LILRA4

Summary

LILRA4 (leukocyte immunoglobulin like receptor A4, HGNC:15503) is a protein-coding gene on chromosome 19q13.42, encoding Leukocyte immunoglobulin-like receptor subfamily A member 4 (P59901). Functions coreceptor to limit the innate immune responses to viral infections; signaling occurs via FCER1G.

This gene encodes an immunoglobulin-like cell surface protein that is expressed predominantly on plasmacytoid dendritic cells (PDCs) and modulates the function of these cells in the immune response. Expression of this gene is downregulated by interleukin 3 (IL3). This gene is one of a cluster of highly related genes located at chromosomal region 19q13.4.

Source: NCBI Gene 23547 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 99 total
• Druggable target: yes
• MANE Select transcript: NM_012276

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15503
Approved symbol	LILRA4
Name	leukocyte immunoglobulin like receptor A4
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	ILT7, CD85g
Ensembl gene	ENSG00000239961
Ensembl biotype	protein_coding
OMIM	607517
Entrez	23547

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 retained_intron, 1 non_stop_decay

ENST00000291759, ENST00000421056, ENST00000595581

RefSeq mRNA: 1 — MANE Select: NM_012276 NM_012276

CCDS: CCDS12890

Canonical transcript exons

ENST00000291759 — 8 exons

Exon	Start	End
ENSE00001051641	54333185	54333765
ENSE00001114912	54337936	54338235
ENSE00001415855	54339060	54339162
ENSE00002434470	54338866	54338901
ENSE00002505079	54337400	54337696
ENSE00002526909	54336841	54337143
ENSE00003568384	54333915	54333965
ENSE00003621447	54338396	54338680

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 86.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.4335 / max 1374.2918, expressed in 153 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182629	1.1762	119
182628	1.0282	108
182627	0.1594	18
182630	0.0698	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	86.81	gold quality
spleen	UBERON:0002106	84.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.65	gold quality
leukocyte	CL:0000738	81.08	gold quality
lymph node	UBERON:0000029	80.98	gold quality
monocyte	CL:0000576	80.74	gold quality
blood	UBERON:0000178	79.25	gold quality
vermiform appendix	UBERON:0001154	73.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.76	gold quality
substantia nigra	UBERON:0002038	66.96	gold quality
gall bladder	UBERON:0002110	66.71	gold quality
bone marrow cell	CL:0002092	66.14	gold quality
bone element	UBERON:0001474	65.88	gold quality
bone marrow	UBERON:0002371	65.88	gold quality
prefrontal cortex	UBERON:0000451	59.53	gold quality
mucosa of transverse colon	UBERON:0004991	59.24	gold quality
smooth muscle tissue	UBERON:0001135	58.48	gold quality
tonsil	UBERON:0002372	57.90	gold quality
Ammon’s horn	UBERON:0001954	56.80	gold quality
temporal lobe	UBERON:0001871	56.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	56.09	gold quality
amygdala	UBERON:0001876	55.89	gold quality
colonic epithelium	UBERON:0000397	54.63	silver quality
frontal cortex	UBERON:0001870	54.62	gold quality
small intestine	UBERON:0002108	54.57	gold quality
putamen	UBERON:0001874	53.96	gold quality
rectum	UBERON:0001052	53.83	gold quality
hypothalamus	UBERON:0001898	53.58	gold quality
urinary bladder	UBERON:0001255	53.57	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	929.64
E-GEOD-150728	yes	496.28
E-HCAD-36	yes	470.49
E-HCAD-32	yes	317.73
E-HCAD-4	yes	66.97
E-HCAD-1	yes	25.06
E-MTAB-6701	yes	17.76
E-MTAB-9467	yes	17.47
E-CURD-112	yes	16.08
E-CURD-46	yes	10.20
E-HCAD-10	yes	7.91
E-ANND-3	yes	3.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting LILRA4, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-556-5P	97.75	66.17	473
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-558	97.50	67.16	977
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-5588-3P	94.96	65.59	500

Literature-anchored findings (GeneRIF, showing 7)

• the expression of immunoglobulin-like transcript 7, in plasmacytoid dendritic cells (PMID:12384430)
• ILT7 protein associates with the signal adapter protein Fc epsilonRI gamma to form a receptor complex in dendritic cells. (PMID:16735691)
• key regulator of human pDC function and interferon type I production. (PMID:18048391)
• Data show that BST2 directly binds to purified ILT7, initiates signaling via the ILT7-FcepsilonRIgamma complex, and regulates TLR7/9 responses in plasmacytoid dendritic cells. (PMID:19564354)
• Intracellular expression of the TCL1 as well as membrane and intracellular expression of ILT7 in plasmacytoid dendritic cell leukemia (pDCL) samples and 61 non-pDC acute leukemia samples, were tested. (PMID:22674796)
• ILT7 may exert its immunomodulatory activity only on immature circulating plasmacytoid dendritic cells (pDCs), providing a basic homeostatic mechanism rather than negative feedback control on activated pDCs. (PMID:23401591)
• Crosslinked ILT7 favours the differentiation of immature plasmacytoid dendritic cells into antigen-presenting cells rather than IPC. (PMID:24586760)

