CLEC7A

Summary

CLEC7A (C-type lectin domain containing 7A, HGNC:14558) is a protein-coding gene on chromosome 12p13.2, encoding C-type lectin domain family 7 member A (Q9BXN2). Lectin that functions as a pattern recognizing receptor (PRR) specific for beta-1,3-linked and beta-1,6-linked glucans, which constitute cell wall constituents from pathogenic bacteria and fungi.

This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with an immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor that recognizes a variety of beta-1,3-linked and beta-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.

Source: NCBI Gene 64581 — RefSeq curated summary.

At a glance

• Gene–disease (curated): chronic mucocutaneous candidiasis (Supportive, GenCC)
• Clinical variants (ClinVar): 52 total
• Phenotypes (HPO): 34
• Druggable target: yes
• MANE Select transcript: NM_197947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14558
Approved symbol	CLEC7A
Name	C-type lectin domain containing 7A
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	DECTIN-1, hDectin-1, CD369, SCARE2
Ensembl gene	ENSG00000172243
Ensembl biotype	protein_coding
OMIM	606264
Entrez	64581

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000298523, ENST00000304084, ENST00000310002, ENST00000349926, ENST00000353231, ENST00000396484, ENST00000465100, ENST00000525605, ENST00000528799, ENST00000529761, ENST00000531192, ENST00000533022, ENST00000534609, ENST00000960576, ENST00000960577, ENST00000960578

RefSeq mRNA: 6 — MANE Select: NM_197947 NM_022570, NM_197947, NM_197948, NM_197949, NM_197950, NM_197954

CCDS: CCDS41753, CCDS41754, CCDS53744, CCDS8613, CCDS8614, CCDS8617

Canonical transcript exons

ENST00000304084 — 6 exons

Exon	Start	End
ENSE00001355450	10129980	10130199
ENSE00003579126	10116777	10118590
ENSE00003675098	10127747	10127845
ENSE00003683192	10126571	10126708
ENSE00003688618	10125297	10125448
ENSE00003692966	10123245	10123363

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 99.17.

FANTOM5 (CAGE): breadth broad, TPM avg 28.6415 / max 2963.8725, expressed in 459 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129476	23.9278	442
129477	2.6338	279
129475	1.5422	191
129473	0.4513	105
129474	0.0864	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.17	gold quality
mononuclear cell	CL:0000842	99.16	gold quality
leukocyte	CL:0000738	99.03	gold quality
granulocyte	CL:0000094	97.29	gold quality
blood	UBERON:0000178	97.15	gold quality
buccal mucosa cell	CL:0002336	96.89	gold quality
periodontal ligament	UBERON:0008266	94.60	gold quality
tendon of biceps brachii	UBERON:0008188	94.05	silver quality
right lung	UBERON:0002167	93.49	gold quality
vermiform appendix	UBERON:0001154	91.61	gold quality
spleen	UBERON:0002106	90.72	gold quality
upper lobe of left lung	UBERON:0008952	90.70	gold quality
upper lobe of lung	UBERON:0008948	90.23	gold quality
bone marrow	UBERON:0002371	90.16	gold quality
gingival epithelium	UBERON:0001949	90.12	gold quality
gingiva	UBERON:0001828	89.17	gold quality
bone marrow cell	CL:0002092	88.53	gold quality
palpebral conjunctiva	UBERON:0001812	87.27	gold quality
visceral pleura	UBERON:0002401	86.78	gold quality
lung	UBERON:0002048	85.53	gold quality
decidua	UBERON:0002450	85.39	gold quality
caecum	UBERON:0001153	85.38	gold quality
right coronary artery	UBERON:0001625	84.48	gold quality
lower lobe of lung	UBERON:0008949	84.26	gold quality
gall bladder	UBERON:0002110	83.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.78	gold quality
pleura	UBERON:0000977	83.31	gold quality
amniotic fluid	UBERON:0000173	83.14	gold quality
skin of hip	UBERON:0001554	82.61	gold quality
tendon	UBERON:0000043	82.57	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	412.26
E-HCAD-4	yes	198.16
E-CURD-122	yes	65.68
E-MTAB-10553	yes	47.99
E-MTAB-6678	yes	43.65
E-GEOD-84465	yes	41.10
E-MTAB-9467	yes	36.14
E-CURD-46	yes	35.68
E-MTAB-6701	yes	30.26
E-MTAB-9221	yes	29.90
E-GEOD-134144	yes	26.12
E-ANND-3	yes	26.06
E-HCAD-9	yes	24.50
E-HCAD-1	yes	21.87
E-CURD-88	yes	19.61

