Desmoid tumor caused by somatic mutation

Summary

Desmoid tumor caused by somatic mutation (MONDO:0100168) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers; 2 ClinVar predisposition records) and 1 clinical trial.

At a glance

• Classification: Cancer
• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	desmoid tumor caused by somatic mutation
Mondo ID	MONDO:0100168
DOID	DOID:0111349
UMLS	C2675440
MedGen	436434
GARD	0026071
Is cancer (heuristic)	yes

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › mesenchymal cell neoplasm › fibroblastic neoplasm › fibromatosis › desmoid tumor › desmoid tumor caused by somatic mutation

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

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
838	APC, 1-BP DEL, 3720T	APC	Pathogenic	no assertion criteria provided
17580	NM_001904.4(CTNNB1):c.121A>G (p.Thr41Ala)	CTNNB1	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 17 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CTNNB1	Act	ACC,COAD,COADREAD,ESCA,HCC,LIHB,LUAD,MBL,MEL,NSCLC,OVT,PAST,PRAD,PROSTATE,RMS,SKIN,SOFT_TISSUE,STAD,UCEC,WT	CIViC #1290
APC	LoF	AML,ANSC,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,HCC,LUAD,MEL,MT,NETNOS,NSCLC,PRAD,PROSTATE,READ,STAD,STOMACH,UM,VULVA	CIViC #66

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTNNB1	Orphanet:1501	Adrenocortical carcinoma
CTNNB1	Orphanet:210159	Adult hepatocellular carcinoma
CTNNB1	Orphanet:2780	Osteopathia striata-cranial sclerosis syndrome
CTNNB1	Orphanet:33402	Pediatric hepatocellular carcinoma
CTNNB1	Orphanet:404473	Intellectual disability-eye abnormalities-microcephaly-peripheral spasticity syndrome
CTNNB1	Orphanet:54595	Craniopharyngioma
CTNNB1	Orphanet:569248	Microcystic stromal tumor
CTNNB1	Orphanet:689430	Adenoid ameloblastoma
CTNNB1	Orphanet:873	Desmoid tumor
CTNNB1	Orphanet:891	Familial exudative vitreoretinopathy
CTNNB1	Orphanet:91414	Pilomatrixoma
CTNNB1	Orphanet:952	Acrofacial dysostosis, Weyers type
APC	Orphanet:220460	Attenuated familial adenomatous polyposis
APC	Orphanet:261584	5q22 microdeletion syndrome
APC	Orphanet:314022	Gastric adenocarcinoma and proximal polyposis of the stomach
APC	Orphanet:3258	Cenani-Lenz syndrome
APC	Orphanet:873	Desmoid tumor

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTNNB1	HGNC:2514	ENSG00000168036	P35222	Catenin beta-1	clinvar
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTNNB1	Catenin beta-1	Key downstream component of the canonical Wnt signaling pathway.
APC	Adenomatous polyposis coli protein	Tumor suppressor.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTNNB1	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
periodontal ligament	1
ventricular zone	1
medial globus pallidus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTNNB1	295	ubiquitous	marker	adrenal tissue, ventricular zone, periodontal ligament
APC	297	ubiquitous	marker	substantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNNB1	15,668
APC	2,903

