Hamartoma

Summary

Hamartoma (MONDO:0006499) is a disease (an umbrella term covering 13 Mondo subtypes) with 3 cohort genes and 1 clinical trial.

At a glance

• Umbrella term: 13 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 3
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hamartoma
Mondo ID	MONDO:0006499
EFO	EFO:1000634
MeSH	D006222
DOID	DOID:3462
NCIT	C3075
SNOMED CT	400006008
UMLS	C0018552
MedGen	6713
Is cancer (heuristic)	no

Also known as: hamartoma · hamartoma (disease)

Data availability: 3 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 13 Mondo subtypes.

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

Related subtypes (47): pre-malignant neoplasm, endocrine gland neoplasm, giant cell tumor, hematopoietic and lymphoid system neoplasm, skin neoplasm, mesenchymal cell neoplasm, epidural spinal canal neoplasm, skeletal muscle neoplasm, trophoblastic neoplasm, cancer, germ cell tumor, benign neoplasm, upper aerodigestive tract neoplasm, histiocytoma, embryonal neoplasm, head and neck neoplasm, epithelial neoplasm, reproductive system neoplasm, non-seminomatous lesion, odontogenic cyst, phosphaturic mesenchymal tumor, thyroglossal duct cyst, mesenchymoma, mesothelial neoplasm, peritoneal neoplasm, virus associated tumor, nail tumor, respiratory tract neoplasm, spindle cell neoplasm, mixed neoplasm, urinary system neoplasm, cystic neoplasm, childhood neoplasm, melanocytic neoplasm, digestive system neoplasm, nervous system neoplasm, neoplasm of thorax, connective tissue neoplasm, bronchial adenomas/carcinoids childhood, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, erythroplakia, retroperitoneal neoplasm, cardiovascular neoplasm, dermoid or epidermoid cyst of the central nervous system, connective and soft tissue neoplasm, NTRK fusion positive cancer, RET fusion positive cancer

Subtypes (13): chondroid hamartoma, gastrointestinal hamartoma, linear nevus sebaceous syndrome, linear and whorled nevoid hypermelanosis, congenital epulis, congenital smooth muscle hamartoma, 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

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16332	NM_000142.5(FGFR3):c.742C>T (p.Arg248Cys)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
48943	NM_000368.5(TSC1):c.2356C>T (p.Arg786Ter)	TSC1	Pathogenic	criteria provided, multiple submitters, no conflicts
373972	NM_000548.5(TSC2):c.5160+4A>C	TSC2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 23 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSC1	Orphanet:210159	Adult hepatocellular carcinoma
TSC1	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC1	Orphanet:538	Lymphangioleiomyomatosis
TSC1	Orphanet:805	Tuberous sclerosis complex
TSC2	Orphanet:210159	Adult hepatocellular carcinoma
TSC2	Orphanet:269001	Isolated focal cortical dysplasia type IIa
TSC2	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC2	Orphanet:538	Lymphangioleiomyomatosis
TSC2	Orphanet:805	Tuberous sclerosis complex
TSC2	Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
FGFR3	Orphanet:15	Achondroplasia
FGFR3	Orphanet:1860	Thanatophoric dysplasia type 1
FGFR3	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR3	Orphanet:251576	Gliosarcoma
FGFR3	Orphanet:251579	Giant cell glioblastoma
FGFR3	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
FGFR3	Orphanet:429	Hypochondroplasia
FGFR3	Orphanet:53271	Muenke syndrome
FGFR3	Orphanet:794	Saethre-Chotzen syndrome
FGFR3	Orphanet:85164	Camptodactyly-tall stature-scoliosis-hearing loss syndrome
FGFR3	Orphanet:85165	Severe achondroplasia-developmental delay-acanthosis nigricans syndrome
FGFR3	Orphanet:93262	Crouzon syndrome-acanthosis nigricans syndrome
FGFR3	Orphanet:93274	Thanatophoric dysplasia type 2

