| Entity (disease/locus/gene) | Identifier(s) (ORPHA, OMIM/MIM, locus name) | Inheritance/notes | Key evidence/variant(s) (HGVS where given) | Key mechanism/pathway note | Key citation ID(s) |
|---|---|---|---|---|---|
| Hereditary gingival fibromatosis (HGF) | ORPHA 2024; MIM 135300; GINGF/HGF | Rare Mendelian gingival overgrowth; usually autosomal dominant, less often autosomal recessive; isolated or syndromic; prevalence estimates in literature include ~1:175,000 and ~1:750,000 depending on phenotype definition/source | Disease-level entity; no single universal causal variant | Core pathology is excessive extracellular matrix accumulation, especially collagen type I; slow progressive fibrotic gingival overgrowth | (pqac-00000002, pqac-00000003, pqac-00000010, pqac-00000016) |
| GINGF1 locus | 2p21-p22; OMIM/MIM 135300; GINGF1/GINGF | Typically autosomal dominant non-syndromic HGF locus | Linked to SOS1 exon 21 insertion in one Brazilian family | Ras/MAPK-related signaling implicated through SOS1 activation | (pqac-00000005, pqac-00000012, pqac-00000014) |
| GINGF2 locus | 5q13-q22; OMIM/MIM 605544; GINGF2 | Autosomal dominant locus; causative gene not firmly established in retrieved evidence; CAMK4 proposed as candidate in reviews | No definitive pathogenic HGVS variant in retrieved evidence | Candidate calcium-signaling contribution; less resolved than SOS1/REST loci | (pqac-00000005, pqac-00000014, pqac-00000040) |
| GINGF3 locus | 2p23.3-p22.3; OMIM/MIM 609955; GINGF3 | Autosomal dominant locus refined in linkage studies; major locus in some families; later digenic evidence reported within this region | No single classic causal variant from early linkage work; later ZNF513 + KIF3C digenic variants reported | Fibroblast proliferation/fibrosis signaling later tied to PI3K/AKT/mTOR and Ras/Raf/MEK/ERK | (pqac-00000005, pqac-00000008, pqac-00000011) |
| GINGF4 locus | 11p15; OMIM/MIM 611010; GINGF4 | Maternally inherited locus reported; gene unresolved in retrieved evidence | No pathogenic HGVS variant retrieved | Suggests additional locus heterogeneity beyond SOS1 and REST | (pqac-00000002, pqac-00000011, pqac-00000014) |
| GINGF5 locus | 4q12; OMIM/MIM 617626; GINGF5 | Autosomal dominant locus associated with REST | Multiple heterozygous truncating REST alleles identified | Likely altered REST repressor activity with downstream profibrotic/TGF-β effects | (pqac-00000000, pqac-00000014, pqac-00000015) |
| SOS1 | MIM 182530; gene at GINGF1 locus | Established causal gene for isolated non-syndromic HGF in a subset of families; autosomal dominant | g.126,142-126,143insC; c.3248-3249insC; chimeric/truncated protein p.K1084fsX1105 | C-terminal truncation removes regulatory domain, producing constitutive/gain-of-function SOS1 activity with increased MAPK signaling; associated with increased fibroblast proliferation and collagen type I synthesis | (pqac-00000012, pqac-00000014) |
| REST | MIM 600571; gene at GINGF5 locus | Established causal gene; autosomal dominant; de novo case and possible parental mosaicism reported | c.2865_2866delAA p.Asn958Serfs*9; c.1310T>A p.Leu437*; c.2413delC p.Leu805Phefs*38 | Final-exon truncating alleles in transcriptional repressor REST; proposed dominant-negative or neomorphic/gain-of-function-like effect rather than simple haploinsufficiency; linked to increased ECM/collagen and TGF-β dysregulation | (pqac-00000010, pqac-00000015) |
| ZNF862 | Gene on chr7q36.1 | Proposed autosomal dominant HGF gene from a large multigeneration family; not mapped to classic GINGF loci | c.2812G>A; p.A938T; absent from gnomAD/ExAC/1000 Genomes in report | Putative transcriptional regulator; associated with increased COL1A1, TIMP1, TGF-β1 and IL-6 signatures and RNA-seq evidence of TGF-β/SMAD involvement | (pqac-00000009, pqac-00000013, pqac-00000028) |
| ZNF513 + KIF3C | Reported within GINGF3 locus context | Digenic/combined requirement in one family; double heterozygosity required for phenotype in knock-in mouse model | ZNF513 c.C748T p.R250W + KIF3C c.G1229A p.R410H | ZNF513 positively regulates KIF3C and SOS1; KIF3C variant activates PI3K and KCNQ1; combined effect drives gingival fibroblast proliferation, migration, and fibrosis via PI3K/AKT/mTOR and Ras/Raf/MEK/ERK | (pqac-00000008, pqac-00000025) |


*Table: This table summarizes the main identifiers, mapped loci, and currently reported genes and variants for hereditary gingival fibromatosis. It highlights locus heterogeneity, established versus emerging gene evidence, and the main profibrotic signaling mechanisms implicated in HGF.*