LILRB5

Summary

LILRB5 (leukocyte immunoglobulin like receptor B5, HGNC:6609) is a protein-coding gene on chromosome 19q13.42, encoding Leukocyte immunoglobulin-like receptor subfamily B member 5 (O75023). May act as 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). Several other LIR subfamily B receptors are expressed on immune cells where they bind to MHC class I molecules on antigen-presenting cells and inhibit stimulation of an immune response. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10990 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 134 total
• MANE Select transcript: NM_001081442

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6609
Approved symbol	LILRB5
Name	leukocyte immunoglobulin like receptor B5
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	LIR-8, LIR8, CD85c
Ensembl gene	ENSG00000105609
Ensembl biotype	protein_coding
OMIM	604814
Entrez	10990

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000316219, ENST00000345866, ENST00000449561, ENST00000615654, ENST00000621581, ENST00000867152, ENST00000867153

RefSeq mRNA: 4 — MANE Select: NM_001081442 NM_001081442, NM_001081443, NM_001304457, NM_006840

CCDS: CCDS12885, CCDS42611, CCDS46176

Canonical transcript exons

ENST00000449561 — 13 exons

Exon	Start	End
ENSE00001311258	54256489	54256773
ENSE00001423362	54249421	54250932
ENSE00001509643	54257160	54257273
ENSE00002479695	54252871	54252987
ENSE00002485403	54254018	54254068
ENSE00003513963	54256043	54256342
ENSE00003535809	54256961	54256996
ENSE00003564926	54252366	54252403
ENSE00003595457	54252486	54252549
ENSE00003600372	54254735	54255037
ENSE00003613329	54252054	54252106
ENSE00003667694	54254365	54254415
ENSE00003674246	54255286	54255582

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 95.50.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9687 / max 471.4138, expressed in 272 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182618	2.6264	263
182619	0.2975	124
182617	0.0449	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	95.50	gold quality
thymus	UBERON:0002370	89.56	gold quality
omental fat pad	UBERON:0010414	88.70	gold quality
adipose tissue	UBERON:0001013	88.54	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.46	gold quality
right adrenal gland cortex	UBERON:0035827	86.93	gold quality
right adrenal gland	UBERON:0001233	86.34	gold quality
left adrenal gland	UBERON:0001234	86.17	gold quality
left adrenal gland cortex	UBERON:0035825	86.04	gold quality
placenta	UBERON:0001987	85.27	gold quality
adrenal gland	UBERON:0002369	83.86	gold quality
duodenum	UBERON:0002114	83.67	gold quality
right coronary artery	UBERON:0001625	82.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.58	gold quality
small intestine	UBERON:0002108	81.36	gold quality
mucosa of stomach	UBERON:0001199	81.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.05	gold quality
rectum	UBERON:0001052	81.02	gold quality
lower esophagus	UBERON:0013473	80.94	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.62	gold quality
right atrium auricular region	UBERON:0006631	80.49	gold quality
transverse colon	UBERON:0001157	80.48	gold quality
gall bladder	UBERON:0002110	79.83	gold quality
quadriceps femoris	UBERON:0001377	79.44	gold quality
blood	UBERON:0000178	79.15	gold quality
liver	UBERON:0002107	79.09	gold quality
intestine	UBERON:0000160	78.96	gold quality
colon	UBERON:0001155	78.78	gold quality
apex of heart	UBERON:0002098	78.64	gold quality
upper lobe of left lung	UBERON:0008952	78.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	636.68
E-ANND-3	yes	9.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting LILRB5, 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-511-3P	99.99	68.85	1467
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-496	98.66	69.80	931
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-1298-5P	95.96	64.81	573

Literature-anchored findings (GeneRIF, showing 5)

• Mature cord-blood-derived mast cells expressed LILRB5 in cytoplasmic granules and upon cross-linking of the high-affinity IgE receptor, released LILRB5 into the culture medium. (PMID:17998301)
• The rs12975366 in the LILRB5 gene was significantly associated with CK levels of statin users. (PMID:25214527)
• LILRB5 binding to intracellular HLA-class I heavy chains suggests a chaperone function (PMID:26098415)
• The transcriptional profile of the orphan receptor LILRB5 is significantly up-regulated following exposure to mycobacteria. (PMID:26908331)
• Identification of the hybrid gene LILRB5-3 by long-read sequencing and implication of its novel signaling function. (PMID:38807600)

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), 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), LILRA4 (ENSG00000239961), LILRA2 (ENSG00000239998), KIR3DL2 (ENSG00000240403), KIR3DL3 (ENSG00000242019), KIR2DL3 (ENSG00000243772), LILRA6 (ENSG00000244482), TARM1 (ENSG00000248385)

Protein

Protein identifiers

Leukocyte immunoglobulin-like receptor subfamily B member 5 — O75023 (reviewed: O75023)

Alternative names: CD85 antigen-like family member C, Leukocyte immunoglobulin-like receptor 8

All UniProt accessions (1): O75023

UniProt curated annotations — full annotation on UniProt →

Function. May act as receptor for class I MHC antigens.

Subcellular location. Membrane.

Tissue specificity. Detected in a natural killer (NK) cells.

Domain organisation. Contains 2 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.

Isoforms (3)

UniProt ID	Names	Canonical?
O75023-1	1	yes
O75023-2	2
O75023-3	3

RefSeq proteins (4): NP_001074911, NP_001074912, NP_001291386, NP_006831 (=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 (32 total): region of interest 4, disulfide bond 4, domain 4, glycosylation site 3, sequence conflict 3, short sequence motif 2, compositionally biased region 2, topological domain 2, splice variant 2, sequence variant 2, signal peptide 1, chain 1, modified residue 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75023-F1	76.31	0.55

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): 514

Disulfide bonds (4): 49–98, 144–195, 244–295, 344–395

Glycosylation sites (3): 139, 279, 339

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: 66 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, MODULE_45, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, GOBP_ADAPTIVE_IMMUNE_RESPONSE, MODULE_46, MODULE_223, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, MARTENS_TRETINOIN_RESPONSE_UP, MODULE_129, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, GOBP_IMMUNE_RESPONSE_INHIBITING_SIGNAL_TRANSDUCTION

GO Biological Process (6): adaptive immune response (GO:0002250), immune response-regulating signaling pathway (GO:0002764), defense response (GO:0006952), cell surface receptor signaling pathway (GO:0007166), cytokine-mediated signaling pathway (GO:0019221), immune system process (GO:0002376)

GO Molecular Function (2): transmembrane signaling receptor activity (GO:0004888), inhibitory MHC class I receptor activity (GO:0032396)

GO Cellular Component (2): plasma membrane (GO:0005886), 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
immune response	1
regulation of immune response	1
response to stress	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
biological_process	1
signaling receptor activity	1
MHC class I receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LILRB5	CD300C	Q08708	751
LILRB5	PTPN6	P29350	553
LILRB5	CD80	P33681	486
LILRB5	ANGPTL2	Q9UKU9	323
LILRB5	ANGPTL5	Q86XS5	304
LILRB5	HLA-G	P17693	301
LILRB5	TIMD4	Q96H15	298
LILRB5	HLA-DRA	P01903	297
LILRB5	OR5L2	Q8NGL0	294
LILRB5	OR4C11	Q6IEV9	279
LILRB5	SLCO1B1	Q9Y6L6	271
LILRB5	TMEM190	Q8WZ59	270
LILRB5	CARD6	Q9BX69	267
LILRB5	RFXAP	O00287	263
LILRB5	HLA-F	P30511	246

IntAct

9 interactions, top by confidence:

A	B	Type	Score
MOG	LILRB5	psi-mi:“MI:0915”(physical association)	0.400
LILRB5	MPZ	psi-mi:“MI:0915”(physical association)	0.400
PILRA	LILRB5	psi-mi:“MI:0915”(physical association)	0.400
LILRB5	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.400
TYRO3	LILRB5	psi-mi:“MI:0915”(physical association)	0.400
ECE1	LILRB5	psi-mi:“MI:0915”(physical association)	0.370
CREB3	LILRB5	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (2): LILRB5 (Two-hybrid), LILRB5 (Cross-Linking-MS (XL-MS))

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	106
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2373 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54252364:A:AC	donor_gain	1.0000
19:54252365:C:CC	donor_gain	1.0000
19:54252546:TGGG:T	acceptor_gain	1.0000
19:54252550:C:CC	acceptor_gain	1.0000
19:54251010:T:A	donor_gain	0.9900
19:54251014:AGTGT:A	donor_gain	0.9900
19:54252545:ATGGG:A	acceptor_gain	0.9900
19:54252547:GGG:G	acceptor_gain	0.9900
19:54252547:GGGC:G	acceptor_loss	0.9900
19:54252550:CTGGA:C	acceptor_loss	0.9900
19:54253002:C:CT	acceptor_gain	0.9900
19:54255280:CCTCA:C	donor_loss	0.9900
19:54255281:CTCAC:C	donor_loss	0.9900
19:54255282:TCAC:T	donor_loss	0.9900
19:54255283:CAC:C	donor_loss	0.9900
19:54255285:C:CA	donor_loss	0.9900
19:54256190:T:TA	donor_gain	0.9900
19:54256225:T:TA	donor_gain	0.9900
19:54257217:G:C	donor_gain	0.9900
19:54250931:GCCTG:G	acceptor_loss	0.9800
19:54250934:T:A	acceptor_loss	0.9800
19:54252361:CTCA:C	donor_gain	0.9800
19:54252548:GG:G	acceptor_gain	0.9800
19:54252869:AC:A	donor_gain	0.9800
19:54252870:CC:C	donor_gain	0.9800
19:54253003:G:C	acceptor_gain	0.9800
19:54253004:T:TC	acceptor_gain	0.9800
19:54254729:CCTCA:C	donor_loss	0.9800
19:54254730:CTCAC:C	donor_loss	0.9800
19:54254731:TCA:T	donor_loss	0.9800

AlphaMissense

3749 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54254850:G:C	F380L	0.985
19:54254850:G:T	F380L	0.985
19:54254852:A:G	F380L	0.985
19:54256514:A:C	S110R	0.971
19:54256514:A:T	S110R	0.971
19:54256516:T:G	S110R	0.971
19:54256595:G:C	F83L	0.971
19:54256595:G:T	F83L	0.971
19:54256597:A:G	F83L	0.971
19:54256267:C:G	C144S	0.970
19:54256268:A:T	C144S	0.970
19:54254851:A:C	F380C	0.969
19:54255479:G:C	F253L	0.965
19:54255479:G:T	F253L	0.965
19:54255481:A:G	F253L	0.965
19:54256159:A:C	F180C	0.962
19:54256698:C:G	C49S	0.962
19:54256699:A:T	C49S	0.962
19:54256239:A:C	F153L	0.960
19:54256239:A:T	F153L	0.960
19:54256241:A:G	F153L	0.960
19:54256068:A:C	S210R	0.956
19:54256068:A:T	S210R	0.956
19:54256070:T:G	S210R	0.956
19:54256114:C:G	C195S	0.953
19:54256115:A:T	C195S	0.953
19:54256551:C:G	C98S	0.950
19:54256552:A:T	C98S	0.950
19:54254851:A:G	F380S	0.949
19:54256119:G:C	F193L	0.949

dbSNP variants (sampled 300 via entrez): RS1000067660 (19:54253845 C>G), RS1000234223 (19:54257705 G>T), RS1000678478 (19:54258299 C>T), RS1001068589 (19:54257578 C>T), RS1001296328 (19:54249804 G>A), RS1001709415 (19:54259609 A>C), RS1001767992 (19:54258933 C>T), RS1001860725 (19:54251314 G>A,T), RS1001880873 (19:54257866 G>A), RS1002075699 (19:54258726 C>G), RS1002109737 (19:54257539 C>T), RS1003560742 (19:54255850 G>A,T), RS1003802622 (19:54252191 AG>A), RS1004117839 (19:54255438 G>T), RS1004153202 (19:54258292 A>G)

Disease associations

OMIM: gene MIM:604814 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002603_2	Creatine kinase levels in statin users	2.000000e-10
GCST006013_10	Lactate dehydrogenase levels	4.000000e-08
GCST006014_37	Creatine kinase levels	5.000000e-46
GCST90000025_573	Appendicular lean mass	4.000000e-14
GCST90011899_142	Aspartate aminotransferase levels	3.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004534	creatine kinase measurement
EFO:0004808	L lactate dehydrogenase measurement
EFO:0004980	appendicular lean mass
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12975366	LILRB5		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
kojic acid	decreases expression	1
butyraldehyde	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Estradiol	affects binding, increases expression	1
Nickel	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E6R3	Genomeditech CHO-K1 H_LILRB5	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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