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TSC1	HGNC:12362	ENSG00000165699	Q92574	Hamartin	clinvar
TSC2	HGNC:12363	ENSG00000103197	P49815	Tuberin	clinvar
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSC1	Hamartin	Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…
TSC2	Tuberin	Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule…
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	9.2×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TSC1	Other/Unknown	no		Hamartin
TSC2	Other/Unknown	no		Rap/Ran_GAP_dom, Tuberin, ARM-like
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gluteal muscle	1
lateral globus pallidus	1
substantia nigra pars compacta	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
skin of hip	1
upper arm skin	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSC1	297	ubiquitous	marker	substantia nigra pars compacta, gluteal muscle, lateral globus pallidus
TSC2	282	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSC1	5,445
FGFR3	4,510
TSC2	4,135

Intra-cohort edges

A	B	Sources
TSC1	TSC2	biogrid_interaction, intact, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR3	P22607	15
TSC1	Q92574	5
TSC2	P49815	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Inhibition of TSC complex formation by AKT (PKB)	2	1522.7×	1e-05	TSC1, TSC2
Energy dependent regulation of mTOR by LKB1-AMPK	2	262.5×	2e-04	TSC1, TSC2
TBC/RABGAPs	2	173.0×	3e-04	TSC1, TSC2
t(4;14) translocations of FGFR3	1	3806.7×	9e-04	FGFR3
Signaling by FGFR3 fusions in cancer	1	3806.7×	9e-04	FGFR3
TP53 Regulates Metabolic Genes	2	86.5×	9e-04	TSC1, TSC2
Macroautophagy	2	76.9×	9e-04	TSC1, TSC2
FGFR3b ligand binding and activation	1	543.8×	0.005	FGFR3
Signaling by activated point mutants of FGFR3	1	317.2×	0.007	FGFR3
FGFR3c ligand binding and activation	1	292.8×	0.007	FGFR3
Phospholipase C-mediated cascade; FGFR3	1	292.8×	0.007	FGFR3
AKT phosphorylates targets in the cytosol	1	271.9×	0.007	TSC2
PI-3K cascade:FGFR3	1	211.5×	0.008	FGFR3
SHC-mediated cascade:FGFR3	1	200.3×	0.008	FGFR3
FRS-mediated FGFR3 signaling	1	181.3×	0.008	FGFR3
Signaling by FGFR3 in disease	1	165.5×	0.009	FGFR3
Negative regulation of FGFR3 signaling	1	146.4×	0.009	FGFR3
Constitutive Signaling by AKT1 E17K in Cancer	1	141.0×	0.009	TSC2
PI3K Cascade	1	90.6×	0.013	FGFR3
Constitutive Signaling by Aberrant PI3K in Cancer	1	42.3×	0.027	FGFR3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	32.3×	0.034	FGFR3
PIP3 activates AKT signaling	1	22.3×	0.046	FGFR3
RAF/MAP kinase cascade	1	20.4×	0.048	FGFR3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of TOR signaling	2	374.5×	6e-04	TSC1, TSC2
negative regulation of TORC1 signaling	2	216.1×	9e-04	TSC1, TSC2
cellular response to starvation	2	129.1×	0.001	TSC1, TSC2
neural tube closure	2	124.8×	0.001	TSC1, TSC2
negative regulation of developmental growth	1	5617.3×	0.002	FGFR3
fibroblast growth factor receptor apoptotic signaling pathway	1	2808.7×	0.004	FGFR3
memory T cell differentiation	1	1872.4×	0.004	TSC1
bone maturation	1	1872.4×	0.004	FGFR3
regulation of cell cycle	2	49.7×	0.004	TSC1, TSC2
cellular response to decreased oxygen levels	1	1404.3×	0.005	TSC1
positive regulation of phospholipase activity	1	1123.5×	0.005	FGFR3
endochondral bone growth	1	561.7×	0.007	FGFR3
negative regulation of ATP-dependent activity	1	561.7×	0.007	TSC1
negative regulation of cell size	1	561.7×	0.007	TSC1
regulation of insulin receptor signaling pathway	1	561.7×	0.007	TSC2
negative regulation of cell population proliferation	2	28.1×	0.007	TSC1, TSC2
negative regulation of mitophagy	1	510.7×	0.008	TSC2
regulation of cell-matrix adhesion	1	432.1×	0.008	TSC1
anoikis	1	432.1×	0.008	TSC2
negative regulation of macroautophagy	1	374.5×	0.009	TSC1
chondrocyte proliferation	1	351.1×	0.009	FGFR3
regulation of stress fiber assembly	1	330.4×	0.009	TSC1
obsolete D-glucose import	1	280.9×	0.010	TSC1
positive chemotaxis	1	267.5×	0.010	TSC2
positive regulation of tyrosine phosphorylation of STAT protein	1	244.2×	0.010	FGFR3
activation of GTPase activity	1	244.2×	0.010	TSC1
cardiac muscle cell differentiation	1	224.7×	0.011	TSC1
positive regulation of focal adhesion assembly	1	216.1×	0.011	TSC1
bone morphogenesis	1	200.6×	0.011	FGFR3
endochondral ossification	1	181.2×	0.012	FGFR3

