IgA nephropathy, susceptibility to, 3

Summary

IgA nephropathy, susceptibility to, 3 (MONDO:0014786) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	IgA nephropathy, susceptibility to, 3
Mondo ID	MONDO:0014786
OMIM	616818
UMLS	C4225194
MedGen	897340
Is cancer (heuristic)	no

Also known as: IgA glomerulonephritis caused by mutation in SPRY2 · IgA nephropathy, susceptibility to, 3 · IgA nephropathy, susceptibility to, 3; IGAN3 · IgA nephropathy, susceptibility to, type 3 · IGAN3 · SPRY2 IgA glomerulonephritis

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

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › IgA nephropathy, susceptibility to › IgA nephropathy, susceptibility to, 3

Related subtypes (2): IgA nephropathy, susceptibility to, 1, IgA nephropathy, susceptibility to, 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

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
222032	NM_005842.4(SPRY2):c.355C>T (p.Arg119Trp)	SPRY2	risk factor	no assertion criteria provided
1028429	NM_005842.4(SPRY2):c.410G>C (p.Gly137Ala)	SPRY2	Uncertain significance	criteria provided, single submitter
1177429	NM_005842.4(SPRY2):c.944C>T (p.Thr315Ile)	SPRY2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
SPRY2	Limited	Autosomal dominant	IgA nephropathy, susceptibility to, 3	3

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
SPRY2	HGNC:11270	ENSG00000136158	O43597	Protein sprouty homolog 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPRY2	Protein sprouty homolog 2	Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2.

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)
SPRY2	Other/Unknown	no		Sprouty, Sprouty_domain

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
cartilage tissue	1
right hemisphere of cerebellum	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPRY2	281	ubiquitous	marker	cartilage tissue, tibial nerve, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPRY2	1,995

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPRY2	O43597	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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 FGFR3	1	1142.0×	0.004	SPRY2
Signaling by FGFR4	1	1038.2×	0.004	SPRY2
Signaling by FGFR1	1	815.7×	0.004	SPRY2
Spry regulation of FGF signaling	1	713.8×	0.004	SPRY2
Negative regulation of FGFR3 signaling	1	439.2×	0.004	SPRY2
Negative regulation of FGFR4 signaling	1	407.9×	0.004	SPRY2
Signaling by FGFR2	1	407.9×	0.004	SPRY2
Negative regulation of FGFR1 signaling	1	368.4×	0.004	SPRY2
Negative regulation of FGFR2 signaling	1	368.4×	0.004	SPRY2
EGFR downregulation	1	346.1×	0.004	SPRY2
Signaling by FGFR	1	346.1×	0.004	SPRY2
Signaling by EGFR	1	326.3×	0.004	SPRY2
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.021	SPRY2
Signal Transduction	1	10.2×	0.098	SPRY2

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
lung growth	1	8426.0×	0.002	SPRY2
negative regulation of cell projection organization	1	5617.3×	0.002	SPRY2
negative regulation of neurotrophin TRK receptor signaling pathway	1	4213.0×	0.002	SPRY2
negative regulation of lens fiber cell differentiation	1	2808.7×	0.003	SPRY2
bud elongation involved in lung branching	1	2407.4×	0.003	SPRY2
negative regulation of vascular endothelial growth factor signaling pathway	1	1296.3×	0.004	SPRY2
negative regulation of fibroblast growth factor receptor signaling pathway	1	1053.2×	0.004	SPRY2
positive regulation of peptidyl-serine phosphorylation	1	766.0×	0.004	SPRY2
negative regulation of epidermal growth factor receptor signaling pathway	1	766.0×	0.004	SPRY2
animal organ development	1	732.7×	0.004	SPRY2
negative regulation of Ras protein signal transduction	1	674.1×	0.004	SPRY2
cellular response to vascular endothelial growth factor stimulus	1	561.7×	0.005	SPRY2
positive regulation of epidermal growth factor receptor signaling pathway	1	495.6×	0.005	SPRY2
establishment of mitotic spindle orientation	1	481.5×	0.005	SPRY2
negative regulation of epithelial to mesenchymal transition	1	411.0×	0.005	SPRY2
ERK1 and ERK2 cascade	1	318.0×	0.005	SPRY2
inner ear morphogenesis	1	300.9×	0.005	SPRY2
cell fate commitment	1	295.6×	0.005	SPRY2
fibroblast growth factor receptor signaling pathway	1	285.6×	0.005	SPRY2
negative regulation of protein ubiquitination	1	285.6×	0.005	SPRY2
negative regulation of ERK1 and ERK2 cascade	1	216.1×	0.007	SPRY2
negative regulation of transforming growth factor beta receptor signaling pathway	1	173.7×	0.008	SPRY2
negative regulation of angiogenesis	1	168.5×	0.008	SPRY2
cellular response to leukemia inhibitory factor	1	159.0×	0.008	SPRY2
sensory perception of sound	1	100.9×	0.012	SPRY2
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.014	SPRY2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.015	SPRY2
positive regulation of cell migration	1	61.7×	0.018	SPRY2
negative regulation of cell population proliferation	1	42.1×	0.025	SPRY2
positive regulation of gene expression	1	38.7×	0.027	SPRY2

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
SPRY2	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	SPRY2

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)
SPRY2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.