SPRY1

Chr 4

sprouty RTK signaling antagonist 1

Also known as: hSPRY1

The SPRY1 protein inhibits fibroblast growth factor (FGF) receptor signaling by blocking FGF-mediated phosphorylation of ERK1/2 and prevents TGF-β-induced epithelial-to-mesenchymal transition in lens epithelial cells. Mutations cause autosomal recessive congenital cataract, affecting lens development in the eye. The gene shows tolerance to loss-of-function variants (pLI 0.003), suggesting that complete loss of protein function may be required for disease manifestation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
24
Pubs (1 yr)
23
P/LP submissions
0%
P/LP missense
1.22
LOEUF
Multiple*
Mechanism· predicted
Clinical SummarySPRY1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 60 VUS of 99 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.22LOEUF
pLI 0.003
Z-score 1.14
OE 0.58 (0.301.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.95Z-score
OE missense 1.21 (1.081.36)
200 obs / 165.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.58 (0.301.22)
00.351.4
Missense OE1.21 (1.081.36)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 5 / 8.6Missense obs/exp: 200 / 165.6Syn Z: -0.72
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedSPRY1-related craniosynostosis with inner ear and renal anomaliesOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7326th %ile
GOF
0.73top 25%
LOF
0.3356th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

99 submitted variants in ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic2
VUS60
Likely Benign4
Benign6
21
Pathogenic
2
Likely Pathogenic
60
VUS
4
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
1
0
1
0
2
VUS
0
55
5
0
60
Likely Benign
0
2
0
2
4
Benign
0
0
5
1
6
Total15732393

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SPRY1 · 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

No active trials found for this gene.

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Clinical Literature
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