TICAM1 (TIR domain containing adaptor molecule 1)

Gene

• Entrez ID: 148022
• Gene name: TIR domain containing adaptor molecule 1
• Gene symbol: TICAM1
• Synonyms (NCBI Gene): IIAE6, MyD88-3, PRVTIRB, TICAM-1, TRIF
• Chromosome: 19
• Chromosome location: 19p13.3
• Summary: This gene encodes an adaptor protein containing a Toll/interleukin-1 receptor (TIR) homology domain, which is an intracellular signaling domain that mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction compo

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs143679494	C>A,T	Likely-benign, risk-factor	Missense variant, coding sequence variant
rs387907307	G>A,C	Risk-factor	Stop gained, coding sequence variant, missense variant
rs1555730283	G>A	Risk-factor	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005475	hsa-miR-221-3p	Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	21236259
MIRT041391	hsa-miR-193b-3p	CLASH	23622248

Transcription factors

Transcription factor	Regulation	Reference
SP1	Repression	14960149
TRAF6	Unknown	14530355;20047764

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002224	Process	Toll-like receptor signaling pathway	IDA	12471095
GO:0002281	Process	Macrophage activation involved in immune response	IEA
GO:0002376	Process	Immune system process	IEA
GO:0002735	Process	Positive regulation of myeloid dendritic cell cytokine production	IEA
GO:0002735	Process	Positive regulation of myeloid dendritic cell cytokine production	ISS
GO:0002756	Process	MyD88-independent toll-like receptor signaling pathway	IEA
GO:0005515	Function	Protein binding	IPI	14982987, 15142865, 15841462, 19416887, 21903422, 22948160, 25736436, 33961781, 36232715
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	ISS
GO:0005768	Component	Endosome	IBA
GO:0005768	Component	Endosome	IDA	18222170
GO:0005769	Component	Early endosome	IDA	17982077
GO:0005776	Component	Autophagosome	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006809	Process	Nitric oxide biosynthetic process	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0006954	Process	Inflammatory response	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	IEA
GO:0010008	Component	Endosome membrane	IDA	18222170
GO:0010008	Component	Endosome membrane	TAS
GO:0010508	Process	Positive regulation of autophagy	IEA
GO:0010508	Process	Positive regulation of autophagy	ISS
GO:0010628	Process	Positive regulation of gene expression	IEA
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0019901	Function	Protein kinase binding	IPI	14530355
GO:0030890	Process	Positive regulation of B cell proliferation	IEA
GO:0031398	Process	Positive regulation of protein ubiquitination	IEA
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IEA
GO:0032481	Process	Positive regulation of type I interferon production	IBA
GO:0032481	Process	Positive regulation of type I interferon production	IDA	14703513, 19898473
GO:0032481	Process	Positive regulation of type I interferon production	IDA	28049150
GO:0032481	Process	Positive regulation of type I interferon production	IEA
GO:0032481	Process	Positive regulation of type I interferon production	IEA
GO:0032496	Process	Response to lipopolysaccharide	IEA
GO:0032722	Process	Positive regulation of chemokine production	IEA
GO:0032728	Process	Positive regulation of interferon-beta production	IEA
GO:0032755	Process	Positive regulation of interleukin-6 production	IEA
GO:0032760	Process	Positive regulation of tumor necrosis factor production	IEA
GO:0032816	Process	Positive regulation of natural killer cell activation	IEA
GO:0034138	Process	Toll-like receptor 3 signaling pathway	IDA	12471095
GO:0034142	Process	Toll-like receptor 4 signaling pathway	IDA	18222170, 25636800, 28747347
GO:0034142	Process	Toll-like receptor 4 signaling pathway	IDA	12471095
GO:0035591	Function	Signaling adaptor activity	IBA
GO:0035591	Function	Signaling adaptor activity	IEA
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IBA
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IEA
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IMP	25636800
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	ISS
GO:0042100	Process	B cell proliferation	IEA
GO:0042113	Process	B cell activation	IEA
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	HMP	12761501
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	IBA
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	IEA
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	IMP	14982987
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	ISS
GO:0043254	Process	Regulation of protein-containing complex assembly	IEA
GO:0043330	Process	Response to exogenous dsRNA	IEA
GO:0043330	Process	Response to exogenous dsRNA	IEA
GO:0043330	Process	Response to exogenous dsRNA	IMP	21266579
GO:0043330	Process	Response to exogenous dsRNA	ISS
GO:0045087	Process	Innate immune response	IEA
GO:0045429	Process	Positive regulation of nitric oxide biosynthetic process	IEA
GO:0050871	Process	Positive regulation of B cell activation	IEA
GO:0051607	Process	Defense response to virus	IEA
GO:0051607	Process	Defense response to virus	IEA
GO:0060090	Function	Molecular adaptor activity	IDA	12471095
GO:0060090	Function	Molecular adaptor activity	IEA
GO:0060907	Process	Positive regulation of macrophage cytokine production	IEA
GO:0071222	Process	Cellular response to lipopolysaccharide	IEA
GO:0071222	Process	Cellular response to lipopolysaccharide	ISS
GO:0097190	Process	Apoptotic signaling pathway	IEA
GO:0097342	Component	Ripoptosome	IDA	21737330
GO:0140052	Process	Cellular response to oxidised low-density lipoprotein particle stimulus	IEA
GO:0140052	Process	Cellular response to oxidised low-density lipoprotein particle stimulus	ISS
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	IEA
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	ISS

Other IDs

• MIM: 607601
• HGNC: 18348
• e!Ensembl: ENSG00000127666

Protein

• UniProt ID: Q8IUC6
• Protein name: TIR domain-containing adapter molecule 1 (TICAM-1) (Proline-rich, vinculin and TIR domain-containing protein B) (Putative NF-kappa-B-activating protein 502H) (Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta) (MyD88-3
• Protein function: Involved in innate immunity against invading pathogens. Adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis (PubMed:12471095, PubMed:12539043, PubM
• PDB: 2M1X, 2M63, 3RC4, 4BSX, 4C0M, 5JEL, 9DK8
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF17798	TRIF-NTD	1 → 148	TRIF N-terminal domain	Domain
  PF12721	RHIM	642 → 697	RIP homotypic interaction motif	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed but with higher levels in liver. {ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:12539043}.
• Sequence:

  MACTGPSLPSAFDILGAAGQDKLLYLKHKLKTPRPGCQGQDLLHAMVLLKLGQETEARIS
  LEALKADAVARLVARQWAGVDSTEDPEEPPDVSWAVARLYHLLAEEKLCPASLRDVAYQE
  AVRTLSSRDDHRLGELQDEARNRCGWDIAGDPGSIRTLQSNLGCLPPSSALPSGTRSLPR
  PIDGVSDWSQGCSLRSTGSPASLASNLEISQSPTMPFLSLHRSPHGPSKLCDDPQASLVP
  EPVPGGCQEPEEMSWPPSGEIASPPELPSSPPPGLPEVAPDATSTGLPDTPAAPETSTNY
  PVECTEGSAGPQSLPLPILEPVKNPCSVKDQTPLQLSVEDTTSPNTKPCPPTPTTPETSP
  PPPPPPPSSTPCSAHLTPSSLFPSSLESSSEQKFYNFVILHARADEHIALRVREKLEALG
  VPDGATFCEDFQVPGRGELSCLQDAIDHSAFIILLLTSNFDCRLSLHQVNQAMMSNLTRQ
  GSPDCVIPFLPLESSPAQLSSDTASLLSGLVRLDEHSQIFARKVANTFKPHRLQARKAMW
  RKEQDTRALREQSQHLDGERMQAAALNAAYSAYLQSYLSYQAQMEQLQVAFGSHMSFGTG
  APYGARMPFGGQVPLGAPPPFPTWPGCPQPPPLHAWQAGTPPPPSPQPAAFPQSLPFPQS
  PAFPTASPAPPQSPGLQPLIIHHAQMVQLGLNNHMWNQRGSQAPEDKTQEAE

