SPRED1

Chr 15AD

sprouty related EVH1 domain containing 1

Also known as: LGSS, NFLS, PPP1R147, hSpred1, spred-1

NCBI Gene: 161742 ENSG00000166068 UniProt: Q7Z699 OMIM: 609291

The SPRED1 protein regulates activation of the MAP kinase cascade by forming homodimers or heterodimers with SPRED2, and is phosphorylated by tyrosine kinases in response to growth factors. Loss-of-function mutations cause Legius syndrome (also known as neurofibromatosis type 1-like syndrome), which follows autosomal dominant inheritance. The pathogenic mechanism involves loss of normal MAP kinase regulation due to reduced SPRED1 function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a member of the Sprouty family of proteins and is phosphorylated by tyrosine kinase in response to several growth factors. The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade. Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS). [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Legius syndromeMIM #611431

Clinical highlights

Gene-disease validity (ClinGen)

Legius syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.32

LOEUF· LoF intol.

LOF

Mechanism· G2P