SPRY2

Chr 13AD

sprouty RTK signaling antagonist 2

Also known as: IGAN3, hSPRY2

NCBI Gene: 10253ENSG00000136158UniProt: O43597OMIM: 602466

The protein antagonizes fibroblast growth factor (FGF) signaling pathways by inhibiting FGF-mediated ERK1/2 phosphorylation and also inhibits CBL-mediated EGFR ubiquitination. Mutations cause IgA nephropathy with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants (pLI = 0.97), suggesting additional phenotypes may be associated with pathogenic variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.271 OMIM phenotype
Clinical Summary— SPRY2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.971
Z-score 3.07
OE 0.00 (0.00–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.97Z-score
OE missense 0.79 (0.69–0.91)
139 obs / 175.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.27)
0≤0.351.4
Missense OE0.79 (0.69–0.91)
0≤0.61.4
Synonymous OE1.21
0≤1.21.6
LoF obs/exp: 0 / 11.0Missense obs/exp: 139 / 175.3Syn Z: -1.37
DN
0.3296th %ile
GOF
0.4775th %ile
LOF
0.74top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.27

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SPRY2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Functional Variant Discovery Identifies a Novel Genetic Link between SPRY2, Wood Smoke, and Asthma.
Gupta A et al.·Am J Respir Cell Mol Biol
2026Functional
A Novel lncRNA MSTRG.16386.1 as ceRNA Promotes Kidney Injury Induced by Deep Hypothermic Circulatory Arrest via Mediating miR-466b-5p/Spry2 Axis.
Zhao J et al.·FASEB J
2026
Investigating SPRY2 Single-Nucleotide Polymorphisms in the Etiology of Nonsyndromic Orofacial Cleft in the Chinese Han Population.
Yang MX et al.·Cleft Palate Craniofac J
2025
Proteomics- and BRET- screens identify SPRY2 as a Ras effector that impacts its membrane organization.
Pavic K et al.·iScience
2025Open Access
Poricoic Acid A attenuated TGF-β1-induced epithelial-mesenchymal transition in renal tubular epithelial cells through SPRY2/ERK signaling pathway.
Xiang M et al.·Korean J Physiol Pharmacol
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients