CD96

Chr 3AD

CD96 molecule

Also known as: TACTILE

NCBI Gene: 10225 ENSG00000153283 UniProt: P40200 OMIM: 606037

CD96 encodes a type I membrane protein of the immunoglobulin superfamily that mediates adhesive interactions between activated T and NK cells and their targets during immune responses, particularly by binding to PVR on target cells. Mutations cause C syndrome with autosomal dominant inheritance. The gene shows minimal constraint against loss-of-function variants, suggesting the clinical phenotype may not result from simple protein loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the immunoglobulin superfamily. It is a type I membrane protein. The protein may play a role in the adhesive interactions of activated T and NK cells during the late phase of the immune response. It may also function in antigen presentation. Alternative splicing generates multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

C syndromeMIM #211750

Clinical highlights

Gene–disease validity (ClinGen)

Limited · C syndrome · AD · ClinGen 2025

not for standalone diagnostic reporting

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

LOF*

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.000

Z-score 1.69

OE 0.68 (0.48–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.47Z-score

OE missense 1.08 (0.98–1.18)

329 obs / 306.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.68 (0.48–0.97)

0≤0.351.4

Missense OE?1.08 (0.98–1.18)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 22 / 32.4Missense obs/exp: 329 / 306.0Syn Z: -1.21

Background carrier burden — how many people carry a rare variant somewhere in CD96?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 59

885 rare PASS variants

Rare truncating (LoF)

1 in 370

160 rare PASS variants

Rare synonymous (reference)

1 in 170

294 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CD96. 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 75	1 in 680
South Asian	~43k	1 in 59	1 in 500
Remaining (unassigned)	~30k	1 in 56	1 in 290
European (Finnish)	~27k	1 in 400	1 in 670
Admixed American	~22k	1 in 78	1 in 380
African / African American	~21k	1 in 59	1 in 1,100
East Asian	~20k	1 in 75	1 in 1,000
Ashkenazi Jewish	~13k	1 in 1,200	1 in 650
Middle Eastern	~2,884	1 in 69	1 in 370

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 14 coding exons well covered in gnomAD exomes; exons 3, 4, 5, 6, 8 and 4 more marginal. Genomes: all 14.? see exons ↓