.0000
10:71773356:A:AGdonor_loss1.0000
10:71751666:AC:Adonor_gain0.9900
10:71751667:CC:Cdonor_gain0.9900
10:71751857:TGTTG:Tacceptor_gain0.9900
10:71751858:GTTG:Gacceptor_gain0.9900
10:71751859:TTG:Tacceptor_gain0.9900
10:71751859:TTGC:Tacceptor_loss0.9900
10:71751860:TG:Tacceptor_gain0.9900
10:71751860:TGCT:Tacceptor_loss0.9900
10:71751862:C:CCacceptor_gain0.9900
10:71751863:T:Cacceptor_loss0.9900
10:71751866:C:CTacceptor_gain0.9900
10:71751868:C:CTacceptor_gain0.9900
10:71751874:C:CTacceptor_gain0.9900
10:71753000:CAC:Cacceptor_gain0.9900

AlphaMissense

2009 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
10:71755416:A:GC207R0.998
10:71761895:A:GW72R0.997
10:71761895:A:TW72R0.997
10:71755424:C:TG204E0.995
10:71755425:C:GG204R0.995
10:71755425:C:TG204R0.995
10:71755434:A:GC201R0.995
10:71761893:C:AW72C0.995
10:71761893:C:GW72C0.995
10:71761671:G:CC146W0.994
10:71761673:A:GC146R0.994
10:71755409:G:CP209R0.993
10:71761949:A:GC54R0.993
10:71755436:G:TA200D0.992
10:71761612:A:GL166P0.992
10:71761672:C:TC146Y0.992
10:71761947:G:CC54W0.992
10:71761948:C:TC54Y0.992
10:71755412:A:CL208R0.991
10:71755445:G:TA197D0.991
10:71761979:A:GC44R0.991
10:71761672:C:GC146S0.989
10:71761673:A:TC146S0.989
10:71761954:A:GL52P0.989
10:71755412:A:TL208H0.988
10:71761674:G:CC145W0.988
10:71761723:A:GF129S0.988
10:71761948:C:GC54S0.988
10:71761949:A:TC54S0.988
10:71755412:A:GL208P0.987

dbSNP variants (sampled 300 via entrez): RS1000365134 (10:71767466 T>C), RS1000491513 (10:71772674 T>C), RS1000696419 (10:71768664 G>A), RS1000711085 (10:71774277 T>C), RS1000748766 (10:71769027 A>C), RS1001107123 (10:71747732 A>G), RS1001129358 (10:71767762 T>A), RS1001283730 (10:71761720 G>A,T), RS1001322668 (10:71772963 G>A), RS1001372701 (10:71766256 C>G), RS1001412789 (10:71759475 C>T), RS1001424930 (10:71766399 C>T), RS1001449357 (10:71754611 A>G), RS1001501015 (10:71753299 G>A,T), RS1001566191 (10:71747908 A>G)

Disease associations

OMIM: gene MIM:615608 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

StudyTraitp-value
GCST004610_113White blood cell count1.000000e-12
GCST004625_180Monocyte count2.000000e-09
GCST004626_80Myeloid white cell count7.000000e-09
GCST004627_13Lymphocyte count1.000000e-20
GCST004632_72Lymphocyte percentage of white cells1.000000e-09
GCST005973_39White blood cell count2.000000e-09
GCST006585_1083Blood protein levels2.000000e-13
GCST006585_2352Blood protein levels4.000000e-09
GCST90002388_564Lymphocyte count4.000000e-56
GCST90002389_446Lymphocyte percentage of white cells1.000000e-20
GCST90002393_355Monocyte count1.000000e-11
GCST90002393_356Monocyte count1.000000e-20
GCST90002398_176Neutrophil count1.000000e-17
GCST90002399_48Neutrophil percentage of white cells8.000000e-12
GCST90002407_100White blood cell count4.000000e-18
GCST90002407_99White blood cell count6.000000e-15

