Trigonitis

Summary

Trigonitis (MONDO:0001732) 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	trigonitis
Mondo ID	MONDO:0001732
DOID	DOID:13507
ICD-10-CM	N30.3
ICD-11	1938116176
NCIT	C123175
SNOMED CT	74445007
UMLS	C1261278
MedGen	687797
Is cancer (heuristic)	no

Also known as: inflammation of trigone of urinary bladder · trigone of urinary bladder inflammation

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › urinary system disorder › urinary bladder disorder › cystitis › trigonitis

Related subtypes (13): hemorrhagic cystitis, prostatocystitis, acute cystitis, diphtheritic cystitis, radiation cystitis, cystitis cystica, emphysematous cholecystitis, chronic cystitis, acalculous cholecystitis, gonococcal cystitis, pyelocystitis, eosinophilic cryptitis, Trichomonas cystitis

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 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3602792	NM_002880.4(RAF1):c.581+5G>A	RAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAF1	Orphanet:154	Familial isolated dilated cardiomyopathy
RAF1	Orphanet:251615	Pilomyxoid astrocytoma
RAF1	Orphanet:500	Noonan syndrome with multiple lentigines
RAF1	Orphanet:626	Large/giant congenital melanocytic nevus
RAF1	Orphanet:648	Noonan syndrome

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
RAF1	HGNC:9829	ENSG00000132155	P04049	RAF proto-oncogene serine/threonine-protein kinase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAF1	RAF proto-oncogene serine/threonine-protein kinase	Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including prolifer…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RAF1	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE

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
gastrocnemius	1
muscle of leg	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAF1	299	ubiquitous	marker	gastrocnemius, muscle of leg, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAF1	6,574

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAF1	P04049	76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. 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
Negative feedback regulation of MAPK pathway	1	1903.3×	0.003	RAF1
SHOC2 M1731 mutant abolishes MRAS complex function	1	1427.5×	0.003	RAF1
Gain-of-function MRAS complexes activate RAF signaling	1	1427.5×	0.003	RAF1
IFNG signaling activates MAPKs	1	1427.5×	0.003	RAF1
GP1b-IX-V activation signalling	1	951.7×	0.004	RAF1
Rap1 signalling	1	713.8×	0.004	RAF1
CD209 (DC-SIGN) signaling	1	519.1×	0.004	RAF1
RAF activation	1	335.9×	0.004	RAF1
Signaling by high-kinase activity BRAF mutants	1	317.2×	0.004	RAF1
MAP2K and MAPK activation	1	285.5×	0.004	RAF1
Signaling by RAF1 mutants	1	278.5×	0.004	RAF1
Negative regulation of MAPK pathway	1	265.6×	0.004	RAF1
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.004	RAF1
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.004	RAF1
Signaling downstream of RAS mutants	1	253.8×	0.004	RAF1
Signaling by BRAF and RAF1 fusions	1	170.4×	0.006	RAF1
Stimuli-sensing channels	1	135.9×	0.007	RAF1

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
death-inducing signaling complex assembly	1	8426.0×	0.004	RAF1
ERBB2-ERBB3 signaling pathway	1	1685.2×	0.004	RAF1
insulin secretion involved in cellular response to glucose stimulus	1	1296.3×	0.004	RAF1
type II interferon-mediated signaling pathway	1	1203.7×	0.004	RAF1
Schwann cell development	1	1053.2×	0.004	RAF1
neurotrophin TRK receptor signaling pathway	1	1053.2×	0.004	RAF1
intermediate filament cytoskeleton organization	1	936.2×	0.004	RAF1
type B pancreatic cell proliferation	1	887.0×	0.004	RAF1
face development	1	802.5×	0.004	RAF1
positive regulation of peptidyl-serine phosphorylation	1	766.0×	0.004	RAF1
response to muscle stretch	1	766.0×	0.004	RAF1
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	581.1×	0.004	RAF1
thyroid gland development	1	543.6×	0.004	RAF1
regulation of Rho protein signal transduction	1	510.7×	0.004	RAF1
insulin-like growth factor receptor signaling pathway	1	495.6×	0.004	RAF1
negative regulation of protein-containing complex assembly	1	455.5×	0.004	RAF1
regulation of cell differentiation	1	432.1×	0.004	RAF1
extrinsic apoptotic signaling pathway via death domain receptors	1	401.2×	0.004	RAF1
thymus development	1	337.0×	0.005	RAF1
myelination	1	251.5×	0.006	RAF1
somatic stem cell population maintenance	1	247.8×	0.006	RAF1
wound healing	1	227.7×	0.006	RAF1
insulin receptor signaling pathway	1	221.7×	0.006	RAF1
MAPK cascade	1	153.2×	0.009	RAF1
regulation of apoptotic process	1	83.4×	0.015	RAF1
positive regulation of MAPK cascade	1	80.6×	0.015	RAF1
protein phosphorylation	1	68.0×	0.017	RAF1
negative regulation of cell population proliferation	1	42.1×	0.027	RAF1
negative regulation of apoptotic process	1	34.8×	0.032	RAF1
apoptotic process	1	28.7×	0.037	RAF1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RAF1	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RAF1	31	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	RAF1
SORAFENIB	4	RAF1
REGORAFENIB	4	RAF1
DABRAFENIB	4	RAF1
NILOTINIB	4	RAF1
TOVORAFENIB	4	RAF1
PAZOPANIB	4	RAF1
DASATINIB	4	RAF1
ERLOTINIB	4	RAF1
IMATINIB	4	RAF1
PLINABULIN	3	RAF1
AVUTOMETINIB	3	RAF1
NAPORAFENIB	3	RAF1
MOTESANIB	3	RAF1
DORAMAPIMOD	2	RAF1
CI-1040	2	RAF1
FORETINIB	2	RAF1
REBASTINIB	2	RAF1
TOLONIUM CHLORIDE	2	RAF1
CEP-32496	2	RAF1
BELVARAFENIB	2	RAF1
R-406	2	RAF1
RISOVALISIB	2	RAF1
EXARAFENIB	2	RAF1
RAF-265	2	RAF1
BRIMARAFENIB	2	RAF1
OSI-930	1	RAF1
PLUMBAGIN	1	RAF1
LY-3009120	1	RAF1
XP-102	1	RAF1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
RAF1	839	Binding:803, Functional:31, ADMET:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RAF1	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
RAF1	839

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
VEMURAFENIB	4	RAF1
SORAFENIB	4	RAF1
REGORAFENIB	4	RAF1
DABRAFENIB	4	RAF1
NILOTINIB	4	RAF1
TOVORAFENIB	4	RAF1
PAZOPANIB	4	RAF1
DASATINIB	4	RAF1
ERLOTINIB	4	RAF1
IMATINIB	4	RAF1
PLINABULIN	3	RAF1
AVUTOMETINIB	3	RAF1
NAPORAFENIB	3	RAF1
MOTESANIB	3	RAF1
DORAMAPIMOD	2	RAF1
CI-1040	2	RAF1
FORETINIB	2	RAF1
REBASTINIB	2	RAF1
TOLONIUM CHLORIDE	2	RAF1
CEP-32496	2	RAF1
BELVARAFENIB	2	RAF1
R-406	2	RAF1
RISOVALISIB	2	RAF1
EXARAFENIB	2	RAF1
RAF-265	2	RAF1
BRIMARAFENIB	2	RAF1
OSI-930	1	RAF1
PLUMBAGIN	1	RAF1
LY-3009120	1	RAF1
XP-102	1	RAF1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RAF1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.