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), LILRB2 (ENSG00000131042), IGSF1 (ENSG00000147255), LAIR2 (ENSG00000167618), KIR3DL1 (ENSG00000167633), OSCAR (ENSG00000170909), FCAR (ENSG00000186431), LILRB4 (ENSG00000186818), LILRA5 (ENSG00000187116), KIR2DL4 (ENSG00000189013), VSTM1 (ENSG00000189068), NCR1 (ENSG00000189430), LILRB3 (ENSG00000204577), KIR2DS4 (ENSG00000221957), LILRA2 (ENSG00000239998), KIR3DL2 (ENSG00000240403), KIR3DL3 (ENSG00000242019), KIR2DL3 (ENSG00000243772), LILRA6 (ENSG00000244482), TARM1 (ENSG00000248385)

Protein

Protein identifiers

Leukocyte immunoglobulin-like receptor subfamily A member 4 — P59901 (reviewed: P59901)

Alternative names: CD85 antigen-like family member G, Immunoglobulin-like transcript 7

All UniProt accessions (2): P59901, A0A075B7A5

UniProt curated annotations — full annotation on UniProt →

Function. Functions coreceptor to limit the innate immune responses to viral infections; signaling occurs via FCER1G. Down-regulates the production of IFNA1, IFNA2, IFNA4, IFNB1 and TNF by plasmacytoid dendritic cells that have been exposed to influenza virus or cytidine-phosphate-guanosine (CpG) dinucleotides, indicating it functions as a negative regulator of TLR7 and TLR9 signaling cascades. Down-regulates interferon production in response to interaction with BST2 on HIV-1 infected cells. Activates a signaling cascade in complex with FCER1G that results in phosphorylation of Src family and Syk kinases and thereby triggers mobilization of intracellular Ca(2+). Does not interfere with the differentiation of plasmacytoid dendritic cells into antigen-presenting cells.

Subunit / interactions. Interacts with FCER1G; this stabilizes the expression of both proteins at the cell membrane. Interacts with BST2; leads to activation of LILRA4-mediated signaling and down-regulation of the innate immune response to viral pathogens.

Subcellular location. Cell membrane.

Tissue specificity. Detected on plasmacytoid dendritic cells (at protein level). Detected on plasmacytoid dendritic cells, but not on monocytes or B cells.

Isoforms (2)

UniProt ID	Names	Canonical?
P59901-1	1	yes
P59901-2	2

RefSeq proteins (1): NP_036408* (*=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
IPR016332	A1B_glyco/leuk_Ig-like_rcpt	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050412	Ig-like_Receptors_ImmuneReg	Family

Pfam: PF00047, PF13895, PF13927

UniProt features (26 total): sequence conflict 5, glycosylation site 4, disulfide bond 4, domain 4, sequence variant 2, topological domain 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59901-F1	83.06	0.65

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): 404

Disulfide bonds (4): 49–98, 143–195, 244–295, 344–395

Glycosylation sites (4): 138, 239, 279, 300

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: 150 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_TOLL_LIKE_RECEPTOR_9_SIGNALING_PATHWAY, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, BOYLAN_MULTIPLE_MYELOMA_D_DN, MORF_RAD51L3, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_FC_EPSILON_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (10): immune response-regulating signaling pathway (GO:0002764), cytokine-mediated signaling pathway (GO:0019221), negative regulation of interferon-alpha production (GO:0032687), negative regulation of tumor necrosis factor production (GO:0032720), negative regulation of toll-like receptor 7 signaling pathway (GO:0034156), negative regulation of toll-like receptor 9 signaling pathway (GO:0034164), Fc-epsilon receptor signaling pathway (GO:0038095), innate immune response (GO:0045087), immune system process (GO:0002376), cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (4): signaling receptor binding (GO:0005102), coreceptor activity (GO:0015026), inhibitory MHC class I receptor activity (GO:0032396), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), Fc-epsilon receptor I complex (GO:0032998), 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
signal transduction	2
negative regulation of cytoplasmic pattern recognition receptor signaling pathway	2
regulation of immune response	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
negative regulation of type I interferon production	1
interferon-alpha production	1
regulation of interferon-alpha production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
toll-like receptor 7 signaling pathway	1
regulation of toll-like receptor 7 signaling pathway	1
toll-like receptor 9 signaling pathway	1
regulation of toll-like receptor 9 signaling pathway	1
Fc receptor signaling pathway	1
immune response	1
defense response to symbiont	1
biological_process	1
protein binding	1
signaling receptor activity	1
MHC class I receptor activity	1
binding	1
membrane	1
cell periphery	1
Fc receptor complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LILRA4	BST2	Q10589	993
LILRA4	FCER1G	P30273	937
LILRA4	CLEC4C	Q8WTT0	778
LILRA4	CD300C	Q08708	675
LILRA4	FCER1A	P12319	654
LILRA4	IL3RA	P26951	579
LILRA4	FCGR2A	P12318	577
LILRA4	IL3	P08700	567
LILRA4	LAIR1	Q6GTX8	533
LILRA4	TLR7	Q9NYK1	510
LILRA4	TLR9	Q9NR96	481
LILRA4	CD1C	P29017	479
LILRA4	CLEC9A	Q6UXN8	479
LILRA4	LAIR2	Q6ISS4	478
LILRA4	LILRB4	Q8NHJ6	463