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CD40	Activation
CD86	Activation

Upstream regulators (CollecTRI, top): EGR1, SPI1

Literature-anchored findings (GeneRIF, showing 40)

• Dectin-1b cDNA encodes for a transmembrane protein of the C-type lectin-like receptor family. It is selectively expressed in several purified DC subpopulations but not in monocytes and is up-regulated upon stimulation with lipopolysaccharide. (PMID:12423684)
• Uptake of zymosan particles can occur by beta glucan receptor (or SIGNR1) and results in TNF-alpha production by macrophages. (PMID:14707091)
• Dectin-1 activates Syk tyrosine kinase in macrophages for reactive oxygen production (PMID:15956283)
• hDectin-1E was not secreted and it mainly resided in the cytoplasm. The binding of hDectin-1E and RanBPM was further confirmed in vivo by co-immunoprecipitation assay and confocal microscopic analysis. (PMID:16870151)
• CD37 is important for dectin-1 stabilization in APC membranes and controls dectin-1-mediated IL-6 production. (PMID:17182550)
• hDectin-1 is involved in the uptake and cross-presentation of cellular antigens. (PMID:17698636)
• dectin-1 synergizes with both TLR2 and TLR4 pathways for the production of TNF-alpha in human primary PBMCs and in monocyte-derived macrophages. (PMID:18549457)
• dectin-1 activates two independent signaling pathways, one through Syk and one through Raf-1, to induce immune responses. (PMID:19122653)
• Our results demonstrate that TLR2, TLR4 and Dectin-1 actively sense, internalize and respond in an innate way to Mycobacterium ulcerans in human epidermal keratinocytes. (PMID:19134118)
• co-stimulation of dendritic cell-specific ICAM-3 receptor and Dectin-1 induces the metabolism of arachidonic acid (PMID:19223162)
• Collectively, these findings identify Dectin-1 as a key receptor influencing critical biological functions of DC in response to C. albicans leading to T cells response alteration. (PMID:19358895)
• This study suggests a crucial role played by dectin-1 in the mucosal antifungal mechanisms in immunocompromised hosts. (PMID:19614557)
• demonstrate the novel induction of Dectin-1 in type II airway epithelial cells and its critical role in the innate immune response against Mtb in non-phagocytic cells (PMID:19633936)
• Dectin-1 engagement by Mtb enables DC to promote a Th1/Th17 response, whereas DC-SIGN and MR costimulation limits dectin-1-dependent Th17 generation and favors a Th1 response, probably by interfering with release of cytokines. (PMID:19773555)
• Dectin-1, although indispensable for recognition of beta-glucan-bearing particles in mice, is not the major receptor for yeast particles in human neutrophils. (PMID:19811837)
• mutated form of dectin-1 was poorly expressed, did not mediate beta-glucan binding, and led to defective production of cytokines…higlights specific role of dectin-1 in human mucosal antifungal defense (PMID:19864674)
• Results demonstrate a decrease of TLRs and dectin-1 expression mainly on monocytes as opposed to neutrophils, as soon as 30 minutes after Paracoccidioides brasiliensis stimulation. (PMID:19888805)
• dectin-1 expression is elevated on macrophages, neutrophils, and other immune cells involved in the inflammatory reaction in inflammatory bowel disease (IBD), but is not the major susceptibility factor for IBD. (PMID:19915667)
• loss of one functional allele of DECTIN-1 is not associated with either susceptibility to or severity of rheumatoid arthritis (PMID:20158887)
• the MTB-induced IL-17A response relies strongly on the endogenous IL-1 pathway and IL-1R signaling. TLR4 and dectin-1 are the main receptors responsible for mediating the signals responsible for IL-17A production by MTB. (PMID:20299682)
