CD160

Summary

CD160 (CD160 molecule, HGNC:17013) is a protein-coding gene on chromosome 1q21.1, encoding CD160 antigen (O95971). Receptor on immune cells capable to deliver stimulatory or inhibitory signals that regulate cell activation and differentiation.

CD160 is an 27 kDa glycoprotein which was initially identified with the monoclonal antibody BY55. Its expression is tightly associated with peripheral blood NK cells and CD8 T lymphocytes with cytolytic effector activity. The cDNA sequence of CD160 predicts a cysteine-rich, glycosylphosphatidylinositol-anchored protein of 181 amino acids with a single Ig-like domain weakly homologous to KIR2DL4 molecule. CD160 is expressed at the cell surface as a tightly disulfide-linked multimer. RNA blot analysis revealed CD160 mRNAs of 1.5 and 1.6 kb whose expression was highly restricted to circulating NK and T cells, spleen and small intestine. Within NK cells CD160 is expressed by CD56dimCD16+ cells whereas among circulating T cells its expression is mainly restricted to TCRgd bearing cells and to TCRab+CD8brightCD95+CD56+CD28-CD27-cells. In tissues, CD160 is expressed on all intestinal intraepithelial lymphocytes. CD160 shows a broad specificity for binding to both classical and nonclassical MHC class I molecules.

Source: NCBI Gene 11126 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 58 total — 1 pathogenic
• MANE Select transcript: NM_007053

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17013
Approved symbol	CD160
Name	CD160 molecule
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	BY55, NK1, NK28
Ensembl gene	ENSG00000117281
Ensembl biotype	protein_coding
OMIM	604463
Entrez	11126

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000235933, ENST00000369288, ENST00000401557, ENST00000584442, ENST00000616463, ENST00000907346, ENST00000907347, ENST00000907348, ENST00000907349, ENST00000907350, ENST00000907351, ENST00000953042

RefSeq mRNA: 1 — MANE Select: NM_007053 NM_007053

CCDS: CCDS72861

Canonical transcript exons

ENST00000369288 — 6 exons

Exon	Start	End
ENSE00000787494	145730744	145731070
ENSE00001449409	145724801	145724906
ENSE00001449410	145719499	145719559
ENSE00001449415	145738486	145739288
ENSE00002706019	145735997	145736134
ENSE00003702422	145728256	145728400

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 93.26.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6070 / max 170.3121, expressed in 68 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4947	0.5262	62
4945	0.0484	23
4946	0.0324	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.26	gold quality
jejunal mucosa	UBERON:0000399	79.80	gold quality
blood	UBERON:0000178	78.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.89	gold quality
spleen	UBERON:0002106	76.82	gold quality
duodenum	UBERON:0002114	73.74	gold quality
stromal cell of endometrium	CL:0002255	73.28	gold quality
bone marrow	UBERON:0002371	71.40	gold quality
bone marrow cell	CL:0002092	71.20	gold quality
leukocyte	CL:0000738	70.99	gold quality
mononuclear cell	CL:0000842	69.26	gold quality
monocyte	CL:0000576	68.67	gold quality
lymph node	UBERON:0000029	68.61	gold quality
right coronary artery	UBERON:0001625	67.84	gold quality
cerebellar cortex	UBERON:0002129	67.84	gold quality
descending thoracic aorta	UBERON:0002345	67.62	gold quality
cerebellar hemisphere	UBERON:0002245	67.61	gold quality
thoracic aorta	UBERON:0001515	67.07	gold quality
ascending aorta	UBERON:0001496	66.97	gold quality
small intestine	UBERON:0002108	66.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	66.07	gold quality
right lobe of liver	UBERON:0001114	65.64	gold quality
ileal mucosa	UBERON:0000331	65.62	silver quality
cerebellum	UBERON:0002037	65.51	gold quality
mucosa of stomach	UBERON:0001199	65.22	gold quality
liver	UBERON:0002107	65.03	gold quality
aorta	UBERON:0000947	65.02	gold quality
palpebral conjunctiva	UBERON:0001812	65.02	silver quality
colonic epithelium	UBERON:0000397	64.95	silver quality
lower esophagus muscularis layer	UBERON:0035833	64.62	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	1269.84
E-HCAD-1	yes	84.21
E-HCAD-4	yes	83.42
E-CURD-122	yes	49.10
E-HCAD-9	yes	24.29
E-CURD-46	yes	14.91
E-MTAB-8410	yes	13.72
E-ANND-3	yes	7.31
E-MTAB-9067	yes	3.82
E-HCAD-32	no	710.27
E-GEOD-83139	no	24.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX1

miRNA regulators (miRDB)