EFO canonical traits (5, from GWAS)

EFO IDTrait name
EFO:0005091monocyte count
EFO:0004587lymphocyte count
EFO:0007993lymphocyte percentage of leukocytes
EFO:0004833neutrophil count
EFO:0007990neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523457 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Other immune checkpoint proteins

Most potent curated ligand interactions (1 total), top 1:

LigandActionAffinityParameter
PD-L1/VISTA dual inhibitor P17Inhibition6.57pIC50

ChEMBL bioactivities

126 potent at pChembl≥5 of 138 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
7.77IC5017nMCHEMBL5197008
7.42Kd38nMCHEMBL5613352
7.08EC5082.9nMCHEMBL5169494
7.08EC5082.9nMCHEMBL5268408
6.97Kd107nMCHEMBL5611916
6.90Kd127nMCHEMBL5613174
6.89Kd130nMCHEMBL5613499
6.85Kd140nMCHEMBL5613565
6.82Kd153nMCHEMBL5176642
6.73Kd187nMCHEMBL5176642
6.68Kd210nMCHEMBL5614265
6.61Kd247nMCHEMBL5568380
6.59Kd256nMCHEMBL5406611
6.57Kd268nMCHEMBL5613963
6.57IC50272nMCHEMBL6101892
6.57Kd272nMCHEMBL6101892
6.44Kd364nMCHEMBL5613558
6.44IC50360nMCHEMBL5561473
6.43Kd374nMCHEMBL5402947
6.42Kd381nMCHEMBL6176431
6.39IC50404nMCHEMBL6162827
6.38Kd420nMCHEMBL6176938
6.35Kd447nMCHEMBL6176433
6.34Kd452nMCHEMBL6168452
6.33Kd470nMCHEMBL5406611
6.32IC50480nMCHEMBL5176557
6.32Kd481nMCHEMBL5613420
6.31Kd491nMCHEMBL5434012
6.31Kd490nMCHEMBL5561473
6.31IC50490nMCHEMBL6162483
6.30Kd506nMCHEMBL5613657
6.29IC50519nMCHEMBL6166770
6.28Kd530nMCHEMBL6168425
6.25IC50562nMCHEMBL6161064
6.24IC50581nMCHEMBL6147199
6.24Kd573nMCHEMBL6177498
6.22Kd597nMCHEMBL5611985
6.21IC50613nMCHEMBL6132737
6.21IC50616nMCHEMBL6151043
6.20Kd632nMCHEMBL6177293
6.19Kd647nMCHEMBL1322633
6.16Kd693nMCHEMBL5612029
6.13Kd741nMCHEMBL6177062
6.12Kd763nMCHEMBL5421948
6.12Kd760nMCHEMBL5555853
6.11IC50774nMCHEMBL6151365
6.08Kd828nMCHEMBL6176520
6.02Kd959nMCHEMBL6176423
6.02Kd948nMCHEMBL6174824
6.01IC50970nMCHEMBL6134309

