LY86

Summary

LY86 (lymphocyte antigen 86, HGNC:16837) is a protein-coding gene on chromosome 6p25.1, encoding Lymphocyte antigen 86 (O95711). May cooperate with CD180 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) and cytokine production.

Acts upstream of or within positive regulation of lipopolysaccharide-mediated signaling pathway. Predicted to be located in extracellular region.

Source: NCBI Gene 9450 — RefSeq curated summary.

At a glance

• GWAS associations: 56
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_004271

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16837
Approved symbol	LY86
Name	lymphocyte antigen 86
Location	6p25.1
Locus type	gene with protein product
Status	Approved
Aliases	MD-1, dJ80N2.1
Ensembl gene	ENSG00000112799
Ensembl biotype	protein_coding
OMIM	605241
Entrez	9450

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000230568, ENST00000379953, ENST00000901320, ENST00000901321

RefSeq mRNA: 1 — MANE Select: NM_004271 NM_004271

CCDS: CCDS4498

Canonical transcript exons

ENST00000230568 — 5 exons

Exon	Start	End
ENSE00000681599	6624926	6625012
ENSE00000681605	6626293	6626421
ENSE00000681610	6649625	6649677
ENSE00000847898	6588720	6588870
ENSE00001009133	6654544	6654982

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 98.51.

FANTOM5 (CAGE): breadth broad, TPM avg 12.4838 / max 670.5447, expressed in 445 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65607	8.8255	425
65608	3.4666	363
65606	0.1036	41
65605	0.0880	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.51	gold quality
mononuclear cell	CL:0000842	98.41	gold quality
leukocyte	CL:0000738	98.32	gold quality
granulocyte	CL:0000094	96.18	gold quality
spleen	UBERON:0002106	95.36	gold quality
lymph node	UBERON:0000029	93.91	gold quality
blood	UBERON:0000178	92.64	gold quality
vermiform appendix	UBERON:0001154	90.41	gold quality
epithelium of nasopharynx	UBERON:0001951	88.84	gold quality
nasopharynx	UBERON:0001728	88.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.80	gold quality
bone marrow	UBERON:0002371	87.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.84	gold quality
spinal cord	UBERON:0002240	87.79	gold quality
ileal mucosa	UBERON:0000331	87.08	gold quality
bone marrow cell	CL:0002092	86.62	gold quality
caecum	UBERON:0001153	86.28	gold quality
inferior vagus X ganglion	UBERON:0005363	85.01	gold quality
right lung	UBERON:0002167	84.34	gold quality
diaphragm	UBERON:0001103	84.00	gold quality
cranial nerve II	UBERON:0000941	83.66	gold quality
gall bladder	UBERON:0002110	83.57	gold quality
visceral pleura	UBERON:0002401	83.32	gold quality
pancreatic ductal cell	CL:0002079	83.17	silver quality
superficial temporal artery	UBERON:0001614	82.19	gold quality
rectum	UBERON:0001052	81.67	gold quality
substantia nigra	UBERON:0002038	81.61	gold quality
midbrain	UBERON:0001891	81.17	gold quality
decidua	UBERON:0002450	81.13	gold quality
upper lobe of left lung	UBERON:0008952	80.50	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	101.73
E-CURD-122	yes	91.74
E-HCAD-4	yes	73.36
E-MTAB-6701	yes	64.32
E-CURD-88	yes	54.24
E-MTAB-10553	yes	36.79
E-HCAD-10	yes	31.48
E-MTAB-9467	yes	23.85
E-ANND-3	yes	19.71
E-MTAB-8410	yes	13.27
E-MTAB-6678	yes	8.09
E-MTAB-9801	yes	7.77
E-MTAB-6075	no	403.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting LY86, 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-7152-3P	99.97	67.47	849
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4448	97.04	66.22	752
HSA-MIR-365A-5P	94.91	63.72	471
HSA-MIR-365B-5P	94.91	63.79	470

Literature-anchored findings (GeneRIF, showing 10)

