LILRB2

Summary

LILRB2 (leukocyte immunoglobulin like receptor B2, HGNC:6606) is a protein-coding gene on chromosome 19q13.4, encoding Leukocyte immunoglobulin-like receptor subfamily B member 2 (Q8N423). Receptor for class I MHC antigens.

This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10288 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 152 total
• MANE Select transcript: NM_001080978

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6606
Approved symbol	LILRB2
Name	leukocyte immunoglobulin like receptor B2
Location	19q13.4
Locus type	gene with protein product
Status	Approved
Aliases	LIR-2, ILT4, MIR-10, LIR2, CD85d, MIR10
Ensembl gene	ENSG00000131042
Ensembl biotype	protein_coding
OMIM	604815
Entrez	10288

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000314446, ENST00000391746, ENST00000391748, ENST00000391749, ENST00000434421, ENST00000455108, ENST00000471216, ENST00000493242, ENST00000872963, ENST00000872964, ENST00000872965, ENST00000872966, ENST00000872967, ENST00000872968, ENST00000949068, ENST00000949069, ENST00000949070, ENST00000949071

RefSeq mRNA: 6 — MANE Select: NM_001080978 NM_001080978, NM_001278403, NM_001278404, NM_001278405, NM_001278406, NM_005874

CCDS: CCDS12886, CCDS42612, CCDS62791, CCDS62792

Canonical transcript exons

ENST00000314446 — 14 exons

Exon	Start	End
ENSE00001627760	54273812	54274829
ENSE00002510213	54277550	54277597
ENSE00002521530	54276807	54276929
ENSE00003458970	54276381	54276456
ENSE00003482630	54278260	54278562
ENSE00003543316	54280264	54280299
ENSE00003559071	54277889	54277939
ENSE00003575221	54280463	54280544
ENSE00003592333	54275951	54276003
ENSE00003604374	54278812	54279108
ENSE00003606164	54279345	54279647
ENSE00003678213	54279791	54280075
ENSE00003682102	54276264	54276301
ENSE00003907625	54280961	54281110

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 98.46.

FANTOM5 (CAGE): breadth broad, TPM avg 2.4815 / max 173.4563, expressed in 273 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182624	1.7653	248
182623	0.4023	137
182622	0.2643	101
208926	0.0497	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.46	gold quality
leukocyte	CL:0000738	98.41	gold quality
granulocyte	CL:0000094	98.23	gold quality
blood	UBERON:0000178	97.81	gold quality
spleen	UBERON:0002106	96.14	gold quality
vermiform appendix	UBERON:0001154	94.29	gold quality
bone marrow	UBERON:0002371	93.01	gold quality
bone marrow cell	CL:0002092	90.97	gold quality
right lung	UBERON:0002167	89.26	gold quality
upper lobe of left lung	UBERON:0008952	86.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.36	silver quality
lung	UBERON:0002048	81.50	gold quality
right coronary artery	UBERON:0001625	80.38	gold quality
gall bladder	UBERON:0002110	79.86	gold quality
omental fat pad	UBERON:0010414	79.80	gold quality
lymph node	UBERON:0000029	78.23	gold quality
adipose tissue	UBERON:0001013	78.07	gold quality
smooth muscle tissue	UBERON:0001135	77.92	gold quality
placenta	UBERON:0001987	77.55	gold quality
left uterine tube	UBERON:0001303	76.88	gold quality
subcutaneous adipose tissue	UBERON:0002190	76.64	gold quality
descending thoracic aorta	UBERON:0002345	76.43	gold quality
left coronary artery	UBERON:0001626	76.37	gold quality
left adrenal gland cortex	UBERON:0035825	76.00	gold quality
right adrenal gland	UBERON:0001233	75.64	gold quality
thoracic aorta	UBERON:0001515	75.53	gold quality
ascending aorta	UBERON:0001496	75.38	gold quality
left adrenal gland	UBERON:0001234	75.35	gold quality
duodenum	UBERON:0002114	75.29	gold quality
liver	UBERON:0002107	75.02	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-55	yes	885.60
E-MTAB-9467	yes	19.41
E-ANND-3	yes	12.38
E-MTAB-9801	yes	8.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, TRERF1

miRNA regulators (miRDB)

40 targeting LILRB2, 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-8485	100.00	77.57	4731
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-325	99.58	66.55	358
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-628-3P	99.04	68.37	814
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-384	98.71	67.34	1229

Literature-anchored findings (GeneRIF, showing 40)

• inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G (PMID:12853576)
• Two single nucleotide polymorphisms of ILT4 were identified at positions 113 and 144 of domain 1, which is engaged in protein-protein interactions between APC and T cells. (PMID:15301858)
• report that ILT2 receptor, ILT3 receptor, ILT4 receptor, and KIR2DL4 receptor expression is up-regulated by HLA-G histocompatibility antigen in antigen-presenting cells, natural killer cells, and T cells (PMID:15670976)
• subtle structural differences between LILRB family members cause the distinct binding specificities to various forms of HLA-G and other MHCIs, which may in turn regulate immune suppression (PMID:17056715)
• Blocking HLA-G receptors ILT2 and ILT4 prevents HLA-G inhibitory effects, leading to the conclusion that that HLA-G acts mainly through these receptors. (PMID:17400057)
• constitutive cis binding between leukocyte immunoglobulin (Ig)-like receptor B2 or paired-Ig-like receptor B and major histocompatibility complex class I has an essential role in regulating allergic responses (PMID:17420263)
• Tolerogenicity of professional and non-professional human APC, such as dendritic cells and endothelial cells, respectively is due to the upregulation of the inhibitory receptors ILT3 and ILT4. (PMID:17923119)
• Progenitor mast cells expressed cell surface inhibitory LILRB2. Mature cord-blood-derived mast cells had detectable mRNA encoding multiple LILRs, none were expressed on the cell surface. (PMID:17998301)
• our results suggest that both the nonfunctional LILRA3 alleles and the low-expressing LILRB2 alleles identified in our study have increased in Northeast Asians because of natural selection. (PMID:18439545)
• The presence of LILRB1 in placental stromal cells and LILRB2 in vascular smooth muscle strongly suggest that HLA-G has novel functions in regulation of placental immunity, development and function of the extraembryonic vasculature. (PMID:18538388)
• Triggering of ILT4 in vitro and in vivo by certain isoforms of HLA-G phosphorylates ILT4 receptor, recruits SHP-1 and SHP-2, up-regulates the expression of IL-6, and down-regulates the differentiation of DCs via the IL-6-STAT3 pathway. (PMID:18550825)
• A significant association is observed between ILT4 dendritic cells in kidney transplants and donor age. (PMID:19010139)
• Membrane-associated ILT4 is a a novel receptor for CD1d antigen that inhibits CD1d-mediated immune responses by blocking the loading of lipid antigens such as alpha-galactosylceramide, consequently inhibiting natural killer (NK)T cell recognition. (PMID:19124746)
• crystals of the LILRB2/HLA-G complex belong to space group P3(1)21 (a=b=81.4 A, c=186.7 A, gamma=120 degrees). (PMID:19356145)
• Low-tryptophan-conditioned dendritic cells acquire strong tolerogenic capacity associated with a significant increase in inhibitory receptors ILT3 and ILT4 and favor induction of CD4+CD25+Foxp3+ T cells with suppressive function. (PMID:19535644)
• upregulated on antigen-presenting cells in response to Salmonella infection (PMID:19860908)
• DC-10 represents a novel subset of tolerogenic dendritic cells, which secrete high levels of IL-10, express ILT4 and HLA-G, and have the specific function to induce Tr1 cells (PMID:20448110)
• Soluble HLA-G inhibits myeloid dendritic cell function in HIV-1 infection by interacting with leukocyte immunoglobulin-like receptor B2. (PMID:20702625)
• IL-10 up-regulates ILT4 expression on monocytes via increasing ILT4 gene promoter activity. (PMID:21063840)
• Inhibitory receptors LILRB1 and LILRB2 vary in their level of binding to different HLA alleles, correlating in some cases with specific amino acid motifs. (PMID:21270408)
• LILRA3 binds both classical and non-classical HLA class I molecules but with reduced affinities compared to LILRB1/LILRB2 (PMID:21559424)
• B27 H chain dimers and multimers are stronger ligands for LILRB2 than HLA class I heterotrimers and H chains (PMID:22593621)
• study indicates an unexpected functional significance of classical immune-inhibitory receptors in maintenance of stemness of normal adult stem cells and in support of cancer development (PMID:22660330)
• Cyclosporine up-regulated the expression of ILT3 and ILT4 on natural killer cells, which influenced their cytotoxicity against tumor cells. (PMID:22664025)
• Data show that the leukocyte antigen G HLA-G alpha1-alpha3 structure, which constitutes the extracellular part of HLA-G2 and HLA-G6, binds the immunologic receptor LILRB2 but not LILRB1. (PMID:22802125)
• Data suggest that when CD1c is up-regulated, ILT4 is recruited to CD1c, thus reducing the inhibitory effect of immunoglobulin-like transcript 4 (ILT4) on CD1d recognition. (PMID:22888216)
• Upregulation of the inhibitory receptor ILT4 in monocytes from septic patients. (PMID:23911358)
• we report the crystal structures of the D3D4 domains of both LILRB1 and LILRB2. (PMID:23955630)
• These findings imply that LilrB2 contributes to human Alzheimer’s disease neuropathology and suggest therapeutic uses of blocking LilrB2 function. (PMID:24052308)
• Exocytosis acts as a modulator of the ILT4-mediated inhibition of neutrophil functions. (PMID:24133137)
• These data support a bystander role for the miR-10 family in NPM1 mutated acute myeloid leukemia (PMID:24596420)
• we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement (PMID:24603468)
• ILT4 was found to be highly expressed in primary human ductal and lobular breast cancer cells, and its expression was significantly correlated with more IL-10 expression. (PMID:24762057)
• A novel motif in the first and fourth Ig domains of LILRB2 was identified that is necessary for the receptor to be bound and activated by Angptl2. (PMID:24899623)
• PIRB and LILRB2 were expressed in mouse and human platelets, respectively. (PMID:25075127)
• involvement of ILT3 and ILT4 in the modulation of immune responsiveness in multiple sclerosis by both interferon and vitamin D (PMID:25551576)
• Findings suggest that ILT4 drives NSCLC development in part on activation of ERK signaling which in turn upregulates VEGF-C. (PMID:25948790)
• signaling involving ANGPTL2 and LILRB2 is important for lung cancer development (PMID:26056041)
• Data show that immunoglobulin-like transcript 4 (ILT4) increases the expression of the co-inhibitory molecule B7-H3 through PI3K/AKT/mTOR signalling. (PMID:26149216)
• High MicroRNA-10b promotes migration and invasion in gastric cancer. (PMID:26311318)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lilra6	ENSMUSG00000030427
mus_musculus	Pirb	ENSMUSG00000058818
mus_musculus	Lilra5	ENSMUSG00000070873
mus_musculus	Pira12	ENSMUSG00000074417
mus_musculus	Pira13	ENSMUSG00000074419
mus_musculus	Pira1	ENSMUSG00000081665
mus_musculus	Pira2	ENSMUSG00000089942
rattus_norvegicus	Lilra5	ENSRNOG00000027808
rattus_norvegicus	Lilrb3	ENSRNOG00000046683
rattus_norvegicus	Lilrb2	ENSRNOG00000054954
rattus_norvegicus	Lilrc2	ENSRNOG00000058087
rattus_norvegicus	Pirb	ENSRNOG00000058422
rattus_norvegicus	LOC134485274	ENSRNOG00000062907
rattus_norvegicus		ENSRNOG00000067708
rattus_norvegicus		ENSRNOG00000069029

