Herpes simplex encephalitis, susceptibility to, 4

Summary

Herpes simplex encephalitis, susceptibility to, 4 (MONDO:0013921) is a disease caused by TICAM1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TICAM1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 396

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	herpes simplex encephalitis, susceptibility to, 4
Mondo ID	MONDO:0013921
OMIM	614850
UMLS	C3553869
MedGen	766783
Is cancer (heuristic)	no

Also known as: herpes simplex encephalitis caused by mutation in TICAM1 · herpes simplex encephalitis, susceptibility to, 4 · Herpes simplex encephalitis, susceptibility to, type 4 · IIAE6 · TICAM1 herpes simplex encephalitis

Data availability: 396 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › herpes simplex encephalitis, susceptibility to, 4

Related subtypes (283): microvascular complications of diabetes, susceptibility, Mycobacterium tuberculosis, susceptibility, bacteremia, susceptibility, pregnancy loss, recurrent, susceptibility, autoimmune thyroid disease, susceptibility to, susceptibility to HIV infection, appendicitis, proneness to, atherosclerosis susceptibility, multiple sclerosis, susceptibility to, dyslexia, susceptibility to, 1, endometriosis, susceptibility to, 1, osteoarthritis susceptibility 2, essential hypertension, genetic, osteoarthritis susceptibility 1, otitis media, susceptibility to, pelvic organ prolapse, susceptibility to, pulmonary edema of mountaineers, susceptibility to, sarcoidosis, susceptibility to, 1, strabismus, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 1, predisposition to invasive fungal disease due to CARD9 deficiency, celiac disease, susceptibility to, 1, hemolytic uremic syndrome, atypical, susceptibility to, 1, hypervitaminosis a, susceptibility to, kuru, susceptibility to, leprosy, susceptibility to, 3, nonarteritic anterior ischemic optic neuropathy, susceptibility to, diabetes mellitus, insulin-dependent, X-linked, susceptibility to, coronary heart disease, susceptibility to, 3, dyslexia, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 15, Leber optic atrophy, susceptibility to, dyslexia, susceptibility to, 2, Helicobacter pylori infection, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 1, inherited susceptibility to asthma, renal dysplasia, cystic, susceptibility to, systemic lupus erythematosus, susceptibility to, 1, leishmaniasis, tegumentary, susceptibility to, xanthomatosis, susceptibility to, hyperlipidemia, combined, 1, urinary tract infections, recurrent, susceptibility to, hypertension, essential, susceptibility to, 1, hepatic fibrosis, severe, susceptibility to, due to Schistosoma mansoni infection, dyslexia, susceptibility to, 3, Ascaris lumbricoides infection, susceptibility to, hypertension, essential, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 3, nephrolithiasis, uric acid, susceptibility to, atrioventricular septal defect, susceptibility to, 2, vitiligo-associated multiple autoimmune disease susceptibility 1, polysubstance abuse, susceptibility to, dyslexia, susceptibility to, 6, glaucoma, normal tension, susceptibility to, anorexia nervosa, susceptibility to, 1, stroke, susceptibility to, 1, dyslexia, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 2, familial meningioma, celiac disease, susceptibility to, 5, systemic lupus erythematosus with hemolytic anemia, susceptibility to, 1, hypertension, essential, susceptibility to, 3, coronary heart disease, susceptibility to, 1, bulimia nervosa, susceptibility to, 1, leprosy, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 9, Parkinson disease 11, autosomal dominant, susceptibility to, focal segmental glomerulosclerosis 3, susceptibility to, autoimmune disease, susceptibility to, 1, osteoarthritis susceptibility 3, systemic lupus erythematosus with nephritis, susceptibility to, 1, systemic lupus erythematosus with nephritis, susceptibility to, 2, systemic lupus erythematosus with nephritis, susceptibility to, 3, coronary heart disease, susceptibility to, 2, coronary heart disease, susceptibility to, 4, autoimmune disease, susceptibility to, 2, autoimmune disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 4, myocardial infarction, susceptibility to, major depressive disorder 1, legionnaire disease, susceptibility to, myocardial