CD69

Chr 12

CD69 molecule

Also known as: AIM, BL-AC/P26, CLEC2C, EA1, GP32/28, MLR-3

NCBI Gene: 969 ENSG00000110848 UniProt: Q07108 OMIM: 107273

The CD69 protein is a transmembrane receptor that regulates immune cell homeostasis by controlling T-cell differentiation, promoting regulatory T-cell conversion, and modulating inflammatory responses in various immune cell types including T-lymphocytes, NK cells, and platelets. Based on current medical literature, pathogenic mutations in CD69 have not been definitively associated with recognized human genetic diseases. The gene shows tolerance to loss-of-function variants (pLI = 0.03, LOEUF = 0.92), suggesting that complete loss of CD69 function may not cause severe developmental disorders.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the calcium dependent lectin superfamily of type II transmembrane receptors. Expression of the encoded protein is induced upon activation of T lymphocytes, and may play a role in proliferation. Furthermore, the protein may act to transmit signals in natural killer cells and platelets. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

Active trials

588

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.92

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.030

Z-score 1.75

OE 0.40 (0.20–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.26Z-score

OE missense 1.07 (0.92–1.25)

112 obs / 104.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.40 (0.20–0.92)

0≤0.351.4

Missense OE?1.07 (0.92–1.25)

0≤0.61.4

Synonymous OE?0.78

0≤1.21.6

LoF obs/exp: 4 / 10.0Missense obs/exp: 112 / 104.5Syn Z: 1.05

Background carrier burden — how many people carry a rare variant somewhere in CD69?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 280

223 rare PASS variants

Rare truncating (LoF)

1 in 5,500

30 rare PASS variants

Rare synonymous (reference)

1 in 1,400

73 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CD69. 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 630	1 in 4,600
South Asian	~43k	1 in 98	1 in 2,300
Remaining (unassigned)	~30k	1 in 230	≈ 1 in 7,400
European (Finnish)	~27k	1 in 640	none seen
Admixed American	~22k	1 in 180	none seen
African / African American	~21k	1 in 210	≈ 1 in 5,200
East Asian	~20k	1 in 230	≈ 1 in 9,900
Ashkenazi Jewish	~13k	≈ 1 in 4,300	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 260	none seen

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): 3 of 5 coding exons well covered in gnomAD exomes; exons 4, 5 marginal. Genomes: all 5.? see exons ↓