• distinct roles of CR3, Dectin-1, and sialic acids in the interaction with Histoplasma and suggested that multiple receptor use might be important to host defense against Histoplasma. (PMID:20360401)
• beta-glucans are recognized by membrane-associated dectin-1 and cytoplasmic NLRP3 inflammasome (PMID:20421639)
• The effects of the dectin-1 Y238X polymorphism on graft-versus-host disease and Candida sp. colonization in stem cell transplantation patients are reported. (PMID:20452827)
• Mast cells from atopic eczema patients have impaired upregulation of the fungal recognition receptor Dectin-1. (PMID:20608913)
• A remarkably high expression of dectin-1 mRNA was observed in psoriatic epidermis (PMID:20631729)
• Dectin-1, a pattern recognition receptor involved in antifungal immunity, polymorphisms in the gene may play a role in human disease (Review) (PMID:20700596)
• role for Dectin-1 in antifungal immunity that is the ability to control both resistance and tolerance to the fungus contingent on hematopoietic/nonhematopoietic compartmentalization (PMID:20807886)
• dectin-1 Y238X heterozygosity has a limited influence on susceptibility to invasive aspergillosis and may be important in susceptible non-hematopoietic stem cell transplantation patients; this is partly due to redundancy inherent in innate immune system (PMID:21242599)
• Thus, dectin-1 and dectin-2 control adaptive T(H)-17 immunity to fungi via Malt1-dependent activation of c-Rel. (PMID:21283787)
• Regulation of dectin-1-mediated dendritic cell activation by peroxisome proliferator-activated receptor-gamma ligand troglitazone. (PMID:21296999)
• TLR2 and Dectin-1 were expressed by endothelial cells in response to Aspergillus fumigatus stimulation. (PMID:21426724)
• Expressions of TLR2, TLR4 and dectin-1 increased in HaCaT cells in response to Trichophyton rubrum exposure. (PMID:21515468)
• results define the dectin-1/inflammasome pathway as the mechanism that enables the host immune system to mount a protective Th17 response and distinguish between colonization and tissue invasion by Candida albicans (PMID:21531876)
• Mycobacterium abscessus activates the NLRP3 inflammasome via dectin-1/Syk-dependent signaling and the cytoplasmic scaffold protein p62/SQSTM1 in human macrophages. (PMID:21876553)
• genetic variation in DECTIN-1 was not associated with susceptibility to candidemia. (PMID:21881131)
• We demonstrate that heterozygosity for the Y238X DECTIN-1 polymorphism in HIV-infected patients predisposes to bacterial infections, and in particular to pneumonia. (PMID:21985303)
• Yeast-derived beta-glucan lacks cytotoxic effects towards B-lymphoma cells but up-regulation of CD86 suggests maturation of the cells via dectin-1 by the carbohydrate (PMID:22199280)
• dectin-1 acted as an extracellular sensor for pathogens that induced both IL-1beta production and maturation through a noncanonical caspase-8-dependent inflammasome for protective immunity (PMID:22267217)
• Dectin-1 and DC-SIGN polymorphisms are associated with invasive pulmonary Aspergillosis infection (PMID:22384201)
• Dectin-1 contributes to the Aspergillus fumigatus-induced chemokine synthesis in human bronchial epithelial cells. (PMID:22562430)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-193e13.5	ENSDARG00000052656
danio_rerio		ENSDARG00000074732
danio_rerio	si:dkey-26c10.5	ENSDARG00000088023
danio_rerio	si:ch211-170d8.8	ENSDARG00000090945
mus_musculus	Clec7a	ENSMUSG00000079293
rattus_norvegicus	Clec7a	ENSRNOG00000054251
drosophila_melanogaster	rgn	FBGN0261258
caenorhabditis_elegans		WBGENE00009156
caenorhabditis_elegans		WBGENE00013008

