Fibromatosis, gingival, 5

Summary

Fibromatosis, gingival, 5 (MONDO:0033493) is a disease caused by REST (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: REST (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 50

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fibromatosis, gingival, 5
Mondo ID	MONDO:0033493
OMIM	617626
DOID	DOID:0080280
UMLS	C4539942
MedGen	1624392
GARD	0018357
Is cancer (heuristic)	no

Also known as: fibromatosis, gingival, 5 · GGF5 · GINGF5

Data availability: 50 ClinVar variants · 3 GenCC gene-disease records.

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, 5

Related subtypes (5): fibromatosis, gingival, 1, fibromatosis, gingival, 2, fibromatosis, gingival, 3, fibromatosis, gingival, 4, 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

50 retrieved; paginated sample, class counts are floors:

38 uncertain significance, 5 conflicting classifications of pathogenicity, 3 pathogenic, 3 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1189032	NM_005612.5(REST):c.2771_2793dup (p.Glu932delinsLysThrTer)	REST	Pathogenic	no assertion criteria provided
2429888	NM_005612.5(REST):c.2809A>T (p.Lys937Ter)	REST	Pathogenic	criteria provided, single submitter
3370397	REST, 2-BP DEL, 1901AG	REST	Pathogenic	no assertion criteria provided
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
807670	NM_005612.5(REST):c.2770C>T (p.Gln924Ter)	REST	Likely pathogenic	criteria provided, single submitter
1019336	NM_005612.5(REST):c.843C>T (p.Cys281=)	REST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2631848	NM_005612.5(REST):c.2945G>A (p.Arg982His)	REST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3590636	NM_005612.5(REST):c.458G>A (p.Ser153Asn)	REST	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
944664	NM_005612.5(REST):c.3098A>G (p.His1033Arg)	REST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000502	NM_005612.5(REST):c.2992G>A (p.Ala998Thr)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1013675	NM_005612.5(REST):c.1747A>G (p.Thr583Ala)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1021123	NM_005612.5(REST):c.2065C>T (p.Pro689Ser)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1047303	NM_005612.5(REST):c.2068C>T (p.Pro690Ser)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1189031	NM_005612.5(REST):c.2449C>T (p.Arg817Ter)	REST	Uncertain significance	criteria provided, single submitter
1347535	NM_005612.5(REST):c.2050C>G (p.His684Asp)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1352070	NM_005612.5(REST):c.2307A>G (p.Ile769Met)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1357352	NM_005612.5(REST):c.2917A>G (p.Met973Val)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1418725	NM_005612.5(REST):c.416A>G (p.Asp139Gly)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1446534	NM_005612.5(REST):c.2780A>G (p.Asn927Ser)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1524176	NM_005612.5(REST):c.2032G>T (p.Ala678Ser)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1931844	NM_005612.5(REST):c.2753A>G (p.His918Arg)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
2170568	NM_005612.5(REST):c.2741A>G (p.Asn914Ser)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
2174361	NM_005612.5(REST):c.608C>G (p.Ser203Cys)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
2178538	NM_005612.5(REST):c.3239A>G (p.Asn1080Ser)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
2181622	NM_005612.5(REST):c.2053A>G (p.Met685Val)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts
3590638	NM_005612.5(REST):c.461C>T (p.Ser154Leu)	REST	Uncertain significance	criteria provided, single submitter
3590639	NM_005612.5(REST):c.657C>G (p.Asp219Glu)	REST	Uncertain significance	criteria provided, single submitter
3590640	NM_005612.5(REST):c.737G>A (p.Arg246Gln)	REST	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
REST	Orphanet:2024	Hereditary gingival fibromatosis
REST	Orphanet:654	Nephroblastoma

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
REST	HGNC:9966	ENSG00000084093	Q13127	RE1-silencing transcription factor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 1 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
REST	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger/UBP_domain

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
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
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
REST	2,499

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
REST	Q13127	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Regulation of NPAS4 gene transcription	1	2284.0×	0.002	REST
NGF-stimulated transcription	1	285.5×	0.009	REST
Regulation of PTEN gene transcription	1	178.4×	0.009	REST
HDACs deacetylate histones	1	120.2×	0.009	REST
Potential therapeutics for SARS	1	114.2×	0.009	REST

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
negative regulation of dense core granule biogenesis	1	16852.0×	0.001	REST
negative regulation of amniotic stem cell differentiation	1	16852.0×	0.001	REST
modification of synaptic structure	1	8426.0×	0.001	REST
negative regulation of mesenchymal stem cell differentiation	1	8426.0×	0.001	REST
negative regulation of aldosterone biosynthetic process	1	4213.0×	0.002	REST
negative regulation of cortisol biosynthetic process	1	4213.0×	0.002	REST
negative regulation of calcium ion-dependent exocytosis	1	1872.4×	0.003	REST
cardiac muscle cell myoblast differentiation	1	1404.3×	0.003	REST
host-mediated suppression of viral transcription	1	1296.3×	0.003	REST
regulation of osteoblast differentiation	1	1296.3×	0.003	REST
cellular response to electrical stimulus	1	1296.3×	0.003	REST
nervous system process	1	1203.7×	0.003	REST
positive regulation of programmed cell death	1	1123.5×	0.003	REST
detection of mechanical stimulus involved in sensory perception of sound	1	936.2×	0.003	REST
cellular response to stress	1	842.6×	0.003	REST
auditory receptor cell stereocilium organization	1	842.6×	0.003	REST
neuronal stem cell population maintenance	1	674.1×	0.003	REST
negative regulation of neurogenesis	1	624.1×	0.003	REST
cellular response to glucocorticoid stimulus	1	624.1×	0.003	REST
negative regulation of miRNA transcription	1	624.1×	0.003	REST
negative regulation of insulin secretion	1	495.6×	0.004	REST
positive regulation of stem cell population maintenance	1	343.9×	0.005	REST
neuromuscular process controlling balance	1	330.4×	0.005	REST
negative regulation of neuron differentiation	1	271.8×	0.006	REST
response to ischemia	1	251.5×	0.006	REST
somatic stem cell population maintenance	1	247.8×	0.006	REST
regulation of alternative mRNA splicing, via spliceosome	1	244.2×	0.006	REST
hematopoietic progenitor cell differentiation	1	237.3×	0.006	REST
positive regulation of neuron differentiation	1	198.3×	0.007	REST
response to hypoxia	1	95.8×	0.013	REST

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
REST	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	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.