CLEC7A

Chr 12AR

C-type lectin domain containing 7A

Also known as: BGR, CANDF4, CD369, CLECSF12, DECTIN1, SCARE2

NCBI Gene: 64581 ENSG00000172243 UniProt: Q9BXN2 OMIM: 606264

The protein functions as a pattern recognition receptor that recognizes beta-1,3-linked and beta-1,6-linked glucans from fungi, activating innate immune responses through NF-kappa-B and MAP kinase signaling pathways. Mutations cause autosomal recessive susceptibility to aspergillosis and familial candidiasis type 4, reflecting impaired antifungal immunity. The gene shows extremely low constraint against loss-of-function variants (pLI near zero), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Aspergillosis, susceptibility to}MIM #614079

Candidiasis, familial, 4, autosomal recessiveMIM #613108

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Candidiasis, familial, 4, autosomal recessive; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.88

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.88LOEUF

pLI 0.000

Z-score -1.08

OE 1.35 (0.89–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.12Z-score

OE missense 0.97 (0.83–1.13)

120 obs / 123.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.35 (0.89–1.88)

0≤0.351.4

Missense OE?0.97 (0.83–1.13)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 15 / 11.1Missense obs/exp: 120 / 123.7Syn Z: 0.06

Background carrier burden — how many people carry a rare variant somewhere in CLEC7A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

398 rare PASS variants

Rare truncating (LoF)

1 in 2,000

62 rare PASS variants

Rare synonymous (reference)

1 in 550

134 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLEC7A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 300	1 in 2,400
South Asian	~43k	1 in 110	1 in 1,100
Remaining (unassigned)	~30k	1 in 180	1 in 770
European (Finnish)	~27k	1 in 400	none seen
Admixed American	~22k	1 in 95	1 in 1,900
African / African American	~21k	1 in 78	1 in 700
East Asian	~20k	1 in 210	1 in 730
Ashkenazi Jewish	~13k	≈ 1 in 11,000	none seen
Middle Eastern	~2,884	1 in 85	≈ 1 in 710

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 6 coding exons well covered in gnomAD exomes; exons 1, 5 marginal. Genomes: all 6.? see exons ↓