Paralogs (23): CLEC2D (ENSG00000069493), CD69 (ENSG00000110848), CLEC2B (ENSG00000110852), KLRB1 (ENSG00000111796), KLRD1 (ENSG00000134539), KLRC1 (ENSG00000134545), KLRG1 (ENSG00000139187), KLRF1 (ENSG00000150045), CLEC1A (ENSG00000150048), CLEC1B (ENSG00000165682), CLEC12A (ENSG00000172322), OLR1 (ENSG00000173391), KLRC4 (ENSG00000183542), CLEC2A (ENSG00000188393), KLRG2 (ENSG00000188883), CLEC9A (ENSG00000197992), KLRC2 (ENSG00000205809), KLRC3 (ENSG00000205810), KLRK1 (ENSG00000213809), CLEC2L (ENSG00000236279), CLEC12B (ENSG00000256660), KLRF2 (ENSG00000256797), CLEC5A (ENSG00000258227)

Protein

Protein identifiers

C-type lectin domain family 7 member A — Q9BXN2 (reviewed: Q9BXN2)

Alternative names: Beta-glucan receptor, C-type lectin superfamily member 12, Dendritic cell-associated C-type lectin 1

All UniProt accessions (3): A0A0S2Z5Q1, Q9BXN2, Q68D78

UniProt curated annotations — full annotation on UniProt →

Function. Lectin that functions as a pattern recognizing receptor (PRR) specific for beta-1,3-linked and beta-1,6-linked glucans, which constitute cell wall constituents from pathogenic bacteria and fungi. Necessary for the TLR2-mediated inflammatory response and activation of NF-kappa-B: upon beta-glucan binding, recruits SYK via its ITAM motif and promotes a signaling cascade that activates some CARD domain-BCL10-MALT1 (CBM) signalosomes, leading to the activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines. Enhances cytokine production in macrophages and dendritic cells. Mediates production of reactive oxygen species in the cell. Mediates phagocytosis of C.albicans conidia. Binds T-cells in a way that does not involve their surface glycans and plays a role in T-cell activation. Stimulates T-cell proliferation. Induces phosphorylation of SCIMP after binding beta-glucans.

Subunit / interactions. Homodimer. Interacts with SYK; participates in leukocyte activation in presence of fungal pathogens. Interacts with CD37; this interaction controls CLEC7A-mediated IL-6 production. Interacts with RANBP9.

Subcellular location. Cell membrane Cytoplasm Cytoplasm Cytoplasm.

Tissue specificity. Highly expressed in peripheral blood leukocytes and dendritic cells. Detected in spleen, bone marrow, lung, muscle, stomach and placenta.

Post-translational modifications. Phosphorylated on tyrosine residues in response to beta-glucan binding.

Disease relevance. Candidiasis, familial, 4 (CANDF4) [MIM:613108] A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans. The disease may be caused by variants affecting the gene represented in this entry.

Induction. Up-regulated during differentiation from monocytes into dendritic cells.

Polymorphism. A stop polymorphism at position 238 may be associated with invasive aspergillosis following hematopoietic stem cell transplantation. The risk is highest when the polymorphism is present in both donors and recipients [MIM:614079].

Miscellaneous. Predominant isoform.

