CD86

Chr 3

CD86 molecule

Also known as: B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6, FUN-1, LAB72

NCBI Gene: 942 ENSG00000114013 UniProt: P42081 OMIM: 601020

CD86 encodes a costimulatory molecule expressed on antigen-presenting cells that provides essential secondary signals for T-cell activation by binding to CD28 receptors, and also regulates immune responses through interaction with CTLA-4. Mutations cause autosomal dominant immunodeficiency with recurrent infections, autoimmune manifestations, and variable immunological abnormalities. This gene is highly constrained against loss-of-function variants, reflecting its critical role in immune system regulation.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a type I membrane protein that is a member of the immunoglobulin superfamily. This protein is expressed by antigen-presenting cells, and it is the ligand for two proteins at the cell surface of T cells, CD28 antigen and cytotoxic T-lymphocyte-associated protein 4. Binding of this protein with CD28 antigen is a costimulatory signal for activation of the T-cell. Binding of this protein with cytotoxic T-lymphocyte-associated protein 4 negatively regulates T-cell activation and diminishes the immune response. Alternative splicing results in several transcript variants encoding different isoforms.[provided by RefSeq, May 2011]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

1534

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.34

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.949

Z-score 3.19

OE 0.07 (0.03–0.34)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.08Z-score

OE missense 0.77 (0.68–0.89)

140 obs / 180.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.34)

0≤0.351.4

Missense OE?0.77 (0.68–0.89)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 1 / 13.8Missense obs/exp: 140 / 180.7Syn Z: 0.73

Background carrier burden — how many people carry a rare variant somewhere in CD86?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

380 rare PASS variants

Rare truncating (LoF)

1 in 3,500

32 rare PASS variants

Rare synonymous (reference)

1 in 280

143 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CD86. 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 290	1 in 3,200
South Asian	~43k	1 in 230	1 in 1,900
Remaining (unassigned)	~30k	1 in 140	1 in 6,000
European (Finnish)	~27k	1 in 720	≈ 1 in 13,000
Admixed American	~22k	1 in 160	1 in 4,400
African / African American	~21k	1 in 160	≈ 1 in 5,600
East Asian	~20k	1 in 100	none seen
Ashkenazi Jewish	~13k	1 in 2,600	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 190	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): 6 of 7 coding exons well covered in gnomAD exomes; exon 7 marginal. Genomes: all 7.? see exons ↓