CLEC4E

Summary

CLEC4E (C-type lectin domain family 4 member E, HGNC:14555) is a protein-coding gene on chromosome 12p13.31, encoding C-type lectin domain family 4 member E (Q9ULY5). Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: recognizes damage-associated molecular patterns (DAMPs) of abnormal self and pathogen-associated molecular patterns (PAMPs) of bacteria and fungi.

This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type II transmembrane protein is a downstream target of CCAAT/enhancer binding protein (C/EBP), beta (CEBPB) and may play a role in inflammation. Alternative splice variants have been described but their full-length sequence has not been determined. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.

Source: NCBI Gene 26253 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 34 total
• Druggable target: yes
• MANE Select transcript: NM_014358

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14555
Approved symbol	CLEC4E
Name	C-type lectin domain family 4 member E
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	MINCLE
Ensembl gene	ENSG00000166523
Ensembl biotype	protein_coding
OMIM	609962
Entrez	26253

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000299663, ENST00000446457, ENST00000446809, ENST00000450725, ENST00000537698, ENST00000545274

RefSeq mRNA: 2 — MANE Select: NM_014358 NM_001410969, NM_014358

CCDS: CCDS8594, CCDS91649

Canonical transcript exons

ENST00000299663 — 6 exons

Exon	Start	End
ENSE00001103828	8533305	8534809
ENSE00001103831	8537115	8537266
ENSE00001103836	8539217	8539306
ENSE00002287141	8540761	8540905
ENSE00003596814	8536090	8536205
ENSE00003657418	8539855	8539947

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 98.30.

FANTOM5 (CAGE): breadth broad, TPM avg 16.0240 / max 2607.3470, expressed in 370 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129330	11.0921	343
129333	3.7099	227
129332	1.1404	172
129331	0.0816	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.30	gold quality
mononuclear cell	CL:0000842	97.34	gold quality
leukocyte	CL:0000738	97.30	gold quality
blood	UBERON:0000178	95.73	gold quality
granulocyte	CL:0000094	95.31	gold quality
right lung	UBERON:0002167	95.05	gold quality
spleen	UBERON:0002106	90.72	gold quality
trabecular bone tissue	UBERON:0002483	90.66	gold quality
bone marrow	UBERON:0002371	89.38	gold quality
upper lobe of left lung	UBERON:0008952	87.51	gold quality
gall bladder	UBERON:0002110	87.33	gold quality
upper lobe of lung	UBERON:0008948	86.65	gold quality
vermiform appendix	UBERON:0001154	84.03	gold quality
lower lobe of lung	UBERON:0008949	81.68	gold quality
buccal mucosa cell	CL:0002336	81.15	silver quality
descending thoracic aorta	UBERON:0002345	80.96	gold quality
left uterine tube	UBERON:0001303	80.73	gold quality
sperm	CL:0000019	80.56	gold quality
left lobe of thyroid gland	UBERON:0001120	80.39	gold quality
omental fat pad	UBERON:0010414	79.24	gold quality
bone marrow cell	CL:0002092	79.23	gold quality
caecum	UBERON:0001153	79.17	gold quality
peritoneum	UBERON:0002358	79.17	gold quality
adipose tissue of abdominal region	UBERON:0007808	78.69	gold quality
male germ cell	CL:0000015	78.02	gold quality
thyroid gland	UBERON:0002046	77.51	gold quality
smooth muscle tissue	UBERON:0001135	77.43	gold quality
left coronary artery	UBERON:0001626	76.79	gold quality
lung	UBERON:0002048	76.17	gold quality
lymph node	UBERON:0000029	75.78	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	25.83
E-ANND-3	yes	15.48
E-CURD-88	yes	11.73
E-MTAB-9801	yes	6.26
E-GEOD-111727	no	257.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting CLEC4E, 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-548P	99.98	72.25	3784
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-7153-3P	99.00	65.35	608
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-7851-3P	98.72	64.88	980

Literature-anchored findings (GeneRIF, showing 29)