46 targeting CD160, 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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-1537-5P	98.70	68.33	999

Literature-anchored findings (GeneRIF, showing 38)

• BY55 functions as a co-receptor in TCR signal transduction of a human cytotoxic effector T lymphocyte subset lacking CD28 expression (PMID:11978774)
• CD94-expressing cells with cytolytic activity against the recipient’s leukemic and tumor cells without enhancement of alloresponse might be able to be expanded from donor G-PBMCs. (PMID:15073036)
• The CD160 receptor represents a unique triggering surface molecule expressed by cytotoxic NK cells that participates in the inflammatory response and determines the type of subsequent specific immunity. (PMID:15494480)
• We report that CD160 acts as a co-activator receptor for CD3-induced proliferation of CD4+ CD160+ T cells isolated from inflammatory skin lesions. (PMID:17218942)
• short-time incubation of NK lymphocytes with IL-15 converts the membrane-bound CD160 to a soluble form; activated NK lymphocytes release a soluble form of CD160 that functionally impairs the MHC-I-specific cytotoxic CD8(+) T lymphocyte responsiveness (PMID:17237375)
• CD160 serves as a negative regulator of CD4+ T cell activation through its interaction with HVEM. (PMID:18193050)
• Apart from CD160 mRNA, three additional transcripts generated through alternative splicings of the CD160 gene can be detected in peripheral blood natural killer (NK) cells but not in peripheral blood CD8-positive T cells, upon activation. (PMID:19109136)
• Site-directed mutagenesis showed that the predicted AML-1 site is essential for the regulation of CD160 gene expression. (PMID:19626042)
• Activation through CD160 leads to PI3K-dependent chronic lymphocytic leukemia protection from spontaneous in vitro apoptosis, as well as cellular activation with cell cycle progression and cytokine production. (PMID:20164468)
• soluble CD160, produced by mast cells, may have a role in T-cell-mast cell interactions in vivo (PMID:21191401)
• results indicate that CD160+ lymphocytes could be able to play a role in the maintenance of healthy pregnancy (PMID:21276121)
• A novel antiangiogenic and vascular normalization therapy targeted against human CD160 receptor. (PMID:21482699)
• demonstrated CD160 expression in 98% of chronic lymphocytic leukemia cases, 100% of hairy cell leukemia cases, 15% of mantle cell lymphoma in the leukemic phase, and 16% of other B-cell lymphoproliferative disorders (PMID:21715317)
• The results of a mutagenesis study of HVEM suggest that the CD160 binding region on HVEM was slightly different from, but overlapped with, the BTLA binding site. (PMID:21959263)
• circulating NK cells from PNH patients exhibit a self-MHC class I molecule reactive effector function, which could be mediated through the recruitment of CD160-TM receptor. (PMID:22172098)
• CD160 and PD-1 co-expression on HIV-specific CD8 T cells defines a subset with advanced dysfunction. (PMID:22916009)
• CD160-expressing human NK cells are costimulated by HVEM expressed in the environment to enhance cytolytic function and cytokine production. (PMID:23761635)
• Data suggest that CD160 may become a useful marker in the clinical diagnosis and prognosis of chronic lymphocytic leukemia. (PMID:24882258)
• A population of CD4+ CD160+ T lymphocytes was identified in circulating cutaneous T cells. (PMID:25044837)
• Antibodies targeting CD160-GPI complement the blockade of PD-1 to enhance HIV-specific T-cell responses and warrant further investigation in the development of novel immunotherapeutic approaches. (PMID:25179432)
• report high frequencies of CD160 on CD8+ T cells, with significantly higher levels on HTLV-1 specific CD8+ T cells (PMID:25277889)
• identified 13 ADCC-activated genes. Six gene expression assays including 8 of the 13 genes (CCL3, CCL4/CCL4L1/CCL4L2, CD160, IFNG, NR4A3 and XCL1/XCL2) were analyzed in 127 kidney biopsies (PMID:25449536)
• CD160 and CD200 are expressed in B cells in chronic lymphocytic leukemia and are absent in other mature B-cell neoplasms. (PMID:25470765)
• CD160FCA offers a simple assay for minimal residual disease detection in CLL and gives prognostic information across different CLL risk groups. (PMID:25615279)
• elevated CD160 expression on natural killer (NK) cells plays an important role in NK cell loss in atherosclerosis. (PMID:26071079)
• analysis of how NK1 receptor Gs versus Gq proteins and beta-arrestin signaling is determined by interactions in the water hydrogen bond network (PMID:26269596)
• Data report the crystal structures of the human CD160 extracellular domain and its complex with human HVEM. CD160 adopts a unique variation of the immunoglobulin fold and exists as a monomer in solution. The CD160:HVEM assembly exhibits a 1:1 stoichiometry and a binding interface similar to that observed in the BTLA:HVEM complex. (PMID:31230945)
• Redesigning HVEM Interface for Selective Binding to LIGHT, BTLA, and CD160. (PMID:32795404)
• CD160 Plays a Protective Role During Chronic Infection by Enhancing Both Functionalities and Proliferative Capacity of CD8+ T Cells. (PMID:33072082)
• Expanded antigen-experienced CD160(+)CD8(+)effector T cells exhibit impaired effector functions in chronic lymphocytic leukemia. (PMID:33931471)
• Associations between CD160 polymorphisms and autoimmune thyroid disease: a case-control study. (PMID:34238277)
• CD160 protein as a new therapeutic target in a battle against autoimmune, infectious and lifestyle diseases. Analysis of the structure, interactions and functions. (PMID:34273660)
• HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160. (PMID:34709351)
• The soluble form of CD160 acts as a tumor mediator of immune escape in melanoma. (PMID:35428910)
• CD160 Promotes NK Cell Functions by Upregulating Glucose Metabolism and Negatively Correlates With HIV Disease Progression. (PMID:36110864)
• [Expression of CD160 in natural killer (NK) cells from patients with active tuberculosis and its relationship with cell functions]. (PMID:36163624)
• Plasma extracellular vesicle transcriptomics identifies CD160 for predicting immunochemotherapy efficacy in lung cancer. (PMID:37014183)
• TIM-3/Galectin-9 and CD160 expression in salivary adenoid cystic carcinoma. (PMID:37455567)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd160	ENSMUSG00000038304
rattus_norvegicus	Cd160	ENSRNOG00000000097

