Glomerulopathy with fibronectin deposits 1

Summary

Glomerulopathy with fibronectin deposits 1 (MONDO:0024527) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glomerulopathy with fibronectin deposits 1
Mondo ID	MONDO:0024527
OMIM	137950
UMLS	C0403557
MedGen	98017
GARD	0009268
Is cancer (heuristic)	no

Also known as: GFND1 · glomerulopathy with fibronectin deposits 1

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › glomerular disorder › fibronectin glomerulopathy › glomerulopathy with fibronectin deposits 1

Related subtypes (1): glomerulopathy with fibronectin deposits 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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1367318	NM_212482.4(FN1):c.3866C>T (p.Pro1289Leu)	FN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FN1	Orphanet:84090	Fibronectin glomerulopathy
FN1	Orphanet:93315	Spondylometaphyseal dysplasia, ‘corner fracture’ type

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
FN1	HGNC:3778	ENSG00000115414	P02751	Fibronectin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FN1	Fibronectin	Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin.

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)
FN1	Antibody/Immunoglobulin	yes		Fibronectin_type1, FN_type2_dom, FN3_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
decidua	1
right coronary artery	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FN1	292	ubiquitous	marker	synovial joint, right coronary artery, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FN1	8,860

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FN1	P02751	65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. 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
ALK mutants bind TKIs	1	951.7×	0.007	FN1
p130Cas linkage to MAPK signaling for integrins	1	761.3×	0.007	FN1
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	713.8×	0.007	FN1
Fibronectin matrix formation	1	571.0×	0.007	FN1
Attachment of bacteria to epithelial cells	1	496.5×	0.007	FN1
Syndecan interactions	1	423.0×	0.007	FN1
Integrin signaling	1	423.0×	0.007	FN1
MET activates PTK2 signaling	1	380.7×	0.007	FN1
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	356.9×	0.007	FN1
Signaling by high-kinase activity BRAF mutants	1	317.2×	0.007	FN1
Molecules associated with elastic fibres	1	308.6×	0.007	FN1
MAP2K and MAPK activation	1	285.5×	0.007	FN1
Signaling by RAF1 mutants	1	278.5×	0.007	FN1
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.007	FN1
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.007	FN1
Signaling downstream of RAS mutants	1	253.8×	0.007	FN1
GPER1 signaling	1	248.3×	0.007	FN1
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.007	FN1
Signaling by BRAF and RAF1 fusions	1	170.4×	0.009	FN1
Non-integrin membrane-ECM interactions	1	154.3×	0.009	FN1
ECM proteoglycans	1	150.3×	0.009	FN1
Signaling by ALK fusions and activated point mutants	1	150.3×	0.009	FN1
Integrin cell surface interactions	1	134.3×	0.009	FN1
Degradation of the extracellular matrix	1	117.7×	0.010	FN1
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.011	FN1
Post-translational protein phosphorylation	1	100.2×	0.011	FN1
Cell surface interactions at the vascular wall	1	95.2×	0.011	FN1
Platelet degranulation	1	87.8×	0.012	FN1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	FN1

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
negative regulation of monocyte activation	1	5617.3×	0.002	FN1
calcium-independent cell-matrix adhesion	1	4213.0×	0.002	FN1
positive regulation of substrate-dependent cell migration, cell attachment to substrate	1	4213.0×	0.002	FN1
negative regulation of transforming growth factor beta production	1	3370.4×	0.002	FN1
cell-substrate junction assembly	1	2808.7×	0.002	FN1
biological process involved in interaction with symbiont	1	2808.7×	0.002	FN1
neural crest cell migration involved in autonomic nervous system development	1	1872.4×	0.002	FN1
blood coagulation, fibrin clot formation	1	1685.2×	0.002	FN1
integrin activation	1	1404.3×	0.003	FN1
regulation of protein phosphorylation	1	1123.5×	0.003	FN1
enteric nervous system development	1	991.3×	0.003	FN1
response to muscle activity	1	581.1×	0.004	FN1
regulation of ERK1 and ERK2 cascade	1	581.1×	0.004	FN1
positive regulation of axon extension	1	510.7×	0.004	FN1
endodermal cell differentiation	1	495.6×	0.004	FN1
acute-phase response	1	421.3×	0.005	FN1
endothelial cell migration	1	411.0×	0.005	FN1
substrate adhesion-dependent cell spreading	1	343.9×	0.005	FN1
neural crest cell migration	1	337.0×	0.005	FN1
positive regulation of fibroblast proliferation	1	295.6×	0.006	FN1
negative regulation of autophagy	1	259.3×	0.006	FN1
response to wounding	1	221.7×	0.007	FN1
cell-matrix adhesion	1	163.6×	0.009	FN1
integrin-mediated signaling pathway	1	160.5×	0.009	FN1
regulation of cell shape	1	123.0×	0.011	FN1
autophagy	1	110.1×	0.012	FN1
heart development	1	78.8×	0.015	FN1
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.015	FN1
angiogenesis	1	62.4×	0.018	FN1
nervous system development	1	45.9×	0.024	FN1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
FN1	1	Binding:1

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	1	FN1
D	Druggable family + AlphaFold only, no drug	0
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)
FN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.