Lacrimoauriculodentodigital syndrome 3

Summary

Lacrimoauriculodentodigital syndrome 3 (MONDO:0859578) is a disease caused by FGF10 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: FGF10 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lacrimoauriculodentodigital syndrome 3
Mondo ID	MONDO:0859578
OMIM	620193
DOID	DOID:0081372
UMLS	C5774287
MedGen	1824060
GARD	0026751
Is cancer (heuristic)	no

Data availability: 19 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › LADD syndrome › lacrimoauriculodentodigital syndrome 3

Related subtypes (2): LADD syndrome 1, lacrimoauriculodentodigital syndrome 2

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

19 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 5 pathogenic, 2 conflicting classifications of pathogenicity, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2664283	NM_004465.2(FGF10):c.237G>A (p.Trp79Ter)	FGF10	Pathogenic	no assertion criteria provided
2691789	NM_004465.2(FGF10):c.234dup (p.Trp79fs)	FGF10	Pathogenic	no assertion criteria provided
7531	NM_004465.2(FGF10):c.317G>T (p.Cys106Phe)	FGF10	Pathogenic	no assertion criteria provided
7532	NM_004465.2(FGF10):c.467T>G (p.Ile156Arg)	FGF10	Pathogenic	no assertion criteria provided
7533	NM_004465.2(FGF10):c.409A>T (p.Lys137Ter)	FGF10	Pathogenic	no assertion criteria provided
4072334	NM_004465.2(FGF10):c.324C>A (p.Tyr108Ter)	FGF10	Likely pathogenic	criteria provided, single submitter
4759488	NM_004465.2(FGF10):c.245T>A (p.Leu82Gln)	FGF10	Likely pathogenic	no assertion criteria provided
2171727	NM_004465.2(FGF10):c.64T>C (p.Cys22Arg)	FGF10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
907811	NM_004465.2(FGF10):c.610A>G (p.Met204Val)	FGF10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1913342	NM_004465.2(FGF10):c.613G>A (p.Val205Met)	FGF10	Uncertain significance	criteria provided, multiple submitters, no conflicts
2147681	NM_004465.2(FGF10):c.367G>A (p.Val123Ile)	FGF10	Uncertain significance	criteria provided, multiple submitters, no conflicts
3592693	NM_004465.2(FGF10):c.452A>T (p.Lys151Met)	FGF10	Uncertain significance	criteria provided, single submitter
3592694	NM_004465.2(FGF10):c.386A>G (p.Asn129Ser)	FGF10	Uncertain significance	criteria provided, single submitter
3592695	NM_004465.2(FGF10):c.367G>T (p.Val123Phe)	FGF10	Uncertain significance	criteria provided, single submitter
3592696	NM_004465.2(FGF10):c.325+6T>C	FGF10	Uncertain significance	criteria provided, single submitter
3592697	NM_004465.2(FGF10):c.156TTC[1] (p.Ser56del)	FGF10	Uncertain significance	criteria provided, single submitter
3592698	NM_004465.2(FGF10):c.70T>C (p.Phe24Leu)	FGF10	Uncertain significance	criteria provided, single submitter
3592699	NM_004465.2(FGF10):c.58T>A (p.Cys20Ser)	FGF10	Uncertain significance	criteria provided, single submitter
3592700	NM_004465.2(FGF10):c.17T>C (p.Leu6Pro)	FGF10	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
FGF10	Definitive	Autosomal dominant	lacrimoauriculodentodigital syndrome 3	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGF10	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGF10	Orphanet:86815	Aplasia of lacrimal and salivary glands

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
FGF10	HGNC:3666	ENSG00000070193	O15520	Fibroblast growth factor 10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGF10	Fibroblast growth factor 10	Plays an important role in the regulation of embryonic development, 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)
FGF10	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
endocervix	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGF10	169	broad	marker	buccal mucosa cell, synovial joint, endocervix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGF10	4,233