• Several functional states mediating the interaction of Mincle and yeast at the surface of the macrophage. (PMID:18509109)
• important for the initiation of an innate immune response to Candida albicans (PMID:19120481)
• progenitor-derived mast cells expressed the macrophage-inducible C-type lectin receptor Mincle, and exposure of these cells to M. sympodialis induced up-regulation of the mRNA expression of Mincle (PMID:20608913)
• Our data suggest that Mincle is induced in adipose tissue macrophages in obesity at least partly through the saturated fatty acid/TLR4/NF-kappaB pathway, thereby suggesting its pathophysiologic role in obesity-induced adipose tissue inflammation. (PMID:21282371)
• silencing of renal DNaseI gene expression initiates a cascade of inflammatory signals including activation of Toll like receptors and Clec4e, leading to progression of both murine and human lupus nephritis (PMID:22479529)
• Data indicate an unusual pattern of reciprocal expression of Mincle on peripheral blood monocytes or neutrophils. (PMID:22641025)
• Mincle is a potentially critical player in human B cell responses. (PMID:22698596)
• Macrophage-inducible C-type lectin is associated with anti-cyclic citrullinated peptide antibodies-positive rheumatoid arthritis in men. (PMID:22932191)
• Results show the molecular mechanism of glycolipid recognition through C-type lectin receptors, which may provide clues to rational design for effective adjuvants. (PMID:24101491)
• mincle is a fungal receptor that can suppress antifungal immunity and, as such, is a potential therapeutic target. (PMID:24721577)
• These results demonstrated that GroMM is a unique ligand for human Mincle that is not recognized by mouse Mincle. (PMID:24733387)
• our findings identify mincle as a contributor to the inflammatory response after traumatic brain injury (PMID:25111533)
• Data indicate that MINCLE receptor is able to mediate the response to trehalose-6,6-dimycolate (TDM) dependent on SYK kinase and CARD9 protein. (PMID:26202982)
• results suggest that cholesterol crystals are an endogenous ligand for hMincle and that they activate innate immune responses (PMID:26296894)
• Induction of Mincle by Helicobacter pylori and consequent anti-inflammatory signaling denote a bacterial survival strategy. (PMID:26456705)
• No association was detected with any of the SNPs analysed and susceptibility to tuberculosis. (PMID:27363694)
• a nonredundant role for Clec4e in coordinating major biological pathways involved in atherosclerosis (PMID:27587433)
• Mincle has the ability to survey mycolate-derived glycolipids from actinomycetes, distinguishing non-pathogenic (e.g. Rhodococcus spp.) and pathogenic (e.g. Mycobacterium tuberculosis) species on the basis of alpha-chain length. (PMID:27714279)
• combination adjuvant systems demonstrate markedly different immune activation with age, with combined DC activation via Macrophage-inducible C-type lectin and TLR7/8 representing a novel approach to enhance the efficacy of early-life vaccines. (PMID:27793997)
• We here show that Mincle gene expression was induced in alveolar macrophages and neutrophils in bronchoalveolar lavage fluids of mice and patients with pneumococcal pneumonia (PMID:27923071)
• CLEC4E expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• The expression of Mincle increases significantly during the early period of Aspergillus fumigatus infection, while expression of eight corresponding cytokines changes. Mincle, as a pattern recognition receptor, may play a role in the early innate immune response of the corneal resistance against fungus. (PMID:28141595)
• Spontaneous labour is associated with up-regulated Mincle expression in the myometrium and fetal membranes. Mincle expression was also increased in fetal membranes and myometrium in the presence of pro-labour mediators. (PMID:30793298)
• variations at rs10841845 and rs10841847 of CLEC4E gene are associated with increased individual protection against Pulmonary tuberculosis (PMID:31075410)
• Molecular mechanism of obesity-induced adipose tissue inflammation; the role of Mincle in adipose tissue fibrosis and ectopic lipid accumulation. (PMID:31852849)
• overview of the accumulated knowledge of the multi-task danger receptor Mincle from its discovery to the latest findings (PMID:32152942)
• CLEC4E (Mincle) genetic variation associates with pulmonary tuberculosis in Guinea-Bissau (West Africa). (PMID:32971250)
• A case-control study on correlation between the single nucleotide polymorphism of CLEC4E and the susceptibility to tuberculosis among Han people in Western China. (PMID:34376176)
• Coarse-Graining the Recognition of a Glycolipid by the C-Type Lectin Mincle Receptor. (PMID:39368102)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
mus_musculus	Clec4e	ENSMUSG00000030142
rattus_norvegicus	Clec4e	ENSRNOG00000061394
drosophila_melanogaster	CG14866	FBGN0038315
drosophila_melanogaster	lectin-46Cb	FBGN0040092
drosophila_melanogaster	lectin-46Ca	FBGN0040093
drosophila_melanogaster	lectin-33A	FBGN0040096
drosophila_melanogaster	CG34033	FBGN0054033
caenorhabditis_elegans	clec-87	WBGENE00007709
caenorhabditis_elegans	clec-91	WBGENE00014117
caenorhabditis_elegans		WBGENE00016088
caenorhabditis_elegans		WBGENE00019606

