PVR

Summary

PVR (PVR cell adhesion molecule, HGNC:9705) is a protein-coding gene on chromosome 19q13.31, encoding Poliovirus receptor (P15151). Mediates NK cell adhesion and triggers NK cell effector functions.

The protein encoded by this gene is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5817 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_006505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9705
Approved symbol	PVR
Name	PVR cell adhesion molecule
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Aliases	CD155, HVED, Necl-5, NECL5, Tage4
Ensembl gene	ENSG00000073008
Ensembl biotype	protein_coding
OMIM	173850
Entrez	5817

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000187830, ENST00000344956, ENST00000403059, ENST00000406449, ENST00000425690, ENST00000587785, ENST00000706603, ENST00000706604, ENST00000706605, ENST00000706606, ENST00000706607, ENST00000706608, ENST00000937736, ENST00000971444, ENST00000971445

RefSeq mRNA: 4 — MANE Select: NM_006505 NM_001135768, NM_001135769, NM_001135770, NM_006505

CCDS: CCDS12640, CCDS46105, CCDS46106, CCDS46107

Canonical transcript exons

ENST00000425690 — 8 exons

Exon	Start	End
ENSE00000711638	44647223	44647570
ENSE00003500390	44657762	44657910
ENSE00003508640	44649809	44650105
ENSE00003603474	44653900	44654017
ENSE00003633879	44661292	44661323
ENSE00003671062	44658742	44658900
ENSE00003996291	44661740	44666162
ENSE00003996294	44643910	44644175

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 94.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.9136 / max 237.0141, expressed in 1740 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176264	26.2772	1734
176266	0.9289	372
176265	0.7075	401

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	94.30	gold quality
islet of Langerhans	UBERON:0000006	92.23	gold quality
tendon of biceps brachii	UBERON:0008188	91.18	gold quality
heart left ventricle	UBERON:0002084	90.60	gold quality
apex of heart	UBERON:0002098	90.60	gold quality
cardiac ventricle	UBERON:0002082	90.22	gold quality
right lobe of liver	UBERON:0001114	90.01	gold quality
upper lobe of left lung	UBERON:0008952	89.60	gold quality
adenohypophysis	UBERON:0002196	89.46	gold quality
upper lobe of lung	UBERON:0008948	89.09	gold quality
left adrenal gland	UBERON:0001234	89.06	gold quality
right atrium auricular region	UBERON:0006631	88.98	gold quality
sural nerve	UBERON:0015488	88.85	gold quality
right adrenal gland	UBERON:0001233	88.80	gold quality
right adrenal gland cortex	UBERON:0035827	88.74	gold quality
adrenal tissue	UBERON:0018303	88.64	gold quality
heart	UBERON:0000948	88.43	gold quality
adrenal gland	UBERON:0002369	88.39	gold quality
left adrenal gland cortex	UBERON:0035825	88.35	gold quality
pituitary gland	UBERON:0000007	88.22	gold quality
cardiac atrium	UBERON:0002081	87.83	gold quality
adrenal cortex	UBERON:0001235	87.74	gold quality
liver	UBERON:0002107	87.40	gold quality
ascending aorta	UBERON:0001496	87.38	gold quality
popliteal artery	UBERON:0002250	87.33	gold quality
thoracic aorta	UBERON:0001515	87.31	gold quality
tibial artery	UBERON:0007610	87.30	gold quality
cartilage tissue	UBERON:0002418	87.28	gold quality
aorta	UBERON:0000947	87.26	gold quality
right coronary artery	UBERON:0001625	87.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.88
E-MTAB-5061	no	3.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF2, ATM, DBP, E4F1, MYOD1, NFIL3, NRF1, SHH, SSRP1, TBP, TCF3, TFAP2A, TP53

miRNA regulators (miRDB)

120 targeting PVR, 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-4776-3P	100.00	68.73	1340
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471

Literature-anchored findings (GeneRIF, showing 40)

• We propose that the cytoplasmic domain may target CD155-containing endocytic vesicles to the microtubular network (PMID:11751937)
• activation of expression of sonic hedgehog protein (PMID:11983699)
• Data show that both PVR and Nectin-2 represent specific ligands for the DNAM-1 triggering receptor. (PMID:12913096)
• CD155 may have an important role in cellular function (PMID:12943679)
• These data indicate that Tage4 represents the functional orthologue of CD155 in mouse. (PMID:14652024)
• that DNAM-1 regulates monocyte extravasation via its interaction with CD226 expressed at endothelial junctions on normal cells. (PMID:15136589)
• These results suggest that CD155alpha plays a role in the regulation of cell adhesion and cell motility. (PMID:15194502)
• cytoplasmic domain of PVR directly interacts with Tctex-1 and plays an important role in retrograde transport of poliovirus-containing vesicles along microtubules in vivo (PMID:15194795)
• Upregulation of the molecular target CD155 renders explant cultures of high-grade malignant gliomas highly susceptible to a prototype oncolytic poliovirus recombinant. (PMID:15279713)
• Analysis of the ligands for triggering NK receptors revealed the consistent expression of cd155 and cd112 in myeloid leukemias, and less frequent expression in lymphoblastic leukemias (PMID:15536144)
• Evasion of NK cell killing was mediated by human cytomegalovirus UL141 blocking surface expression of CD155 (PMID:15640804)
• Necl-5 has a critical role in integrin alphavbeta3 clustering and focal complex formation (PMID:17446174)
• Results describe the establishment of a poliovirus oral infection system in human poliovirus receptor-expressing transgenic mice that are deficient in alpha/beta interferon receptor. (PMID:17507470)
• no statistically significant association between this marker allele and non-syndromic clefting (PMID:17534374)
• CD155, at least in part, enhances the proliferation of ras-mutated cells (PMID:17893876)
• crystal structure of C155 D1D2 has been determined to 3.5-A resolution and fitted into approximately 8.5-A resolution cryoelectron microscopy reconstructions of the virus-receptor complexes for the 3 PV serotypes (PMID:19011098)
• CD96-driven adhesion to CD155 may be crucial in developmental processes (PMID:19056733)
• The Ala67Thr mutation in the poliovirus receptor is a possible risk factor for the development of vaccine-associated or paralytic poliomyelitis associated with wild-type virus. (PMID:19319949)
• evidence provided for the contribution of DNAM-1/CD155 interactions to the reduction of DNAM-1 expression, suggesting that chronic receptor-ligand interactions in the tumor environment may induce loss of DNAM-1 on tumor-associated NK cells. (PMID:19801517)
• TIGIT is expressed by all NK cells, it binds PVR and PVRL2 but not PVRL3, and it inhibits NK cytotoxicity (PMID:19815499)
• Necl-5 plays a role in mediating tumor cell invasion and that the overexpression of Necl-5 in cancer cells has clinical significance for prognostic evaluation of patients with primary pulmonary adenocarcinoma. (PMID:20331633)
• CD155 is an IFNgamma-inducible immune regulatory protein on the surface of human endothelial cells that attenuates the acquisition of effector functions in CD8 T cells. (PMID:21330602)
