LILRA5

Summary

LILRA5 (leukocyte immunoglobulin like receptor A5, HGNC:16309) is a protein-coding gene on chromosome 19q13.42, encoding Leukocyte immunoglobulin-like receptor subfamily A member 5 (A6NI73). May play a role in triggering innate immune responses.

The protein encoded by this gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family. LIR family members are known to have activating and inibitory functions in leukocytes. Crosslink of this receptor protein on the surface of monocytes has been shown to induce calcium flux and secretion of several proinflammatory cytokines, which suggests the roles of this protein in triggering innate immune responses. This gene is one of the leukocyte receptor genes that form a gene cluster on the chromosomal region 19q13.4. Four alternatively spliced transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 353514 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_021250

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16309
Approved symbol	LILRA5
Name	leukocyte immunoglobulin like receptor A5
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	ILT11, LIR9, CD85, CD85f
Ensembl gene	ENSG00000187116
Ensembl biotype	protein_coding
OMIM	606047
Entrez	353514

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 retained_intron

ENST00000432233, ENST00000446712, ENST00000477720, ENST00000486742, ENST00000489504, ENST00000862984

RefSeq mRNA: 4 — MANE Select: NM_021250 NM_021250, NM_181879, NM_181985, NM_181986

CCDS: CCDS12888, CCDS12889

Canonical transcript exons

ENST00000432233 — 7 exons

Exon	Start	End
ENSE00003477145	54312537	54312621
ENSE00003546774	54312335	54312370
ENSE00003632614	54311864	54312148
ENSE00003685173	54311414	54311716
ENSE00003719071	54307698	54307748
ENSE00003722462	54313017	54313166
ENSE00003738782	54307070	54307549

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 98.64.

FANTOM5 (CAGE): breadth broad, TPM avg 7.5114 / max 407.2373, expressed in 300 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182626	6.8496	288
182625	0.6619	174

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	98.64	gold quality
monocyte	CL:0000576	98.33	gold quality
leukocyte	CL:0000738	98.31	gold quality
granulocyte	CL:0000094	97.90	gold quality
spleen	UBERON:0002106	94.62	gold quality
bone marrow	UBERON:0002371	92.89	gold quality
bone marrow cell	CL:0002092	90.58	gold quality
vermiform appendix	UBERON:0001154	88.18	gold quality
right lung	UBERON:0002167	87.64	gold quality
upper lobe of left lung	UBERON:0008952	85.88	gold quality
lung	UBERON:0002048	79.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.79	gold quality
smooth muscle tissue	UBERON:0001135	74.13	gold quality
omental fat pad	UBERON:0010414	73.77	gold quality
left uterine tube	UBERON:0001303	73.16	gold quality
gall bladder	UBERON:0002110	72.32	gold quality
placenta	UBERON:0001987	71.85	gold quality
descending thoracic aorta	UBERON:0002345	71.22	gold quality
adipose tissue	UBERON:0001013	71.15	gold quality
apex of heart	UBERON:0002098	70.79	gold quality
right coronary artery	UBERON:0001625	70.32	gold quality
liver	UBERON:0002107	69.13	gold quality
subcutaneous adipose tissue	UBERON:0002190	68.88	gold quality
left coronary artery	UBERON:0001626	67.87	gold quality
thoracic aorta	UBERON:0001515	67.53	gold quality
ascending aorta	UBERON:0001496	67.51	gold quality
heart left ventricle	UBERON:0002084	67.05	gold quality
lymph node	UBERON:0000029	66.43	gold quality
rectum	UBERON:0001052	66.02	gold quality
right lobe of liver	UBERON:0001114	65.97	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	37.82
E-MTAB-9801	yes	7.55
E-ANND-3	no	2.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting LILRA5, 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-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808

Literature-anchored findings (GeneRIF, showing 1)

• LILRA5/LIR9/ILT11 does not play a role in any MHCI recognition but could possibly bind to non-MHCI ligand(s) on the target cells to provide a novel immune regulation mechanism (PMID:16675463)

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), 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 A member 5 — A6NI73 (reviewed: A6NI73)

Alternative names: CD85 antigen-like family member F, Immunoglobulin-like transcript 11, Leukocyte immunoglobulin-like receptor 9

All UniProt accessions (1): A6NI73

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in triggering innate immune responses. Does not seem to play a role for any class I MHC antigen recognition.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Expressed mostly in tissues of the hematopoietic system, including bone marrow, spleen, lymph node and peripheral leukocytes. Among leukocytes, monocytes and neutrophils express the highest level. Expressed in CD14+ monocytes, but not in T-cells, B-cells or natural killer (NK) cells (at protein level).

