Congenital smooth muscle hamartoma

Summary

Congenital smooth muscle hamartoma (MONDO:0016986) is a disease with 1 cohort gene.

At a glance

• Prevalence: 1-5 / 10 000 (Israel) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-5 / 10 000	38.5	Israel	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital smooth muscle hamartoma
Mondo ID	MONDO:0016986
Orphanet	263435
SNOMED CT	239144007
UMLS	C0406819
MedGen	590701
GARD	0020902
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › hamartoma › congenital smooth muscle hamartoma

Related subtypes (12): chondroid hamartoma, gastrointestinal hamartoma, linear nevus sebaceous syndrome, linear and whorled nevoid hypermelanosis, congenital epulis, hamartoma of skin appendage, hamartoma of lung, basaloid follicular hamartoma, angiomyomatous hamartoma, giant mammary hamartoma, mesenchymal hamartoma, odontoma

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

5 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 2 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1344710	NM_001101.5(ACTB):c.439C>A (p.Arg147Ser)	ACTB	Pathogenic	criteria provided, single submitter
1344712	NM_001101.5(ACTB):c.437G>C (p.Gly146Ala)	ACTB	Pathogenic/Likely pathogenic	no assertion criteria provided
1344713	NM_001101.5(ACTB):c.436G>A (p.Gly146Ser)	ACTB	Pathogenic/Likely pathogenic	no assertion criteria provided
1344711	NM_001101.5(ACTB):c.411G>T (p.Gln137His)	ACTB	Likely pathogenic	no assertion criteria provided
1344714	NM_001101.5(ACTB):c.331A>G (p.Asn111Asp)	ACTB	Likely pathogenic	no assertion criteria provided

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
ACTB	Orphanet:2995	Baraitser-Winter cerebrofrontofacial syndrome
ACTB	Orphanet:64755	Becker nevus syndrome
ACTB	Orphanet:673556	Pseudomyogenic hemangioendothelioma
ACTB	Orphanet:674653	Actinomyopathy-associated syndromic thrombocytopenia
ACTB	Orphanet:79107	Developmental malformations-deafness-dystonia 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
ACTB	HGNC:132	ENSG00000075624	P60709	Actin, cytoplasmic 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACTB	Actin, cytoplasmic 1	Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells.

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)
ACTB	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS

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
postcentral gyrus	1
saphenous vein	1
urethra	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACTB	295	ubiquitous	marker	urethra, postcentral gyrus, saphenous vein

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACTB	2,212

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACTB	P60709	88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 100. 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
Folding of actin by CCT/TriC	1	1142.0×	0.009	ACTB
Formation of annular gap junctions	1	1038.2×	0.009	ACTB
GBP-mediated host defense	1	1038.2×	0.009	ACTB
Gap junction degradation	1	951.7×	0.009	ACTB
Regulation of CDH1 Function	1	951.7×	0.009	ACTB
Cell-extracellular matrix interactions	1	671.8×	0.009	ACTB
Formation of the non-canonical BAF (ncBAF) complex	1	671.8×	0.009	ACTB
Formation of the canonical BAF (cBAF) complex	1	634.4×	0.009	ACTB
Formation of the polybromo-BAF (pBAF) complex	1	634.4×	0.009	ACTB
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.009	ACTB
Gap junction trafficking and regulation	1	475.8×	0.009	ACTB
Gap junction trafficking	1	475.8×	0.009	ACTB
Global Genome Nucleotide Excision Repair (GG-NER)	1	456.8×	0.009	ACTB
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.009	ACTB
Signaling by RAS mutants	1	423.0×	0.009	ACTB
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	407.9×	0.009	ACTB
Prefoldin mediated transfer of substrate to CCT/TriC	1	393.8×	0.009	ACTB
Interaction between L1 and Ankyrins	1	368.4×	0.009	ACTB
Regulation of endogenous retroelements	1	368.4×	0.009	ACTB
Positive epigenetic regulation of rRNA expression	1	346.1×	0.009	ACTB
RHO GTPases activate IQGAPs	1	346.1×	0.009	ACTB
Parasite infection	1	346.1×	0.009	ACTB
Leishmania phagocytosis	1	346.1×	0.009	ACTB
RHO GTPases Activate WASPs and WAVEs	1	317.2×	0.009	ACTB
Signaling by high-kinase activity BRAF mutants	1	317.2×	0.009	ACTB
Sensory processing of sound	1	308.6×	0.009	ACTB
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.009	ACTB
Chaperonin-mediated protein folding	1	300.5×	0.009	ACTB
MAP2K and MAPK activation	1	285.5×	0.009	ACTB
DNA Damage Recognition in GG-NER	1	285.5×	0.009	ACTB

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 norepinephrine uptake	1	16852.0×	0.001	ACTB
cellular response to cytochalasin B	1	16852.0×	0.001	ACTB
regulation of norepinephrine uptake	1	8426.0×	0.001	ACTB
morphogenesis of a polarized epithelium	1	4213.0×	0.002	ACTB
regulation of transepithelial transport	1	4213.0×	0.002	ACTB
protein localization to adherens junction	1	3370.4×	0.002	ACTB
adherens junction assembly	1	1296.3×	0.004	ACTB
apical protein localization	1	991.3×	0.004	ACTB
regulation of synaptic vesicle endocytosis	1	887.0×	0.004	ACTB
regulation of G0 to G1 transition	1	674.1×	0.004	ACTB
regulation of protein localization to plasma membrane	1	648.1×	0.004	ACTB
regulation of nucleotide-excision repair	1	601.9×	0.004	ACTB
regulation of double-strand break repair	1	581.1×	0.004	ACTB
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.004	ACTB
maintenance of blood-brain barrier	1	481.5×	0.004	ACTB
positive regulation of T cell differentiation	1	455.5×	0.004	ACTB
establishment or maintenance of cell polarity	1	401.2×	0.004	ACTB
cell motility	1	401.2×	0.004	ACTB
positive regulation of double-strand break repair via homologous recombination	1	383.0×	0.004	ACTB
substantia nigra development	1	366.4×	0.004	ACTB
positive regulation of myoblast differentiation	1	366.4×	0.004	ACTB
positive regulation of stem cell population maintenance	1	343.9×	0.004	ACTB
positive regulation of double-strand break repair	1	343.9×	0.004	ACTB
platelet aggregation	1	337.0×	0.004	ACTB
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.005	ACTB
negative regulation of cell differentiation	1	285.6×	0.005	ACTB
positive regulation of cell differentiation	1	267.5×	0.005	ACTB
axonogenesis	1	160.5×	0.008	ACTB
cytoskeleton organization	1	132.7×	0.009	ACTB
regulation of apoptotic process	1	83.4×	0.014	ACTB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACTB	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	ACTB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ACTB	21	Binding:21

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

1 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)
MOLIBRESIB	2	ACTB

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	1	ACTB
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.