Intra-cohort edges

A	B	Sources
APC	CTNNB1	intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTNNB1	P35222	50
APC	P25054	31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 67. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by GSK3beta mutants	2	761.3×	2e-05	CTNNB1, APC
CTNNB1 S33 mutants aren’t phosphorylated	2	761.3×	2e-05	CTNNB1, APC
CTNNB1 S37 mutants aren’t phosphorylated	2	761.3×	2e-05	CTNNB1, APC
CTNNB1 S45 mutants aren’t phosphorylated	2	761.3×	2e-05	CTNNB1, APC
CTNNB1 T41 mutants aren’t phosphorylated	2	761.3×	2e-05	CTNNB1, APC
Beta-catenin phosphorylation cascade	2	671.8×	2e-05	CTNNB1, APC
Disassembly of the destruction complex and recruitment of AXIN to the membrane	2	356.9×	7e-05	CTNNB1, APC
Deactivation of the beta-catenin transactivating complex	2	233.1×	2e-04	CTNNB1, APC
Degradation of beta-catenin by the destruction complex	2	173.0×	2e-04	CTNNB1, APC
TCF dependent signaling in response to WNT	2	117.7×	5e-04	CTNNB1, APC
APC truncation mutants are not K63 polyubiquitinated	1	5710.0×	0.001	APC
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	1142.0×	0.005	CTNNB1
CDH11 homotypic and heterotypic interactions	1	815.7×	0.006	CTNNB1
Regulation of CDH19 Expression and Function	1	713.8×	0.006	CTNNB1
InlA-mediated entry of Listeria monocytogenes into host cells	1	634.4×	0.006	CTNNB1
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	571.0×	0.006	CTNNB1
RUNX3 regulates WNT signaling	1	571.0×	0.006	CTNNB1
Apoptotic cleavage of cell adhesion proteins	1	519.1×	0.006	CTNNB1
Signaling by AXIN mutants	1	519.1×	0.006	APC
Signaling by CTNNB1 phospho-site mutants	1	519.1×	0.006	APC
Signaling by APC mutants	1	519.1×	0.006	APC
Signaling by AMER1 mutants	1	519.1×	0.006	APC
Regulation of CDH11 function	1	519.1×	0.006	CTNNB1
Regulation of CDH1 Function	1	475.8×	0.006	CTNNB1
APC truncation mutants have impaired AXIN binding	1	407.9×	0.006	APC
AXIN missense mutants destabilize the destruction complex	1	407.9×	0.006	APC
Truncations of AMER1 destabilize the destruction complex	1	407.9×	0.006	APC
Formation of axial mesoderm	1	407.9×	0.006	CTNNB1
Formation of definitive endoderm	1	356.9×	0.006	CTNNB1
Germ layer formation at gastrulation	1	335.9×	0.007	CTNNB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cell fate specification	2	526.6×	6e-04	CTNNB1, APC
glial cell fate determination	1	8426.0×	0.002	CTNNB1
canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation	1	8426.0×	0.002	CTNNB1
cranial ganglion development	1	8426.0×	0.002	CTNNB1
neural plate development	1	4213.0×	0.002	CTNNB1
negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	1	4213.0×	0.002	CTNNB1
regulation of centriole-centriole cohesion	1	4213.0×	0.002	CTNNB1
negative regulation of mitotic cell cycle, embryonic	1	4213.0×	0.002	CTNNB1
regulation of timing of anagen	1	4213.0×	0.002	CTNNB1
positive regulation of branching involved in lung morphogenesis	1	4213.0×	0.002	CTNNB1
renal vesicle formation	1	4213.0×	0.002	CTNNB1
renal inner medulla development	1	4213.0×	0.002	CTNNB1
renal outer medulla development	1	4213.0×	0.002	CTNNB1
nephron tubule formation	1	4213.0×	0.002	CTNNB1
regulation of nephron tubule epithelial cell differentiation	1	4213.0×	0.002	CTNNB1
mesenchymal stem cell differentiation	1	4213.0×	0.002	CTNNB1
positive regulation of determination of dorsal identity	1	4213.0×	0.002	CTNNB1
negative regulation of canonical Wnt signaling pathway	2	117.8×	0.002	CTNNB1, APC
astrocyte-dopaminergic neuron signaling	1	2808.7×	0.003	CTNNB1
regulation of fibroblast proliferation	1	2808.7×	0.003	CTNNB1
oviduct development	1	2808.7×	0.003	CTNNB1
lung induction	1	2808.7×	0.003	CTNNB1
positive regulation of epithelial cell proliferation involved in prostate gland development	1	2808.7×	0.003	CTNNB1
fungiform papilla formation	1	2808.7×	0.003	CTNNB1
regulation of centromeric sister chromatid cohesion	1	2808.7×	0.003	CTNNB1
positive regulation of apoptotic process	2	56.7×	0.003	CTNNB1, APC
proteasome-mediated ubiquitin-dependent protein catabolic process	2	52.2×	0.003	CTNNB1, APC
regulation of secondary heart field cardioblast proliferation	1	2106.5×	0.003	CTNNB1
metanephros morphogenesis	1	2106.5×	0.003	CTNNB1
positive regulation of heparan sulfate proteoglycan biosynthetic process	1	2106.5×	0.003	CTNNB1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
CTNNB1	DITHIAZANINE IODIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTNNB1	4	4
APC	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DITHIAZANINE IODIDE	4	CTNNB1
QUERCETIN	3	CTNNB1
SALINOMYCIN	2	CTNNB1
DALOSIRVAT	2	CTNNB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CTNNB1	361	Binding:358, Functional:3
APC	24	Binding:24

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CTNNB1	361

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

4 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
DITHIAZANINE IODIDE	4	CTNNB1
QUERCETIN	3	CTNNB1
SALINOMYCIN	2	CTNNB1
DALOSIRVAT	2	CTNNB1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CTNNB1
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	APC

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)
APC	24	CTNNB1

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03966742	PHASE2	COMPLETED	Doxorubicin Eluting Intra-arterial Embolization for Aggressive Desmoid Fibromatosis