Isoforms (4)

UniProt ID	Names	Canonical?
A6NI73-1	1, LIR9m1	yes
A6NI73-2	2, LIR9m2
A6NI73-3	3, LIR9s1
A6NI73-4	4, LIR9s2

RefSeq proteins (4): NP_067073, NP_870994, NP_871714, NP_871715 (=MANE)

Domains & families (InterPro)

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

Pfam: PF13895

UniProt features (33 total): strand 16, glycosylation site 3, disulfide bond 2, splice variant 2, sequence conflict 2, topological domain 2, domain 2, signal peptide 1, chain 1, helix 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2D3V	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NI73-F1	81.12	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 (2): 67–116, 162–214

Glycosylation sites (3): 43, 157, 248

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: 155 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_PROTEIN_TYROSINE_KINASE_ACTIVITY, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_INTERLEUKIN_1_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_SUPERFAMILY_CYTOKINE_PRODUCTION

GO Biological Process (15): immune response-regulating signaling pathway (GO:0002764), cytokine-mediated signaling pathway (GO:0019221), negative regulation of interleukin-12 production (GO:0032695), negative regulation of interleukin-13 production (GO:0032696), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-10 production (GO:0032733), positive regulation of interleukin-6 production (GO:0032755), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of MAPK cascade (GO:0043410), innate immune response (GO:0045087), positive regulation of inflammatory response (GO:0050729), positive regulation of cell activation (GO:0050867), positive regulation of calcium ion transport (GO:0051928), positive regulation of protein tyrosine kinase activity (GO:0061098), immune system process (GO:0002376)

GO Molecular Function (1): inhibitory MHC class I receptor activity (GO:0032396)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell surface (GO:0009986), 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
cellular anatomical structure	3
negative regulation of cytokine production	2
positive regulation of cytokine production	2
signal transduction	1
regulation of immune response	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
interleukin-12 production	1
regulation of interleukin-12 production	1
interleukin-13 production	1
regulation of interleukin-13 production	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
interleukin-10 production	1
regulation of interleukin-10 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
cell activation	1
positive regulation of cellular process	1
regulation of cell activation	1
positive regulation of multicellular organismal process	1
calcium ion transport	1
positive regulation of monoatomic ion transport	1
regulation of calcium ion transport	1
protein tyrosine kinase activity	1
positive regulation of protein kinase activity	1
positive regulation of peptidyl-tyrosine phosphorylation	1

Protein interactions and networks

STRING

690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LILRA5	CD300C	Q08708	472
LILRA5	BST2	Q10589	438
LILRA5	LENG8	Q96PV6	406
LILRA5	LENG1	Q96BZ8	398
LILRA5	HFE	Q30201	396
LILRA5	HLA-DMB	P28068	391
LILRA5	TTYH1	Q9H313	385
LILRA5	RPS9	P46781	384
LILRA5	ALCAM	Q13740	378
LILRA5	TRIM22	Q8IYM9	355
LILRA5	ANGPTL2	Q9UKU9	354
LILRA5	MBOAT7	Q96N66	353
LILRA5	CNOT3	O75175	353
LILRA5	FCGRT	P55899	353
LILRA5	UNK	Q9C0B0	352

IntAct

7 interactions, top by confidence:

A	B	Type	Score
IZUMO1	LILRA5	psi-mi:“MI:0915”(physical association)	0.400
LILRA5	MPZ	psi-mi:“MI:0915”(physical association)	0.400
EBF2	LILRA5	psi-mi:“MI:0914”(association)	0.350
LILRA5	BOLA3	psi-mi:“MI:0914”(association)	0.350
CDCA8	LILRA5	psi-mi:“MI:0914”(association)	0.350
LILRA5	HGS	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): LILRA5 (Affinity Capture-RNA), BOLA3 (Affinity Capture-MS), STAM (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), LILRA5 (Affinity Capture-MS), WRAP73 (Affinity Capture-MS), MFI2 (Affinity Capture-MS), HGS (Affinity Capture-MS), TMEM132A (Affinity Capture-MS), VWDE (Affinity Capture-MS), KDELC2 (Affinity Capture-MS), JAG2 (Affinity Capture-MS), IL17RA (Affinity Capture-MS), CCT2 (Affinity Capture-MS), FAM132B (Affinity Capture-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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

713 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54311599:T:TA	donor_gain	1.0000
19:54311717:C:CC	acceptor_gain	1.0000
19:54311863:C:G	donor_loss	1.0000
19:54307545:TGAGG:T	acceptor_gain	0.9900
19:54307548:GG:G	acceptor_gain	0.9900
19:54307550:C:CC	acceptor_gain	0.9900
19:54307748:CCTGA:C	acceptor_loss	0.9900
19:54307749:C:CC	acceptor_gain	0.9900
19:54307749:C:G	acceptor_loss	0.9900
19:54307750:T:A	acceptor_loss	0.9900
19:54310677:T:TA	donor_gain	0.9900
19:54311545:TGCC:T	donor_gain	0.9900
19:54311550:A:AC	donor_gain	0.9900
19:54311551:C:CC	donor_gain	0.9900
19:54311715:TC:T	acceptor_gain	0.9900
19:54311716:CC:C	acceptor_gain	0.9900
19:54311717:C:CA	acceptor_loss	0.9900
19:54312145:TTCC:T	acceptor_gain	0.9900
19:54312146:TCC:T	acceptor_gain	0.9900
19:54312147:CC:C	acceptor_gain	0.9900
19:54312147:CCC:C	acceptor_gain	0.9900
19:54312148:CC:C	acceptor_gain	0.9900
19:54312149:C:CC	acceptor_gain	0.9900
19:54312150:T:A	acceptor_loss	0.9900
19:54312516:C:A	donor_gain	0.9900
19:54312526:T:TA	donor_gain	0.9900
19:54312531:TCTCA:T	donor_loss	0.9900
19:54312532:CTCA:C	donor_loss	0.9900
19:54312533:TCAC:T	donor_loss	0.9900
19:54312534:CA:C	donor_loss	0.9900

AlphaMissense

1920 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54311613:G:C	F171L	0.947
19:54311613:G:T	F171L	0.947
19:54311615:A:G	F171L	0.947
19:54311889:G:C	S128R	0.920
19:54311889:G:T	S128R	0.920
19:54311891:T:G	S128R	0.920
19:54311970:G:C	F101L	0.914
19:54311970:G:T	F101L	0.914
19:54311972:A:G	F101L	0.914
19:54311622:G:C	F168L	0.913
19:54311622:G:T	F168L	0.913
19:54311624:A:G	F168L	0.913
19:54311530:A:C	F199C	0.903
19:54311439:A:C	S229R	0.901
19:54311439:A:T	S229R	0.901
19:54311441:T:G	S229R	0.901
19:54311529:G:C	F199L	0.891
19:54311529:G:T	F199L	0.891
19:54311531:A:G	F199L	0.891
19:54311641:C:G	C162S	0.887
19:54311642:A:T	C162S	0.887
19:54311614:A:G	F171S	0.884
19:54311485:C:G	C214S	0.868
19:54311486:A:T	C214S	0.868
19:54311971:A:G	F101S	0.864
19:54311541:G:C	F195L	0.860
19:54311541:G:T	F195L	0.860
19:54311543:A:G	F195L	0.860
19:54311933:A:C	Y114D	0.859
19:54311971:A:C	F101C	0.859

dbSNP variants (sampled 300 via entrez): RS1000476591 (19:54312746 TC>T,TCC), RS1000502200 (19:54313469 G>C), RS1001247425 (19:54309059 G>C), RS1001330477 (19:54314152 C>T), RS1001572447 (19:54313858 G>A), RS1001841077 (19:54313604 C>A), RS1001909249 (19:54312492 C>A,T), RS1002241389 (19:54308560 C>T), RS1003276001 (19:54310046 C>A,T), RS1003948430 (19:54312337 G>C,T), RS1003989789 (19:54310019 G>A), RS1004091360 (19:54315035 G>A), RS1004167547 (19:54307313 C>CAGA), RS1005495439 (19:54310254 C>T), RS1005792651 (19:54307655 C>A,T)

Disease associations

OMIM: gene MIM:606047 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002899_35	HDL cholesterol	6.000000e-13
GCST007827_2	Alzheimer’s disease or HDL levels (pleiotropy)	6.000000e-12
GCST011348_57	High density lipoprotein cholesterol levels	7.000000e-18

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

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
triphenyl phosphate	affects expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
fipronil	decreases expression	1
CGP 52608	affects binding, increases reaction	1
gardiquimod	decreases reaction, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Methapyrilene	increases methylation	1
Tretinoin	increases expression	1
Cyclosporine	decreases expression	1
Sodium Selenite	decreases expression	1
Antirheumatic Agents	decreases expression	1
Zinc Sulfate	decreases expression	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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