• Data show that a high expression of CD112 and CD155 (DNAM-1 ligands) on leukemic blasts. (PMID:21383766)
• The host TICAM-1 pathway, particularly in macrophages, serves as a source of type I interferon induction that protects poliovirus (PV) receptor-bearing transgenic mice from PV infection and paralytic death. (PMID:21998457)
• Expression of PVR in B-ALL cells is modulated by epigenetic mechanisms. (PMID:22169283)
• the PVR downmodulation by Nef and Vpu is a strategy evolved by HIV-1 to prevent NK cell-mediated lysis of infected cells. (PMID:22301152)
• This investigation has enhanced understanding of cell invasion and confirmed CD44 to play a more significant role in this biological process than CD155. (PMID:22363471)
• we demonstrated the expression of both CD155 mRNA and protein in bone and soft tissue sarcoma cell lines (PMID:22692919)
• The concordant computational and experimental data of the present study indicate that the extent of NECL-5 expression correlates with melanoma progression. (PMID:22929570)
• findings suggest Necl-5 expression in lung cancer cells is crucial for their invasiveness in the cancer-stromal interaction (PMID:23276719)
• PVR resides in the recently identified lateral border recycling compartment, similar to PECAM and CD99. (PMID:23333754)
• The CD226/CD155 interaction regulates the proinflammatory (Th1/Th17)/anti-inflammatory (Th2) balance in humans. (PMID:23980210)
• Vpr upregulates PVR during Hiv-1 infection by activating ATR kinase that triggers the DNA damage rsponse pathway and G2 arrest. (PMID:24045107)
• UL141 can inhibit cell-surface expression of both natural killer (NK) cell-activating ligand CD155 as well as TRAIL death receptors (TRAIL-R1 and TRAIL-R2). (PMID:24598754)
• TIGIT/PVR ligation signaling mediates suppression of IFN-gamma production via the NF-kappaB pathway. (PMID:24817116)
• In granulosa cells, there are significant changes in expression during follicular maturation. (PMID:24828608)
• Ala residues 10, 14 and 18 in the TM domain of Vpu are required for CD155 downregulation. (PMID:25113908)
• UPR decreases CD226 ligand CD155 expression and sensitivity to NK cell-mediated cytotoxicity in hepatoma cells. (PMID:25209846)
• Our findings suggest that loss of CD155 expression may play an important role in the immune escape of HCC cells and thus CD155 may serve as a prognostic marker as well as a potential therapeutic target for HCC. (PMID:25320021)
• The present study provides evidence that regulation of the PVR/CD155 DNAM-1 ligand expression by nitric oxide may represent an additional immune-mediated mechanism and supports the anti-myeloma activity of nitric oxide donors. (PMID:25609078)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:113337	ENSDARG00000041998
danio_rerio	si:ch211-222f23.6	ENSDARG00000042880
danio_rerio	si:ch73-22o12.1	ENSDARG00000062831
danio_rerio	pvrl2l	ENSDARG00000063390
danio_rerio	zgc:172122	ENSDARG00000079191
danio_rerio	si:ch211-214p13.3	ENSDARG00000087403
danio_rerio	si:ch211-141e20.2	ENSDARG00000093349
danio_rerio	sc:d189	ENSDARG00000102858
mus_musculus	Pvr	ENSMUSG00000040511
rattus_norvegicus	Pvr	ENSRNOG00000019202
drosophila_melanogaster	Fas3	FBGN0000636

