CLEC4E

protein-coding

C-type lectin domain family 4 member E, the group of C-type lectin domain containing

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:

CLECSF9

MANE transcript

NM_014358.4

Inheritance

—

ClinVar variants

U:28B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr12:8,533,305-8,540,905

External References & Databases

Ensembl (ENSG00000166523)

Transcript & Mutation Effects

hg38 • Region Span ~7.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLEC4E variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 27

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014358.4. 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			1
missense			24 clinvar	4 clinvar		28
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	28	4	0	32

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014358.4	RefSeq	NP_055173.1	6	MANE Select
ENST00000299663.8	Ensembl	ENSP00000299663.3	6	MANE Select
NM_001410969.1	RefSeq	NP_001397898.1	5	Standard
ENST00000446457.6	Ensembl	ENSP00000387737.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

C-type lectin receptor signaling pathway - Homo sapiens (human)
Tuberculosis - Homo sapiens (human)
Dectin-2 family
C-type lectin receptors (CLRs)
Innate Immune System

Biological Process

stimulatory C-type lectin receptor signaling pathway
T cell differentiation involved in immune response
Fc-gamma receptor signaling pathway
defense response to bacterium
innate immune response

Molecular Function

carbohydrate binding
signaling receptor activity
metal ion binding

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299663
Coding exons: 6
Length: 7659
Individuals with no LoFs: 125689
Homozygous LoFs: 0
Heterozygous LoFs: 57
Defined: 125746
p: 0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.117	110	114	0.969	0.00000533	1446
Missense (PolyPhen)		30	37.738	0.79495		490
Synonymous	-0.868	47	40.0	1.17	0.00000199	381
Loss of Function	0.837	9	12.2	0.741	5.13e-7	149

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00099	0.00098	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: A calcium-dependent lectin that acts as a pattern recognition receptor of the innate immune system. Recognizes damage-associated molecular patterns (DAMPs) of abnormal self and pathogen-associated molecular patterns (PAMPs) of bacteria and fungi (PubMed:18509109, PubMed:23602766). The PAMPs notably include mycobacterial trehalose 6,6'-dimycolate (TDM), a cell wall glycolipid with potent adjuvant immunomodulatory functions (PubMed:23602766, PubMed:24101491). 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. Specifically 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 (By similarity). {ECO:0000250|UniProtKB:Q9R0Q8, ECO:0000269|PubMed:18509109, ECO:0000269|PubMed:23602766, ECO:0000269|PubMed:24101491}.;

Intolerance Scores

LoFtool: 0.674
RVIS EVS: 0.08
RVIS percentile EVS: 60.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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