Paralogs (25): GP6 (ENSG00000088053), LILRB1 (ENSG00000104972), LILRA1 (ENSG00000104974), LILRB5 (ENSG00000105609), A1BG (ENSG00000121410), KIR2DL1 (ENSG00000125498), IGSF1 (ENSG00000147255), LAIR2 (ENSG00000167618), KIR3DL1 (ENSG00000167633), OSCAR (ENSG00000170909), FCAR (ENSG00000186431), LILRB4 (ENSG00000186818), LILRA5 (ENSG00000187116), KIR2DL4 (ENSG00000189013), VSTM1 (ENSG00000189068), NCR1 (ENSG00000189430), LILRB3 (ENSG00000204577), KIR2DS4 (ENSG00000221957), LILRA4 (ENSG00000239961), LILRA2 (ENSG00000239998), KIR3DL2 (ENSG00000240403), KIR3DL3 (ENSG00000242019), KIR2DL3 (ENSG00000243772), LILRA6 (ENSG00000244482), TARM1 (ENSG00000248385)

Protein

Protein identifiers

Leukocyte immunoglobulin-like receptor subfamily B member 2 — Q8N423 (reviewed: Q8N423)

Alternative names: CD85 antigen-like family member D, Immunoglobulin-like transcript 4, Monocyte/macrophage immunoglobulin-like receptor 10

All UniProt accessions (2): Q8N423, H7C0C3

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C, HLA-G and HLA-F alleles. Involved in the down-regulation of the immune response and the development of tolerance. Recognizes HLA-G in complex with B2M/beta-2 microglobulin and a nonamer self-peptide (peptide-bound HLA-G-B2M) triggering differentiation of type 1 regulatory T cells and myeloid-derived suppressor cells, both of which actively maintain maternal-fetal tolerance. Competes with CD8A for binding to class I MHC antigens. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions.