Paralogs (14): CD200 (ENSG00000091972), CADM4 (ENSG00000105767), CRTAM (ENSG00000109943), NECTIN1 (ENSG00000110400), NECTIN2 (ENSG00000130202), NECTIN4 (ENSG00000143217), CD226 (ENSG00000150637), CADM3 (ENSG00000162706), SMAGP (ENSG00000170545), CADM2 (ENSG00000175161), NECTIN3 (ENSG00000177707), TIGIT (ENSG00000181847), CADM1 (ENSG00000182985), NCR3 (ENSG00000204475)

Protein

Protein identifiers

Poliovirus receptor — P15151 (reviewed: P15151)

Alternative names: Nectin-like protein 5

All UniProt accessions (9): P15151, A0A0A0MSA9, A0A0C4DG49, A0A9L9PX39, A0A9L9PXB8, A0A9L9PXN8, A0A9L9PY64, F8W7D4, K7EMC6

UniProt curated annotations — full annotation on UniProt →

Function. Mediates NK cell adhesion and triggers NK cell effector functions. Binds two different NK cell receptors: CD96 and CD226. These interactions accumulates at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytotoxicity of activated NK cells. May also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Plays a role in mediating tumor cell invasion and migration. (Microbial infection) Acts as a receptor for poliovirus. May play a role in axonal transport of poliovirus, by targeting virion-PVR-containing endocytic vesicles to the microtubular network through interaction with DYNLT1. This interaction would drive the virus-containing vesicle to the axonal retrograde transport. (Microbial infection) Acts as a receptor for Pseudorabies virus. (Microbial infection) Is prevented to reach cell surface upon infection by Human cytomegalovirus /HHV-5, presumably to escape immune recognition of infected cell by NK cells.

Subunit / interactions. Can form trans-heterodimers with NECTIN3. The extracellular domain interacts with VTN, CD226 and CD96. The cytoplasmic domain interacts with DYNLT1. Binds with high affinity to TIGIT. (Microbial infection) Interacts with poliovirus capsid proteins. (Microbial infection) Interacts with human cytomegalovirus /HHV-5 UL141 protein. (Microbial infection) Interacts with pseudorabies virus gD protein.

Subcellular location. Cell membrane Cell membrane Secreted Secreted.

Post-translational modifications. N-glycosylated. N-glycan at Asn-120: Hex5HexNAc4. Phosphorylated by Src kinases on tyrosine residues in the ITIM motif upon ligation. Interaction with TIGIT is required for Phosphorylation.

Domain organisation. Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Induction. Transcriptionally regulated by SHH.

Miscellaneous. The V-type domain is necessary and sufficient for virus binding and uptake.

Similarity. Belongs to the nectin family.

Isoforms (4)

UniProt ID	Names	Canonical?
P15151-1	Alpha	yes
P15151-2	Beta
P15151-3	Gamma
P15151-4	Delta

RefSeq proteins (4): NP_001129240, NP_001129241, NP_001129242, NP_006496* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR052659	Nectin/PVR	Family

Pfam: PF07686, PF08205

UniProt features (64 total): strand 28, glycosylation site 10, splice variant 5, disulfide bond 3, sequence variant 3, domain 3, topological domain 2, turn 2, signal peptide 1, chain 1, modified residue 1, transmembrane region 1, mutagenesis site 1, helix 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
6ISC	X-RAY DIFFRACTION	2.2
6O3O	X-RAY DIFFRACTION	2.8
6ARQ	X-RAY DIFFRACTION	2.88
3UDW	X-RAY DIFFRACTION	2.9
3URO	X-RAY DIFFRACTION	3.5
4FQP	X-RAY DIFFRACTION	3.6
3J8F	ELECTRON MICROSCOPY	4
3EPC	ELECTRON MICROSCOPY	8
3EPD	ELECTRON MICROSCOPY	9
3EPF	ELECTRON MICROSCOPY	9
3J9F	ELECTRON MICROSCOPY	9
1NN8	ELECTRON MICROSCOPY	15
1DGI	ELECTRON MICROSCOPY	22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15151-F1	85.08	0.67

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): 398

Disulfide bonds (3): 49–123, 166–221, 266–312

Glycosylation sites (10): 105, 120, 188, 218, 237, 278, 307, 313, 360, 352

Mutagenesis-validated functional residues (1):

Position	Phenotype
369–372	partial loss of dynlt1 binding.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-420597	Nectin/Necl trans heterodimerization

MSigDB gene sets: 227 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_MSH3, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY

GO Biological Process (11): positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target (GO:0002860), homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), natural killer cell mediated cytotoxicity (GO:0042267), susceptibility to natural killer cell mediated cytotoxicity (GO:0042271), negative regulation of natural killer cell mediated cytotoxicity (GO:0045953), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), susceptibility to T cell mediated cytotoxicity (GO:0060370), cell adhesion (GO:0007155), signal transduction (GO:0007165), symbiont entry into host cell (GO:0046718)