Isoforms (10)

UniProt ID	Names	Canonical?
Q9BXN2-1	1, A	yes
Q9BXN2-2	2, Beta, B
Q9BXN2-3	3, C
Q9BXN2-4	4, G
Q9BXN2-5	5, E
Q9BXN2-6	6
Q9BXN2-7	7, D
Q9BXN2-8	8, F
Q9BXN2-9	9
Q9BXN2-10	10

RefSeq proteins (6): NP_072092, NP_922938, NP_922939, NP_922940, NP_922941, NP_922945 (=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
IPR033992	NKR-like_CTLD	Domain
IPR042808	CLEC7A	Family

Pfam: PF00059

UniProt features (33 total): splice variant 14, binding site 6, disulfide bond 3, topological domain 2, sequence variant 2, chain 1, glycosylation site 1, transmembrane region 1, sequence conflict 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXN2-F1	77.90	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.

Ligand- & substrate-binding residues (6): 195; 242; 146–153; 157; 159; 163

Disulfide bonds (3): 120–131, 148–241, 220–233

Glycosylation sites (1): 91

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5607764	CLEC7A (Dectin-1) signaling

MSigDB gene sets: 448 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_REGULATION_OF_RESPIRATORY_BURST, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_CELL_MATURATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (50): cell activation (GO:0001775), response to yeast (GO:0001878), detection of yeast (GO:0001879), stimulatory C-type lectin receptor signaling pathway (GO:0002223), positive regulation of cytokine production involved in immune response (GO:0002720), positive regulation of dendritic cell cytokine production (GO:0002732), cell surface pattern recognition receptor signaling pathway (GO:0002752), phagocytosis, recognition (GO:0006910), inflammatory response (GO:0006954), cell recognition (GO:0008037), positive regulation of cell population proliferation (GO:0008284), carbohydrate mediated signaling (GO:0009756), positive regulation of gene expression (GO:0010628), detection of fungus (GO:0016046), positive regulation of cell migration (GO:0030335), positive regulation of protein-containing complex assembly (GO:0031334), detection of molecule of fungal origin (GO:0032491), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-10 production (GO:0032733), positive regulation of interleukin-12 production (GO:0032735), positive regulation of interleukin-2 production (GO:0032743), positive regulation of interleukin-23 production (GO:0032747), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of superoxide anion generation (GO:0032930), T cell activation (GO:0042110), defense response to protozoan (GO:0042832), regulation of canonical NF-kappaB signal transduction (GO:0043122), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of MAPK cascade (GO:0043410), innate immune response (GO:0045087), positive regulation of nitric oxide biosynthetic process (GO:0045429), positive regulation of phagocytosis (GO:0050766), positive regulation of calcium-mediated signaling (GO:0050850), positive regulation of lymphocyte activation (GO:0051251), positive regulation of respiratory burst (GO:0060267), antifungal innate immune response (GO:0061760), regulation of calcineurin-NFAT signaling cascade (GO:0070884)

GO Molecular Function (7): (1->3)-beta-D-glucan binding (GO:0001872), carbohydrate binding (GO:0030246), pattern recognition receptor activity (GO:0038187), MHC protein binding (GO:0042287), identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

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
positive regulation of cytokine production	3
cellular anatomical structure	3
cellular process	2
response to fungus	2
innate immune response activating cell surface receptor signaling pathway	2
binding	2
multicellular organismal process	1
response to yeast	1
detection of fungus	1
cellular response to lectin	1
cytokine production involved in immune response	1
positive regulation of production of molecular mediator of immune response	1
regulation of cytokine production involved in immune response	1
dendritic cell cytokine production	1
positive regulation of leukocyte mediated immunity	1
positive regulation of cytokine production involved in immune response	1
regulation of dendritic cell cytokine production	1
pattern recognition receptor signaling pathway	1
phagocytosis	1
cell recognition	1
cargo receptor activity	1
defense response	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
signal transduction	1
cellular response to carbohydrate stimulus	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
detection of other organism	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
response to molecule of fungal origin	1
detection of chemical stimulus	1