Subunit / interactions. Binds PTPN6 when phosphorylated. Binds FCGR1A. Interacts with peptide-bound HLA-G-B2M; this interaction is direct. Interacts with peptide-bound HLA-F-B2M; this interaction is direct.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in monocytes and at lower levels in myeloid and plasmacytoid dendritic cells. Expressed in tolerogenic IL10-producing dendritic cells. Expressed in myeloid-derived suppressor cells during pregnancy. Detected at low levels in natural killer (NK) cells. Expressed in B cells.

Post-translational modifications. Phosphorylated on tyrosine residues. Dephosphorylated by PTPN6.

Domain organisation. Contains 3 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Induction. Induced on monocyte-derived macrophages by S.typhimurium infection.

Miscellaneous. Alternative use of an acceptor site.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8N423-2	2	yes
Q8N423-1	1
Q8N423-3	3
Q8N423-4	4

RefSeq proteins (6): NP_001074447, NP_001265332, NP_001265333, NP_001265334, NP_001265335, NP_005865 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050412	Ig-like_Receptors_ImmuneReg	Family

Pfam: PF00047, PF13895

UniProt features (78 total): strand 35, sequence variant 10, disulfide bond 5, splice variant 4, helix 4, domain 4, region of interest 3, short sequence motif 3, glycosylation site 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9C9C	X-RAY DIFFRACTION	1.66
2GW5	X-RAY DIFFRACTION	1.8
6BCS	X-RAY DIFFRACTION	2.1
2DYP	X-RAY DIFFRACTION	2.5
4LLA	X-RAY DIFFRACTION	2.5
9C9D	X-RAY DIFFRACTION	2.9
6AED	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N423-F1	76.24	0.56

Functional residue map

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

Disulfide bonds (5): 49–98, 144–196, 156–166, 245–296, 345–396

Glycosylation sites (3): 280, 301, 340

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-6798695	Neutrophil degranulation
R-HSA-1280218	Adaptive Immune System
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 304 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_92, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_DENDRITIC_CELL_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_TOLERANCE_INDUCTION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_DENDRITIC_CELL_DIFFERENTIATION, GOCC_SECRETORY_GRANULE

GO Biological Process (28): adaptive immune response (GO:0002250), negative regulation of antigen processing and presentation (GO:0002578), positive regulation of tolerance induction (GO:0002645), positive regulation of T cell tolerance induction (GO:0002666), immune response-regulating signaling pathway (GO:0002764), immune response-inhibiting cell surface receptor signaling pathway (GO:0002767), Fc receptor mediated inhibitory signaling pathway (GO:0002774), immune response (GO:0006955), cellular defense response (GO:0006968), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), cell-cell signaling (GO:0007267), learning or memory (GO:0007611), positive regulation of interleukin-6 production (GO:0032755), heterotypic cell-cell adhesion (GO:0034113), positive regulation of T cell proliferation (GO:0042102), negative regulation of T cell proliferation (GO:0042130), positive regulation of regulatory T cell differentiation (GO:0045591), negative regulation of protein metabolic process (GO:0051248), negative regulation of calcium ion transport (GO:0051926), cellular response to lipopolysaccharide (GO:0071222), interleukin-10-mediated signaling pathway (GO:0140105), regulation of long-term synaptic potentiation (GO:1900271), positive regulation of long-term synaptic depression (GO:1900454), negative regulation of postsynaptic density organization (GO:1905875), negative regulation of T cell costimulation (GO:2000524), regulation of dendritic cell differentiation (GO:2001198), immune system process (GO:0002376)