GO Molecular Function (6): virus receptor activity (GO:0001618), signaling receptor activity (GO:0038023), receptor ligand activity (GO:0048018), cell adhesion molecule binding (GO:0050839), cell adhesion mediator activity (GO:0098631), protein binding (GO:0005515)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), adherens junction (GO:0005912), focal adhesion (GO:0005925), cell surface (GO:0009986), membrane (GO:0016020), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Adherens junctions interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
positive regulation of natural killer cell mediated cytotoxicity	2
cell-cell adhesion	2
natural killer cell mediated cytotoxicity	2
regulation of natural killer cell mediated cytotoxicity	2
cellular process	2
natural killer cell mediated cytotoxicity directed against tumor cell target	1
positive regulation of natural killer cell mediated immune response to tumor cell	1
regulation of natural killer cell mediated cytotoxicity directed against tumor cell target	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
negative regulation of leukocyte mediated cytotoxicity	1
negative regulation of natural killer cell mediated immunity	1
positive regulation of leukocyte mediated cytotoxicity	1
positive regulation of natural killer cell mediated immunity	1
positive regulation of T cell mediated cytotoxicity	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
molecular transducer activity	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
protein binding	1
cell adhesion	1
cell adhesion molecule binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cell-cell junction	1
cell-substrate junction	1

Protein interactions and networks

STRING

1558 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PVR	CD96	P40200	999
PVR	CD226	Q15762	999
PVR	TIGIT	Q495A1	997
PVR	CTLA4	P16410	950
PVR	NCR3	O14931	938
PVR	KLRK1	P26718	930
PVR	KLRC1	P26715	896
PVR	PDCD1	Q15116	883
PVR	HAVCR2	Q8TDQ0	882
PVR	NCR1	O76036	822
PVR	DYNLT1	P63172	813
PVR	PVRIG	Q6DKI7	776
PVR	NECTIN3	Q9NQS3	774
PVR	KLRD1	Q13241	765
PVR	ICOS	Q9Y6W8	762

IntAct

279 interactions, top by confidence:

A	B	Type	Score
TIGIT	PVR	psi-mi:“MI:0407”(direct interaction)	0.790
SLC30A2	PVR	psi-mi:“MI:0915”(physical association)	0.780
PVR	SLC30A2	psi-mi:“MI:0915”(physical association)	0.780
KRTAP10-8	PVR	psi-mi:“MI:0915”(physical association)	0.720
PVR	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
PVR	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
NOTCH2NLA	PVR	psi-mi:“MI:0915”(physical association)	0.670
SFTPC	PVR	psi-mi:“MI:0915”(physical association)	0.670
KRTAP10-7	PVR	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	PVR	psi-mi:“MI:0915”(physical association)	0.560
	PVR	psi-mi:“MI:0915”(physical association)	0.560
PVR		psi-mi:“MI:0915”(physical association)	0.560
PVR	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
VAMP5	PVR	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	PVR	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (211): SLC30A2 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), PVR (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), C4A (Affinity Capture-MS), UBE2C (Affinity Capture-MS), RYK (Affinity Capture-MS), CDON (Affinity Capture-MS), PI4K2A (Affinity Capture-MS), RAB5B (Affinity Capture-MS), LRBA (Affinity Capture-MS)

ESM2 similar proteins: A0A5B9, A6NDV4, A6QLK4, B1AWJ5, E9PTA2, O75051, O94759, P01850, P01851, P01852, P01857, P01859, P01860, P01861, P01869, P01870, P01906, P01909, P03987, P06333, P0DSE2, P0DTU4, P11364, P15151, P15981, P20759, P20762, P32506, P54900, Q1WIM1, Q1WIM3, Q3TMX7, Q6P767, Q6ZRP7, Q7TQ33, Q812F8, Q8N126, Q8NFZ8, Q8R143, Q8R464

