CLEC7A

protein-coding

C-type lectin domain containing 7A, the group of C-type lectin domain containing|CD molecules|Scavenger receptors

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:

CLECSF12

MANE transcript

NM_197947.3

Inheritance

AD, AR

ClinVar variants

U:33B:9

Top phenotype

Candidiasis, familial, 4

gnomAD constraint

pLI —, LoF o/e 1.35

Max pathogenic AF

—

Genomic locus

chr12:10,116,777-10,130,258

External References & Databases

Ensembl (ENSG00000172243)

Transcript & Mutation Effects

hg38 • Region Span ~13.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

chronic mucocutaneous candidiasisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015279

Submitter: Orphanet

Clinical Genomic Database (CGD)

Candidiasis, familial, 4AR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals are highly susceptible to recurrent fungal infections, and recognition may allow prompt treatment, which may be beneficial

Comments: Heterozygous variants may result in milder manifestations

Refs: 18946062; 19864674; 20807886; 20107226; 22674328; 23374272

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLEC7A variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 40

not providedTotal: 6

Familial chronic mucocutaneous candidiasisTotal: 4

Aspergillosis, susceptibility toTotal: 3

CLEC7A-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_197947.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	5 clinvar		6
missense			30 clinvar	2 clinvar	2 clinvar	34
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	33	7	2	42

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_197947.3	RefSeq	NP_922938.1	6	MANE Select
ENST00000304084.13	Ensembl	ENSP00000302569.8	6	MANE Select
NM_022570.5	RefSeq	NP_072092.2	5	Standard
NM_197948.3	RefSeq	NP_922939.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Phagosome - Homo sapiens (human)
C-type lectin receptor signaling pathway - Homo sapiens (human)
Tuberculosis - Homo sapiens (human)
CLEC7A (Dectin-1) signaling
C-type lectin receptors (CLRs)

Biological Process

pattern recognition receptor signaling pathway
phagocytosis, recognition
inflammatory response
cell recognition
carbohydrate mediated signaling

Molecular Function

protein binding
signaling pattern recognition receptor activity
carbohydrate binding
MHC protein binding
metal ion binding

Cellular Component

nucleoplasm
cytoplasm
plasma membrane
integral component of membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304084
Coding exons: 6
Length: 13482
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125746
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.119	120	124	0.970	0.00000575	1589
Missense (PolyPhen)		30	35.771	0.83866		482
Synonymous	0.0564	43	43.5	0.989	0.00000203	457
Loss of Function	-1.08	15	11.1	1.35	4.70e-7	142

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lectin that functions as pattern receptor specific for beta-1,3-linked and beta-1,6-linked glucans, such as cell wall constituents from pathogenic bacteria and fungi. Necessary for the TLR2-mediated inflammatory response and for TLR2-mediated activation of NF-kappa-B. 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 (By similarity). {ECO:0000250, ECO:0000269|PubMed:11567029, ECO:0000269|PubMed:12423684, ECO:0000269|PubMed:17230442}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:19864674}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.770
RVIS EVS: 0.35
RVIS percentile EVS: 74.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00481

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium