Hereditary gingival fibromatosis

Summary

Hereditary gingival fibromatosis (MONDO:0016070) is a disease (an umbrella term covering 6 Mondo subtypes) with 4 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 4
• Phenotypes (HPO): 2

Clinical features

Signs & symptoms

Clinical features (HPO)

2 HPO clinical features (Orphanet curated; top 2 by frequency):

HPO ID	Term	Frequency
HP:0000169	Gingival fibromatosis	Very frequent (80-99%)
HP:0000212	Gingival overgrowth	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary gingival fibromatosis
Mondo ID	MONDO:0016070
OMIM	135300
Orphanet	2024
DOID	DOID:0060466
ICD-11	1911315646
SNOMED CT	109620006
UMLS	C0399440
MedGen	140775
GARD	0016582
Is cancer (heuristic)	no

Also known as: autosomal dominant gingival fibromatosis · autosomal dominant gingival hyperplasia · hereditary gingival fibromatosis · hereditary gingival hyperplasia

Data availability: 4 GenCC gene-disease records.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › periodontal disorder › gingival disorder › gingival overgrowth › hereditary gingival fibromatosis

Related subtypes (2): epulis, gingival hypertrophy

Subtypes (6): fibromatosis, gingival, 1, fibromatosis, gingival, 2, fibromatosis, gingival, 3, fibromatosis, gingival, 4, fibromatosis, gingival, 5, fibromatosis, gingival, 6

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
REST	Strong	Autosomal dominant	fibromatosis, gingival, 5	10
SOS1	Strong	Autosomal dominant	fibromatosis, gingival, 1	10
DUSP8	Limited	Autosomal dominant	hereditary gingival fibromatosis
ZNF862	Limited	Autosomal dominant	hereditary gingival fibromatosis

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOS1	Orphanet:2024	Hereditary gingival fibromatosis
SOS1	Orphanet:648	Noonan syndrome
REST	Orphanet:2024	Hereditary gingival fibromatosis
REST	Orphanet:654	Nephroblastoma

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SOS1	HGNC:11187	ENSG00000115904	Q07889	Son of sevenless homolog 1	gencc
DUSP8	HGNC:3074	ENSG00000184545	Q13202	Dual specificity protein phosphatase 8	gencc
ZNF862	HGNC:34519	ENSG00000106479	O60290	Zinc finger protein 862	gencc
REST	HGNC:9966	ENSG00000084093	Q13127	RE1-silencing transcription factor	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SOS1	Son of sevenless homolog 1	Promotes the exchange of Ras-bound GDP by GTP.
DUSP8	Dual specificity protein phosphatase 8	Has phosphatase activity with synthetic phosphatase substrates and negatively regulates mitogen-activated protein kinase activity, presumably by catalysing their dephosphorylation.
ZNF862	Zinc finger protein 862	May be involved in transcriptional regulation.
REST	RE1-silencing transcription factor	Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells.

Protein-family classification

Druggable: 1 · Difficult: 3 · Unknown: 0 · Druggable fraction: 0.25

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
Phosphatase	1	21.0×	0.112
Transcription factor	2	4.1×	0.112
Scaffold/PPI	1	4.3×	0.212

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SOS1	Scaffold/PPI	no		DH_dom, Ras-like_Gua-exchang_fac_N, PH_domain
DUSP8	Phosphatase	yes		Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, Rhodanese-like_dom
ZNF862	Transcription factor	no		KRAB, Znf_TTF, HATC_C_dom
REST	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger/UBP_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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
jejunal mucosa	1
tendon of biceps brachii	1
mucosa of stomach	1
primary visual cortex	1
superior frontal gyrus	1
diaphragm	1
olfactory bulb	1
type B pancreatic cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
mucosa of paranasal sinus	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SOS1	289	ubiquitous	marker	colonic epithelium, jejunal mucosa, tendon of biceps brachii
DUSP8	132	ubiquitous	yes	mucosa of stomach, superior frontal gyrus, primary visual cortex
ZNF862	257	ubiquitous	yes	diaphragm, type B pancreatic cell, olfactory bulb
REST	281	ubiquitous	marker	primordial germ cell in gonad, mucosa of paranasal sinus, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOS1	3,625
REST	2,499
DUSP8	1,722
ZNF862	844

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SOS1	Q07889	91
REST	Q13127	3
DUSP8	Q13202	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZNF862	O60290	67.08