GO Molecular Function (10): amyloid-beta binding (GO:0001540), protein phosphatase 1 binding (GO:0008157), MHC class Ib protein complex binding (GO:0023025), MHC class Ib protein binding (GO:0023029), inhibitory MHC class I receptor activity (GO:0032396), MHC class I protein binding (GO:0042288), protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), cell adhesion molecule binding (GO:0050839), protein binding (GO:0005515)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), tertiary granule membrane (GO:0070821), ficolin-1-rich granule membrane (GO:0101003)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Immune System	2
Adaptive Immune System	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
cell communication	2
signaling	2
T cell proliferation	2
regulation of T cell proliferation	2
MHC protein binding	2
binding	2
secretory granule membrane	2
tertiary granule	2
immune response	1
regulation of antigen processing and presentation	1
negative regulation of immune system process	1
antigen processing and presentation	1
tolerance induction	1
regulation of tolerance induction	1
positive regulation of immune system process	1
positive regulation of multicellular organismal process	1
T cell tolerance induction	1
positive regulation of tolerance induction	1
regulation of T cell tolerance induction	1
regulation of immune response	1
immune response-inhibiting signal transduction	1
immune response-regulating cell surface receptor signaling pathway	1
immune response-inhibiting cell surface receptor signaling pathway	1
immune system process	1
response to stimulus	1
defense response	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
behavior	1
cognition	1
positive regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
cell-cell adhesion	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
negative regulation of lymphocyte proliferation	1

Protein interactions and networks

STRING

2038 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LILRB2	HLA-G	P17693	996
LILRB2	HLA-A	P01891	973
LILRB2	HLA-F	P30511	968
LILRB2	ANGPTL2	Q9UKU9	963
LILRB2	HLA-B	P01889	959
LILRB2	CD300C	Q08708	816
LILRB2	RPL5	P46777	812
LILRB2	ANGPTL1	O95841	804
LILRB2	CD86	P42081	797
LILRB2	CD28	P10747	745
LILRB2	HLA-C	P04222	743
LILRB2	HLA-E	P13747	722
LILRB2	IL10	P22301	694
LILRB2	STAC	Q99469	671
LILRB2	OMG	P23515	669

IntAct

85 interactions, top by confidence:

A	B	Type	Score
HLA-B	B2M	psi-mi:“MI:0915”(physical association)	0.930
HLA-G	LILRB2	psi-mi:“MI:0915”(physical association)	0.870
LILRB2	HLA-G	psi-mi:“MI:0915”(physical association)	0.870
LILRB2	HLA-G	psi-mi:“MI:0407”(direct interaction)	0.870
HLA-G	B2M	psi-mi:“MI:0915”(physical association)	0.780
LILRB2	ANGPTL5	psi-mi:“MI:0915”(physical association)	0.710
LILRB2	HLA-C	psi-mi:“MI:0407”(direct interaction)	0.710
ANGPTL5	LILRB2	psi-mi:“MI:0407”(direct interaction)	0.710
ANGPTL5	LILRB2	psi-mi:“MI:0915”(physical association)	0.710
LILRB2	HLA-B	psi-mi:“MI:0915”(physical association)	0.700
APP	LILRB2	psi-mi:“MI:0915”(physical association)	0.680
APP	LILRB2	psi-mi:“MI:0407”(direct interaction)	0.680
LILRB2	APP	psi-mi:“MI:0915”(physical association)	0.680
LILRB2	APP	psi-mi:“MI:0403”(colocalization)	0.680
LILRB2	ANGPTL2	psi-mi:“MI:0915”(physical association)	0.670
ANGPTL2	LILRB2	psi-mi:“MI:0915”(physical association)	0.670
LILRB2	ANGPTL2	psi-mi:“MI:0407”(direct interaction)	0.670
HLA-G	LILRB2	psi-mi:“MI:0915”(physical association)	0.590

ESM2 similar proteins: A0A0K2S4Q6, A2A7V7, A6NI73, A8K4G0, O43699, O75019, O75022, O75023, O75871, O76036, P0C191, P20138, P24071, P40198, P59901, P80943, Q08708, Q13410, Q28110, Q3U497, Q496F6, Q64JA4, Q6GTX8, Q6ISS4, Q6PI73, Q6UXZ3, Q7TSN2, Q863H2, Q8C567, Q8K249, Q8MJZ2, Q8MJZ7, Q8N149, Q8N423, Q8N6C8, Q8NHJ6, Q8NHL6, Q8VBT3, Q8VCH2, Q95JB9

Diamond homologs: A0A0G2KBC9, A6NI73, C0HJX2, C0HJX3, D3ZQX2, O75019, O75022, O75023, O76036, P0C191, P24071, P43626, P43629, P43630, P59901, P83556, P97484, Q14943, Q14954, Q61450, Q64281, Q6GTX8, Q6ISS4, Q6PI73, Q7TQA1, Q863H2, Q8C567, Q8IYS5, Q8MJZ2, Q8MJZ7, Q8N109, Q8N149, Q8N423, Q8N6C8, Q8N743, Q8NHJ6, Q8NHK3, Q8NHL6, Q95JB9, Q9HCN6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
sirolimus	“down-regulates quantity by repression”	LILRB2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	6	118.1×	5e-10
Interferon alpha/beta signaling	6	45.7×	1e-07
Interferon gamma signaling	7	43.9×	6e-09
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	9	39.2×	5e-11
ER-Phagosome pathway	6	38.9×	2e-07
SARS-CoV-2 activates/modulates innate and adaptive immune responses	8	35.7×	1e-09
Neutrophil degranulation	6	6.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of T cell mediated cytotoxicity	7	170.2×	3e-12
immune response	8	17.9×	8e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	116
Likely benign	21
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2249 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54274911:AGTGT:A	donor_gain	1.0000
19:54276226:ATCTC:A	donor_gain	1.0000
19:54276230:C:CA	donor_gain	1.0000
19:54276233:T:TA	donor_gain	1.0000
19:54276251:T:TA	donor_gain	1.0000
19:54276262:A:AC	donor_gain	1.0000
19:54276263:C:CC	donor_gain	1.0000
19:54276805:A:AC	donor_gain	1.0000
19:54276806:C:CC	donor_gain	1.0000
19:54278285:A:AC	donor_gain	1.0000
19:54278286:C:CC	donor_gain	1.0000
19:54278806:CCTCA:C	donor_loss	1.0000
19:54278807:CTCAC:C	donor_loss	1.0000
19:54278808:TCAC:T	donor_loss	1.0000
19:54278809:CACCT:C	donor_loss	1.0000
19:54278810:ACCTG:A	donor_loss	1.0000
19:54280073:TCCC:T	acceptor_loss	1.0000
19:54280075:CCTGG:C	acceptor_loss	1.0000
19:54280076:CTG:C	acceptor_loss	1.0000
19:54274907:T:A	donor_gain	0.9900
19:54276195:T:A	donor_gain	0.9900
19:54276215:T:TA	donor_gain	0.9900
19:54276227:T:C	donor_gain	0.9900
19:54276258:A:AC	donor_gain	0.9900
19:54276259:C:CC	donor_gain	0.9900
19:54276457:C:CC	acceptor_gain	0.9900
19:54276806:CT:C	donor_gain	0.9900
19:54276943:A:AC	acceptor_gain	0.9900
19:54276943:A:C	acceptor_gain	0.9900
19:54276947:C:CT	acceptor_gain	0.9900

AlphaMissense

3791 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000093839 (19:54365825 C>T), RS1000097651 (19:54274253 A>G), RS1000127728 (19:54366570 C>G,T), RS1000146034 (19:54365928 G>A), RS1000224057 (19:54378324 C>T), RS1000244294 (19:54366678 C>T), RS1000381319 (19:54375457 G>A,C), RS1000390963 (19:54366361 T>C), RS1000409716 (19:54281937 C>T), RS1000576961 (19:54357085 C>T), RS1000717025 (19:54374569 A>C), RS1000752244 (19:54280971 G>A), RS1000865871 (19:54384878 A>G), RS1000895011 (19:54380851 G>A), RS1000978668 (19:54385056 G>A,T)

Disease associations

OMIM: gene MIM:604815 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000755_38	HDL cholesterol	4.000000e-16
GCST006013_10	Lactate dehydrogenase levels	4.000000e-08
GCST006585_1265	Blood protein levels	8.000000e-117
GCST007827_2	Alzheimer’s disease or HDL levels (pleiotropy)	6.000000e-12
GCST009357_9	Nonsyndromic cleft lip	8.000000e-06
GCST009367_39	HDL cholesterol levels x short total sleep time interaction (2df test)	2.000000e-08
GCST009367_90	HDL cholesterol levels x short total sleep time interaction (2df test)	6.000000e-27
GCST009368_76	HDL cholesterol levels x long total sleep time interaction (2df test)	9.000000e-22

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004808	L lactate dehydrogenase measurement
EFO:0003959	cleft lip

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium bichromate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Ozone	increases expression	1
Tretinoin	increases expression	1
Fenretinide	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_E6R0	Genomeditech CHO-K1 H_LILRB2(ILT4)	Spontaneously immortalized cell line	Female
CVCL_E6UE	Genomeditech HEK-293 H_LILRB2(ILT4)	Transformed cell line	Female
CVCL_E6VV	Genomeditech Jurkat H_LILRB2(ILT4) Reporter	Cancer cell line	Male

Clinical trials (associated diseases)

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