LILRA1

Summary

LILRA1 (leukocyte immunoglobulin like receptor A1, HGNC:6602) is a protein-coding gene on chromosome 19q13.42, encoding Leukocyte immunoglobulin-like receptor subfamily A member 1 (O75019). May act as receptor for class I MHC antigens.

This gene encodes an activating member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein is predominantly expressed in B cells, interacts with major histocompatibility complex class I ligands, and contributes to the regulation of immune responses. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 11024 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 141 total
• MANE Select transcript: NM_006863

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6602
Approved symbol	LILRA1
Name	leukocyte immunoglobulin like receptor A1
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	LIR-6, CD85i, LIR6
Ensembl gene	ENSG00000104974
Ensembl biotype	protein_coding
OMIM	604810
Entrez	11024

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000251372, ENST00000453777, ENST00000473156, ENST00000477255, ENST00000495417

RefSeq mRNA: 3 — MANE Select: NM_006863 NM_001278318, NM_001278319, NM_006863

CCDS: CCDS12901, CCDS62802

Canonical transcript exons

ENST00000251372 — 10 exons

Exon	Start	End
ENSE00001330208	54600699	54602381
ENSE00001350456	54594197	54594278
ENSE00001866586	54593632	54593781
ENSE00003492043	54594441	54594476
ENSE00003517545	54599236	54599286
ENSE00003543900	54595100	54595402
ENSE00003623663	54600512	54600550
ENSE00003632090	54596189	54596491
ENSE00003653577	54594665	54594952
ENSE00003667921	54595639	54595935

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 96.64.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2567 / max 81.6781, expressed in 227 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177532	1.2567	227

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.64	gold quality
leukocyte	CL:0000738	96.58	gold quality
granulocyte	CL:0000094	94.68	gold quality
blood	UBERON:0000178	93.13	gold quality
spleen	UBERON:0002106	84.84	gold quality
vermiform appendix	UBERON:0001154	84.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.40	gold quality
bone marrow	UBERON:0002371	77.01	gold quality
bone marrow cell	CL:0002092	76.17	gold quality
right lung	UBERON:0002167	70.66	gold quality
upper lobe of left lung	UBERON:0008952	68.05	gold quality
lymph node	UBERON:0000029	67.30	gold quality
smooth muscle tissue	UBERON:0001135	67.04	gold quality
spinal cord	UBERON:0002240	64.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.96	gold quality
lung	UBERON:0002048	64.55	gold quality
gall bladder	UBERON:0002110	64.20	gold quality
placenta	UBERON:0001987	63.12	gold quality
substantia nigra	UBERON:0002038	61.56	gold quality
right coronary artery	UBERON:0001625	60.89	gold quality
rectum	UBERON:0001052	59.44	gold quality
liver	UBERON:0002107	59.08	gold quality
apex of heart	UBERON:0002098	58.77	gold quality
right adrenal gland	UBERON:0001233	58.76	gold quality
omental fat pad	UBERON:0010414	58.47	gold quality
right adrenal gland cortex	UBERON:0035827	57.71	gold quality
tonsil	UBERON:0002372	57.62	gold quality
adipose tissue	UBERON:0001013	57.27	gold quality
right lobe of liver	UBERON:0001114	56.66	gold quality
left adrenal gland	UBERON:0001234	56.29	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting LILRA1, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-1249-5P	99.61	66.55	2049

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

Protein

Protein identifiers

Leukocyte immunoglobulin-like receptor subfamily A member 1 — O75019 (reviewed: O75019)

Alternative names: CD85 antigen-like family member I, Leukocyte immunoglobulin-like receptor 6

All UniProt accessions (1): O75019

UniProt curated annotations — full annotation on UniProt →

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

Subcellular location. Membrane.

Tissue specificity. Detected in monocytes and B-cells.

Isoforms (2)

UniProt ID	Names	Canonical?
O75019-1	1, LIR-6a	yes
O75019-2	2, LIR-6b

RefSeq proteins (3): NP_001265247, NP_001265248, NP_006854* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_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: PF13895, PF13927

UniProt features (27 total): glycosylation site 6, disulfide bond 5, domain 4, sequence variant 3, topological domain 2, signal peptide 1, chain 1, compositionally biased region 1, splice variant 1, sequence conflict 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75019-F1	84.32	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.

Disulfide bonds (5): 49–98, 145–197, 157–167, 246–297, 346–397

Glycosylation sites (6): 140, 281, 302, 341, 431, 448

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: 171 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, MODULE_522, MODULE_64, MORF_RAD51L3, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, GNF2_MCL1, GNF2_CD1D, ROSS_LEUKEMIA_WITH_MLL_FUSIONS, MORF_CTSB, GNF2_S100A4, MORF_IL4, MORF_PRKCA

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), interleukin-10-mediated signaling pathway (GO:0140105), immune system process (GO:0002376)

GO Molecular Function (3): antigen binding (GO:0003823), 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
cytokine-mediated signaling pathway	1
biological_process	1
binding	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

1220 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LILRA1	HLA-C	P04222	803
LILRA1	CD300C	Q08708	789
LILRA1	TYROBP	O43914	679
LILRA1	FCER1G	P30273	629
LILRA1	HLA-A	P01891	548
LILRA1	LILRB2	Q8N423	424
LILRA1	RNASE2	P10153	386
LILRA1	HLA-G	P17693	380
LILRA1	HLA-F	P30511	367
LILRA1	RPL5	P46777	305
LILRA1	HYDIN	Q4G0P3	303
LILRA1	FCAR	P24071	259
LILRA1	CDC42EP5	Q6NZY7	256
LILRA1	LENG8	Q96PV6	255
LILRA1	HLA-B	P01889	231
LILRA1	BST2	Q10589	231

IntAct

15 interactions, top by confidence:

A	B	Type	Score
LILRA3	NARS1	psi-mi:“MI:0914”(association)	0.530
LILRA3	LILRA1	psi-mi:“MI:0914”(association)	0.530
LILRA1	BTNL8	psi-mi:“MI:0915”(physical association)	0.400
LILRA1	CD300LB	psi-mi:“MI:0915”(physical association)	0.400
LILRA1	FSTL5	psi-mi:“MI:0915”(physical association)	0.400
IL23A	LILRA1	psi-mi:“MI:0915”(physical association)	0.400
IFNGR1	LILRA1	psi-mi:“MI:0915”(physical association)	0.400
LILRA1	IFNGR1	psi-mi:“MI:0915”(physical association)	0.400
LILRA1	MOG	psi-mi:“MI:0915”(physical association)	0.400
PILRA	LILRA1	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF12A	LILRA1	psi-mi:“MI:0915”(physical association)	0.400
ECE1	LILRA1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): LILRA1 (Affinity Capture-MS), LILRA1 (Affinity Capture-MS), LILRA1 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	14
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1672 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54599226:T:A	acceptor_gain	1.0000
19:54599234:A:AG	acceptor_gain	1.0000
19:54599235:G:GG	acceptor_gain	1.0000
19:54599347:G:T	donor_gain	1.0000
19:54600395:G:GT	donor_gain	1.0000
19:54593779:ATGG:A	donor_loss	0.9900
19:54593782:G:GA	donor_loss	0.9900
19:54593782:G:GG	donor_gain	0.9900
19:54593783:T:A	donor_loss	0.9900
19:54594662:CAG:C	acceptor_loss	0.9900
19:54594663:A:AG	acceptor_gain	0.9900
19:54594663:AG:A	acceptor_gain	0.9900
19:54594664:G:GG	acceptor_gain	0.9900
19:54594664:GG:G	acceptor_gain	0.9900
19:54594876:G:T	donor_gain	0.9900
19:54595254:GCCCC:G	donor_gain	0.9900
19:54595271:G:GA	donor_gain	0.9900
19:54595931:CGCAG:C	donor_loss	0.9900
19:54595932:GCAGG:G	donor_loss	0.9900
19:54595933:CAGG:C	donor_loss	0.9900
19:54595936:GTGA:G	donor_loss	0.9900
19:54595937:T:A	donor_loss	0.9900
19:54596188:GGACA:G	acceptor_gain	0.9900
19:54596357:C:CG	donor_gain	0.9900
19:54596357:C:G	donor_gain	0.9900
19:54599221:T:TA	acceptor_gain	0.9900
19:54599233:CA:C	acceptor_loss	0.9900
19:54599234:A:AT	acceptor_loss	0.9900
19:54599235:GGA:G	acceptor_gain	0.9900
19:54599282:GGCTG:G	donor_gain	0.9900

AlphaMissense

3112 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54596374:T:C	F382L	0.964
19:54596376:C:A	F382L	0.964
19:54596376:C:G	F382L	0.964
19:54596375:T:G	F382C	0.958
19:54595740:T:C	F255L	0.953
19:54595742:T:A	F255L	0.953
19:54595742:T:G	F255L	0.953
19:54596293:T:C	F355L	0.946
19:54596295:C:A	F355L	0.946
19:54596295:C:G	F355L	0.946
19:54596266:T:A	C346S	0.943
19:54596267:G:C	C346S	0.943
19:54596413:T:G	Y395D	0.930
19:54596375:T:C	F382S	0.929
19:54596419:T:A	C397S	0.927
19:54596420:G:C	C397S	0.927
19:54595908:A:C	S311R	0.926
19:54595910:C:A	S311R	0.926
19:54595910:C:G	S311R	0.926
19:54595821:T:C	F282L	0.922
19:54595823:C:A	F282L	0.922
19:54595823:C:G	F282L	0.922
19:54595713:T:C	C246R	0.921
19:54595866:T:A	C297S	0.919
19:54595867:G:C	C297S	0.919
19:54595860:T:G	Y295D	0.917
19:54595713:T:A	C246S	0.916
19:54595714:G:C	C246S	0.916
19:54595375:A:C	S212R	0.911
19:54595377:T:A	S212R	0.911

dbSNP variants (sampled 300 via entrez): RS1000024978 (19:54597053 C>T), RS1000034909 (19:54597180 T>C), RS1001087448 (19:54598164 G>A), RS1001358288 (19:54593790 C>A,T), RS1001959545 (19:54594714 C>G,T), RS1002307347 (19:54594540 G>A,T), RS1002634883 (19:54592259 T>C,G), RS1002997867 (19:54600099 C>A), RS1003331553 (19:54598869 C>A,T), RS1004920302 (19:54596755 T>C), RS1004982995 (19:54593299 G>A), RS1005077991 (19:54593471 G>A), RS1005596059 (19:54598604 T>C,G), RS1005927814 (19:54597644 G>A), RS1005985963 (19:54594148 G>A)

Disease associations

OMIM: gene MIM:604810 | 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
GCST005547_14	Major depressive disorder	1.000000e-06

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
Nickel	decreases expression, increases expression	3
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Am 580	increases expression	1
CGP 52608	affects binding, increases reaction	1
Rosiglitazone	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Zidovudine	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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