infarction, susceptibility to, 2, major depressive disorder 2, hypertension, essential, susceptibility to, 4, epilepsy, idiopathic generalized, susceptibility to, 3, myoclonic epilepsy, juvenile, susceptibility to, 3, orofacial cleft 6, susceptibility to, coronary heart disease, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 1, attention deficit-hyperactivity disorder, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 3, attention deficit-hyperactivity disorder, susceptibility to, 4, Alzheimer disease 9, susceptibility to respiratory infections associated with CD8alpha chain mutation, dyslexia, susceptibility to, 8, autoimmune disease, susceptibility to, 4, hepatitis C virus, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 4, celiac disease, susceptibility to, 4, celiac disease, susceptibility to, 2, celiac disease, susceptibility to, 3, leprosy, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 5, systemic lupus erythematosus, susceptibility to, 6, opioid dependence, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 8, hypertension, essential, susceptibility to, 5, hypertension, essential, susceptibility to, 6, Parkinson disease 13, autosomal dominant, susceptibility to, West Nile virus, susceptibility to, hepatitis B virus, susceptibility to, Buruli ulcer, susceptibility to, osteoarthritis susceptibility 4, systemic lupus erythematosus, susceptibility to, 9, coronary heart disease, susceptibility to, 7, hypertension, essential, susceptibility to, 7, leprosy, susceptibility to, 4, hypertension, essential, susceptibility to, 8, epilepsy, idiopathic generalized, susceptibility to, 13, coronary heart disease, susceptibility to, 8, myoclonic epilepsy, juvenile, susceptibility to, 4, susceptibility to visceral leishmaniasis, 2, susceptibility to visceral leishmaniasis, 3, celiac disease, susceptibility to, 6, epilepsy, idiopathic generalized, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 6, celiac disease, susceptibility to, 7, celiac disease, susceptibility to, 8, celiac disease, susceptibility to, 9, celiac disease, susceptibility to, 10, celiac disease, susceptibility to, 11, celiac disease, susceptibility to, 12, celiac disease, susceptibility to, 13, coronary heart disease, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 10, systemic lupus erythematosus, susceptibility to, 11, systemic lupus erythematosus, susceptibility to, 12, epilepsy, childhood absence, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 6, systemic lupus erythematosus, susceptibility to, 13, sarcoidosis, susceptibility to, 2, sarcoidosis, susceptibility to, 3, osteoarthritis susceptibility 5, osteoarthritis susceptibility 6, focal segmental glomerulosclerosis 4, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 8, herpes simplex encephalitis, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 10, pelvic organ prolapse, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 14, leprosy, susceptibility to, 5, thyrotoxic periodic paralysis, susceptibility to, 2, hearing loss, cisplatin-induced, susceptibility to, susceptibility to mononeuropathy of the median nerve, mild, fatty liver disease, nonalcoholic, susceptibility to, 2, leprosy, susceptibility to, 6, autoimmune disease, susceptibility to, 6, Parkinson disease 5, autosomal dominant, susceptibility to, aspergillosis, susceptibility to, sick sinus syndrome 3, susceptibility to, Parkinson disease 18, autosomal dominant, susceptibility to, epilepsy, juvenile myoclonic, susceptibility to, 9, dengue virus, susceptibility to, coronary heart disease, susceptibility to, 6, podoconiosis, susceptibility to, peripartum cardiomyopathy, susceptibility to, influenza, severe, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 3, human herpesvirus 8, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 12, herpes simplex encephalitis, susceptibility to, 3, pulmonary hypertension, neonatal, susceptibility to, craniosynostosis 5, susceptibility to, melioidosis, susceptibility to, chronic mountain sickness, susceptibility to, herpes simplex encephalitis, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 14, hereditary neoplastic syndrome, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, susceptibility to localized juvenile periodontitis, inherited susceptibility to mycobacterial diseases, neural