LILRA6

Summary

LILRA6 (leukocyte immunoglobulin like receptor A6, HGNC:15495) is a protein-coding gene on chromosome 19q13.42, encoding Leukocyte immunoglobulin-like receptor subfamily A member 6 (Q6PI73). May act as receptor for class I MHC antigens.

Predicted to enable inhibitory MHC class I receptor activity. Predicted to be involved in cytokine-mediated signaling pathway and immune response-regulating signaling pathway. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 79168 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_024318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15495
Approved symbol	LILRA6
Name	leukocyte immunoglobulin like receptor A6
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	ILT8, CD85b
Ensembl gene	ENSG00000244482
Ensembl biotype	protein_coding
Entrez	79168

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000245621, ENST00000270464, ENST00000396365, ENST00000430421

RefSeq mRNA: 1 — MANE Select: NM_024318 NM_024318

CCDS: CCDS42610

Canonical transcript exons

ENST00000396365 — 8 exons

Exon	Start	End
ENSE00001275721	54242718	54242790
ENSE00001524705	54236590	54239089
ENSE00003505278	54242519	54242554
ENSE00003548745	54240831	54241127
ENSE00003573161	54242026	54242310
ENSE00003656504	54240274	54240576
ENSE00003681373	54239901	54239951
ENSE00003744229	54241576	54241878

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 97.06.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1978 / max 18.2486, expressed in 105 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182615	0.1978	105

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	97.06	gold quality
granulocyte	CL:0000094	95.11	gold quality
monocyte	CL:0000576	94.65	gold quality
leukocyte	CL:0000738	94.48	gold quality
spleen	UBERON:0002106	91.01	gold quality
vermiform appendix	UBERON:0001154	85.80	gold quality
upper lobe of left lung	UBERON:0008952	82.39	gold quality
right lung	UBERON:0002167	81.84	gold quality
bone marrow cell	CL:0002092	81.43	gold quality
bone marrow	UBERON:0002371	81.06	gold quality
omental fat pad	UBERON:0010414	76.85	gold quality
adipose tissue	UBERON:0001013	76.25	gold quality
lung	UBERON:0002048	76.23	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.82	gold quality
right coronary artery	UBERON:0001625	75.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.24	gold quality
placenta	UBERON:0001987	73.81	gold quality
right adrenal gland cortex	UBERON:0035827	73.69	gold quality
right adrenal gland	UBERON:0001233	73.44	gold quality
left adrenal gland cortex	UBERON:0035825	73.44	gold quality
left adrenal gland	UBERON:0001234	73.12	gold quality
mucosa of stomach	UBERON:0001199	72.47	gold quality
descending thoracic aorta	UBERON:0002345	71.45	gold quality
left coronary artery	UBERON:0001626	71.31	gold quality
left uterine tube	UBERON:0001303	71.28	gold quality
apex of heart	UBERON:0002098	71.21	gold quality
gall bladder	UBERON:0002110	70.49	gold quality
thoracic aorta	UBERON:0001515	70.17	gold quality
smooth muscle tissue	UBERON:0001135	70.08	gold quality
ascending aorta	UBERON:0001496	69.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.88

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• Allogeneic disparities in immunoglobulin-like transcript 5 induce potent antibody responses in hematopoietic stem cell transplant recipients (PMID:19617579)
• LILRA6 copy number variation may influence the level of the activating receptor on the cell surface, potentially affecting signaling upon LILRB3/A6 ligation (PMID:24096970)
• LILRA6 copy number variation correlates with susceptibility to atopic dermatitis. (PMID:27333811)
• Characterization of LILRB3 and LILRA6 allelic variants in the Japanese population. (PMID:33526815)
• Distinct frequency patterns of LILRB3 and LILRA6 allelic variants in Europeans. (PMID:36449053)

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

Protein

Protein identifiers

Leukocyte immunoglobulin-like receptor subfamily A member 6 — Q6PI73 (reviewed: Q6PI73)

Alternative names: Immunoglobulin-like transcript 8, Leukocyte Ig-like receptor

All UniProt accessions (3): B5ME96, Q6PI73, U5XH19

UniProt curated annotations — full annotation on UniProt →

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

Subcellular location. Membrane.

Miscellaneous. Belongs to the leukocyte receptor cluster (LRC) present on 19q13.4. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6PI73-1	1	yes
Q6PI73-2	2

RefSeq proteins (1): NP_077294* (*=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

UniProt features (62 total): strand 35, disulfide bond 4, sequence variant 4, glycosylation site 3, helix 3, splice variant 2, topological domain 2, domain 2, region of interest 2, signal peptide 1, chain 1, turn 1, transmembrane region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8GRX	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PI73-F1	85.95	0.69

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 (4): 49–98, 144–196, 245–296, 345–396

Glycosylation sites (3): 139, 301, 340

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: 82 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GNF2_MCL1, GNF2_CD1D, GNF2_MYD88, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GNF2_HCK, GNF2_PECAM1, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GNF2_FOS, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, GOBP_IMMUNE_RESPONSE_INHIBITING_SIGNAL_TRANSDUCTION, GOMF_MHC_CLASS_I_RECEPTOR_ACTIVITY, ALK_DN.V1_DN

GO Biological Process (5): adaptive immune response (GO:0002250), immune response-regulating signaling pathway (GO:0002764), cytokine-mediated signaling pathway (GO:0019221), immune system process (GO:0002376), cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (1): 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
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
biological_process	1
MHC class I receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

838 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LILRA6	RPL5	P46777	901
LILRA6	CD300C	Q08708	728
LILRA6	HLA-G	P17693	679
LILRA6	HLA-E	P13747	609
LILRA6	TYROBP	O43914	578
LILRA6	HLA-F	P30511	532
LILRA6	HLA-A	P01891	522
LILRA6	PTPN11	Q06124	515
LILRA6	KIR2DL1	P43626	478
LILRA6	HLA-C	P04222	478
LILRA6	KLRC1	P26715	472
LILRA6	KLRD1	Q13241	447
LILRA6	RPS9	P46781	423
LILRA6	KIR3DL1	P43629	413
LILRA6	LILRB1	Q8NHL6	392

IntAct

8 interactions, top by confidence:

A	B	Type	Score
LILRA6	BOC	psi-mi:“MI:0915”(physical association)	0.400
LILRA6	CEACAM21	psi-mi:“MI:0915”(physical association)	0.400
FGFR4	LILRA6	psi-mi:“MI:0915”(physical association)	0.400
MOG	LILRA6	psi-mi:“MI:0915”(physical association)	0.400
LILRA6	MPZ	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF12A	LILRA6	psi-mi:“MI:0915”(physical association)	0.400
LILRB3	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): LILRA6 (Affinity Capture-MS), LRRC34 (Affinity Capture-MS), KCTD21 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), LILRB3 (Two-hybrid), LILRB3 (Two-hybrid), LILRB3 (Two-hybrid), TMEM192 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS), LRRC34 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3088 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001019188 (19:54239319 G>A,C,T), RS1001131953 (19:54239589 C>A), RS1002172155 (19:54236754 A>G), RS1003139311 (19:54236940 A>G), RS1005869756 (19:54237627 G>A), RS1007567544 (19:54241008 C>A,G,T), RS1007850085 (19:54238279 G>A), RS1008158439 (19:54244787 G>T), RS1009545384 (19:54238068 C>T), RS1009999285 (19:54239343 A>T), RS1010538069 (19:54240666 T>C), RS1010688547 (19:54239569 G>C), RS1011785075 (19:54236921 G>A), RS1011955240 (19:54237227 A>G), RS1012144176 (19:54236539 A>G)

Disease associations

OMIM: gene `` | 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
GCST003264_1355	Post bronchodilator FEV1/FVC ratio	1.000000e-06
GCST003264_17	Post bronchodilator FEV1/FVC ratio	1.000000e-06
GCST003264_18	Post bronchodilator FEV1/FVC ratio	1.000000e-06
GCST003264_295	Post bronchodilator FEV1/FVC ratio	5.000000e-06
GCST006585_2439	Blood protein levels	1.000000e-29

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
hydroxyhydroquinone	decreases expression	1
beta-lapachone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
(+)-JQ1 compound	decreases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, decreases expression	1
Valproic Acid	increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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