Pilomatrixoma

Summary

Pilomatrixoma (MONDO:0007564) is a disease with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• ClinVar variants: 31
• Phenotypes (HPO): 6
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0030434	Pilomatrixoma	Obligate (100%)
HP:0001482	Subcutaneous nodule	Very frequent (80-99%)
HP:0012288	Neoplasm of head and neck	Very frequent (80-99%)
HP:0010766	Ectopic calcification	Occasional (5-29%)
HP:0000989	Pruritus	Very rare (<1-4%)
HP:0033559	Anti-myeloperoxidase antibody positivity	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	pilomatrixoma
Mondo ID	MONDO:0007564
EFO	EFO:0009082
MeSH	D018296
OMIM	132600
Orphanet	91414
DOID	DOID:5374
ICD-11	378820295
NCIT	C7368
SNOMED CT	274901004
UMLS	C0206711
MedGen	61666
GARD	0009452
MedDRA	10035040
Is cancer (heuristic)	no

Also known as: benign hair follicle neoplasm · benign pilomatricoma · benign pilomatrixoma · calcifying epithelioma of Malherbe · calcifying Epitherlioma of Malherbe · epithelioma calcificans of Malherbe · pilomatricoma · pilomatricoma, somatic · pilomatrixoma · pilomatrixoma, benign · PTR

Data availability: 31 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › skin neoplasm › epidermal appendage tumor › hair follicle neoplasm › pilomatrixoma

Related subtypes (2): follicular infundibulum tumor, proliferating trichilemmal cyst

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

31 retrieved; paginated sample, class counts are floors:

7 conflicting classifications of pathogenicity, 7 pathogenic/likely pathogenic, 6 pathogenic, 4 benign/likely benign, 3 pathogenic; other, 2 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
17577	NM_001904.4(CTNNB1):c.98C>A (p.Ser33Tyr)	CTNNB1	Pathogenic	no assertion criteria provided
17578	NM_001904.4(CTNNB1):c.95A>G (p.Asp32Gly)	CTNNB1	Pathogenic/Likely pathogenic	no assertion criteria provided
17579	NM_001904.4(CTNNB1):c.110C>G (p.Ser37Cys)	CTNNB1	Pathogenic/Likely pathogenic	no assertion criteria provided
17584	NM_001904.4(CTNNB1):c.101G>A (p.Gly34Glu)	CTNNB1	Pathogenic; other	no assertion criteria provided
17586	NM_001904.4(CTNNB1):c.110C>T (p.Ser37Phe)	CTNNB1	Pathogenic	no assertion criteria provided
265443	NM_001904.4(CTNNB1):c.283C>T (p.Arg95Ter)	CTNNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
39655	NM_001904.4(CTNNB1):c.1543C>T (p.Arg515Ter)	CTNNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
17581	NM_001904.4(CTNNB1):c.94G>T (p.Asp32Tyr)	LOC126806658	Pathogenic; other	no assertion criteria provided
17583	NM_001904.4(CTNNB1):c.98C>T (p.Ser33Phe)	LOC126806658	Pathogenic; other	no assertion criteria provided
559636	NM_001904.4(CTNNB1):c.1420C>T (p.Arg474Ter)	LOC126806659	Pathogenic	criteria provided, multiple submitters, no conflicts
127845	NM_001048174.2(MUTYH):c.13C>T (p.Arg5Ter)	MUTYH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
135990	NM_001048174.2(MUTYH):c.652G>T (p.Val218Phe)	MUTYH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140877	NM_001048174.2(MUTYH):c.650G>A (p.Arg217His)	MUTYH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
187280	NM_001048174.2(MUTYH):c.460C>T (p.Arg154Cys)	MUTYH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
234229	NM_001048174.2(MUTYH):c.305-1G>C	MUTYH	Pathogenic	criteria provided, multiple submitters, no conflicts
5294	NM_001048174.2(MUTYH):c.1103G>A (p.Gly368Asp)	MUTYH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17580	NM_001904.4(CTNNB1):c.121A>G (p.Thr41Ala)	CTNNB1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
17587	NM_001904.4(CTNNB1):c.122C>T (p.Thr41Ile)	CTNNB1	Likely pathogenic	criteria provided, single submitter
127840	NM_001048174.2(MUTYH):c.1409A>G (p.Gln470Arg)	MUTYH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127846	NM_001048174.2(MUTYH):c.488G>A (p.Arg163Gln)	MUTYH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134859	NM_001048174.2(MUTYH):c.901G>A (p.Val301Met)	MUTYH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135983	NM_001048174.2(MUTYH):c.1171G>A (p.Ala391Thr)	MUTYH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
142736	NM_001048174.2(MUTYH):c.263G>A (p.Arg88Gln)	MUTYH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
182694	NM_001048174.2(MUTYH):c.848G>A (p.Arg283Lys)	MUTYH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
183823	NM_001048174.2(MUTYH):c.916C>G (p.Pro306Ala)	MUTYH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1403921	NM_001904.4(CTNNB1):c.1571A>G (p.His524Arg)	CTNNB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
41754	NM_001048174.2(MUTYH):c.1336C>T (p.Arg446Cys)	MUTYH	Uncertain significance	criteria provided, multiple submitters, no conflicts
128866	NM_001904.4(CTNNB1):c.14-4A>G	CTNNB1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1599823	NM_001904.4(CTNNB1):c.1683+17A>G	CTNNB1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
210805	NM_001904.4(CTNNB1):c.2320C>T (p.Leu774=)	CTNNB1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
MUTYH	Orphanet:247798	MUTYH-related polyposis
MUTYH	Orphanet:440437	Familial colorectal cancer Type X