Protein

Protein identifiers

CD160 antigen — O95971 (reviewed: O95971)

Alternative names: Natural killer cell receptor BY55

All UniProt accessions (2): O95971, Q6FH89

UniProt curated annotations — full annotation on UniProt →

Function. Receptor on immune cells capable to deliver stimulatory or inhibitory signals that regulate cell activation and differentiation. Exists as a GPI-anchored and as a transmembrane form, each likely initiating distinct signaling pathways via phosphoinositol 3-kinase in activated NK cells and via LCK and CD247/CD3 zeta chain in activated T cells. Receptor for both classical and non-classical MHC class I molecules. In the context of acute viral infection, recognizes HLA-C and triggers NK cell cytotoxic activity, likely playing a role in anti-viral innate immune response. On CD8+ T cells, binds HLA-A2-B2M in complex with a viral peptide and provides a costimulatory signal to activated/memory T cells. Upon persistent antigen stimulation, such as occurs during chronic viral infection, may progressively inhibit TCR signaling in memory CD8+ T cells, contributing to T cell exhaustion. On endothelial cells, recognizes HLA-G and controls angiogenesis in immune privileged sites. Receptor or ligand for TNF superfamily member TNFRSF14, participating in bidirectional cell-cell contact signaling between antigen presenting cells and lymphocytes. Upon ligation of TNFRSF14, provides stimulatory signal to NK cells enhancing IFNG production and anti-tumor immune response. On activated CD4+ T cells, interacts with TNFRSF14 and down-regulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response. In the context of bacterial infection, acts as a ligand for TNFRSF14 on epithelial cells, triggering the production of antimicrobial proteins and pro-inflammatory cytokines. The soluble GPI-cleaved form, usually released by activated lymphocytes, might play an immune regulatory role by limiting lymphocyte effector functions.