IntAct

5 interactions, top by confidence:

A	B	Type	Score
LILRA4	BST2	psi-mi:“MI:0407”(direct interaction)	0.680
LILRA4	BST2	psi-mi:“MI:0915”(physical association)	0.680
LILRA4		psi-mi:“MI:0915”(physical association)	0.000

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

786 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54333761:TGGGG:T	acceptor_gain	1.0000
19:54333762:GGGG:G	acceptor_gain	1.0000
19:54333764:GG:G	acceptor_gain	1.0000
19:54333766:C:CC	acceptor_gain	1.0000
19:54333909:A:AC	donor_gain	1.0000
19:54333910:C:CC	donor_gain	1.0000
19:54333911:TCA:T	donor_loss	1.0000
19:54333912:CAC:C	donor_loss	1.0000
19:54333913:A:AC	donor_gain	1.0000
19:54333913:A:C	donor_loss	1.0000
19:54333914:C:CC	donor_gain	1.0000
19:54333914:CCAGT:C	donor_gain	1.0000
19:54333961:TGCTC:T	acceptor_gain	1.0000
19:54333963:CTC:C	acceptor_gain	1.0000
19:54333964:TC:T	acceptor_gain	1.0000
19:54333965:CC:C	acceptor_gain	1.0000
19:54333965:CCTA:C	acceptor_loss	1.0000
19:54333966:C:A	acceptor_loss	1.0000
19:54333966:C:CC	acceptor_gain	1.0000
19:54333974:C:CT	acceptor_gain	1.0000
19:54337394:CCTCA:C	donor_loss	1.0000
19:54337395:CTCA:C	donor_loss	1.0000
19:54337396:TCAC:T	donor_loss	1.0000
19:54337397:CACCT:C	donor_loss	1.0000
19:54337398:ACCT:A	donor_loss	1.0000
19:54337399:C:CA	donor_loss	1.0000
19:54333763:GGG:G	acceptor_gain	0.9900
19:54333765:GC:G	acceptor_loss	0.9900
19:54333766:C:CG	acceptor_loss	0.9900
19:54333772:A:AC	acceptor_gain	0.9900

AlphaMissense

3188 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54336956:G:C	F380L	0.974
19:54336956:G:T	F380L	0.974
19:54336958:A:G	F380L	0.974
19:54337961:A:C	S210R	0.970
19:54337961:A:T	S210R	0.970
19:54337963:T:G	S210R	0.970
19:54336957:A:C	F380C	0.965
19:54338007:C:G	C195S	0.958
19:54338008:A:T	C195S	0.958
19:54338421:G:C	S110R	0.956
19:54338421:G:T	S110R	0.956
19:54338423:T:G	S110R	0.956
19:54337065:C:G	C344S	0.954
19:54337066:A:T	C344S	0.954
19:54338605:C:G	C49S	0.953
19:54338606:A:T	C49S	0.953
19:54337512:G:C	F280L	0.950
19:54337512:G:T	F280L	0.950
19:54337514:A:G	F280L	0.950
19:54337425:A:C	S309R	0.949
19:54337425:A:T	S309R	0.949
19:54337427:T:G	S309R	0.949
19:54337037:G:C	F353L	0.946
19:54337037:G:T	F353L	0.946
19:54337039:A:G	F353L	0.946
19:54338135:G:C	F152L	0.946
19:54338135:G:T	F152L	0.946
19:54338137:A:G	F152L	0.946
19:54338163:C:G	C143S	0.945
19:54338164:A:T	C143S	0.945

dbSNP variants (sampled 300 via entrez): RS1000066853 (19:54340504 A>C), RS1000494182 (19:54334317 C>T), RS1001091800 (19:54337205 C>A,G), RS1002404506 (19:54337492 C>A,G,T), RS1002604426 (19:54332699 G>T), RS1002958584 (19:54334730 G>A), RS1003064859 (19:54332989 C>A,G,T), RS1003113220 (19:54337255 C>G,T), RS1003293720 (19:54333423 A>G), RS1003612855 (19:54338289 T>C), RS1003821489 (19:54338477 G>A,C), RS1004742467 (19:54334411 G>A), RS1005592797 (19:54340422 A>C,G), RS1005993775 (19:54335140 T>A), RS1006980747 (19:54341156 C>G)

Disease associations

OMIM: gene MIM:607517 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_248	Blood protein levels	1.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4804246 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — CD molecules

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
propionaldehyde	decreases expression	1
terbufos	increases methylation	1
sodium arsenite	affects methylation	1
abrine	increases expression	1
ON 01910	decreases expression	1
Allergens	increases expression	1
Benzo(a)pyrene	affects methylation	1
Diazinon	increases methylation	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Valproic Acid	increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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