PubChem BioAssay actives

62 with measured affinity, of 100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(2S)-2-[[(1S)-3-amino-1-[5-[(1S)-1-amino-2-hydroxyethyl]-1,3,4-thiadiazol-2-yl]-3-oxopropyl]carbamoylamino]-3-hydroxybutanoic acid1845756: Inhibition of VISTA (unknown origin)ic500.0170uM
2-[[3-[6-[3-[3-(4-aminopiperidin-1-yl)propoxy]-2-methylphenyl]-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.0380uM
(2S,3R)-2-[[(1S)-3-amino-1-[3-[(1S)-1-amino-2-hydroxyethyl]-1,2,4-oxadiazol-5-yl]-3-oxopropyl]carbamoylamino]-3-hydroxybutanoic acid1856145: Inhibition of VISTA in human PBMCec500.0829uM
(2S,3S)-2-[[(1S)-3-amino-1-[3-[(1R)-1-amino-2-hydroxyethyl]-1,2,4-oxadiazol-5-yl]-3-oxopropyl]carbamoylamino]-3-hydroxybutanoic acid1930079: Inhibition of VISTA (unknown origin) incubated for 15 mins by LANCE Ultra TR-FRET assayec500.0829uM
1-[3-[3-[2-[3-[(2-hydroxyethylamino)methyl]phenyl]-1,3-benzoxazol-6-yl]-2-methylphenoxy]propyl]piperidin-4-ol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.1070uM
2-[[3-[6-(2-methylphenyl)-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.1270uM
2-[[3-[6-(2-fluorophenyl)-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.1300uM
2-[[3-[6-[3-[3-[(3R)-3-aminopyrrolidin-1-yl]propoxy]-2-methylphenyl]-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.1400uM
N-[2-[[3-(4-methyl-5-phenyl-1H-benzimidazol-2-yl)phenyl]methylamino]ethyl]acetamide1856153: Binding affinity to VISTA (unknown origin) assessed as dissociation constantkd0.1530uM
2-[[3-[6-[2-methyl-3-(3-piperazin-1-ylpropoxy)phenyl]-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.2100uM
N-ethyl-N-phenyl-5-[(5-phenylfuran-2-yl)methylimino]-1,2,4-dithiazol-3-amine2081065: Binding affinity to human VISTA assessed as dissociation constant by SPR analysiskd0.2470uM
2-[[3-(4-methyl-5-phenyl-1H-benzimidazol-2-yl)phenyl]methylamino]ethanol1971693: Binding affinity to human VISTA assessed as dissociation constant by SPR assaykd0.2560uM
2-[[3-[7-methyl-6-(2-methylphenyl)-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.2680uM
2-[[3-[6-(2-fluorophenyl)-7-methyl-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.3640uM
N-[2-[[4-(4-methyl-5-phenyl-1H-benzimidazol-2-yl)phenyl]methylamino]ethyl]acetamide1971693: Binding affinity to human VISTA assessed as dissociation constant by SPR assaykd0.3740uM
(3R)-1-[3-[3-[2-[3-[(2-hydroxyethylamino)methyl]phenyl]-1,3-benzoxazol-6-yl]-2-methylphenoxy]propyl]pyrrolidin-3-ol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.4810uM
3-[[4-[(2-hydroxyethylamino)methyl]-6-methoxypyrimidin-2-yl]amino]phenol2081018: Binding affinity to human VISTA assessed as dissociation constant by MST analysiskd0.4900uM
N’-[[3-(4-methyl-5-phenyl-1H-benzimidazol-2-yl)phenyl]methyl]ethane-1,2-diamine1971693: Binding affinity to human VISTA assessed as dissociation constant by SPR assaykd0.4910uM
2-[[3-[6-(3-fluorophenyl)-7-methyl-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.5060uM
2-[[3-[6-(3-fluorophenyl)-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.5970uM
2-[(4,6-dimethylquinazolin-2-yl)amino]-4-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-1H-pyrimidin-6-one1856149: Binding affinity to VISTA (unknown origin) assessed as dissociation constant by MST methodkd0.6470uM
(3S)-1-[3-[3-[2-[3-[(2-hydroxyethylamino)methyl]phenyl]-1,3-benzoxazol-6-yl]-2-methylphenoxy]propyl]pyrrolidin-3-ol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd0.6930uM