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGF10	O15520	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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 gene expression in early pancreatic precursor cells	1	1427.5×	0.003	FGF10
FGFR1b ligand binding and activation	1	1268.9×	0.003	FGF10
FGFR2b ligand binding and activation	1	1142.0×	0.003	FGF10
FGFRL1 modulation of FGFR1 signaling	1	878.5×	0.003	FGF10
Developmental Lineage of Mammary Stem Cells	1	761.3×	0.003	FGF10
Activated point mutants of FGFR2	1	671.8×	0.003	FGF10
Phospholipase C-mediated cascade: FGFR1	1	671.8×	0.003	FGF10
Phospholipase C-mediated cascade; FGFR2	1	634.4×	0.003	FGF10
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	601.0×	0.003	FGF10
Downstream signaling of activated FGFR1	1	543.8×	0.003	FGF10
PI-3K cascade:FGFR1	1	519.1×	0.003	FGF10
SHC-mediated cascade:FGFR1	1	496.5×	0.003	FGF10
PI-3K cascade:FGFR2	1	496.5×	0.003	FGF10
SHC-mediated cascade:FGFR2	1	475.8×	0.003	FGF10
FRS-mediated FGFR1 signaling	1	456.8×	0.003	FGF10
FRS-mediated FGFR2 signaling	1	439.2×	0.003	FGF10
Negative regulation of FGFR1 signaling	1	368.4×	0.004	FGF10
Negative regulation of FGFR2 signaling	1	368.4×	0.004	FGF10
PI3K Cascade	1	271.9×	0.005	FGF10
Signaling by FGFR2 in disease	1	265.6×	0.005	FGF10
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.009	FGF10
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.011	FGF10
PIP3 activates AKT signaling	1	66.8×	0.016	FGF10
RAF/MAP kinase cascade	1	61.1×	0.016	FGF10

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
embryonic genitalia morphogenesis	1	16852.0×	6e-04	FGF10
regulation of activin receptor signaling pathway	1	16852.0×	6e-04	FGF10
urothelial cell proliferation	1	16852.0×	6e-04	FGF10
positive regulation of urothelial cell proliferation	1	16852.0×	6e-04	FGF10
bronchiole morphogenesis	1	16852.0×	6e-04	FGF10
mesenchymal-epithelial cell signaling involved in lung development	1	16852.0×	6e-04	FGF10
fibroblast growth factor receptor signaling pathway involved in mammary gland specification	1	16852.0×	6e-04	FGF10
submandibular salivary gland formation	1	16852.0×	6e-04	FGF10
semicircular canal fusion	1	16852.0×	6e-04	FGF10
lung proximal/distal axis specification	1	16852.0×	6e-04	FGF10
positive regulation of hair follicle cell proliferation	1	16852.0×	6e-04	FGF10
regulation of saliva secretion	1	8426.0×	7e-04	FGF10
mammary gland bud formation	1	8426.0×	7e-04	FGF10
branch elongation involved in salivary gland morphogenesis	1	8426.0×	7e-04	FGF10
mesenchymal cell differentiation involved in lung development	1	8426.0×	7e-04	FGF10
positive regulation of white fat cell proliferation	1	8426.0×	7e-04	FGF10
fibroblast growth factor receptor apoptotic signaling pathway	1	8426.0×	7e-04	FGF10
female genitalia morphogenesis	1	5617.3×	9e-04	FGF10
bud outgrowth involved in lung branching	1	5617.3×	9e-04	FGF10
secretion by lung epithelial cell involved in lung growth	1	5617.3×	9e-04	FGF10
metanephros morphogenesis	1	4213.0×	1e-03	FGF10
salivary gland development	1	4213.0×	1e-03	FGF10
prostatic bud formation	1	4213.0×	1e-03	FGF10
tear secretion	1	4213.0×	1e-03	FGF10
white fat cell proliferation	1	4213.0×	1e-03	FGF10
male genitalia morphogenesis	1	3370.4×	0.001	FGF10
epithelial cell proliferation involved in salivary gland morphogenesis	1	3370.4×	0.001	FGF10
regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	1	3370.4×	0.001	FGF10
Harderian gland development	1	3370.4×	0.001	FGF10
muscle cell fate commitment	1	2808.7×	0.001	FGF10

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
FGF10	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	FGF10

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)
FGF10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.