tube defects, susceptibility to, multiple system atrophy 1, susceptibility to, nephrolithiasis susceptibility caused by SLC26A1, myoclonic epilepsy, juvenile, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 1, autism, susceptiblity to, susceptibility to visceral leishmaniasis, 1, malaria, susceptibility to, spondyloarthropathy, susceptibility to, herpes simplex encephalitis, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 18, epilepsy, idiopathic generalized, susceptibility to, 15, hepatitis, fulminant viral, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 16, autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency, aortic aneurysm, familial thoracic 11, susceptibility to, craniosynostosis 7, amyotrophic lateral sclerosis, susceptibility to, 24, amyotrophic lateral sclerosis, susceptibility to, 25, epilepsy, juvenile myoclonic, susceptibility to, 10, susceptibility to angioedema induced by ACE inhibitors, epidermodysplasia verruciformis, susceptibility to, exfoliation syndrome, susceptibility to, basal cell carcinoma, susceptibility to, graft-versus-host disease, susceptibility to, narcolepsy, susceptibility to, pulmonary disease, chronic obstructive, susceptibility to, restless legs syndrome, susceptibility to, psoriasis, susceptibility to, age related macular degeneration, susceptibility to, allergic rhinitis, susceptibility to, dermatitis, atopic, susceptibility to, Hirschsprung disease, susceptibility to, diabetes mellitus, ketosis-prone, schizophrenia, susceptibility to, radioulnar synostosis, nonsyndromic, susceptibility to, lumbar disk herniation, susceptibility to, lumbar disk degeneration, susceptibility to, psoriatic arthritis, susceptibility to, migraine with or without aura, susceptibility to, Alzheimer disease, susceptibility to, mitochondrial, Asperger syndrome, susceptibility to, tobacco addiction, susceptibility to, lipodystrophy, partial, acquired, susceptibility to, Graves disease, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 17, breast-ovarian cancer, familial, susceptibility to, blepharospasm, benign essential, susceptibility to, hemorrhage, intracerebral, susceptibility to, IgA nephropathy, susceptibility to, hemolytic uremic syndrome, atypical, susceptibility to, 7, vitiligo-associated multiple autoimmune disease susceptibility 6, delayed sleep phase syndrome, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, malignant hyperthermia, susceptibility to, multicentric Castleman disease, susceptibility to, pelvic organ prolapse, susceptibility to, 1, amyotrophic lateral sclerosis, susceptibility to, 13, Graves disease, susceptibility to, X-linked 2, autoimmune thyroid disease, susceptibility to, 5, atrioventricular septal defect, susceptibility to, 1, epilepsy, juvenile myoclonic, susceptibility to, 6, autoimmune disease, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 6, seasonal affective disorder, susceptibility to, ventricular fibrillation during myocardial infarction, susceptibility to, UV-induced skin damage, susceptibility to, antisocial behavior, susceptibility to, aplastic anemia, susceptibility to, cardiomyopathy, familial hypertrophic, 4, susceptibility to, cirrhosis, noncryptogenic, susceptibility to, coronary artery disease, severe, susceptibility to, dengue fever, susceptibility to, dengue hemorrhagic fever, susceptibility to, dengue shock syndrome, susceptibility to, dyslexia, susceptibility to, 4, dyslexia, susceptibility to, 7, efavirenz central nervous system toxicity, susceptibility to, obesity, susceptibility to, bleeding disorder, platelet-type, 13, susceptibility to, Schistosoma mansoni infection, susceptibility/resistance to, Parkinson disease 24, autosomal dominant, susceptibility to, iron overload, susceptibility to, hydrocephalus, congenital, 5, susceptibility to, hearing loss, noise-induced, susceptibility to, hyperemesis gravidarum, susceptibility to, Parkinson disease 26, autosomal dominant, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 19, polycystic kidney disease 9, susceptibility to, rhabdomyolysis, susceptibility to, scoliosis, isolated, susceptibility to, dystonia 38, susceptibility to, gallbladder disease 4, epilepsy, juvenile absence, susceptibility to, GBA1-related Parkinson disease, susceptibility, SH2B3-related immune system disorder