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 140. Enrichment computed across 4 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
Downstream signaling of activated FGFR2	1	1903.3×	0.012	SOS1
Downstream signaling of activated FGFR3	1	1903.3×	0.012	SOS1
Downstream signaling of activated FGFR4	1	1268.9×	0.012	SOS1
Signaling by ERBB2 in Cancer	1	761.3×	0.012	SOS1
Signaling by EGFRvIII in Cancer	1	761.3×	0.012	SOS1
Regulation of NPAS4 gene transcription	1	761.3×	0.012	REST
Signaling by Ligand-Responsive EGFR Variants in Cancer	1	634.4×	0.012	SOS1
Signaling by NTRK2 (TRKB)	1	543.8×	0.012	SOS1
Signaling by MAPK mutants	1	543.8×	0.012	DUSP8
Signaling by PDGFR in disease	1	543.8×	0.012	SOS1
SOS-mediated signalling	1	475.8×	0.012	SOS1
IGF1R signaling cascade	1	475.8×	0.012	SOS1
Activated NTRK3 signals through RAS	1	423.0×	0.012	SOS1
Signaling by EGFR in Cancer	1	380.7×	0.012	SOS1
EGFR Transactivation by Gastrin	1	380.7×	0.012	SOS1
SHC-related events triggered by IGF1R	1	380.7×	0.012	SOS1
Signaling by FGFR3	1	380.7×	0.012	SOS1
Activated NTRK2 signals through RAS	1	380.7×	0.012	SOS1
Signaling by NTRK3 (TRKC)	1	380.7×	0.012	SOS1
Signaling by KIT in disease	1	380.7×	0.012	SOS1
FLT3 signaling in disease	1	380.7×	0.012	SOS1
IRS-mediated signalling	1	346.1×	0.012	SOS1
IRS-related events triggered by IGF1R	1	346.1×	0.012	SOS1
Signaling by FGFR4	1	346.1×	0.012	SOS1
Signal attenuation	1	346.1×	0.012	SOS1
MET activates RAS signaling	1	346.1×	0.012	SOS1
Signaling by Erythropoietin	1	346.1×	0.012	SOS1
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	1	317.2×	0.012	SOS1
Signaling by FGFR4 in disease	1	317.2×	0.012	SOS1
Activated NTRK2 signals through FRS2 and FRS3	1	317.2×	0.012	SOS1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 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 dense core granule biogenesis	1	4213.0×	0.006	REST
negative regulation of amniotic stem cell differentiation	1	4213.0×	0.006	REST
response to ischemia	2	125.8×	0.006	SOS1, REST
modification of synaptic structure	1	2106.5×	0.007	REST
negative regulation of mesenchymal stem cell differentiation	1	2106.5×	0.007	REST
negative regulation of aldosterone biosynthetic process	1	1053.2×	0.009	REST
midbrain morphogenesis	1	1053.2×	0.009	SOS1
negative regulation of cortisol biosynthetic process	1	1053.2×	0.009	REST
vitellogenesis	1	842.6×	0.009	SOS1
regulation of pro-B cell differentiation	1	842.6×	0.009	SOS1
cardiac atrium morphogenesis	1	702.2×	0.009	SOS1
regulation of T cell differentiation in thymus	1	601.9×	0.010	SOS1
pericardium morphogenesis	1	526.6×	0.010	SOS1
negative regulation of calcium ion-dependent exocytosis	1	468.1×	0.010	REST
heart trabecula morphogenesis	1	468.1×	0.010	SOS1
cardiac muscle cell myoblast differentiation	1	351.1×	0.011	REST
host-mediated suppression of viral transcription	1	324.1×	0.011	REST
regulation of osteoblast differentiation	1	324.1×	0.011	REST
cellular response to electrical stimulus	1	324.1×	0.011	REST
nervous system process	1	300.9×	0.011	REST
positive regulation of programmed cell death	1	280.9×	0.011	REST
Schwann cell development	1	263.3×	0.011	SOS1
regulation of T cell proliferation	1	263.3×	0.011	SOS1
neurotrophin TRK receptor signaling pathway	1	263.3×	0.011	SOS1
eyelid development in camera-type eye	1	263.3×	0.011	SOS1
detection of mechanical stimulus involved in sensory perception of sound	1	234.1×	0.012	REST
cellular response to stress	1	210.7×	0.012	REST
auditory receptor cell stereocilium organization	1	210.7×	0.012	REST
blood vessel morphogenesis	1	200.6×	0.012	SOS1
Fc-epsilon receptor signaling pathway	1	183.2×	0.012	SOS1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) 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
SOS1	IDARUBICIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SOS1	5	4
DUSP8	0	0
ZNF862	0	0
REST	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IDARUBICIN	4	SOS1
DOXORUBICIN	4	SOS1
SOTORASIB	4	SOS1
ADAGRASIB	4	SOS1
MRTX-0902	1	SOS1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SOS1	421	Binding:409, Functional:12

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SOS1	421

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

5 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)
IDARUBICIN	4	SOS1
DOXORUBICIN	4	SOS1
SOTORASIB	4	SOS1
ADAGRASIB	4	SOS1
MRTX-0902	1	SOS1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SOS1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	DUSP8
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	ZNF862, REST

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DUSP8	0	—
ZNF862	0	—
REST	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.