Paralogs (14): CD209 (ENSG00000090659), FCER2 (ENSG00000104921), CLEC4M (ENSG00000104938), CLEC4A (ENSG00000111729), CD207 (ENSG00000116031), CLEC10A (ENSG00000132514), ASGR1 (ENSG00000141505), CLEC4F (ENSG00000152672), ASGR2 (ENSG00000161944), CLEC4D (ENSG00000166527), CLEC4G (ENSG00000182566), CLEC17A (ENSG00000187912), CLEC4C (ENSG00000198178), CLEC6A (ENSG00000205846)

Protein

Protein identifiers

C-type lectin domain family 4 member E — Q9ULY5 (reviewed: Q9ULY5)

Alternative names: C-type lectin superfamily member 9, Macrophage-inducible C-type lectin

All UniProt accessions (4): Q9ULY5, F5H5X7, F8WFA1, H0YGH9

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: recognizes damage-associated molecular patterns (DAMPs) of abnormal self and pathogen-associated molecular patterns (PAMPs) of bacteria and fungi. The PAMPs notably include mycobacterial trehalose 6,6’-dimycolate (TDM), a cell wall glycolipid with potent adjuvant immunomodulatory functions. Interacts with signaling adapter Fc receptor gamma chain/FCER1G to form a functional complex in myeloid cells. Binding of mycobacterial trehalose 6,6’-dimycolate (TDM) to this receptor complex leads to phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) of FCER1G, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 and T-helper 17 cell subtypes. Also recognizes alpha-mannose residues on pathogenic fungi of the genus Malassezia and mediates macrophage activation. Through recognition of DAMPs released upon nonhomeostatic cell death, enables immune sensing of damaged self and promotes inflammatory cell infiltration into the damaged tissue.

Subunit / interactions. Monomer and homodimer. Interacts with signaling adapter Fc receptor gamma chain/FCER1G to form a functional complex; the interaction is direct. Alternatively, acts as a bridge for interaction between CLEC4D and FCER1G. A heterodimer of CLEC4E and CLEC4D associates with FCER1G to form a functional complex. Interacts with SAP130 nuclear protein that is released from necrotic cells; the interaction is direct.

Subcellular location. Cell membrane. Cell projection. Phagocytic cup.

Tissue specificity. Expressed in monocytes and macrophages.

