Leiomyoma cutis

Summary

Leiomyoma cutis (MONDO:0003291) is a disease with 1 cohort gene and 3 clinical trials. Top therapeutic interventions include botulinum toxin type a.

At a glance

• Cohort genes: 1
• ClinVar variants: 2
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	leiomyoma cutis
Mondo ID	MONDO:0003291
DOID	DOID:5132
NCIT	C4482
SNOMED CT	254767008
UMLS	C0346064
MedGen	87533
GARD	0023435
Anatomy (UBERON)	UBERON:0000014
Is cancer (heuristic)	no

Also known as: cutaneous (skin) leiomyoma · cutaneous leiomyoma · leiomyoma cutis · leiomyoma of skin · leiomyoma of the skin · leiomyoma of zone of skin · skin leiomyoma · zone of skin leiomyoma

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › musculoskeletal system benign neoplasm › benign muscle neoplasm › benign smooth muscle neoplasm › leiomyoma › leiomyoma cutis

Related subtypes (29): laryngeal leiomyoma, gastric leiomyoma, ureter leiomyoma, vaginal leiomyoma, bladder leiomyoma, breast leiomyoma, small intestine leiomyoma, urethra leiomyoma, trachea leiomyoma, prostate leiomyoma, mediastinum leiomyoma, fallopian tube leiomyoma, central nervous system leiomyoma, bizarre leiomyoma, deep leiomyoma, lung leiomyoma, pericardium leiomyoma, leiomyomatosis, cellular leiomyoma, gallbladder leiomyoma, vulvar leiomyoma, colorectal leiomyoma, liver leiomyoma, esophagus leiomyoma, renal leiomyoma, myofibroma, uterine corpus leiomyoma, leiomyoma of ciliary body, benign metastasizing leiomyoma

Subtypes (1): dartoic leiomyoma

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/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
393560	NM_000143.4(FH):c.322C>T (p.Gln108Ter)	FH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2885468	NM_000143.4(FH):c.263T>A (p.Met88Lys)	FH	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FH	Orphanet:24	Fumaric aciduria
FH	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
FH	Orphanet:523	Hereditary leiomyomatosis and renal cell cancer

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
FH	HGNC:3700	ENSG00000091483	P07954	Fumarate hydratase, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FH	Fumarate hydratase, mitochondrial	Catalyzes the reversible stereospecific interconversion of fumarate to L-malate.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FH	Enzyme (other)	yes	4.2.1.2	Fumarate_lyase_fam, Fum_hydII, L-Aspartase-like

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
body of tongue	1
cardiac ventricle	1
heart right ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FH	292	ubiquitous	marker	heart right ventricle, body of tongue, cardiac ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FH	3,709

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FH	P07954	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Citric acid cycle (TCA cycle)	1	423.0×	0.005	FH
Mitochondrial protein degradation	1	114.2×	0.009	FH

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
fumarate metabolic process	1	16852.0×	7e-04	FH
obsolete regulation of arginine metabolic process	1	8426.0×	7e-04	FH
arginine metabolic process	1	2407.4×	0.001	FH
malate metabolic process	1	1872.4×	0.001	FH
urea cycle	1	1296.3×	0.002	FH
positive regulation of double-strand break repair via nonhomologous end joining	1	991.3×	0.002	FH
tricarboxylic acid cycle	1	510.7×	0.003	FH
homeostasis of number of cells within a tissue	1	443.5×	0.003	FH
positive regulation of cold-induced thermogenesis	1	163.6×	0.007	FH
DNA repair	1	63.8×	0.017	FH
DNA damage response	1	53.5×	0.019	FH

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FH	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FH	4.2.1.2	fumarate hydratase

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	1	FH
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
FH	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00971620	PHASE2	COMPLETED	Randomized Pilot Study for the Treatment of Cutaneous Leiomyomas With Botulinum Toxin
NCT00050752	Not specified	RECRUITING	Hereditary Leiomyomatosis Renal Cell Cancer - Study of the Genetic Cause and the Predisposition to Renal Cancer
NCT05534854	Not specified	UNKNOWN	Frequency, Clinical Phenotype and Genetic Analysis of Heritable Kidney Cancer Syndromes

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BOTULINUM TOXIN TYPE A	4	1