• Sequence length: 712

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTOIMMUNE DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BASAL CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BRAIN DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CUTANEOUS MELANOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance; Likely benign; Benign; Conflicting classifications of pathogenicity; risk factor	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOTHYROIDISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KERATINOCYTE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-MELANOMA SKIN CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN NEOPLASM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Susceptibility to severe COVID-19	Likely risk allele; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TICAM1-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VITILIGO	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute pancreatitis	Pancreatitis	BEFREE	30583980		★☆☆☆☆ Found in Text Mining only
Amyloidosis	Amyloidosis	BEFREE	30222725		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	29568058		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	BEFREE	26056004		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	37168851	Associate	★☆☆☆☆ Found in Text Mining only
Brain Ischemia	Cerebral Ischemia	BEFREE	20700129		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	30317464		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	31287789	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Basal Cell	Basal cell carcinoma	Pubtator	34278484	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	22808251	Associate	★☆☆☆☆ Found in Text Mining only
Celiac Disease	Celiac disease	BEFREE	23658628		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	21999375		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	34689394	Associate	★☆☆☆☆ Found in Text Mining only
Complete atrioventricular block	Complete Atrioventricular Block	BEFREE	23433963		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	24168294		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	20067962	Associate	★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down syndrome	Pubtator	31611734	Associate	★☆☆☆☆ Found in Text Mining only
Encephalitis	Encephalitis	Pubtator	29116594	Stimulate	★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophageal neoplasm	Pubtator	36588538	Associate	★☆☆☆☆ Found in Text Mining only
Follicular thyroid carcinoma	Follicular Thyroid Carcinoma	BEFREE	27207655		★☆☆☆☆ Found in Text Mining only
Hepatitis Alcoholic	Alcoholic hepatitis	Pubtator	24997224	Associate	★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	25610879		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	30793936		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	30317464		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	22908323, 29852290		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	24168294		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	34278484	Associate	★☆☆☆☆ Found in Text Mining only
Mucocutaneous Lymph Node Syndrome	Kawasaki disease	Pubtator	25780885	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	29214775	Associate	★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndromes	Myelodysplastic syndrome	Pubtator	37071125	Associate	★☆☆☆☆ Found in Text Mining only
Myocarditis	Myocarditis	BEFREE	21239721		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	19826413		★☆☆☆☆ Found in Text Mining only
Nonalcoholic Steatohepatitis	Non-alcoholic Fatty Liver Disease	BEFREE	24997224		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	29914624		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	22908323, 29852290		★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	BEFREE	22908323, 30583980		★☆☆☆☆ Found in Text Mining only
Polycythemia Vera	Polycythemia Vera	BEFREE	21998457		★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	26498252	Inhibit	★☆☆☆☆ Found in Text Mining only
Renal fibrosis	Renal fibrosis	BEFREE	29253517		★☆☆☆☆ Found in Text Mining only
Septicemia	Septicemia	BEFREE	22427642, 29741098		★☆☆☆☆ Found in Text Mining only
Thromboangiitis Obliterans	Thromboangiitis obliterans	Pubtator	38640750	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Cancer Papillary	Papillary thyroid cancer	Pubtator	27207655	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid cancer, follicular	Thyroid cancer	BEFREE	27207655		★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	35546566	Associate	★☆☆☆☆ Found in Text Mining only
Uveitis	Uveitis	BEFREE	26195555		★☆☆☆☆ Found in Text Mining only
Van der Woude syndrome	Van Der Woude Syndrome	BEFREE	31620122		★☆☆☆☆ Found in Text Mining only
Vitiligo	Vitiligo	GWASCAT_DG	22561518		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Vitiligo	Vitiligo	GWASDB_DG	22561518		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Wilms Tumor	Wilms tumor	Pubtator	35933370	Associate	★☆☆☆☆ Found in Text Mining only