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

396 retrieved; paginated sample, class counts are floors:

204 uncertain significance, 176 likely benign, 9 benign, 3 conflicting classifications of pathogenicity, 2 risk factor, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
37265	NM_182919.4(TICAM1):c.421C>T (p.Arg141Ter)	TICAM1	risk factor	no assertion criteria provided
495309	NM_182919.4(TICAM1):c.749C>T (p.Pro250Leu)	TICAM1	risk factor	no assertion criteria provided
1414486	NM_182919.4(TICAM1):c.356A>G (p.Gln119Arg)	TICAM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1922840	NM_182919.4(TICAM1):c.467G>A (p.Arg156Gln)	TICAM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
473292	NM_182919.4(TICAM1):c.1702G>A (p.Ala568Thr)	TICAM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1001072	NM_182919.4(TICAM1):c.1751T>C (p.Met584Thr)	TICAM1	Uncertain significance	criteria provided, single submitter
1005298	NM_182919.4(TICAM1):c.292C>T (p.Arg98Cys)	TICAM1	Uncertain significance	criteria provided, single submitter
1009279	NM_182919.4(TICAM1):c.2021C>T (p.Pro674Leu)	TICAM1	Uncertain significance	criteria provided, single submitter
1010270	NM_182919.4(TICAM1):c.1102T>C (p.Ser368Pro)	TICAM1	Uncertain significance	criteria provided, single submitter
1010889	NM_182919.4(TICAM1):c.367C>T (p.Arg123Cys)	TICAM1	Uncertain significance	criteria provided, single submitter
1011785	NM_182919.4(TICAM1):c.1783A>T (p.Met595Leu)	TICAM1	Uncertain significance	criteria provided, single submitter
1011997	NM_182919.4(TICAM1):c.223C>A (p.Arg75Ser)	TICAM1	Uncertain significance	criteria provided, single submitter
1016704	NM_182919.4(TICAM1):c.995C>T (p.Thr332Met)	TICAM1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1017601	NM_182919.4(TICAM1):c.1153T>C (p.Ser385Pro)	TICAM1	Uncertain significance	criteria provided, single submitter
1019147	NM_182919.4(TICAM1):c.680C>T (p.Pro227Leu)	TICAM1	Uncertain significance	criteria provided, single submitter
1019203	NM_182919.4(TICAM1):c.466C>T (p.Arg156Trp)	TICAM1	Uncertain significance	criteria provided, single submitter
1021957	NM_182919.4(TICAM1):c.1973C>T (p.Pro658Leu)	TICAM1	Uncertain significance	criteria provided, single submitter
1036897	NM_182919.4(TICAM1):c.122A>G (p.Asp41Gly)	TICAM1	Uncertain significance	criteria provided, single submitter
1037747	NM_182919.4(TICAM1):c.1270G>A (p.Gly424Arg)	TICAM1	Uncertain significance	criteria provided, single submitter
1040969	NM_182919.4(TICAM1):c.1967C>G (p.Pro656Arg)	TICAM1	Uncertain significance	criteria provided, single submitter
1043022	NM_182919.4(TICAM1):c.1355T>C (p.Ile452Thr)	TICAM1	Uncertain significance	criteria provided, single submitter
1045630	NM_182919.4(TICAM1):c.1696C>A (p.Leu566Met)	TICAM1	Uncertain significance	criteria provided, single submitter
1046881	NM_182919.4(TICAM1):c.101G>A (p.Arg34His)	TICAM1	Uncertain significance	criteria provided, single submitter
1054098	NM_182919.4(TICAM1):c.1121C>T (p.Ala374Val)	TICAM1	Uncertain significance	criteria provided, single submitter
1055759	NM_182919.4(TICAM1):c.1640G>A (p.Arg547Gln)	TICAM1	Uncertain significance	criteria provided, single submitter
1057108	NM_182919.4(TICAM1):c.1066C>T (p.Pro356Ser)	TICAM1	Uncertain significance	criteria provided, single submitter
1058464	NM_182919.4(TICAM1):c.1688C>T (p.Ala563Val)	TICAM1	Uncertain significance	criteria provided, single submitter
1059717	NM_182919.4(TICAM1):c.1543G>A (p.Glu515Lys)	TICAM1	Uncertain significance	criteria provided, single submitter
1061096	NM_182919.4(TICAM1):c.1802C>G (p.Ala601Gly)	TICAM1	Uncertain significance	criteria provided, single submitter
1061292	NM_182919.4(TICAM1):c.1130C>T (p.Thr377Ile)	TICAM1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TICAM1	Strong	Autosomal recessive	herpes simplex encephalitis, susceptibility to, 4	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TICAM1	Orphanet:1930	Herpes simplex virus encephalitis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TICAM1	HGNC:18348	ENSG00000127666	Q8IUC6	TIR domain-containing adapter molecule 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TICAM1	TIR domain-containing adapter molecule 1	Involved in innate immunity against invading pathogens.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TICAM1	Other/Unknown	no		TIR_dom, TICAM1, RHIM

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
esophagus mucosa	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TICAM1	227	ubiquitous	marker	lower esophagus mucosa, buccal mucosa cell, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TICAM1	2,038

