TICAM1

TIR domain containing adaptor molecule 1, the group of TIR domain containing

Basic information

Region (hg38): 19:4815931-4831712

Links

ENSG00000127666 ∙ NCBI:148022 ∙ OMIM:607601 ∙ HGNC:18348 ∙ Uniprot:Q8IUC6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• herpes simplex encephalitis, susceptibility to, 4 (Limited), mode of inheritance: Semidominant
• herpes simplex encephalitis, susceptibility to, 4 (Strong), mode of inheritance: AR
• herpes simplex encephalitis, susceptibility to, 4 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Encephalopathy, acute, infection-induceed (herpes-specific), susceptibility to, 6	AD/AR	Allergy/Immunology/Infectious	Individuals may be susceptible to severe herpes simplex virus infections (eg, herpes encephalitis), and awareness may allow early diagnosis and treatment (eg, with acyclovir, which has been reported as effective reported individuals), potentially decreasing morbidity and mortality	Allergy/Immunology/Infectious	22105173

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TICAM1 gene.

• Herpes simplex encephalitis, susceptibility to, 4 (326 variants)
• Inborn genetic diseases (24 variants)
• not provided (15 variants)
• not specified (5 variants)
• Susceptibility to severe COVID-19 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TICAM1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	111	6	120
missense			185	13	3	201
nonsense			3			3
start loss						0
frameshift			3			3
inframe indel			4	3	1	8
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	0	198	127	12

Variants in TICAM1

This is a list of pathogenic ClinVar variants found in the TICAM1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-4816148-A-C		not specified	Benign (Jan 24, 2024)
19-4816229-G-A		not specified	Benign (Mar 29, 2016)
19-4816260-G-A		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (Aug 11, 2023)
19-4816266-G-C		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (Aug 29, 2022)
19-4816271-C-T		Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance (Oct 13, 2022)
19-4816275-G-C		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (May 11, 2023)
19-4816278-C-T		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (Aug 30, 2023)
19-4816287-G-A		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (Jan 09, 2024)
19-4816293-C-A		Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance (Aug 19, 2022)
19-4816305-C-A		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (Aug 09, 2022)
19-4816314-C-T		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (Jun 16, 2023)
19-4816328-C-T		Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance (Jul 06, 2023)
19-4816329-G-A		Herpes simplex encephalitis, susceptibility to, 4 • TICAM1-related disorder	Likely benign (Jan 18, 2022)
19-4816332-G-A		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (Feb 10, 2022)
19-4816344-G-A		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (Jun 13, 2023)
19-4816357-G-A		Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance (May 23, 2018)
19-4816384-G-C		Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance (Nov 03, 2023)
19-4816404-C-A		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (Jun 03, 2022)
19-4816405-G-A		Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance (Nov 08, 2021)
19-4816406-G-A		Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance (Aug 30, 2021)
19-4816411-G-C		Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance (Aug 30, 2020)
19-4816438-T-C		Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance (Apr 29, 2022)
19-4816449-C-G		Herpes simplex encephalitis, susceptibility to, 4	Likely benign (Jun 19, 2022)
19-4816449-C-T		Herpes simplex encephalitis, susceptibility to, 4 • TICAM1-related disorder	Benign/Likely benign (Jan 31, 2024)
19-4816450-G-C		Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance (Aug 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TICAM1	protein_coding	protein_coding	ENST00000248244	1	15773

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.718	400	443	0.904	0.0000270	4534
Missense in Polyphen		67	92.173	0.72689		1013
Synonymous	-0.267	210	205	1.02	0.0000142	1570
Loss of Function

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish
East Asian
Finnish
European (Non-Finnish)
Middle Eastern
South Asian
Other

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in innate immunity against invading pathogens. Adapter used by TLR3 and TLR4 (through TICAM2) to mediate NF- kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis. Ligand binding to these receptors results in TRIF recruitment through its TIR domain. Distinct protein- interaction motifs allow recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, lead to the activation of transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively. Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of proinflammatory cytokines (By similarity). {ECO:0000250|UniProtKB:Q80UF7, ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:12539043, ECO:0000269|PubMed:14739303}.
• Disease: DISEASE: Encephalopathy, acute, infection-induced, Herpes- specific, 6 (IIAE6) [MIM:614850]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269|PubMed:22105173}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Pertussis - Homo sapiens (human);Influenza A - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Necroptosis - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Nanoparticle triggered regulated necrosis;Toll-like Receptor Signaling;Fibrin Complement Receptor 3 Signaling Pathway;Toll-like Receptor Signaling Pathway;TICAM1-dependent activation of IRF3/IRF7;TICAM1, RIP1-mediated IKK complex recruitment ;Toll Like Receptor 3 (TLR3) Cascade;ZBP1(DAI) mediated induction of type I IFNs;Toll-Like Receptors Cascades;Ligand-dependent caspase activation;Caspase activation via extrinsic apoptotic signalling pathway;Innate Immune System;Immune System;Apoptosis;Programmed Cell Death;RIP-mediated NFkB activation via ZBP1;TLR3-mediated TICAM1-dependent programmed cell death;Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon;Cytosolic sensors of pathogen-associated DNA ;IKK complex recruitment mediated by RIP1;TRIF-mediated programmed cell death;TRAF6-mediated induction of TAK1 complex within TLR4 complex;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Endogenous TLR signaling;TICAM1,TRAF6-dependent induction of TAK1 complex (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.350
• rvis_EVS: -0.15
• rvis_percentile_EVS: 42.25

Haploinsufficiency Scores

• pHI: 0.0773
• hipred: Y
• hipred_score: 0.594
• ghis: 0.486

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.613

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ticam1
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: macrophage activation involved in immune response;positive regulation of myeloid dendritic cell cytokine production;MyD88-independent toll-like receptor signaling pathway;inflammatory response;I-kappaB kinase/NF-kappaB signaling;positive regulation of autophagy;positive regulation of gene expression;positive regulation of B cell proliferation;positive regulation of protein ubiquitination;lipopolysaccharide-mediated signaling pathway;positive regulation of protein binding;positive regulation of interleukin-6 production;positive regulation of tumor necrosis factor production;positive regulation of natural killer cell activation;negative regulation of MyD88-independent toll-like receptor signaling pathway;toll-like receptor 3 signaling pathway;TRIF-dependent toll-like receptor signaling pathway;positive regulation of I-kappaB kinase/NF-kappaB signaling;response to exogenous dsRNA;regulation of protein homodimerization activity;positive regulation of chemokine biosynthetic process;innate immune response;positive regulation of interferon-beta biosynthetic process;positive regulation of nitric oxide biosynthetic process;positive regulation of NF-kappaB transcription factor activity;defense response to virus;necroptotic process;cellular response to lipopolysaccharide;apoptotic signaling pathway;cellular response to oxidised low-density lipoprotein particle stimulus;positive regulation of cytokine production involved in inflammatory response
• Cellular component: mitochondrion;autophagosome;cytosol;endosome membrane;ripoptosome
• Molecular function: protein binding;protein kinase binding