RefSeq proteins (2): NP_001397898, NP_055173* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR033989	CD209-like_CTLD	Domain
IPR050111	C-type_lectin/snaclec_domain	Family

Pfam: PF00059

UniProt features (32 total): binding site 8, strand 7, mutagenesis site 4, disulfide bond 3, topological domain 2, glycosylation site 2, helix 2, chain 1, transmembrane region 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3WH2	X-RAY DIFFRACTION	1.3
3WH3	X-RAY DIFFRACTION	1.32

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULY5-F1	85.57	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 171; 193; 194; 206; 117; 119; 123; 169

Disulfide bonds (3): 80–91, 108–205, 179–197

Glycosylation sites (2): 62, 107

Mutagenesis-validated functional residues (4):

Position	Phenotype
169–171	impairs binding to trehalose-6,6’-dimycolate.
172	impairs trehalose-6,6’-dimycolate (tdm)-induced nf-kappa-b activation.
183	reduces trehalose-6,6’-dimycolate (tdm)-induced nf-kappa-b activation.
198–199	reduces trehalose-6,6’-dimycolate (tdm)-induced nf-kappa-b activation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5621480	Dectin-2 family

MSigDB gene sets: 233 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOCC_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, FOSTER_TOLERANT_MACROPHAGE_DN, GOBP_T_CELL_DIFFERENTIATION_INVOLVED_IN_IMMUNE_RESPONSE, MARTINEZ_RB1_TARGETS_DN, GROSS_HYPOXIA_VIA_ELK3_ONLY_UP

GO Biological Process (10): positive regulation of cytokine production (GO:0001819), pattern recognition receptor signaling pathway (GO:0002221), T cell differentiation involved in immune response (GO:0002292), Fc-gamma receptor signaling pathway (GO:0038094), defense response to bacterium (GO:0042742), innate immune response (GO:0045087), antifungal innate immune response (GO:0061760), immune system process (GO:0002376), immune response-regulating signaling pathway (GO:0002764), immune response (GO:0006955)

GO Molecular Function (7): calcium ion binding (GO:0005509), carbohydrate binding (GO:0030246), pattern recognition receptor activity (GO:0038187), glycolipid binding (GO:0051861), protein binding (GO:0005515), signaling receptor activity (GO:0038023), metal ion binding (GO:0046872)

GO Cellular Component (6): phagocytic cup (GO:0001891), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), phagocytic vesicle membrane (GO:0030670), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
C-type lectin receptors (CLRs)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
immune response	2
binding	2
plasma membrane	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
innate immune response-activating signaling pathway	1
T cell activation involved in immune response	1
T cell differentiation	1
Fc receptor signaling pathway	1
defense response	1
response to bacterium	1
defense response to symbiont	1
innate immune response	1
defense response to fungus	1
biological_process	1
signal transduction	1
regulation of immune response	1
immune system process	1
response to stimulus	1
metal ion binding	1
signaling receptor activity	1
lipid binding	1
carbohydrate derivative binding	1
molecular transducer activity	1
cation binding	1
membrane	1
cell periphery	1
cell surface	1
side of membrane	1
endocytic vesicle membrane	1
phagocytic vesicle	1

Protein interactions and networks

STRING

1365 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC4E	FCER1G	P30273	994
CLEC4E	SYK	P43405	952
CLEC4E	SF3B3	Q15393	947
CLEC4E	TYROBP	O43914	918
CLEC4E	CARD9	Q9H257	872
CLEC4E	TLR2	O60603	757
CLEC4E	CLEC4D	Q8WXI8	739
CLEC4E	CLEC1A	Q8NC01	729
CLEC4E	IL1B	P01584	709
CLEC4E	SAP130	Q9H0E3	708
CLEC4E	BCL10	O95999	631
CLEC4E	CEBPB	P17676	620
CLEC4E	MALT1	Q9UDY8	619
CLEC4E	TLR4	O00206	604
CLEC4E	CLEC1B	Q9P126	589

IntAct

18 interactions, top by confidence:

A	B	Type	Score
NKG7	CLEC4E	psi-mi:“MI:0915”(physical association)	0.600
	CLEC4E	psi-mi:“MI:0915”(physical association)	0.560
FAM3C	CLEC4E	psi-mi:“MI:0915”(physical association)	0.560
CXCL9	CLEC4E	psi-mi:“MI:0915”(physical association)	0.560
CLEC4E	TUBB3	psi-mi:“MI:0914”(association)	0.530
ATG16L1		psi-mi:“MI:0914”(association)	0.350
CLEC4E	ESYT2	psi-mi:“MI:0914”(association)	0.350
	CLEC4E	psi-mi:“MI:0915”(physical association)	0.000
FAM3C	CLEC4E	psi-mi:“MI:0915”(physical association)	0.000
NKG7	CLEC4E	psi-mi:“MI:0915”(physical association)	0.000
CXCL9	CLEC4E	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (410): RNF166 (Affinity Capture-MS), SFXN3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), CLEC4E (Two-hybrid), CLEC4E (Two-hybrid), CLEC4E (Two-hybrid), FAM3C (Two-hybrid), CLEC4E (Affinity Capture-RNA), TUBB3 (Affinity Capture-MS), SFXN3 (Affinity Capture-MS), RNF166 (Affinity Capture-MS), TAPBP (Affinity Capture-MS), TAP1 (Affinity Capture-MS), CYP2S1 (Affinity Capture-MS), TMEM30A (Affinity Capture-MS)

ESM2 similar proteins: D3W0D1, D3ZWT9, D4AD02, O54709, O70215, O88713, P02707, P14371, P26717, P27811, P37217, Q07108, Q0H8B9, Q149M0, Q2HXU8, Q2NL33, Q3LUH2, Q504P2, Q63378, Q64335, Q67EQ0, Q67EQ1, Q69FH1, Q6EIG7, Q6UXN8, Q80XD9, Q8BRU4, Q8C1T8, Q8MI05, Q8MIS5, Q8VI21, Q8WTT0, Q8WXI8, Q91ZW7, Q91ZW8, Q91ZW9, Q91ZX1, Q92778, Q95MI5, Q9GME8

Diamond homologs: A4KWA1, A4KWA6, P20693, P20937, P21063, P24765, P27471, P27811, P27812, P27814, P79391, Q0ZUP0, Q0ZUP1, Q12918, Q49BZ4, Q5NKN2, Q5NKN4, Q60651, Q60654, Q61830, Q63378, Q67EQ1, Q8HY06, Q8HY10, Q8HY11, Q8HY12, Q8HYC0, Q8VD98, Q8WTT0, Q90WJ8, Q91ZW8, Q925N7, Q95LG1, Q99JB4, Q9GLF3, Q9GME8, Q9H2X3, Q9JKF4, Q9NY25, Q9QZ15

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

901 predictions. Top by Δscore:

Variant	Effect	Δscore
12:8536204:TCCTA:T	acceptor_loss	1.0000
12:8536205:CCTAT:C	acceptor_loss	1.0000
12:8536206:C:A	acceptor_loss	1.0000
12:8539302:TGTCA:T	acceptor_gain	1.0000
12:8539303:GTCA:G	acceptor_gain	1.0000
12:8539303:GTCAC:G	acceptor_loss	1.0000
12:8539304:TCA:T	acceptor_gain	1.0000
12:8539304:TCACT:T	acceptor_loss	1.0000
12:8539305:CA:C	acceptor_gain	1.0000
12:8539305:CAC:C	acceptor_gain	1.0000
12:8539306:AC:A	acceptor_loss	1.0000
12:8539307:C:CA	acceptor_loss	1.0000
12:8539307:C:CC	acceptor_gain	1.0000
12:8539308:T:G	acceptor_loss	1.0000
12:8534805:AGAAG:A	acceptor_gain	0.9900
12:8534806:GAAG:G	acceptor_gain	0.9900
12:8534807:AAG:A	acceptor_gain	0.9900
12:8534808:AG:A	acceptor_gain	0.9900
12:8534809:GCT:G	acceptor_loss	0.9900
12:8534810:C:CC	acceptor_gain	0.9900
12:8534810:CT:C	acceptor_loss	0.9900
12:8534811:T:G	acceptor_loss	0.9900
12:8536085:ATTAC:A	donor_loss	0.9900
12:8536086:TTA:T	donor_loss	0.9900
12:8536087:TA:T	donor_loss	0.9900
12:8536088:ACCT:A	donor_loss	0.9900
12:8536089:C:A	donor_loss	0.9900
12:8536203:TTC:T	acceptor_gain	0.9900
12:8536205:CCTA:C	acceptor_gain	0.9900
12:8536206:C:CC	acceptor_gain	0.9900