Therapeutics

Drugs indicated for this disease

2 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Cannabidiol	Approved (phase 4)
Everolimus	Approved (phase 4)

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
FGFR3	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR3	64	4
TSC1	0	0
TSC2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR3
PEMIGATINIB	4	FGFR3
NINTEDANIB	4	FGFR3
FEDRATINIB	4	FGFR3
LENVATINIB	4	FGFR3
AXITINIB	4	FGFR3
SORAFENIB	4	FGFR3
INFIGRATINIB PHOSPHATE	4	FGFR3
INFIGRATINIB	4	FGFR3
ENTRECTINIB	4	FGFR3
CERITINIB	4	FGFR3
VANDETANIB	4	FGFR3
NINTEDANIB ESYLATE	4	FGFR3
BRIGATINIB	4	FGFR3
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3
SUNITINIB	4	FGFR3
DASATINIB	4	FGFR3
CRIZOTINIB	4	FGFR3
MIDOSTAURIN	4	FGFR3
LINIFANIB	3	FGFR3
SEMAXANIB	3	FGFR3
BRIVANIB	3	FGFR3
ALISERTIB	3	FGFR3
CEDIRANIB	3	FGFR3
DOVITINIB	3	FGFR3
LESTAURTINIB	3	FGFR3
TANDUTINIB	2	FGFR3
FORETINIB	2	FGFR3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FGFR3	975	Binding:948, Functional:18, ADMET:9
TSC2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR3	2.7.10.1	receptor 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
FGFR3	975

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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)
PONATINIB	4	FGFR3
PEMIGATINIB	4	FGFR3
NINTEDANIB	4	FGFR3
FEDRATINIB	4	FGFR3
LENVATINIB	4	FGFR3
AXITINIB	4	FGFR3
SORAFENIB	4	FGFR3
INFIGRATINIB PHOSPHATE	4	FGFR3
INFIGRATINIB	4	FGFR3
ENTRECTINIB	4	FGFR3
CERITINIB	4	FGFR3
VANDETANIB	4	FGFR3
NINTEDANIB ESYLATE	4	FGFR3
BRIGATINIB	4	FGFR3
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3
SUNITINIB	4	FGFR3
DASATINIB	4	FGFR3
CRIZOTINIB	4	FGFR3
MIDOSTAURIN	4	FGFR3
LINIFANIB	3	FGFR3
SEMAXANIB	3	FGFR3
BRIVANIB	3	FGFR3
ALISERTIB	3	FGFR3
CEDIRANIB	3	FGFR3
DOVITINIB	3	FGFR3
LESTAURTINIB	3	FGFR3
TANDUTINIB	2	FGFR3
FORETINIB	2	FGFR3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	FGFR3
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	2	TSC1, TSC2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TSC1	0	—
TSC2	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
NCT06915649	Not specified	RECRUITING	Exploration and Evaluation of Amygdalo-Hippocampectomy According to Prof. Coubes’ Technique: An Anatomical, Clinical, and Educational Approach