TICAM2
protein-codingTIR domain containing adaptor molecule 2, the group of TIR domain containing
Gene summary
Enables molecular adaptor activity. Involved in several processes, including positive regulation of interleukin-18-mediated signaling pathway; regulation of cytokine production; and regulation of innate immune response. Located in endoplasmic reticulum; endosome; and phagocytic cup. Is active in endosome membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TICAM2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021649.7. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 4 | 1 | 5 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 4 | 0 | 2 | 6 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067681.1 | 1 | MANE Select | |
| Ensembl | ENSP00000415139.3 | 1 | MANE Select | |
| Ensembl | ENSP00000627967.1 | 1 | Standard | |
| Ensembl | ENSP00000627967.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pertussis - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
- Toll-like receptor signaling pathway - Homo sapiens (human)
- Hepatitis B - Homo sapiens (human)
- NF-kappa B signaling pathway - Homo sapiens (human)
Biological Process
- MyD88-independent toll-like receptor signaling pathway
- intracellular protein transport
- endoplasmic reticulum to Golgi vesicle-mediated transport
- inflammatory response
- Golgi organization
Molecular Function
- protein binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum-Golgi intermediate compartment
- Golgi apparatus
- plasma membrane
- endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000408996
- Coding exons
- 4
- Length
- 47538
- Individuals with no LoFs
- 124520
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 72
- Defined
- 124592
- p
- 0.000289
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.831 | 171 | 204 | 0.836 | 0.0000100 | 2648 |
| Missense (PolyPhen) | 60 | 93.613 | 0.64094 | 1256 | ||
| Synonymous | -0.327 | 83 | 79.3 | 1.05 | 0.00000398 | 765 |
| Loss of Function | 2.17 | 7 | 16.5 | 0.423 | 0.00000109 | 184 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000032 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000057 | 0.000054 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00044 | 0.00044 | rare |
| South Asian | 0.00044 | 0.00042 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as sorting adapter in LPS-TLR4 signaling to regulate the MYD88-independent pathway during the innate immune response to LPS. Physically bridges TLR4 and TICAM1 and functionally transmits LPS-TRL4 signal to TICAM1; signaling is proposed to occur in early endosomes after endocytosis of TLR4. May also be involved in IL1-triggered NF-kappa-B activation, functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB; however, reports are controversial. Involved in IL-18 signaling and is proposed to function as a sorting adaptor for MYD88 in IL-18 signaling during adaptive immune response.;
Recessive Scores
- pRec
- 0.100
Intolerance Scores
- LoFtool
- 0.446
- RVIS EVS
- 0.39
- RVIS percentile EVS
- 76.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.611