AlphaMissense

1449 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:8534803:C:A	W165C	0.998
12:8534803:C:G	W165C	0.998
12:8534722:C:A	W192C	0.996
12:8534722:C:G	W192C	0.996
12:8536122:C:A	W152C	0.996
12:8536122:C:G	W152C	0.996
12:8536128:C:A	W150C	0.994
12:8536128:C:G	W150C	0.994
12:8537175:A:C	S104R	0.993
12:8537175:A:T	S104R	0.993
12:8537177:T:G	S104R	0.993
12:8534724:A:G	W192R	0.992
12:8534724:A:T	W192R	0.992
12:8536124:A:G	W152R	0.992
12:8536124:A:T	W152R	0.992
12:8537163:G:C	C108W	0.992
12:8534805:A:G	W165R	0.990
12:8534805:A:T	W165R	0.990
12:8537235:C:A	W84C	0.990
12:8537235:C:G	W84C	0.990
12:8534762:C:G	C179S	0.988
12:8534763:A:T	C179S	0.988
12:8536130:A:G	W150R	0.988
12:8536130:A:T	W150R	0.988
12:8534684:C:G	C205S	0.987
12:8534685:A:T	C205S	0.987
12:8537164:C:G	C108S	0.987
12:8537164:C:T	C108Y	0.987
12:8537165:A:T	C108S	0.987
12:8536156:A:G	L141P	0.984

dbSNP variants (sampled 300 via entrez): RS1000660004 (12:8534389 T>C), RS1001076714 (12:8539920 A>G), RS1001168363 (12:8540273 C>T), RS1001915164 (12:8535685 A>G), RS1002050779 (12:8535437 A>T), RS1002336799 (12:8540631 C>A,G,T), RS1003092697 (12:8537793 A>T), RS1003557722 (12:8542072 G>A), RS1003592843 (12:8537007 G>T), RS1003628339 (12:8541941 T>C), RS1003778290 (12:8536850 A>T), RS1003796062 (12:8542352 G>A), RS1004040658 (12:8542413 C>G), RS1004528818 (12:8538315 T>C), RS1004572899 (12:8542775 A>C)

Disease associations

OMIM: gene MIM:609962 | 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
GCST006575_21	Takayasu arteritis	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105898 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — C-type lectin-like receptors (CLRs)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
GlcC14C18	Agonist	10.0	pEC50

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
Lipopolysaccharides	increases expression, increases reaction, affects response to substance, affects cotreatment	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	decreases expression, decreases reaction	2
aristolochic acid I	increases expression	1
tungsten carbide	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
sulforaphane	increases expression	1
gamma-sitosterol	increases activity	1
tibolone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Cadmium	decreases expression, increases abundance	1
Catechin	affects cotreatment, increases expression	1
Cholesterol	increases expression, decreases reaction, increases reaction, increases response to substance, affects binding (+2 more)	1
Cobalt	affects cotreatment, decreases expression	1
Cord Factors	increases activity, affects cotreatment, increases expression, increases response to substance, affects binding	1
Desmosterol	increases activity	1
Endosulfan	decreases expression, decreases reaction	1
Estradiol	affects cotreatment, increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases expression	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4037321	Binding	Binding affinity to recombinant human mincle extracellular domain fused with human IgG Fc expressed in HEK293T cells at 0.1 nmol by ELISA	Lipidated Brartemicin Analogues Are Potent Th1-Stimulating Vaccine Adjuvants. — J Med Chem

Clinical trials (associated diseases)

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