SPRY1

Chr 4

sprouty RTK signaling antagonist 1

Also known as: hSPRY1

NCBI Gene: 10252 ENSG00000164056 UniProt: O43609 OMIM: 602465

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable protein kinase inhibitor activity. Involved in negative regulation of fibroblast growth factor receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.22

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.003

Z-score 1.14

OE 0.58 (0.30–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.95Z-score

OE missense 1.21 (1.08–1.36)

200 obs / 165.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.58 (0.30–1.22)

0≤0.351.4

Missense OE?1.21 (1.08–1.36)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 5 / 8.6Missense obs/exp: 200 / 165.6Syn Z: -0.72

Background carrier burden — how many people carry a rare variant somewhere in SPRY1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

471 rare PASS variants

Rare truncating (LoF)

1 in 4,500

73 rare PASS variants

Rare synonymous (reference)

1 in 230

171 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPRY1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