CD4
Chr 12ARCD4 molecule
Also known as: CD4mut, IMD79, Leu-3, OKT4D, T4
The CD4 protein functions as a membrane glycoprotein coreceptor that works with the T-cell receptor to recognize antigens presented by MHC class II molecules, playing an essential role in T-helper cell activation and immune responses. Mutations cause autosomal recessive immunodeficiency disorders including Immunodeficiency 79 and OKT4 epitope deficiency, affecting the immune system's ability to mount appropriate responses to pathogens. The gene shows low constraint against loss-of-function variants (pLI 0.0008), consistent with recessive inheritance where one functional copy provides sufficient protein function.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
120 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 | 1 | 1 | 43 | 0 | 45 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 18 | 11 | 0 | 29 |
Likely Benign | 0 | 1 | 0 | 8 | 9 |
Benign | 0 | 4 | 8 | 5 | 17 |
| Total | 1 | 24 | 64 | 13 | 102 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CD4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Dendritic Cells in Patients With Acute or Chronic Skin Graft Versus Host Disease
ACTIVE NOT RECRUITINGDeciphering Mechanisms Underlying Cancer Immunogenicity
RECRUITINGStudy of Safety and Tolerability of Nivolumab Treatment Alone or in Combination With Relatlimab or Ipilimumab in Head and Neck Cancer
RECRUITINGCombining Latency Reversing Agents to Address the HIV Reservoir
NOT YET RECRUITINGAdoptive T Cell Immunotherapy for Advanced Melanoma Using Engineered Lymphocytes
RECRUITINGCD4 CAR+ ZFN-modified T Cells in HIV Therapy
ACTIVE NOT RECRUITINGStudy on the Mechanism of Yifei Moxibustion Improving Immune Function in COPD Based on Plasma Exosome miRNAs
RECRUITINGKey Mechanisms of Abnormal T Cell Activation and Differentiation in IgG4-Related Ophthalmic Disease
NOT YET RECRUITINGA Multiple Antigen Vaccine (STEMVAC) for the Treatment of Patients With Stage IV Non-Small Cell Lung Cancer
ACTIVE NOT RECRUITINGCCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer
ACTIVE NOT RECRUITINGRecombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Advanced Pancreatic Cancer
RECRUITINGEffectiveness and Biological Mechanism of Direct Ischemic Post-conditioning for Acute Stroke Patients Due to Large Vessel Occlusion
RECRUITINGExternal Resources
Links to major genomics databases and tools