Fibromatosis, gingival, 1

Summary

Fibromatosis, gingival, 1 (MONDO:0007609) is a disease caused by SOS1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: SOS1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 382

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fibromatosis, gingival, 1
Mondo ID	MONDO:0007609
OMIM	135300
UMLS	C4551558
MedGen	1647111
GARD	0006509
Is cancer (heuristic)	no

Also known as: fibromatosis gingival, hereditary, 1 · fibromatosis, gingival, 1 · fibromatosis, gingival, type 1 · GGF1 · GINGF · GINGF1 · gingival fibromatosis caused by mutation in SOS1 · gingival fibromatosis, 1 · hereditary gingival fibromatosis caused by mutation in SOS1 · hereditary gingival fibromatosis, 1 · HGF1 · SOS1 gingival fibromatosis · SOS1 hereditary gingival fibromatosis

Data availability: 382 ClinVar variants · 1 GenCC gene-disease record.

Disease family

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 › fibromatosis, gingival, 1

Related subtypes (5): 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

ClinVar germline variants

382 retrieved; paginated sample, class counts are floors:

151 uncertain significance, 80 conflicting classifications of pathogenicity, 62 likely benign, 39 benign/likely benign, 31 benign, 10 pathogenic, 5 pathogenic/likely pathogenic, 4 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
12869	NM_005633.4(SOS1):c.797C>A (p.Thr266Lys)	SOS1	Pathogenic	criteria provided, multiple submitters, no conflicts
12871	NM_005633.4(SOS1):c.1654A>G (p.Arg552Gly)	SOS1	Pathogenic	reviewed by expert panel
12872	NM_005633.4(SOS1):c.1656G>C (p.Arg552Ser)	SOS1	Pathogenic	reviewed by expert panel
181551	NM_005633.4(SOS1):c.1310T>G (p.Ile437Ser)	SOS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
181552	NM_005633.4(SOS1):c.1430A>G (p.Gln477Arg)	SOS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3370396	SOS1, 4-BP INS, 3265TAAC	SOS1	Pathogenic	no assertion criteria provided
40648	NM_005633.4(SOS1):c.253T>C (p.Trp85Arg)	SOS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
40670	NM_005633.4(SOS1):c.1300G>C (p.Gly434Arg)	SOS1	Pathogenic	criteria provided, multiple submitters, no conflicts
40672	NM_005633.4(SOS1):c.1300G>A (p.Gly434Arg)	SOS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
40678	NM_005633.4(SOS1):c.1642A>C (p.Ser548Arg)	SOS1	Pathogenic	reviewed by expert panel
40683	NM_005633.4(SOS1):c.1655G>A (p.Arg552Lys)	SOS1	Pathogenic	reviewed by expert panel
40684	NM_005633.4(SOS1):c.1656G>T (p.Arg552Ser)	SOS1	Pathogenic	reviewed by expert panel
40696	NM_005633.4(SOS1):c.2104T>C (p.Tyr702His)	SOS1	Pathogenic	criteria provided, multiple submitters, no conflicts
40706	NM_005633.4(SOS1):c.2536G>A (p.Glu846Lys)	SOS1	Pathogenic	reviewed by expert panel
45345	NM_005633.4(SOS1):c.1310T>C (p.Ile437Thr)	SOS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
427772	NM_005612.5(REST):c.1310T>A (p.Leu437Ter)	REST	Likely pathogenic	criteria provided, single submitter
427773	NM_005612.5(REST):c.2413del (p.Leu805fs)	REST	Likely pathogenic	criteria provided, single submitter
521933	NM_005633.4(SOS1):c.2207T>G (p.Ile736Arg)	SOS1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
636262	NM_005633.4(SOS1):c.1867T>A (p.Phe623Ile)	SOS1	Likely pathogenic	reviewed by expert panel
1420008	NM_005633.4(SOS1):c.7G>T (p.Ala3Ser)	LOC129933535	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
427771	NM_005612.5(REST):c.2865_2866del (p.Asn958fs)	REST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1026516	NM_005633.4(SOS1):c.1672A>G (p.Met558Val)	SOS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1034196	NM_005633.4(SOS1):c.3370G>A (p.Val1124Ile)	SOS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1194559	NM_005633.4(SOS1):c.1983A>G (p.Ile661Met)	SOS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
120249	NM_005633.4(SOS1):c.2138G>A (p.Arg713Gln)	SOS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1208648	NM_005633.4(SOS1):c.3737A>G (p.Asn1246Ser)	SOS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12868	NM_005633.4(SOS1):c.3248dup (p.Arg1084fs)	SOS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1308834	NM_005633.4(SOS1):c.1988T>C (p.Ile663Thr)	SOS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1334289	NM_005633.4(SOS1):c.3610A>G (p.Ile1204Val)	SOS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1334293	NM_005633.4(SOS1):c.1935A>G (p.Ile645Met)	SOS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
SOS1	Strong	Autosomal dominant	fibromatosis, gingival, 1	10

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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SOS1	HGNC:11187	ENSG00000115904	Q07889	Son of sevenless homolog 1	gencc,clinvar
REST	HGNC:9966	ENSG00000084093	Q13127	RE1-silencing transcription factor	clinvar