• in the promoter region we identified 3 SNPs, rs1334710, rs4959389 and rs977785 that are associated with mite-sensitive allergy in Taiwanese children; results suggested that MD-1 could be a susceptible gene for mite-sensitive allergy in Taiwanese children (PMID:18001295)
• Identified MD-1 SNP (rs7740529) association with asthma in Taiwanese children and adults. (PMID:19255686)
• In this study, we produced variants of MD-1 and MD-2 in Pichia pastoris. Contrary to previous reports, this study suggests that MD-1 can bind to LPS. (PMID:21130168)
• MD-1 may be a disease susceptibility gene for adult asthma in a Southern Han population in China. (PMID:21426727)
• Both mouse and human RP105/MD-1 exhibit dimerization of the 1:1 RP105/MD-1 complex, demonstrating a novel organization. (PMID:21959264)
• DNA methylation of the LY86 gene is associated with obesity, insulin resistance, and inflammation. (PMID:24735745)
• our results reveal that MD-1 deficiency is of critical importance in down-regulating induction and progression of colitis, thereby suggesting that MD-1 might be a target for future interventional therapies of inflammatory bowel disease. (PMID:27209086)
• LY86 knockdown results in reduced monocyte migration towards the chemokine MCP-1, thereby implying that this reduced migration may underlie the increased susceptibility to candidemia. (PMID:32251450)
• Genetic variability of immune-related lncRNAs: polymorphisms in LINC-PINT and LY86-AS1 are associated with pemphigus foliaceus susceptibility. (PMID:33394553)
• Higher expression of PLEK and LY86 as the potential biomarker of carotid atherosclerosis. (PMID:37861500)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ly86	ENSDARG00000090649
mus_musculus	Ly86	ENSMUSG00000021423
rattus_norvegicus	Ly86	ENSRNOG00000000137

Protein

Protein identifiers

Lymphocyte antigen 86 — O95711 (reviewed: O95711)

Alternative names: Protein MD-1

All UniProt accessions (1): O95711

UniProt curated annotations — full annotation on UniProt →

Function. May cooperate with CD180 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) and cytokine production. Important for efficient CD180 cell surface expression.

Subunit / interactions. M-shaped tetramer of two CD180-LY86 heterodimers.

Subcellular location. Secreted. Extracellular space.

Tissue specificity. Highly expressed in B-cells, monocytes and tonsil.

Induction. In monocytes, down-regulated by the cell-wall fraction of Mycobacterium bovis (BCG-CWS).

RefSeq proteins (1): NP_004262* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003172	ML_dom	Domain
IPR014756	Ig_E-set	Homologous_superfamily
IPR039945	LY86	Family

Pfam: PF02221

UniProt features (21 total): strand 10, disulfide bond 3, sequence variant 3, glycosylation site 2, signal peptide 1, chain 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3B2D	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95711-F1	87.84	0.75

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 (3): 33–58, 45–154, 102–112

Glycosylation sites (2): 96, 156

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades

MSigDB gene sets: 287 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_45, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, MODULE_317, CROONQUIST_NRAS_SIGNALING_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, chr6p25, MODULE_75

GO Biological Process (6): inflammatory response (GO:0006954), lipopolysaccharide-mediated signaling pathway (GO:0031663), positive regulation of lipopolysaccharide-mediated signaling pathway (GO:0031666), innate immune response (GO:0045087), immune system process (GO:0002376), immune response (GO:0006955)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Toll-like Receptor Cascades	1
Immune System	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	1
cell surface receptor signaling pathway	1
cellular response to lipopolysaccharide	1
positive regulation of response to biotic stimulus	1
positive regulation of signal transduction	1
lipopolysaccharide-mediated signaling pathway	1
regulation of lipopolysaccharide-mediated signaling pathway	1
positive regulation of response to external stimulus	1
immune response	1
defense response to symbiont	1
biological_process	1
immune system process	1
response to stimulus	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LY86	CD180	Q99467	999
LY86	LY96	Q9Y6Y9	989
LY86	TLR4	O00206	673
LY86	FBXW2	Q9UKT8	660
LY86	EGLN2	Q96KS0	629
LY86	GZMA	P12544	609
LY86	DHFR	P00374	548
LY86	P4HTM	Q9NXG6	546
LY86	EGLN1	Q9GZT9	546
LY86	CD19	P15391	535
LY86	CTSS	P25774	517
LY86	TYROBP	O43914	508
LY86	EGLN3	Q9H6Z9	504
LY86	ADGRE1	Q14246	501
LY86	CSF1R	P07333	483