2-(3-hydroxyanilino)-4-[(2-hydroxyethylamino)methyl]-1H-pyrimidin-6-one2081018: Binding affinity to human VISTA assessed as dissociation constant by MST analysiskd0.7600uM
(5S)-5-[2-[[3-(4-methyl-5-phenyl-1H-benzimidazol-2-yl)phenyl]methylamino]ethyl]pyrrolidin-2-one1971693: Binding affinity to human VISTA assessed as dissociation constant by SPR assaykd0.7630uM
2-[[3-(4-methyl-5-phenyl-1H-benzimidazol-2-yl)phenyl]methylamino]acetic acid1971693: Binding affinity to human VISTA assessed as dissociation constant by SPR assaykd1.0450uM
2-[[4-(4-methyl-5-phenyl-1H-benzimidazol-2-yl)phenyl]methylamino]ethanol1971693: Binding affinity to human VISTA assessed as dissociation constant by SPR assaykd1.1250uM
N-[2-[[3-(5-bromo-4-methyl-1H-benzimidazol-2-yl)phenyl]methylamino]ethyl]acetamide1971693: Binding affinity to human VISTA assessed as dissociation constant by SPR assaykd1.1550uM
2-[[3-(6-phenyl-1,3-benzoxazol-2-yl)phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd1.1700uM
2-[[4-[3-[2-[3-[(2-hydroxyethylamino)methyl]phenyl]-1,3-benzoxazol-6-yl]-2-methylphenyl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd1.2600uM
1-[3-[3-[2-[3-[(2-hydroxyethylamino)methyl]phenyl]-1,3-benzoxazol-6-yl]-2-methylphenoxy]propyl]azetidin-3-ol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd1.4400uM
2-[[3-[6-[2-methyl-3-(3-morpholin-4-ylpropoxy)phenyl]-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd1.4800uM
2-[[6-methoxy-2-(3-phenylanilino)pyrimidin-4-yl]methylamino]ethanol2081018: Binding affinity to human VISTA assessed as dissociation constant by MST analysiskd1.6200uM
2-[[3-[6-[3-[3-[4-(hydroxymethyl)piperidin-1-yl]propoxy]-2-methylphenyl]-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd1.6300uM
N-[2-[[3-(6-phenyl-1,3-benzoxazol-2-yl)phenyl]methylamino]ethyl]acetamide2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd1.7200uM
(3R)-3-hydroxy-4-[[3-(4-methyl-5-phenyl-1H-benzimidazol-2-yl)phenyl]methylamino]butanoic acid1971693: Binding affinity to human VISTA assessed as dissociation constant by SPR assaykd1.7750uM
1-[3-[3-[2-[3-[(2-hydroxyethylamino)methyl]phenyl]-7-methyl-1,3-benzoxazol-6-yl]phenoxy]propyl]piperidin-4-ol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd1.8900uM
1-[3-[3-[2-[3-[(2-hydroxyethylamino)methyl]phenyl]-1,3-benzoxazol-6-yl]-2-methylphenoxy]propyl]piperidine-4-carboxylic acid2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd1.9700uM
1-[3-[3-[2-[3-[(2-hydroxyethylamino)methyl]phenyl]-1,3-benzoxazol-6-yl]phenoxy]propyl]piperidin-4-ol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd2.0800uM
1-[3-[3-[2-[3-[(2-hydroxyethylamino)methyl]phenyl]-7-methyl-1,3-benzoxazol-6-yl]-2-methylphenoxy]propyl]piperidin-4-ol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd2.1200uM
N’,N’-dimethyl-N-[[3-(6-phenyl-1,3-benzoxazol-2-yl)phenyl]methyl]ethane-1,2-diamine2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd2.3100uM
2-[[4-[(2-hydroxyethylamino)methyl]-6-methoxypyrimidin-2-yl]amino]phenol2081018: Binding affinity to human VISTA assessed as dissociation constant by MST analysiskd2.3900uM
2-[[3-(7-methyl-6-phenyl-1,3-benzoxazol-2-yl)phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd2.5600uM
4-[(2-hydroxyethylamino)methyl]-2-(3-phenylanilino)-1H-pyrimidin-6-one2081018: Binding affinity to human VISTA assessed as dissociation constant by MST analysiskd2.7500uM
(3S)-1-[3-[3-[2-[3-[(2-hydroxyethylamino)methyl]phenyl]-1,3-benzoxazol-6-yl]-2-methylphenoxy]propyl]pyrrolidine-3-carboxylic acid2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd2.7500uM
