Bacteremia, susceptibility to, 1

Summary

Bacteremia, susceptibility to, 1 (MONDO:0013723) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bacteremia, susceptibility to, 1
Mondo ID	MONDO:0013723
OMIM	614382
UMLS	C3280645
MedGen	482275
Is cancer (heuristic)	no

Also known as: bacteremia, protection against · bacteremia, susceptibility caused by mutation in TIRAP · bacteremia, susceptibility to, 1 · bacteremia, susceptibility to, type 1 · BACTS1 · TIRAP bacteremia, susceptibility

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › bacteremia, susceptibility › bacteremia, susceptibility to, 1

Related subtypes (1): bacteremia, susceptibility to, 2

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

1 retrieved; paginated sample, class counts are floors:

1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4467	NM_001318777.2(TIRAP):c.539C>T (p.Ser180Leu)	TIRAP	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
TIRAP	HGNC:17192	ENSG00000150455	P58753	Toll/interleukin-1 receptor domain-containing adapter protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TIRAP	Toll/interleukin-1 receptor domain-containing adapter protein	Adapter involved in TLR2, TLR4 and RAGE signaling pathways in the innate immune response.

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)
TIRAP	Other/Unknown	no		TIR_dom, Tol-interleuk_rcpt_adapt_Tirap, Toll_tir_struct_dom_sf

Expression context

Cohort genes with no expression data: 0.

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
monocyte	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TIRAP	171	ubiquitous	yes	oviduct epithelium, buccal mucosa cell, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TIRAP	1,334

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TIRAP	P58753	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
MyD88 deficiency (TLR2/4)	1	601.0×	0.004	TIRAP
IRAK4 deficiency (TLR2/4)	1	571.0×	0.004	TIRAP
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	152.3×	0.008	TIRAP
ER-Phagosome pathway	1	129.8×	0.008	TIRAP

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 interleukin-15 production	1	8426.0×	0.002	TIRAP
TIRAP-dependent toll-like receptor 4 signaling pathway	1	8426.0×	0.002	TIRAP
toll-like receptor TLR1:TLR2 signaling pathway	1	5617.3×	0.002	TIRAP
cellular response to bacterial lipopeptide	1	4213.0×	0.002	TIRAP
regulation of interferon-beta production	1	3370.4×	0.002	TIRAP
positive regulation of chemokine (C-X-C motif) ligand 1 production	1	2808.7×	0.002	TIRAP
positive regulation of toll-like receptor 3 signaling pathway	1	2407.4×	0.002	TIRAP
positive regulation of toll-like receptor 2 signaling pathway	1	2106.5×	0.002	TIRAP
cellular response to lipoteichoic acid	1	1532.0×	0.002	TIRAP
positive regulation of chemokine (C-X-C motif) ligand 2 production	1	1532.0×	0.002	TIRAP
positive regulation of toll-like receptor 4 signaling pathway	1	991.3×	0.003	TIRAP
MyD88-dependent toll-like receptor signaling pathway	1	936.2×	0.003	TIRAP
3’-UTR-mediated mRNA stabilization	1	702.2×	0.003	TIRAP
myeloid cell differentiation	1	648.1×	0.003	TIRAP
regulation of innate immune response	1	648.1×	0.003	TIRAP
positive regulation of neutrophil chemotaxis	1	648.1×	0.003	TIRAP
toll-like receptor 4 signaling pathway	1	526.6×	0.003	TIRAP
positive regulation of interleukin-12 production	1	391.9×	0.004	TIRAP
positive regulation of B cell proliferation	1	343.9×	0.005	TIRAP
positive regulation of protein-containing complex assembly	1	337.0×	0.005	TIRAP
positive regulation of interleukin-8 production	1	244.2×	0.006	TIRAP
positive regulation of interleukin-6 production	1	166.8×	0.008	TIRAP
positive regulation of JNK cascade	1	163.6×	0.008	TIRAP
positive regulation of tumor necrosis factor production	1	153.2×	0.008	TIRAP
defense response to Gram-positive bacterium	1	127.7×	0.010	TIRAP
response to lipopolysaccharide	1	124.8×	0.010	TIRAP
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.013	TIRAP
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.015	TIRAP
cell surface receptor signaling pathway	1	64.1×	0.017	TIRAP
inflammatory response	1	37.7×	0.027	TIRAP

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
TIRAP	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	TIRAP

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)
TIRAP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.