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TICAM1	Q8IUC6	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TICAM1 deficiency - HSE	1	5710.0×	0.003	TICAM1
TRAF3 deficiency - HSE	1	3806.7×	0.003	TICAM1
TLR3-mediated TICAM1-dependent programmed cell death	1	1903.3×	0.003	TICAM1
Caspase activation via extrinsic apoptotic signalling pathway	1	1427.5×	0.003	TICAM1
TRIF-mediated programmed cell death	1	1268.9×	0.003	TICAM1
ZBP1(DAI) mediated induction of type I IFNs	1	1038.2×	0.003	TICAM1
TICAM1,TRAF6-dependent induction of TAK1 complex	1	1038.2×	0.003	TICAM1
Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation	1	951.7×	0.003	TICAM1
Diseases of Immune System	1	878.5×	0.003	TICAM1
Diseases associated with the TLR signaling cascade	1	878.5×	0.003	TICAM1
TICAM1-dependent activation of IRF3/IRF7	1	815.7×	0.003	TICAM1
Caspase activation via Death Receptors in the presence of ligand	1	761.3×	0.003	TICAM1
IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation	1	761.3×	0.003	TICAM1
Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7	1	761.3×	0.003	TICAM1
TRAF6-mediated induction of TAK1 complex within TLR4 complex	1	713.8×	0.003	TICAM1
RIP-mediated NFkB activation via ZBP1	1	671.8×	0.003	TICAM1
TICAM1, RIP1-mediated IKK complex recruitment	1	601.0×	0.003	TICAM1
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1	601.0×	0.003	TICAM1
IKK complex recruitment mediated by RIP1	1	496.5×	0.004	TICAM1
Cytosolic sensors of pathogen-associated DNA	1	285.5×	0.006	TICAM1
Toll Like Receptor 3 (TLR3) Cascade	1	193.6×	0.007	TICAM1
TRIF (TICAM1)-mediated TLR4 signaling	1	190.3×	0.007	TICAM1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	190.3×	0.007	TICAM1
MyD88 dependent cascade initiated on endosome	1	190.3×	0.007	TICAM1
MyD88-independent TLR4 cascade	1	184.2×	0.007	TICAM1
Toll Like Receptor 7/8 (TLR7/8) Cascade	1	184.2×	0.007	TICAM1
Toll Like Receptor 9 (TLR9) Cascade	1	175.7×	0.007	TICAM1
Apoptosis	1	167.9×	0.007	TICAM1
Programmed Cell Death	1	146.4×	0.008	TICAM1
Toll Like Receptor 4 (TLR4) Cascade	1	131.3×	0.009	TICAM1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of myeloid dendritic cell cytokine production	1	2808.7×	0.004	TICAM1
positive regulation of natural killer cell activation	1	2106.5×	0.004	TICAM1
TRIF-dependent toll-like receptor signaling pathway	1	1532.0×	0.004	TICAM1
cellular response to oxidised low-density lipoprotein particle stimulus	1	1404.3×	0.004	TICAM1
macrophage activation involved in immune response	1	1123.5×	0.004	TICAM1
toll-like receptor 3 signaling pathway	1	1123.5×	0.004	TICAM1
regulation of protein-containing complex assembly	1	732.7×	0.004	TICAM1
positive regulation of macrophage cytokine production	1	732.7×	0.004	TICAM1
nitric oxide biosynthetic process	1	702.2×	0.004	TICAM1
toll-like receptor signaling pathway	1	601.9×	0.004	TICAM1
positive regulation of cytokine production involved in inflammatory response	1	543.6×	0.004	TICAM1
lipopolysaccharide-mediated signaling pathway	1	526.6×	0.004	TICAM1
toll-like receptor 4 signaling pathway	1	526.6×	0.004	TICAM1
response to exogenous dsRNA	1	526.6×	0.004	TICAM1
B cell proliferation	1	481.5×	0.004	TICAM1
positive regulation of nitric oxide biosynthetic process	1	455.5×	0.004	TICAM1
positive regulation of type I interferon production	1	421.3×	0.004	TICAM1
positive regulation of interferon-beta production	1	391.9×	0.004	TICAM1
positive regulation of chemokine production	1	374.5×	0.004	TICAM1
positive regulation of B cell proliferation	1	343.9×	0.005	TICAM1
apoptotic signaling pathway	1	224.7×	0.006	TICAM1
positive regulation of protein ubiquitination	1	213.3×	0.006	TICAM1
positive regulation of autophagy	1	208.1×	0.006	TICAM1
positive regulation of interleukin-6 production	1	166.8×	0.008	TICAM1
positive regulation of tumor necrosis factor production	1	153.2×	0.008	TICAM1
cellular response to lipopolysaccharide	1	98.0×	0.012	TICAM1
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.016	TICAM1
defense response to virus	1	69.3×	0.016	TICAM1
positive regulation of gene expression	1	38.7×	0.027	TICAM1
inflammatory response	1	37.7×	0.027	TICAM1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TICAM1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TICAM1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TICAM1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.