CD96
Chr 3ADCD96 molecule
Also known as: TACTILE
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.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
200 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 2 | 0 | 2 |
Likely Pathogenic | 4 | 0 | 0 | 0 | 4 |
VUS | 6 | 131 | 8 | 0 | 145 |
Likely Benign | 0 | 9 | 11 | 12 | 32 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 3 | |||
| Total | 10 | 140 | 21 | 12 | 186 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CD96 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Growing Up in Multifactorial Risk Conditions
ENROLLING BY INVITATIONMultimodal Imaging and Biospecimen Collection for Low Back Pain (LBPB)
NOT YET RECRUITINGPain Biomarker Study
ENROLLING BY INVITATIONCharacterization of the Natural History of Microduplication Syndrome 7q11.23
NOT YET RECRUITINGMapping the Impact of Gut Microbiota on Brain and Behavior Through the Lens of GABA
RECRUITINGTranscriptomics as an Aid in the Histological Diagnosis of Acute Rejection After Liver Transplantation
RECRUITINGNeuroproprioceptive Equine-Assisted Physiotherapy for Spinal Muscular Atrophy
NOT YET RECRUITINGChronic Treatment of Alzheimer's Disease by Gamma Light and Sound Therapy
RECRUITINGEfficacy of a Combined Oral and Topical Collagen Regimen Compared to Topical Collagen or Oral Collagen Regimens in Women With Skin Ageing Signs
NOT YET RECRUITINGComprehensive Study of Post-surgical Pain After Pectus or Spine Surgery
ACTIVE NOT RECRUITINGInsomnia´s Impact on DNA Stability, Cardio-metabolic Health and Lifestyle Behaviors
RECRUITINGExternal Resources
Links to major genomics databases and tools