Diamond homologs: A0A8M2B818, B0JYH6, P15151, P32506, P32507, Q15223, Q5FWR8, Q92692, Q9GL76, Q9JKF6, B4KPU0, P06731, P20273, P31997, Q9JLB9, Q9N1E4, Q9N1E5, Q9N1E6, Q9NQS3, P41217, Q5ZPR3, Q7TPB4, Q8VE98, P28685, Q58EG3, Q5E9Z9, A2AJ76, P35969, P53767, Q26474, Q66KX2, Q7Z553, Q8NDA2, Q8R007, Q96NY8, Q9MZ08, O75144, P55803, Q13410, Q16653

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ATM	“up-regulates quantity by expression”	PVR	“transcriptional regulation”
PVR	“up-regulates activity”	CD226	binding
PVR	“up-regulates activity”	TIGIT	binding
MARCHF9	“down-regulates quantity by destabilization”	PVR	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	9	13.6×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	9
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1167 predictions. Top by Δscore:

Variant	Effect	Δscore
19:44644172:ACCGG:A	donor_loss	1.0000
19:44644173:CCGG:C	donor_loss	1.0000
19:44644176:G:C	donor_loss	1.0000
19:44644176:G:GG	donor_gain	1.0000
19:44644177:T:G	donor_loss	1.0000
19:44647220:CA:C	acceptor_loss	1.0000
19:44647221:A:AG	acceptor_gain	1.0000
19:44647221:A:C	acceptor_loss	1.0000
19:44647221:AGG:A	acceptor_gain	1.0000
19:44647222:G:GG	acceptor_gain	1.0000
19:44647222:GGG:G	acceptor_gain	1.0000
19:44647543:A:T	donor_gain	1.0000
19:44647566:GCTTG:G	donor_gain	1.0000
19:44647567:CTTGG:C	donor_loss	1.0000
19:44647568:TTGGT:T	donor_loss	1.0000
19:44647569:TGGTG:T	donor_loss	1.0000
19:44647571:G:T	donor_loss	1.0000
19:44647572:T:G	donor_loss	1.0000
19:44654014:GCAC:G	donor_gain	1.0000
19:44654018:G:GG	donor_gain	1.0000
19:44657906:CAAAG:C	donor_loss	1.0000
19:44657909:AGGT:A	donor_loss	1.0000
19:44657911:GTG:G	donor_loss	1.0000
19:44644178:GAGT:G	donor_loss	0.9900
19:44647221:AG:A	acceptor_gain	0.9900
19:44647221:AGGG:A	acceptor_gain	0.9900
19:44647222:GG:G	acceptor_gain	0.9900
19:44647222:GGGG:G	acceptor_gain	0.9900
19:44647222:GGGGA:G	acceptor_gain	0.9900
19:44647470:G:GT	donor_gain	0.9900

AlphaMissense

2679 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:44649918:G:C	W179C	0.998
19:44649918:G:T	W179C	0.998
19:44654012:G:C	W279C	0.998
19:44654012:G:T	W279C	0.998
19:44647341:G:C	W66C	0.996
19:44647341:G:T	W66C	0.996
19:44657853:T:A	C312S	0.996
19:44657854:G:C	C312S	0.996
19:44647424:T:G	F94C	0.995
19:44653971:T:A	C266S	0.993
19:44653972:G:C	C266S	0.993
19:44654010:T:A	W279R	0.993
19:44654010:T:C	W279R	0.993
19:44649877:T:A	C166S	0.992
19:44649878:G:C	C166S	0.992
19:44647510:T:A	C123S	0.991
19:44647511:G:C	C123S	0.991
19:44650042:T:A	C221S	0.991
19:44650043:G:C	C221S	0.991
19:44653972:G:A	C266Y	0.991
19:44649916:T:A	W179R	0.990
19:44649916:T:C	W179R	0.990
19:44657854:G:A	C312Y	0.989
19:44647288:T:A	C49S	0.988
19:44647289:G:C	C49S	0.988
19:44647423:T:C	F94L	0.988
19:44647425:C:A	F94L	0.988
19:44647425:C:G	F94L	0.988
19:44649883:T:C	S168P	0.988
19:44657853:T:C	C312R	0.988