Subunit / interactions. Homomultimer; disulfide-linked. Interacts with HLA-G. Interacts with HLA-A2-B2M in complex with an HIV-derived peptide. Interacts with TNFRSF14 (via cysteine-rich domain 1); this interaction is direct. Interacts with LCK and CD247/CD3 zeta chain.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Expression is restricted to functional NK and cytotoxic T lymphocytes. Expressed in viral-specific effector memory and terminally differentiated effector memory CD8+ T cells. Expressed in memory and activated CD4+ T cell subsets (at protein level). Expressed at high levels in intraepithelial lymphocytes (at protein level). Expressed in both alpha-beta and gamma-delta CD8+ T cell subsets (at protein level). Expressed in umbilical vein endothelial cells (at protein level). Expressed in monocytes and at lower levels in B cells. Isoform 3: Expressed exclusively in activated NK cells (at protein level).

Induction. Up-regulated on CD4+ T cells upon stimulation via T cell receptor plus costimulation via CD28. Up-regulated by IL15 on immunoregulatory NCAM1/CD56-bright NK cells.

Miscellaneous. Mutagenesis of Tyr-225 to Phe abolishes intracellular signaling.

Isoforms (4)

UniProt ID	Names	Canonical?
O95971-1	1, CD160	yes
O95971-2	2, CD160deltaIg
O95971-3	3, CD160-TM
O95971-4	4, CD160deltaIg-TM

RefSeq proteins (1): NP_008984* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR042385	CD160	Family

UniProt features (27 total): strand 9, splice variant 3, helix 3, chain 2, glycosylation site 2, disulfide bond 2, signal peptide 1, sequence variant 1, turn 1, propeptide 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6NGG	X-RAY DIFFRACTION	1.95
6NG9	X-RAY DIFFRACTION	1.95
6NG3	X-RAY DIFFRACTION	2.88
7MSG	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95971-F1	75.65	0.49

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): 159

Disulfide bonds (2): 44–112, 61–68

Glycosylation sites (2): 28, 137

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 315 (showing top): GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_DEGRANULATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOLDRATH_IMMUNE_MEMORY, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_LYMPHOCYTE_COSTIMULATION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION

GO Biological Process (21): angiogenesis (GO:0001525), adaptive immune response (GO:0002250), mucosal immune response (GO:0002385), positive regulation of natural killer cell cytokine production (GO:0002729), positive regulation of natural killer cell mediated immune response to tumor cell (GO:0002857), negative regulation of angiogenesis (GO:0016525), T cell costimulation (GO:0031295), positive regulation of type II interferon production (GO:0032729), positive regulation of natural killer cell degranulation (GO:0043323), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), innate immune response (GO:0045087), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), defense response to Gram-negative bacterium (GO:0050829), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of CD4-positive, alpha-beta T cell costimulation (GO:1900280), negative regulation of adaptive immune memory response (GO:1905675), positive regulation of endothelial cell apoptotic process (GO:2000353), positive regulation of cytokine production (GO:0001819), immune system process (GO:0002376), positive regulation of natural killer cell mediated immunity (GO:0002717), regulation of adaptive immune response (GO:0002819)

GO Molecular Function (8): signaling receptor binding (GO:0005102), kinase binding (GO:0019900), MHC class I protein complex binding (GO:0023024), MHC class I receptor activity (GO:0032393), MHC class Ib receptor activity (GO:0032394), activating MHC class I receptor activity (GO:0032397), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of natural killer cell mediated immunity	3
cellular anatomical structure	3
immune response	2
transmembrane signaling receptor activity	2
immune receptor activity	2
membrane	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
organ or tissue specific immune response	1
natural killer cell cytokine production	1
positive regulation of cytokine production involved in immune response	1
regulation of natural killer cell cytokine production	1
natural killer cell mediated immune response to tumor cell	1
positive regulation of immune response to tumor cell	1
regulation of natural killer cell mediated immune response to tumor cell	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
positive regulation of leukocyte degranulation	1
natural killer cell degranulation	1
regulation of natural killer cell degranulation	1
positive regulation of natural killer cell mediated cytotoxicity	1
intracellular signaling cassette	1
defense response to symbiont	1
positive regulation of leukocyte mediated cytotoxicity	1
natural killer cell mediated cytotoxicity	1
regulation of natural killer cell mediated cytotoxicity	1
defense response to bacterium	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
CD4-positive, alpha-beta T cell costimulation	1
regulation of CD4-positive, alpha-beta T cell costimulation	1
negative regulation of T cell costimulation	1
negative regulation of adaptive immune response	1