IntAct

11 interactions, top by confidence:

A	B	Type	Score
LY86	GEMIN4	psi-mi:“MI:0915”(physical association)	0.560
CD180	LY86	psi-mi:“MI:0915”(physical association)	0.540
CD180	LY86	psi-mi:“MI:0407”(direct interaction)	0.540
LY96	LY86	psi-mi:“MI:0915”(physical association)	0.400
LY86	PLXNB2	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	MAP2K7	psi-mi:“MI:0914”(association)	0.350
LY86	GEMIN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (219): GEMIN4 (Two-hybrid), CD180 (Affinity Capture-Western), LY86 (Affinity Capture-Western), RPL23 (Affinity Capture-MS), TMEM132A (Affinity Capture-MS), TAZ (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), CALR (Affinity Capture-MS), SUMF1 (Affinity Capture-MS), RBPMS2 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), CNTNAP3 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), RAC3 (Affinity Capture-MS), PXYLP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A7LRQ7, A0A172M485, A0A494C103, A0A6B9L3R4, A0A888, B1A4P8, B7T7N1, C0HK14, C7YS44, D9UBG0, D9UBI3, G5ED65, H2A0L3, L0GB04, O45879, O76411, O95711, P0DKQ8, P0DQG2, P10379, P15501, P25607, P29392, P35495, P35496, P46555, P82292, P86728, P86785, P86983, P93114, P93193, Q09271, Q20170, Q21038, Q25410, Q28920, Q3T0L5, Q45KX2, Q61G93

Diamond homologs: O88188, O95711, Q90890

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1135 predictions. Top by Δscore:

Variant	Effect	Δscore
6:6624924:A:AG	acceptor_gain	1.0000
6:6624925:G:GG	acceptor_gain	1.0000
6:6625011:GA:G	donor_gain	1.0000
6:6625013:G:GG	donor_gain	1.0000
6:6624921:CGTA:C	acceptor_loss	0.9900
6:6624923:TAG:T	acceptor_loss	0.9900
6:6624924:AGAT:A	acceptor_loss	0.9900
6:6624925:G:GA	acceptor_loss	0.9900
6:6624925:GATCC:G	acceptor_gain	0.9900
6:6625008:TCTGA:T	donor_gain	0.9900
6:6625009:CTGA:C	donor_gain	0.9900
6:6625010:TGA:T	donor_gain	0.9900
6:6625011:GAG:G	donor_gain	0.9900
6:6625011:GAGT:G	donor_loss	0.9900
6:6625012:AGT:A	donor_loss	0.9900
6:6625014:TAAG:T	donor_loss	0.9900
6:6625015:AA:A	donor_loss	0.9900
6:6625016:AG:A	donor_loss	0.9900
6:6649623:A:AG	acceptor_gain	0.9900
6:6649624:G:GG	acceptor_gain	0.9900
6:6625017:G:C	donor_loss	0.9800
6:6626291:A:AG	acceptor_gain	0.9800
6:6626292:G:GG	acceptor_gain	0.9800
6:6626292:GGA:G	acceptor_gain	0.9800
6:6626287:CTCCA:C	acceptor_loss	0.9700
6:6626288:TCCA:T	acceptor_loss	0.9700
6:6626290:CAGGA:C	acceptor_loss	0.9700
6:6626292:G:GT	acceptor_loss	0.9700
6:6626418:GGAG:G	donor_gain	0.9700
6:6626419:GAGG:G	donor_gain	0.9700

AlphaMissense

1057 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:6626373:T:A	C102S	0.995
6:6626374:G:C	C102S	0.995
6:6588864:A:C	S44R	0.994
6:6588866:T:A	S44R	0.994
6:6588866:T:G	S44R	0.994
6:6626403:T:A	C112S	0.994
6:6626404:G:C	C112S	0.994
6:6626374:G:A	C102Y	0.993
6:6626311:T:C	L81P	0.992
6:6626404:G:A	C112Y	0.992
6:6654601:G:C	A155P	0.992
6:6626373:T:C	C102R	0.991
6:6654602:C:A	A155D	0.991
6:6654607:G:C	A157P	0.990
6:6626403:T:C	C112R	0.989
6:6588868:G:A	C45Y	0.988
6:6654569:T:C	L144P	0.988
6:6588858:T:G	Y42D	0.987
6:6626375:T:G	C102W	0.986
6:6626401:T:G	F111C	0.986
6:6654608:C:A	A157D	0.985
6:6588815:G:C	W27C	0.984
6:6588815:G:T	W27C	0.984
6:6588831:T:A	C33S	0.984
6:6588832:G:C	C33S	0.984
6:6588867:T:A	C45S	0.984
6:6588868:G:C	C45S	0.984
6:6626311:T:A	L81H	0.984
6:6626374:G:T	C102F	0.984
6:6654596:C:A	A153D	0.984

dbSNP variants (sampled 300 via entrez): RS1000000173 (6:6606447 C>T), RS1000127731 (6:6604455 G>A,T), RS1000136159 (6:6620292 G>C), RS1000179398 (6:6634561 G>T), RS1000181940 (6:6604250 C>A), RS1000194144 (6:6639104 T>A,G), RS1000199312 (6:6597513 G>A), RS1000332399 (6:6632856 C>G), RS1000350789 (6:6594314 T>G), RS1000375877 (6:6646667 T>A,C), RS1000388336 (6:6627214 C>A,G,T), RS1000395802 (6:6614392 T>A), RS1000403037 (6:6594598 G>A,C), RS1000456600 (6:6606378 C>A,G,T), RS1000512325 (6:6589584 A>C,G)

Disease associations

OMIM: gene MIM:605241 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

56 associations (top):

Study	Trait	p-value
GCST000551_6	Major depressive disorder (broad)	7.000000e-06
GCST000829_14	Waist-hip ratio	2.000000e-17
GCST001954_1	Waist-hip ratio	2.000000e-10
GCST002138_6	Waist-hip ratio	1.000000e-06
GCST002782_280	Waist-to-hip ratio adjusted for body mass index	2.000000e-15
GCST002782_281	Waist-to-hip ratio adjusted for body mass index	1.000000e-06
GCST002782_282	Waist-to-hip ratio adjusted for body mass index	2.000000e-18
GCST002782_283	Waist-to-hip ratio adjusted for body mass index	3.000000e-07
GCST002782_284	Waist-to-hip ratio adjusted for body mass index	6.000000e-16
GCST002782_285	Waist-to-hip ratio adjusted for body mass index	8.000000e-20
GCST002829_4	Urate levels in overweight individuals	6.000000e-06
GCST003972_3	Visceral adipose tissue/subcutaneous adipose tissue ratio	3.000000e-09
GCST003973_4	Visceral adipose tissue/subcutaneous adipose tissue ratio adjusted for BMI	2.000000e-09
GCST004064_22	Waist-hip ratio	8.000000e-13
GCST004064_57	Waist-hip ratio	7.000000e-14
GCST004066_31	Hip circumference	5.000000e-07
GCST004066_83	Hip circumference	3.000000e-08
GCST004067_159	Hip circumference adjusted for BMI	3.000000e-08
GCST004067_217	Hip circumference adjusted for BMI	2.000000e-10
GCST004067_25	Hip circumference adjusted for BMI	2.000000e-15
GCST004068_47	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	2.000000e-08
GCST004505_72	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	7.000000e-11
GCST004505_73	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-12
GCST004567_128	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	4.000000e-06
GCST004567_18	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1.000000e-12
GCST004567_2	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	6.000000e-09
GCST004567_44	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	4.000000e-06
GCST004567_77	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1.000000e-12
GCST004567_93	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	6.000000e-09
GCST004576_122	Waist-to-hip ratio adjusted for body mass index	5.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004531	urate measurement
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004340	body mass index
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004761	uric acid measurement
EFO:0006335	systolic blood pressure
EFO:0011015	educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Nickel	increases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
terbufos	increases methylation	1
benzo(e)pyrene	decreases methylation	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Fonofos	increases methylation	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	decreases expression	1
Parathion	increases methylation	1
Tretinoin	increases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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