HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TICAM1
TIR domain containing adaptor molecule 1
Chromosome 19 · 19p13.3
NCBI Gene: 148022Ensembl: ENSG00000127666.12HGNC: HGNC:18348UniProt: Q8IUC6
162PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
response to exogenous dsRNAprotein bindingprotein kinase bindingmolecular adaptor activityHerpetic encephalitishypothyroidismbasal cell carcinomaskin neoplasm
✦AI Summary

TICAM1 (TIR domain containing adaptor molecule 1) is a critical adapter protein mediating innate immune responses against pathogens. TICAM1 functions downstream of toll-like receptors (TLRs) 3, 4, and 5, with ligand binding to these receptors triggering TICAM1 recruitment through its TIR domain 1. Upon recruitment, TICAM1 acts as a molecular hub recruiting effector proteins including TBK1, TRAF6, and RIPK1, which activate transcription factors IRF3, IRF7, and NF-κB to induce type I interferon production and pro-inflammatory responses 2. Phosphorylation by TBK1 on conserved motifs is essential for IRF3 recruitment and activation 2. TICAM1 participates in TLR4-dependent signaling within endosomes, a compartment critical for regulating the magnitude and duration of inflammatory responses 3. TICAM1 also functions as a component of a cytoplasmic multi-helicase complex sensing viral double-stranded RNA and coordinating antiviral responses 4. Beyond its direct signaling functions, TICAM1 is subject to autophagic degradation via the TAX1BP1 receptor, providing a regulatory mechanism for terminating innate immune signaling 5. Dysregulation of TICAM1-mediated signaling is implicated in acute infection-induced encephalopathy and potentially contributes to neuroinflammatory and autoimmune disease pathogenesis.

Sources cited
1
TICAM1 (TRIF) is a TIR domain-containing adaptor essential for TLR3 and TLR4-mediated MyD88-independent signaling
PMID: 14751757
2
TICAM1 (TRIF) is phosphorylated by TBK1 to recruit and activate IRF3 for type I interferon production
PMID: 25636800
3
TICAM1 (TRIF) participates in endosomal TLR4 signaling that regulates the magnitude and duration of LPS-induced inflammatory responses
PMID: 33057840
4
TLR3 is absolutely dependent on TICAM1 (TRIF) for antiviral innate immune responses and type I interferon induction
PMID: 34414698
5
TICAM1 is subject to autophagic degradation via the TAX1BP1 receptor, regulating TLR3-TLR4 signaling
PMID: 35470757
Disease Associationsⓘ21
Herpetic encephalitisOpen Targets
0.64Moderate
hypothyroidismOpen Targets
0.51Moderate
basal cell carcinomaOpen Targets
0.48Moderate
skin neoplasmOpen Targets
0.45Moderate
skin cancerOpen Targets
0.42Moderate
Oral ulcerOpen Targets
0.41Moderate
autoimmune diseaseOpen Targets
0.37Weak
inborn error of immunityOpen Targets
0.37Weak
myxedemaOpen Targets
0.36Weak
thyroid diseaseOpen Targets
0.36Weak
cutaneous melanomaOpen Targets
0.36Weak
bile duct disorderOpen Targets
0.35Weak
VitiligoOpen Targets
0.33Weak
non-melanoma skin carcinomaOpen Targets
0.33Weak
Hashimoto's thyroiditisOpen Targets
0.29Weak
ThyrotoxicosisOpen Targets
0.28Weak
keratinocyte carcinomaOpen Targets
0.28Weak
hyperthyroidismOpen Targets
0.28Weak
neoplasmOpen Targets
0.09Suggestive
Autosomal recessive hyper-IgE syndromeOpen Targets
0.07Suggestive
Encephalopathy, acute, infection-induced, 6, herpes-specificUniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CASP8Protein interaction98%CASP10Protein interaction98%RIPK1Protein interaction98%FADDProtein interaction98%CFLARProtein interaction98%RIPK3Protein interaction98%
Tissue Expression6 tissues
Lung
100%
Liver
95%
Bone Marrow
56%
Ovary
39%
Brain
27%
Heart
19%
Gene Interaction Network
Click a node to explore
TICAM1CASP8CASP10RIPK1FADDCFLARRIPK3
PROTEIN STRUCTURE
Preparing viewer…
PDB3RC4 · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.80LoF Tolerant
pLIⓘ
0.37Tolerant
Observed/Expected LoF0.00 [0.00–1.80]
RankingsWhere TICAM1 stands among ~20K protein-coding genes
  • #2,780of 20,598
    Most Researched162 · top quartile
  • #16,583of 17,882
    Most Constrained (LOEUF)1.80
Genes detectedTICAM1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.
PMID: 33057840
Cell Mol Life Sci · 2021
1.00
2
Multifaceted roles of TAX1BP1 in autophagy.
PMID: 35470757
Autophagy · 2023
0.90
3
Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation.
PMID: 25636800
Science · 2015
0.80
4
Toll-like Receptor Signaling Rewires Macrophage Metabolism and Promotes Histone Acetylation via ATP-Citrate Lyase.
PMID: 31851905
Immunity · 2019
0.72
5
TLR signaling pathways.
PMID: 14751757
Semin Immunol · 2004
0.70