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.
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: 0 · Difficult: 2 · Unknown: 0 · 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
Scaffold/PPI	1	8.6×	0.225
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SOS1	Scaffold/PPI	no		DH_dom, Ras-like_Gua-exchang_fac_N, PH_domain
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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
jejunal mucosa	1
tendon of biceps brachii	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
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

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SOS1	Q07889	91
REST	Q13127	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 137. 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
Downstream signaling of activated FGFR2	1	2855.0×	0.008	SOS1
Downstream signaling of activated FGFR3	1	2855.0×	0.008	SOS1
Downstream signaling of activated FGFR4	1	1903.3×	0.008	SOS1
Signaling by ERBB2 in Cancer	1	1142.0×	0.008	SOS1
Signaling by EGFRvIII in Cancer	1	1142.0×	0.008	SOS1
Regulation of NPAS4 gene transcription	1	1142.0×	0.008	REST
Signaling by Ligand-Responsive EGFR Variants in Cancer	1	951.7×	0.008	SOS1
Signaling by NTRK2 (TRKB)	1	815.7×	0.008	SOS1
Signaling by PDGFR in disease	1	815.7×	0.008	SOS1
SOS-mediated signalling	1	713.8×	0.008	SOS1
IGF1R signaling cascade	1	713.8×	0.008	SOS1
Activated NTRK3 signals through RAS	1	634.4×	0.008	SOS1
Signaling by EGFR in Cancer	1	571.0×	0.008	SOS1
EGFR Transactivation by Gastrin	1	571.0×	0.008	SOS1
SHC-related events triggered by IGF1R	1	571.0×	0.008	SOS1
Signaling by FGFR3	1	571.0×	0.008	SOS1
Activated NTRK2 signals through RAS	1	571.0×	0.008	SOS1
Signaling by NTRK3 (TRKC)	1	571.0×	0.008	SOS1
Signaling by KIT in disease	1	571.0×	0.008	SOS1
FLT3 signaling in disease	1	571.0×	0.008	SOS1
IRS-mediated signalling	1	519.1×	0.008	SOS1
IRS-related events triggered by IGF1R	1	519.1×	0.008	SOS1
Signaling by FGFR4	1	519.1×	0.008	SOS1
Signal attenuation	1	519.1×	0.008	SOS1
MET activates RAS signaling	1	519.1×	0.008	SOS1
Signaling by Erythropoietin	1	519.1×	0.008	SOS1
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	1	475.8×	0.008	SOS1
Signaling by FGFR4 in disease	1	475.8×	0.008	SOS1
Activated NTRK2 signals through FRS2 and FRS3	1	475.8×	0.008	SOS1
Constitutive Signaling by Overexpressed ERBB2	1	475.8×	0.008	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to ischemia	2	251.5×	0.001	SOS1, REST
negative regulation of dense core granule biogenesis	1	8426.0×	0.003	REST
negative regulation of amniotic stem cell differentiation	1	8426.0×	0.003	REST
modification of synaptic structure	1	4213.0×	0.003	REST
negative regulation of mesenchymal stem cell differentiation	1	4213.0×	0.003	REST
negative regulation of aldosterone biosynthetic process	1	2106.5×	0.004	REST
midbrain morphogenesis	1	2106.5×	0.004	SOS1
negative regulation of cortisol biosynthetic process	1	2106.5×	0.004	REST
vitellogenesis	1	1685.2×	0.004	SOS1
regulation of pro-B cell differentiation	1	1685.2×	0.004	SOS1
cardiac atrium morphogenesis	1	1404.3×	0.005	SOS1
regulation of T cell differentiation in thymus	1	1203.7×	0.005	SOS1
pericardium morphogenesis	1	1053.2×	0.005	SOS1
negative regulation of calcium ion-dependent exocytosis	1	936.2×	0.005	REST
heart trabecula morphogenesis	1	936.2×	0.005	SOS1
cardiac muscle cell myoblast differentiation	1	702.2×	0.005	REST
host-mediated suppression of viral transcription	1	648.1×	0.005	REST
regulation of osteoblast differentiation	1	648.1×	0.005	REST
cellular response to electrical stimulus	1	648.1×	0.005	REST
nervous system process	1	601.9×	0.005	REST
positive regulation of programmed cell death	1	561.7×	0.005	REST
Schwann cell development	1	526.6×	0.005	SOS1
regulation of T cell proliferation	1	526.6×	0.005	SOS1
neurotrophin TRK receptor signaling pathway	1	526.6×	0.005	SOS1
eyelid development in camera-type eye	1	526.6×	0.005	SOS1
detection of mechanical stimulus involved in sensory perception of sound	1	468.1×	0.006	REST
cellular response to stress	1	421.3×	0.006	REST
auditory receptor cell stereocilium organization	1	421.3×	0.006	REST
blood vessel morphogenesis	1	401.2×	0.006	SOS1
Fc-epsilon receptor signaling pathway	1	366.4×	0.006	SOS1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
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: 2; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	REST

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)
REST	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.