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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TIMD4
T cell immunoglobulin and mucin domain containing 4
Chromosome 5 · 5q33.3
NCBI Gene: 91937Ensembl: ENSG00000145850.9HGNC: HGNC:25132UniProt: Q96H15
66PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
phosphatidylserine bindingapoptotic cell clearanceplasma membranecytoskeletal rearrangement involved in phagocytosis, engulfmentmetabolic diseaseHypercholesterolemiahyperlipidemiafamilial hyperlipidemia
✦AI Summary

TIMD4 (T cell immunoglobulin and mucin domain containing 4) is a phosphatidylserine-binding receptor that plays a crucial role in efferocytosis, the clearance of apoptotic cells by macrophages 12. The protein is primarily expressed on tissue-resident macrophages, particularly the TLF+ subset that maintains homeostasis through self-renewal 3. TIMD4 binds phosphatidylserine exposed on apoptotic cell surfaces and facilitates their engulfment and clearance 1. The receptor's expression is regulated by microbiota-derived metabolites like butyrate, with antibiotic treatment reducing TIMD4 levels and impairing efferocytosis 1. Disease relevance includes metabolic dysfunction-associated steatohepatitis (MASH), where impaired TIMD4-mediated efferocytosis leads to accumulation of apoptotic hepatocytes and progression to liver fibrosis 4. In cancer, TIMD4+ cavity-resident macrophages can sequester cytotoxic T cells, limiting immunotherapy efficacy 5. TIMD4 is also essential for proper wound healing, as its inhibition abrogates tissue repair despite being dispensable for efferocytosis itself 2. The receptor represents a potential therapeutic target for inflammatory diseases, fibrotic conditions, and cancer immunotherapy enhancement.

Sources cited
1
TIMD4 is a phosphatidylserine-binding efferocytosis receptor regulated by microbiota-derived butyrate
PMID: 39122784
2
TIMD4 inhibition decreases efferocytosis and abrogates wound repair
PMID: 38127424
3
TIMD4 is expressed on TLF+ tissue-resident macrophages maintained through self-renewal
PMID: 34995099
4
Impaired TIMD4-mediated efferocytosis contributes to liver fibrosis in MASH
PMID: 40929246
5
TIMD4+ cavity-resident macrophages sequester cytotoxic T cells and limit immunotherapy efficacy
PMID: 34115989
Disease Associationsⓘ20
metabolic diseaseOpen Targets
0.53Moderate
HypercholesterolemiaOpen Targets
0.53Moderate
hyperlipidemiaOpen Targets
0.53Moderate
familial hyperlipidemiaOpen Targets
0.46Moderate
metabolic syndromeOpen Targets
0.45Moderate
response to statinOpen Targets
0.44Moderate
dengue diseaseOpen Targets
0.37Weak
familial hypercholesterolemiaOpen Targets
0.36Weak
Disorder of lipid metabolismOpen Targets
0.36Weak
physical activityOpen Targets
0.35Weak
self-injurious ideationOpen Targets
0.30Weak
neoplasmOpen Targets
0.12Weak
lung cancerOpen Targets
0.10Weak
non-small cell lung carcinomaOpen Targets
0.10Weak
rheumatoid arthritisOpen Targets
0.09Suggestive
alcohol abuseOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
myocardial infarctionOpen Targets
0.08Suggestive
periodontitisOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MFGE8Shared pathway100%STAB2Protein interaction84%GAS6Protein interaction73%MERTKProtein interaction71%JMJD6Protein interaction71%HAVCR1Protein interaction63%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
26%
Heart
5%
Lung
4%
Brain
1%
Ovary
0%
Gene Interaction Network
Click a node to explore
TIMD4MFGE8STAB2GAS6MERTKJMJD6HAVCR1
PROTEIN STRUCTURE
Preparing viewer…
PDB5F7F · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.05LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.56–1.05]
RankingsWhere TIMD4 stands among ~20K protein-coding genes
  • #7,129of 20,598
    Most Researched66
  • #10,533of 17,882
    Most Constrained (LOEUF)1.05
Genes detectedTIMD4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Three tissue resident macrophage subsets coexist across organs with conserved origins and life cycles.
PMID: 34995099
Sci Immunol · 2022
1.00
2
Broad-spectrum antibiotics disrupt homeostatic efferocytosis.
PMID: 39122784
Nat Metab · 2024
0.90
3
Apoptosis recognition receptors regulate skin tissue repair in mice.
PMID: 38127424
Elife · 2023
0.80
4
Tim-4
PMID: 34115989
Cancer Cell · 2021
0.70
5
Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction-associated steatohepatitis.
PMID: 40929246
Sci Transl Med · 2025
0.60