Protein interactions and networks

STRING

2238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC7A	TLR2	O60603	998
CLEC7A	SYK	P43405	995
CLEC7A	LGALS3	P17931	992
CLEC7A	FCGR2B	P31994	990
CLEC7A	LGALS9	O00182	987
CLEC7A	LGALS9B	Q3B8N2	983
CLEC7A	LGALS9C	Q6DKI2	983
CLEC7A	TLR4	O00206	972
CLEC7A	CARD9	Q9H257	972
CLEC7A	CD37	P11049	930
CLEC7A	TLR6	Q9Y2C9	840
CLEC7A	INPP5D	Q92835	807
CLEC7A	BCL10	O95999	799
CLEC7A	CLEC4D	Q8WXI8	798
CLEC7A	MALT1	Q9UDY8	797

IntAct

63 interactions, top by confidence:

A	B	Type	Score
BNIP3L	CLEC7A	psi-mi:“MI:0915”(physical association)	0.670
SYNE4	CLEC7A	psi-mi:“MI:0915”(physical association)	0.670
CLEC7A	TMEM79	psi-mi:“MI:0915”(physical association)	0.670
CLEC7A	BNIP3L	psi-mi:“MI:0915”(physical association)	0.670
CLEC7A	SYNE4	psi-mi:“MI:0915”(physical association)	0.670
TMEM79	CLEC7A	psi-mi:“MI:0915”(physical association)	0.670
CLEC7A	PTTG1IP	psi-mi:“MI:0915”(physical association)	0.560
CLEC7A	IL1RL1	psi-mi:“MI:0915”(physical association)	0.560
CLEC7A	BNIP3	psi-mi:“MI:0915”(physical association)	0.560
OCLN	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
KTN1	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
CLEC7A	JAGN1	psi-mi:“MI:0915”(physical association)	0.560
CLEC7A		psi-mi:“MI:0915”(physical association)	0.560
FAM3A	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
ADAM33	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
CLEC7A	SMIM3	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS4	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
CLEC7A	NINJ2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (63): CLEC7A (Two-hybrid), CLEC7A (Two-hybrid), CLEC7A (Two-hybrid), CLEC7A (Two-hybrid), CLEC7A (Two-hybrid), CLEC7A (Two-hybrid), CLEC7A (Two-hybrid), CLEC7A (Two-hybrid), CLEC7A (Two-hybrid), CLEC7A (Two-hybrid), CLEC7A (Two-hybrid), ADAM33 (Two-hybrid), TMEM79 (Two-hybrid), JAGN1 (Two-hybrid), SMIM3 (Two-hybrid)

ESM2 similar proteins: A5D7V5, A7TZE6, A7TZF3, A7XUX6, A7XV04, A7XV07, C0HJX2, C0HJX3, P08101, P08508, P0C1X9, P12318, P20138, P27645, P31994, P31995, P42070, P43629, P43630, P97484, Q49BZ4, Q60513, Q63203, Q68SN8, Q6Q8B3, Q6QLQ4, Q6SJQ5, Q6XJV4, Q6XJV6, Q8BG84, Q8BTP3, Q8HZR8, Q8N109, Q8NC01, Q8NHK3, Q8R4Y0, Q8SPV8, Q8TD46, Q8VCH2, Q921W8

Diamond homologs: C0HKZ6, D3W0D1, D3ZWT9, O70156, P02706, P07307, P08290, P0C7M8, P0C7M9, P10716, P20693, P23806, P27471, P27811, P27812, P27814, P34927, P49300, P49301, P70194, P78380, P79391, Q0H8B9, Q0ZCA7, Q0ZUP0, Q0ZUP1, Q13241, Q149M0, Q28768, Q3LUH2, Q49BZ4, Q5NKN2, Q5NKN4, Q60654, Q67EQ1, Q6QLQ4, Q6UXB4, Q6ZS10, Q7LZ71, Q80ZC8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1092 predictions. Top by Δscore:

Variant	Effect	Δscore
12:10127325:AATGT:A	donor_gain	1.0000
12:10127378:T:A	donor_gain	1.0000
12:10129975:TATA:T	donor_loss	1.0000
12:10129976:ATACC:A	donor_loss	1.0000
12:10129977:TA:T	donor_loss	1.0000
12:10129978:ACCTT:A	donor_loss	1.0000
12:10129979:C:A	donor_loss	1.0000
12:10129979:CCTTT:C	donor_gain	1.0000
12:10125446:CCC:C	acceptor_gain	0.9900
12:10125447:CCC:C	acceptor_gain	0.9900
12:10126720:A:T	acceptor_gain	0.9900
12:10127374:A:AC	donor_gain	0.9900
12:10127375:C:CC	donor_gain	0.9900
12:10125289:ACACT:A	donor_loss	0.9800
12:10125290:CACTT:C	donor_loss	0.9800
12:10125291:ACTT:A	donor_loss	0.9800
12:10125292:CTTAC:C	donor_loss	0.9800
12:10125293:T:TC	donor_loss	0.9800
12:10125294:T:TA	donor_loss	0.9800
12:10125295:A:G	donor_loss	0.9800
12:10125296:C:CG	donor_loss	0.9800
12:10127325:A:AC	donor_gain	0.9800
12:10130001:T:A	donor_gain	0.9800
12:10125360:T:TA	donor_gain	0.9700
12:10125445:ACCCC:A	acceptor_gain	0.9700
12:10125446:CCCCT:C	acceptor_gain	0.9700
12:10125447:CC:C	acceptor_gain	0.9700
12:10125447:CCCTG:C	acceptor_loss	0.9700
12:10125448:CC:C	acceptor_gain	0.9700
12:10125449:C:A	acceptor_loss	0.9700

AlphaMissense

1606 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:10123274:C:A	W194C	0.994
12:10123274:C:G	W194C	0.994
12:10125366:C:A	W141C	0.990
12:10125366:C:G	W141C	0.990
12:10123316:C:A	W180C	0.982
12:10123316:C:G	W180C	0.982
12:10125346:C:G	C148S	0.982
12:10125347:A:T	C148S	0.982
12:10125417:C:A	W124C	0.980
12:10125417:C:G	W124C	0.980
12:10123276:A:G	W194R	0.978
12:10123276:A:T	W194R	0.978
12:10118480:C:G	C241S	0.974
12:10118481:A:T	C241S	0.974
12:10125345:G:C	C148W	0.973
12:10123319:A:C	F179L	0.972
12:10123319:A:T	F179L	0.972
12:10123321:A:G	F179L	0.972
12:10118543:C:G	C220S	0.970
12:10118544:A:T	C220S	0.970
12:10118542:A:C	C220W	0.969
12:10118504:C:G	C233S	0.968
12:10118505:A:T	C233S	0.968
12:10123358:A:C	F166L	0.964
12:10123358:A:T	F166L	0.964
12:10123360:A:G	F166L	0.964
12:10123308:A:G	L183P	0.963
12:10123318:A:G	W180R	0.963
12:10123318:A:T	W180R	0.963
12:10123311:C:T	G182D	0.960

dbSNP variants (sampled 300 via entrez): RS1000246367 (12:10120840 C>G,T), RS1000639809 (12:10132178 G>A,T), RS1000642813 (12:10128125 C>G), RS1000722247 (12:10120680 G>A), RS1001871357 (12:10131669 C>T), RS1001986267 (12:10120845 C>G,T), RS1002015568 (12:10120614 G>C), RS1002099985 (12:10125158 G>A,T), RS1002131203 (12:10125025 C>T), RS1002320382 (12:10119152 G>A), RS1002539510 (12:10126924 A>AG), RS1002592215 (12:10116449 C>G,T), RS1002711328 (12:10130933 C>A,T), RS1002799380 (12:10122555 A>G), RS1002800593 (12:10124392 T>C)

Disease associations

OMIM: gene MIM:606264 | disease phenotypes: MIM:613108, MIM:614079

GenCC curated gene-disease

Disease	Classification	Inheritance
chronic mucocutaneous candidiasis	Supportive	Autosomal dominant