Protein interactions and networks

STRING

960 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD160	TNFRSF14	Q92956	998
CD160	HLA-G	P17693	985
CD160	BTLA	Q7Z6A9	949
CD160	HLA-C	P04222	889
CD160	CD8A	P01732	848
CD160	TNFSF14	O43557	802
CD160	LAG3	P18627	795
CD160	CD244	Q9BZW8	774
CD160	KLRG1	Q96E93	772
CD160	HAVCR2	Q8TDQ0	771
CD160	PDCD1	Q15116	766
CD160	TIGIT	Q495A1	727
CD160	CD28	P10747	716
CD160	CTLA4	P16410	705
CD160	ACKR1	Q16570	694

IntAct

30 interactions, top by confidence:

A	B	Type	Score
CD160	MDM4	psi-mi:“MI:0915”(physical association)	0.720
MDM4	CD160	psi-mi:“MI:0915”(physical association)	0.720
TNFRSF14	CD160	psi-mi:“MI:0915”(physical association)	0.610
CD160	TNFRSF14	psi-mi:“MI:0407”(direct interaction)	0.610
AGTRAP	CD160	psi-mi:“MI:0915”(physical association)	0.560
CD160	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
CD160	CMTM5	psi-mi:“MI:0915”(physical association)	0.560
CD160	MAL2	psi-mi:“MI:0915”(physical association)	0.560
CD160	THRA	psi-mi:“MI:0915”(physical association)	0.560
CD160	SYP	psi-mi:“MI:0915”(physical association)	0.560
CD160	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
CD160	E7	psi-mi:“MI:0915”(physical association)	0.370
CD160	PLXNB2	psi-mi:“MI:0914”(association)	0.350
CD160	ITGA6	psi-mi:“MI:0914”(association)	0.350
CD160	CMTM5	psi-mi:“MI:0915”(physical association)	0.000
CD160	MAL2	psi-mi:“MI:0915”(physical association)	0.000
CD160	MDM4	psi-mi:“MI:0915”(physical association)	0.000
CD160	THRA	psi-mi:“MI:0915”(physical association)	0.000
CD160	CMTM6	psi-mi:“MI:0915”(physical association)	0.000
CD160	SYP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (49): CD160 (Two-hybrid), AGTRAP (Two-hybrid), CD160 (Two-hybrid), CD160 (Two-hybrid), THRA (Two-hybrid), MAL2 (Two-hybrid), CMTM5 (Two-hybrid), MDM4 (Two-hybrid), CACNA2D1 (Affinity Capture-MS), ITGA8 (Affinity Capture-MS), TCTN1 (Affinity Capture-MS), CNTNAP3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), FAT1 (Affinity Capture-MS)

ESM2 similar proteins: A5D7B2, G3X8R9, O88875, O95727, O95971, P08101, P09793, P0C1X9, P0DMS9, P0DTI4, P12318, P15530, P16410, P31995, P40259, P42070, P42072, P50283, Q00609, Q149L7, Q1ERP8, Q2YFS1, Q2YFS2, Q2YFS3, Q3LRV9, Q566E6, Q5RDA5, Q5RFR2, Q60513, Q63203, Q68D85, Q6QUN5, Q6SJQ5, Q6SJQ7, Q6TYI6, Q7TSA3, Q7Z6A9, Q7Z6M3, Q8BG84, Q8SPV8

Diamond homologs: O88875, O95971

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
160952	GRCh38/hg38 1q21.1-21.2(chr1:145215697-149076087)x1	Pathogenic

SpliceAI

464 predictions. Top by Δscore:

Variant	Effect	Δscore
1:145728399:CCA:C	donor_gain	1.0000
1:145728401:CAC:C	donor_loss	1.0000
1:145728402:TCA:T	donor_loss	1.0000
1:145728403:CTCAC:C	donor_loss	1.0000
1:145728326:T:TA	donor_gain	0.9900
1:145728405:T:TA	donor_gain	0.9800
1:145728433:C:A	donor_gain	0.9800
1:145728375:G:A	donor_gain	0.9700
1:145728434:C:CA	donor_gain	0.9500
1:145735997:TCTC:T	acceptor_gain	0.9300
1:145728396:CCAGA:C	donor_gain	0.9000
1:145733913:A:AC	donor_gain	0.9000
1:145733912:G:C	donor_gain	0.8900
1:145728406:ATCCT:A	donor_loss	0.8800
1:145735996:CTCT:C	acceptor_gain	0.8800
1:145728406:AT:A	donor_gain	0.8700
1:145735998:GTCTC:G	acceptor_gain	0.8600
1:145738532:T:C	acceptor_gain	0.8600
1:145728391:C:CC	donor_gain	0.8400
1:145728392:A:AC	donor_gain	0.8400
1:145728399:CC:C	donor_gain	0.8400
1:145728399:CCACC:C	donor_gain	0.8400
1:145728400:AC:A	donor_gain	0.8400
1:145728400:ACCAC:A	donor_gain	0.8400
1:145728399:C:CC	donor_gain	0.8300
1:145728400:A:AC	donor_gain	0.8300
1:145728453:C:A	donor_gain	0.8000
1:145730812:ATG:A	donor_gain	0.7600
1:145730897:G:C	donor_gain	0.7400
1:145739204:C:CT	acceptor_gain	0.7400

AlphaMissense

1175 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:145730845:T:C	F59L	0.977
1:145730847:T:A	F59L	0.977
1:145730847:T:G	F59L	0.977
1:145730851:T:A	C61S	0.954
1:145730852:G:C	C61S	0.954
1:145730887:A:C	S73R	0.954
1:145730889:T:A	S73R	0.954
1:145730889:T:G	S73R	0.954
1:145736116:A:C	S174R	0.953
1:145736118:C:A	S174R	0.953
1:145736118:C:G	S174R	0.953
1:145730998:T:G	Y110D	0.947
1:145730800:T:C	C44R	0.943
1:145730795:T:C	L42S	0.936
1:145730856:G:C	K62N	0.936
1:145730856:G:T	K62N	0.936
1:145730851:T:C	C61R	0.935
1:145730846:T:G	F59C	0.929
1:145730800:T:A	C44S	0.927
1:145730801:G:C	C44S	0.927
1:145730853:C:G	C61W	0.926
1:145731004:T:C	C112R	0.926
1:145730802:T:G	C44W	0.923
1:145731004:T:A	C112S	0.922
1:145731005:G:C	C112S	0.922
1:145730954:T:C	L95S	0.920
1:145730801:G:A	C44Y	0.918
1:145730852:G:A	C61Y	0.916
1:145730959:T:C	F97L	0.907
1:145730961:C:A	F97L	0.907

dbSNP variants (sampled 300 via entrez): RS1000009020 (1:145721546 A>G), RS1000059770 (1:145721714 A>G), RS1000309112 (1:145728927 T>G), RS1000407525 (1:145735368 T>C), RS1000743179 (1:145733802 C>T), RS1001360550 (1:145728146 C>A), RS1001405207 (1:145735295 C>A,T), RS1002076074 (1:145739673 G>A), RS1002252742 (1:145720880 T>C), RS1003038773 (1:145719537 G>C), RS1003081487 (1:145733753 T>C), RS1003193684 (1:145738393 G>A,C,T), RS1003358571 (1:145725000 G>A), RS1003376930 (1:145733324 A>G), RS1003750557 (1:145738146 T>C)

Disease associations

OMIM: gene MIM:604463 | disease phenotypes: MIM:189800

GenCC curated gene-disease

Mondo (1): preeclampsia (MONDO:0005081)

Orphanet (1): Preeclampsia (Orphanet:275555)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006630_89	Diastolic blood pressure	4.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011225	Pre-Eclampsia	C12.050.703.395.249

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, decreases methylation	2
aristolochic acid I	increases expression	1
fluorene-9-bisphenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arbutin	decreases expression	1
Lipopolysaccharides	decreases expression	1
Nickel	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Zinc	decreases expression	1
Aflatoxin B1	increases methylation	1
Acrylamide	increases expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1MM	Abcam HeLa CD160 KO	Cancer cell line	Female
CVCL_KA24	CHO-K1/CD160	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	PHASE4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	PHASE4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	PHASE4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	PHASE4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665	PHASE4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial