Familial isolated trichomegaly

Summary

Familial isolated trichomegaly (MONDO:0018472) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	familial isolated trichomegaly
Mondo ID	MONDO:0018472
Orphanet	411788
DOID	DOID:0111566
ICD-11	1611595637
SNOMED CT	764523004
UMLS	C4706941
MedGen	1639703
GARD	0013167
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › trichomegaly › familial isolated trichomegaly

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: 3 · 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
FGF5	Supportive	Autosomal recessive	familial isolated trichomegaly	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGF5	Orphanet:411788	Familial isolated trichomegaly

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
FGF5	HGNC:3683	ENSG00000138675	P12034	Fibroblast growth factor 5	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGF5	Fibroblast growth factor 5	Plays an important role in the regulation of cell proliferation and cell differentiation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGF5	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF

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
buccal mucosa cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGF5	102	broad	marker	buccal mucosa cell, stromal cell of endometrium, 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
FGF5	3,791

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FGF5	P12034	76.62

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. 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
Signaling by activated point mutants of FGFR1	1	951.7×	0.003	FGF5
Signaling by activated point mutants of FGFR3	1	951.7×	0.003	FGF5
FGFR3c ligand binding and activation	1	878.5×	0.003	FGF5
FGFR2c ligand binding and activation	1	878.5×	0.003	FGF5
Phospholipase C-mediated cascade; FGFR3	1	878.5×	0.003	FGF5
FGFRL1 modulation of FGFR1 signaling	1	878.5×	0.003	FGF5
FGFR1c ligand binding and activation	1	761.3×	0.003	FGF5
Activated point mutants of FGFR2	1	671.8×	0.003	FGF5
Phospholipase C-mediated cascade: FGFR1	1	671.8×	0.003	FGF5
Phospholipase C-mediated cascade; FGFR2	1	634.4×	0.003	FGF5
PI-3K cascade:FGFR3	1	634.4×	0.003	FGF5
SHC-mediated cascade:FGFR3	1	601.0×	0.003	FGF5
Downstream signaling of activated FGFR1	1	543.8×	0.003	FGF5
FRS-mediated FGFR3 signaling	1	543.8×	0.003	FGF5
PI-3K cascade:FGFR1	1	519.1×	0.003	FGF5
SHC-mediated cascade:FGFR1	1	496.5×	0.003	FGF5
PI-3K cascade:FGFR2	1	496.5×	0.003	FGF5
Signaling by FGFR3 in disease	1	496.5×	0.003	FGF5
SHC-mediated cascade:FGFR2	1	475.8×	0.003	FGF5
FRS-mediated FGFR1 signaling	1	456.8×	0.003	FGF5
FRS-mediated FGFR2 signaling	1	439.2×	0.003	FGF5
Negative regulation of FGFR3 signaling	1	439.2×	0.003	FGF5
Negative regulation of FGFR1 signaling	1	368.4×	0.004	FGF5
Negative regulation of FGFR2 signaling	1	368.4×	0.004	FGF5
Signaling by FGFR1 in disease	1	292.8×	0.004	FGF5
PI3K Cascade	1	271.9×	0.004	FGF5
Signaling by FGFR2 in disease	1	265.6×	0.004	FGF5
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.009	FGF5
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.011	FGF5
PIP3 activates AKT signaling	1	66.8×	0.015	FGF5

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
glial cell differentiation	1	887.0×	0.007	FGF5
signal transduction involved in regulation of gene expression	1	702.2×	0.007	FGF5
positive regulation of cell division	1	337.0×	0.009	FGF5
fibroblast growth factor receptor signaling pathway	1	285.6×	0.009	FGF5
neurogenesis	1	208.1×	0.010	FGF5
regulation of cell migration	1	157.5×	0.011	FGF5
positive regulation of MAPK cascade	1	80.6×	0.018	FGF5
cell-cell signaling	1	69.6×	0.018	FGF5
nervous system development	1	45.9×	0.024	FGF5
positive regulation of cell population proliferation	1	33.6×	0.030	FGF5

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
FGF5	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	FGF5

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)
FGF5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.