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
MUTYH	HGNC:7527	ENSG00000132781	Q9UIF7	Adenine DNA glycosylase	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.
MUTYH	Adenine DNA glycosylase	Involved in oxidative DNA damage repair.

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
MUTYH	Other/Unknown	no		NUDIX_hydrolase_dom, HhH_motif, HhH-GPD_domain

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	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
MUTYH	134	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNNB1	15,668
MUTYH	1,815

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTNNB1	P35222	50
MUTYH	Q9UIF7	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 51. 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
Defective MUTYH substrate binding	1	5710.0×	0.004	MUTYH
Defective MUTYH substrate processing	1	5710.0×	0.004	MUTYH
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	1142.0×	0.007	CTNNB1
CDH11 homotypic and heterotypic interactions	1	815.7×	0.007	CTNNB1
Regulation of CDH19 Expression and Function	1	713.8×	0.007	CTNNB1
InlA-mediated entry of Listeria monocytogenes into host cells	1	634.4×	0.007	CTNNB1
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	571.0×	0.007	CTNNB1
RUNX3 regulates WNT signaling	1	571.0×	0.007	CTNNB1
Displacement of DNA glycosylase by APEX1	1	519.1×	0.007	MUTYH
Apoptotic cleavage of cell adhesion proteins	1	519.1×	0.007	CTNNB1
Regulation of CDH11 function	1	519.1×	0.007	CTNNB1
Regulation of CDH1 Function	1	475.8×	0.007	CTNNB1
Formation of axial mesoderm	1	407.9×	0.007	CTNNB1
Signaling by GSK3beta mutants	1	380.7×	0.007	CTNNB1
CTNNB1 S33 mutants aren’t phosphorylated	1	380.7×	0.007	CTNNB1
CTNNB1 S37 mutants aren’t phosphorylated	1	380.7×	0.007	CTNNB1
CTNNB1 S45 mutants aren’t phosphorylated	1	380.7×	0.007	CTNNB1
CTNNB1 T41 mutants aren’t phosphorylated	1	380.7×	0.007	CTNNB1
Formation of definitive endoderm	1	356.9×	0.007	CTNNB1
Beta-catenin phosphorylation cascade	1	335.9×	0.007	CTNNB1
Germ layer formation at gastrulation	1	335.9×	0.007	CTNNB1
Formation of the nephric duct	1	317.2×	0.007	CTNNB1
Specification of the neural plate border	1	317.2×	0.007	CTNNB1
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	285.5×	0.007	CTNNB1
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	259.6×	0.008	CTNNB1
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	248.3×	0.008	CTNNB1
Cardiogenesis	1	211.5×	0.009	CTNNB1
VEGFR2 mediated vascular permeability	1	203.9×	0.009	CTNNB1
Formation of paraxial mesoderm	1	203.9×	0.009	CTNNB1
Myogenesis	1	190.3×	0.009	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
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
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
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
embryonic skeletal limb joint morphogenesis	1	2106.5×	0.003	CTNNB1
depurination	1	2106.5×	0.003	MUTYH
central nervous system vasculogenesis	1	1685.2×	0.003	CTNNB1
genitalia morphogenesis	1	1685.2×	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
MUTYH	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
MUTYH	1	Functional:1

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).

Chemical tractability of cohort targets

4 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)
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	MUTYH

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)
MUTYH	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00715819	Not specified	COMPLETED	Use of Otoscope as a Non-invasive Tool for Diagnosis of Pilomatricoma