CCR4
Chr 3C-C motif chemokine receptor 4
Also known as: CC-CKR-4, CD194, CKR4, CMKBR4, ChemR13, HGCN:14099, K5-5
The encoded protein is a phosphatase that converts NADP+ to NAD+ and regulates post-transcriptional control of metabolic genes under circadian control, playing key roles in nutrient metabolism, adipogenesis, and early embryonic development. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and metabolic dysfunction. The gene shows low constraint to loss-of-function variants, consistent with recessive inheritance patterns.
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 (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
54 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 | 16 | 0 | 16 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 33 | 3 | 0 | 36 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 35 | 19 | 0 | 54 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CCR4 · 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
Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL
ACTIVE NOT RECRUITINGATLCAR.CD30.CCR4 for CD30+ HL ATLCAR.CD30.CCR4 Cells
RECRUITINGA Phase I Trial Anti-CC Chemokine Receptor 4 Chimeric Antigen Receptor T Cells (CCR4 CAR T Cells) for CCR4 Expressing T-cell Malignancies Including Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) and Cutaneous T-cell Non-Hodgkin Lymphoma (CTCL)
RECRUITINGThe Fecal Microbiome Transplant (FMT) Study for Anorexia Nervosa
RECRUITINGExternal Resources
Links to major genomics databases and tools