TIMD4 (T Cell Immunoglobulin And Mucin Domain Containing 4)
Gene encoding a phosphatidylserine receptor involved in immune regulation and apoptotic cell clearance
Gene Information Card
| Symbol | TIMD4 |
|---|---|
| Full Name | T Cell Immunoglobulin And Mucin Domain Containing 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q33.3 |
| NCBI Gene ID | 91937 ncbi.nlm.nih.gov/gene/91937 |
| Ensembl ID | ENSG00000145675 |
| UniProt ID | Q96H15 |
| OMIM ID | 605428 |
| HGNC ID | 17813 |
| Aliases | TIM4, TIMD-4, SMUCKLER |
Description
TIMD4 encodes T cell immunoglobulin and mucin domain containing 4 (TIM-4), a transmembrane protein primarily expressed on antigen-presenting cells. It functions as a phosphatidylserine receptor mediating the phagocytosis of apoptotic cells and modulates T cell immune responses. TIMD4 is involved in immune tolerance, inflammation, and cancer biology.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Asthma | TIMD4 polymorphisms are associated with altered T cell responses and airway inflammation. | NCBI Gene, OMIM |
| Autoimmune diseases | Variants in TIMD4 may affect apoptotic cell clearance, contributing to autoimmunity. | NCBI Gene, OMIM |
| Cancer (e.g., ovarian, colorectal) | TIMD4 expression on tumor-associated macrophages promotes immune evasion by binding phosphatidylserine on apoptotic tumor cells. | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Lung | 6.2 | Low |
| Small intestine | 4.1 | Low |
| Liver | 3.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression |
| U937 (histiocytic lymphoma) | 12.8 | High expression |
| HUVEC (endothelial) | 2.1 | Low expression |
| HEK293 (embryonic kidney) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1018G>A (p.Gly340Arg) | Missense | <0.01% | Altered ligand binding; potential impact on phagocytosis |
| c.1243C>T (p.Arg415Trp) | Missense | <0.01% | Reduced cell surface expression |
| c.1456_1457insA | Frameshift | <0.01% | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations leading to truncated or absent TIM-4 protein impair apoptotic cell clearance.
Gain of Function (GOF)
Not well characterized; some missense variants may enhance receptor activity.
Dominant Negative (DN)
Not reported for TIMD4.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylserine binding (GO:0005044) | • phagocytosis (GO:0006911) |
| • signal transduction (GO:0007165) | • integral component of membrane (GO:0016021) |
| • regulation of cell adhesion (GO:0030155) | • regulation of apoptotic process (GO:0042981) |
Pathways
• Phagocytosis of apoptotic cells (Reactome: R-HSA-2029480)
• TIM family signaling (KEGG: hsa04672)
Protein Summary
TIM-4 is a 458-amino acid type I transmembrane glycoprotein with an N-terminal immunoglobulin V-like domain, a mucin-like domain, and a cytoplasmic tail. It binds phosphatidylserine exposed on apoptotic cells, facilitating their clearance by macrophages and dendritic cells. TIM-4 also modulates T cell activation and cytokine production, playing a role in immune homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TIMD4 Knockout HEK293 Cell Line | EDJ-KQ3129 | Human | 91937 | Details Get a Quote |
| TIMD4 Knockout A-549 Cell Line | EDJ-KQ24496 | Human | 91937 | Details Get a Quote |
| TIMD4 Knockout HeLa Cell Line | EDJ-KQ57817 | Human | 91937 | Details Get a Quote |
| TIMD4 Knockout HCT 116 Cell Line | EDJ-KQ74737 | Human | 91937 | Details Get a Quote |
