Gingival fibromatosis-hypertrichosis syndrome

Summary

Gingival fibromatosis-hypertrichosis syndrome (MONDO:0007610) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 10
• Phenotypes (HPO): 13

Clinical features

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0000169	Gingival fibromatosis	Very frequent (80-99%)
HP:0001007	Hirsutism	Very frequent (80-99%)
HP:0002230	Generalized hirsutism	Very frequent (80-99%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000212	Gingival overgrowth	Frequent (30-79%)
HP:0000280	Coarse facial features	Frequent (30-79%)
HP:0000684	Delayed eruption of teeth	Frequent (30-79%)
HP:0002353	EEG abnormality	Frequent (30-79%)
HP:0000574	Thick eyebrow	Occasional (5-29%)
HP:0000664	Synophrys	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0100543	Cognitive impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	gingival fibromatosis-hypertrichosis syndrome
Mondo ID	MONDO:0007610
MeSH	C565016
OMIM	135400
Orphanet	2026
SNOMED CT	716008002
UMLS	C1851120
MedGen	342675
GARD	0002324
Is cancer (heuristic)	no

Also known as: CGHT · congenital generalised hypertrichosis terminalis · congenital generalized hypertrichosis terminalis · extreme hirsutism with gingival fibromatosis · gingival fibromatosis with hypertrichosis · hereditary gingival fibromatosis with hypertrichosis · hirsutism-congenital gingival hyperplasia syndrome · HTC3 · hypertrichosis terminalis, generalized, with gingival hyperplasia · hypertrichosis with or without gingival hyperplasia · hypertrichosis, congenital generalized, with gingival hyperplasia · hypertrichosis, congenital generalized, with or without gingival hyperplasia

Data availability: 10 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › hypertrichosis › gingival fibromatosis-hypertrichosis syndrome

Related subtypes (10): hypertrichosis of eyelid, hypertrichosis cubiti-short stature syndrome, cataract-hypertrichosis-intellectual disability syndrome, cervical hypertrichosis-peripheral neuropathy syndrome, Rabson-Mendenhall syndrome, isolated anterior cervical hypertrichosis, acquired hypertrichosis lanuginosa, hypertrichosis lanuginosa congenita, autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome, hypertrichosis-acromegaloid facial appearance syndrome

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

10 retrieved; paginated sample, class counts are floors:

5 likely pathogenic, 3 uncertain significance, 1 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4845884	NM_172232.4(ABCA5):c.4504C>T (p.Arg1502Ter)	ABCA5	Pathogenic	criteria provided, single submitter
2445995	NM_172232.4(ABCA5):c.2569C>T (p.Arg857Cys)	ABCA5	Likely pathogenic	no assertion criteria provided
3065858	NM_172232.4(ABCA5):c.1632_1633del (p.Arg544fs)	ABCA5	Likely pathogenic	criteria provided, single submitter
3065938	NM_172232.4(ABCA5):c.4315C>T (p.Arg1439Ter)	ABCA5	Likely pathogenic	criteria provided, single submitter
4849385	NM_172232.4(ABCA5):c.4270G>T (p.Glu1424Ter)	ABCA5	Likely pathogenic	criteria provided, single submitter
4849432	NM_172232.4(ABCA5):c.977_978del (p.His326fs)	ABCA5	Likely pathogenic	criteria provided, single submitter
139604	NM_172232.4(ABCA5):c.4320+1G>C	ABCA5	Uncertain significance	criteria provided, single submitter
3366874	NM_172232.4(ABCA5):c.3020C>T (p.Pro1007Leu)	ABCA5	Uncertain significance	criteria provided, single submitter
3517167	NM_172232.4(ABCA5):c.863C>T (p.Ser288Phe)	ABCA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
982933	NM_172232.4(ABCA5):c.569A>G (p.Asn190Ser)	ABCA5	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
ABCA5	Supportive	Autosomal dominant	gingival fibromatosis-hypertrichosis syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCA5	Orphanet:2026	Gingival fibromatosis-hypertrichosis syndrome

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
ABCA5	HGNC:35	ENSG00000154265	Q8WWZ7	Cholesterol transporter ABCA5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCA5	Cholesterol transporter ABCA5	Cholesterol efflux transporter in macrophages that is responsible for APOAI/high-density lipoproteins (HDL) formation at the plasma membrane under high cholesterol levels and participates in reverse cholesterol transport.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCA5	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM

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
adrenal tissue	1
body of pancreas	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCA5	289	ubiquitous	marker	adrenal tissue, body of pancreas, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCA5	817

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABCA5	Q8WWZ7	77.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
ABC transporters in lipid homeostasis	1	601.0×	0.005	ABCA5
ABC-family protein mediated transport	1	121.5×	0.012	ABCA5
Transport of small molecules	1	25.1×	0.040	ABCA5

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
positive regulation of reverse cholesterol transport	1	8426.0×	0.001	ABCA5
regulation of cholesterol efflux	1	2407.4×	0.002	ABCA5
negative regulation of macrophage derived foam cell differentiation	1	1296.3×	0.002	ABCA5
reverse cholesterol transport	1	936.2×	0.002	ABCA5
high-density lipoprotein particle remodeling	1	802.5×	0.002	ABCA5
cholesterol efflux	1	526.6×	0.003	ABCA5
lipid transport	1	263.3×	0.005	ABCA5
cholesterol metabolic process	1	195.9×	0.006	ABCA5
cholesterol homeostasis	1	156.0×	0.006	ABCA5

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
ABCA5	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	1	ABCA5
E	Difficult family or no structure, no drug	0

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)
ABCA5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.