N-[2-[[3-(4-methyl-1H-benzimidazol-2-yl)phenyl]methylamino]ethyl]acetamide1971693: Binding affinity to human VISTA assessed as dissociation constant by SPR assaykd3.1220uM
2-[[6-methoxy-2-(3-morpholin-4-ylanilino)pyrimidin-4-yl]methylamino]ethanol2081018: Binding affinity to human VISTA assessed as dissociation constant by MST analysiskd3.3800uM
2-[[3-[6-[3-[5-[(2-hydroxyethylamino)methyl]-6-methoxy-2-pyridinyl]-2-methylphenyl]-1,3-benzoxazol-2-yl]phenyl]methylamino]ethanol2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd3.5000uM
N’,N’-dimethyl-N-[[3-(7-methyl-6-phenyl-1,3-benzoxazol-2-yl)phenyl]methyl]ethane-1,2-diamine2127595: Binding affinity to human VISTA assessed as dissociation constant by SPR binding assaykd3.8500uM
2-[[6-methoxy-2-(3-methylanilino)pyrimidin-4-yl]methylamino]ethanol2081018: Binding affinity to human VISTA assessed as dissociation constant by MST analysiskd4.1500uM
4-[[4-[(2-hydroxyethylamino)methyl]-6-methoxypyrimidin-2-yl]amino]phenol2081018: Binding affinity to human VISTA assessed as dissociation constant by MST analysiskd4.1600uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Tobacco Smoke Pollutiondecreases expression, increases expression, affects expression3
Tretinoinincreases expression3
Valproic Acidincreases expression3
sodium arsenitedecreases expression, increases expression2
Acetaminophendecreases expression, increases expression2
Cisplatinincreases expression2
Dexamethasoneincreases expression, affects cotreatment2
aristolochic acid Iincreases expression1
GSK-J4decreases expression1
bisphenol Faffects cotreatment, increases expression1
triphenyl phosphateaffects expression1
bisphenol Aaffects cotreatment, increases expression1
tris(2-butoxyethyl) phosphateaffects expression1
beta-lapachoneincreases expression1
sulforaphanedecreases expression1
perfluorooctanoic acidincreases expression1
benzo(e)pyrenedecreases methylation, increases methylation1
cupric chloridedecreases expression1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression, affects cotreatment, decreases expression1
diallyl trisulfidedecreases expression1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamineincreases expression1
di-n-butylphosphoric acidaffects expression1
perfluorooctane sulfonic aciddecreases expression1
abrinedecreases expression1
(+)-JQ1 compounddecreases expression1
Sunitinibincreases expression1
Air Pollutantsdecreases expression, increases abundance1
Vehicle Emissionsdecreases expression, increases abundance1
Benzo(a)pyrenedecreases methylation1
Doxorubicindecreases expression1

ChEMBL screening assays

37 unique, capped per target: 37 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4330226BindingInhibition of VISTA signaling in human PBMC assessed as IFNgamma release at 100 nM after 30 mins by ELISADevelopment of Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Signaling Pathway. — J Med Chem

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 2 spontaneously immortalized cell line, 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_A8AGRaji-hVISTACancer cell lineMale
CVCL_B8RQAbcam HCT 116 VSIR KOCancer cell lineMale
CVCL_B9U5Abcam A-549 VSIR KOCancer cell lineMale
CVCL_D7BXAbeomics CHO-K1 VISTASpontaneously immortalized cell lineFemale
CVCL_D7C4Abeomics HEK293 VISTATransformed cell lineFemale
CVCL_D8DEUbigene A-549 VSIR KOCancer cell lineMale
CVCL_KA62CHO-K1/VISTASpontaneously immortalized cell lineFemale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.