Familial congenital nasolacrimal duct obstruction

Summary

Familial congenital nasolacrimal duct obstruction (MONDO:0007871) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	familial congenital nasolacrimal duct obstruction
Mondo ID	MONDO:0007871
MeSH	C566703
OMIM	149700
Orphanet	451612
UMLS	C1835612
MedGen	332018
GARD	0017784
Is cancer (heuristic)	no

Also known as: lacrimal duct defect · LCDD

Data availability: 3 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary otorhinolaryngologic disease › familial congenital nasolacrimal duct obstruction

Related subtypes (20): otosclerosis, isolated congenital anosmia, second branchial cleft anomaly, Meniere disease, motion sickness, familial thyroglossal duct cyst, bifid nose, autosomal recessive, X-linked mixed hearing loss with perilymphatic gusher, nasal dermoid cyst, short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome, aural atresia, congenital, choanal atresia, BNAR syndrome, familial nasal acilia, tympanic paraganglioma, X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome, cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome, tonsillar lymphoma, benign paroxysmal positional vertigo, vertigo, benign recurrent, 1

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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
162496	NM_001007237.3(IGSF3):c.2935del (p.Arg979fs)	IGSF3	Pathogenic	no assertion criteria provided
915339	NM_001007237.3(IGSF3):c.1724G>A (p.Trp575Ter)	IGSF3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3393298	NM_001007237.3(IGSF3):c.1723_1724inv (p.Trp575Gln)	IGSF3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
IGSF3	Supportive	Autosomal recessive	familial congenital nasolacrimal duct obstruction	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IGSF3	Orphanet:451612	Familial congenital nasolacrimal duct obstruction

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
IGSF3	HGNC:5950	ENSG00000143061	O75054	Immunoglobulin superfamily member 3	gencc,clinvar

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IGSF3	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom

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
cortical plate	1
gingival epithelium	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IGSF3	265	ubiquitous	marker	cortical plate, tongue squamous epithelium, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IGSF3	1,253

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IGSF3	O75054	81.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
lacrimal gland development	1	2106.5×	5e-04	IGSF3

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
IGSF3	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	IGSF3
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)
IGSF3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.