dbSNP variants (sampled 300 via entrez): RS1000114397 (19:44653791 C>G), RS1000155746 (19:44661660 T>C), RS1000311658 (19:44656030 T>C), RS1000492793 (19:44652397 G>A,T), RS1000620113 (19:44644459 T>C), RS1000705241 (19:44657552 T>C), RS1000785654 (19:44656280 ATG>A), RS1000810736 (19:44663290 G>A), RS1001471435 (19:44665648 A>C), RS1001506756 (19:44656509 A>G), RS1001559421 (19:44645822 T>A), RS1001643982 (19:44645549 G>A), RS1001689721 (19:44651347 T>G), RS1001740983 (19:44651703 T>A), RS1001795713 (19:44644544 A>G,T)

Disease associations

OMIM: gene MIM:173850 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST001198_71	Multiple sclerosis	1.000000e-06
GCST002422_1	Alzheimer’s disease	9.000000e-116
GCST004599_151	Mean platelet volume	1.000000e-17
GCST004599_152	Mean platelet volume	1.000000e-09
GCST005950_15	Body mass index x sex x age interaction (4df test)	2.000000e-10
GCST005951_56	Body mass index	1.000000e-06
GCST005952_8	Body mass index (age>50)	9.000000e-12
GCST005954_4	Body mass index x age interaction	2.000000e-07
GCST007124_7	Multiple sclerosis and HDL levels (pleiotropy)	4.000000e-06
GCST007320_31	Alzheimer’s disease or family history of Alzheimer’s disease	4.000000e-17
GCST007827_17	Alzheimer’s disease or HDL levels (pleiotropy)	3.000000e-12
GCST007827_19	Alzheimer’s disease or HDL levels (pleiotropy)	3.000000e-11
GCST007827_5	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-74
GCST007827_6	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-54
GCST007827_8	Alzheimer’s disease or HDL levels (pleiotropy)	3.000000e-36
GCST90002395_414	Mean platelet volume	9.000000e-15
GCST90002395_415	Mean platelet volume	5.000000e-18
GCST90002401_267	Platelet distribution width	6.000000e-15

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009268	family history of Alzheimer’s disease
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Immunoglobulin like domain containing proteins

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, increases expression	4
bisphenol A	affects expression, increases expression	3
Cisplatin	increases expression, affects cotreatment, decreases expression	2
Lipopolysaccharides	increases expression, affects expression, affects response to substance	2
Nickel	increases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Valproic Acid	increases expression, increases methylation	2
dicrotophos	increases expression	1
lasiocarpine	decreases expression	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression, increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
torcetrapib	increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Gold	affects binding, decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Manganese	decreases expression	1

Cellosaurus cell lines

12 cell lines: 6 transformed cell line, 4 cancer cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2PN	Abcam A-549 PVR KO	Cancer cell line	Male
CVCL_B3FF	Abcam HEK293T PVR KO	Transformed cell line	Female
CVCL_D9Q6	Ubigene HEK293 PVR KO	Transformed cell line	Female
CVCL_E1K7	HyCyte HEK293 KO-hPVR	Transformed cell line	Female
CVCL_E5IP	CHO-K1/CD155	Spontaneously immortalized cell line	Female
CVCL_E6RJ	Genomeditech CHO-K1 H_PVR(CD155)	Spontaneously immortalized cell line	Female
CVCL_E6WN	Genomeditech Raji H_PVR(CD155)	Cancer cell line	Male
CVCL_TH76	HAP1 PVR (-) 1	Cancer cell line	Male
CVCL_TH77	HAP1 PVR (-) 2	Cancer cell line	Male
CVCL_U966	TgSVA	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

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