Mondo (3): candidiasis, familial, 4 (MONDO:0013140), aspergillosis, susceptibility to (MONDO:0013562), chronic mucocutaneous candidiasis (MONDO:0015279)

Orphanet (2): Chronic mucocutaneous candidiasis (Orphanet:1334), Aspergillosis (Orphanet:1163)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000142	Abnormal vagina morphology
HP:0000153	Abnormality of the mouth
HP:0000159	Abnormal lip morphology
HP:0000478	Abnormality of the eye
HP:0000504	Abnormality of vision
HP:0000682	Abnormal dental enamel morphology
HP:0000790	Hematuria
HP:0000951	Abnormality of the skin
HP:0000962	Hyperkeratosis
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001231	Abnormal fingernail morphology
HP:0001250	Seizure
HP:0001597	Abnormal nail morphology
HP:0001821	Broad nail
HP:0002105	Hemoptysis
HP:0002205	Recurrent respiratory infections
HP:0002715	Abnormality of the immune system
HP:0002719	Recurrent infections
HP:0004306	Abnormal endocardium morphology
HP:0004370	Abnormality of temperature regulation
HP:0008388	Abnormal toenail morphology
HP:0008872	Feeding difficulties in infancy
HP:0010783	Erythema
HP:0012115	Hepatitis
HP:0012203	Onychomycosis
HP:0012204	Recurrent vulvovaginal candidiasis
HP:0012735	Cough

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002178	Candidiasis, Chronic Mucocutaneous	C01.150.703.160.088; C01.150.703.302.100; C01.800.200.100; C17.800.838.208.165; C23.550.291.500.250

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2034810 (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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Zymosan	decreases expression, decreases reaction, affects binding, increases metabolic processing, increases reaction (+1 more)	4
Nickel	decreases expression, increases expression	3
Cisplatin	increases expression	2
Formaldehyde	decreases expression, increases expression	2
Tretinoin	increases expression	2
Asian ginseng	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
curdlan	decreases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
FSL-1 lipoprotein, synthetic	increases expression, decreases reaction	1
gardiquimod	decreases expression, decreases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Bortezomib	increases expression	1
Resveratrol	decreases reaction, increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	affects cotreatment, decreases expression	1
Succimer	affects cotreatment, increases expression	1
Disulfiram	increases expression	1
Lipopolysaccharides	decreases expression, decreases reaction	1
Paraquat	increases expression	1
Peptidoglycan	increases metabolic processing, increases reaction	1
Tobacco Smoke Pollution	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 2 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2038972	Functional	Agonist activity at Dectin-1 expressed in human 293T cells assessed as LPS-mediated NF-kappaB activation after 6 hrs by dual luciferase reporter gene assay	Synthesis of β(1,3) oligoglucans exhibiting a Dectin-1 binding affinity and their biological evaluation. — Bioorg Med Chem
CHEMBL4726081	Binding	Agonist activity at human Dectin1a expressed in HEK293 cells assessed as increase in NF-kappaB activation up to 10 uM incubated for 24 hrs by quanti-blue SEAP reporter gene assay	Discovery of GS-9688 (Selgantolimod) as a Potent and Selective Oral Toll-Like Receptor 8 Agonist for the Treatment of Chronic Hepatitis B. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7MN	Ubigene A-549 CLEC7A KO	Cancer cell line	Male
CVCL_D8EI	Ubigene BEAS-2B CLEC7A KO	Transformed cell line	Male
CVCL_VV19	HEK-Blue hDectin-1a	Transformed cell line	Female
CVCL_VV20	HEK-Blue hDectin-1b	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01386437	Not specified	RECRUITING	Natural History of Individuals With Immune System Problems That Lead to Fungal Infections
NCT03736252	Not specified	COMPLETED	Effectiveness of a Neoprene CMC Joint Orthosis
NCT05896410	Not specified	UNKNOWN	3D-Printed Hand Orthosis Versus Thermoplastic Orthosis