SPRED1 Gene: Sprouty-Related EVH1 Domain Containing 1
A negative regulator of RAS-MAPK signaling implicated in Legius syndrome and cancer
Gene Information Card
| Symbol | SPRED1 |
|---|---|
| Full Name | Sprouty-Related EVH1 Domain Containing 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q14 |
| NCBI Gene ID | 161742 ncbi.nlm.nih.gov/gene/161742 |
| Ensembl ID | ENSG00000166068 |
| UniProt ID | Q7Z699 |
| OMIM ID | 609291 |
| HGNC ID | 20249 |
| Aliases | FLJ44124, Spred-1, hSPRED1 |
Description
SPRED1 (Sprouty-Related EVH1 Domain Containing 1) is a tumor suppressor gene that encodes a protein belonging to the Sprouty family. It functions as a negative regulator of the RAS-MAPK signaling pathway by inhibiting RAF activation. Loss-of-function mutations in SPRED1 cause Legius syndrome, a condition phenotypically similar to neurofibromatosis type 1 (NF1). SPRED1 is also implicated in various cancers, including melanoma and leukemia, where its downregulation or mutation contributes to aberrant RAS signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Legius syndrome | Loss-of-function mutations in SPRED1 lead to dysregulation of RAS-MAPK signaling, resulting in café-au-lait macules, freckling, and macrocephaly without neurofibromas. | OMIM #611431; multiple case reports and family studies |
| Melanoma | Reduced SPRED1 expression or inactivating mutations promote RAS-MAPK pathway activation, contributing to tumor progression. | COSMIC; PMID: 22773810 |
| Acute myeloid leukemia (AML) | SPRED1 mutations or deletions are recurrent in AML, leading to enhanced ERK signaling and leukemogenesis. | COSMIC; PMID: 25605247 |
| Neurofibromatosis type 1-like syndrome | Phenotypic overlap with NF1 due to shared pathway (RAS-MAPK); SPRED1 mutations identified in NF1-negative patients. | ClinVar; PMID: 17603483 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.5 | Medium |
| Heart | 12.3 | Medium |
| Lung | 8.7 | Low |
| Liver | 5.2 | Low |
| Kidney | 14.1 | Medium |
| Testis | 22.6 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.4 | Embryonic kidney cells |
| K562 | 9.8 | Leukemia cell line |
| A549 | 7.2 | Lung carcinoma |
| MCF7 | 11.5 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.205C>T (p.Arg69*) | Nonsense | Rare | Premature truncation, loss of function |
| c.649_650delAG (p.Ser217fs) | Frameshift | Rare | Frameshift, loss of function |
| c.1048C>T (p.Arg350Trp) | Missense | Rare | Impaired RAF binding, loss of function |
Mutation functional classification
Loss of Function (LOF)
Majority of SPRED1 mutations are loss-of-function, leading to reduced inhibition of RAS-MAPK signaling. These include nonsense, frameshift, splice-site, and missense mutations that disrupt the EVH1 domain or SPRY domain.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SPRED1.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg350Trp) may act in a dominant-negative manner by interfering with wild-type SPRED1 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 – protein binding | • GO:0007165 – signal transduction |
| • GO:0043410 – positive regulation of MAPK cascade | • GO:0009968 – negative regulation of signal transduction |
| • GO:0005737 – cytoplasm |
Pathways
• RAS-MAPK signaling pathway (Reactome: R-HSA-5673001)
• Signaling by Receptor Tyrosine Kinases (Reactome: R-HSA-9006934)
• Negative regulation of MAPK pathway (KEGG: hsa04010)
Protein Summary
The SPRED1 protein (55 kDa) contains an N-terminal EVH1 domain and a C-terminal SPRY domain. It localizes to the cytoplasm and negatively regulates the RAS-MAPK signaling cascade by binding to RAF and inhibiting its activation. SPRED1 also interacts with neurofibromin (NF1) and other signaling molecules. Loss of SPRED1 function leads to sustained ERK activation, contributing to developmental disorders and oncogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPRED1 Knockout HEK293 Cell Line | EDJ-KQ15493 | Human | 161742 | Details Get a Quote |
| SPRED1 Knockout HeLa Cell Line | EDJ-KQ47191 | Human | 161742 | Details Get a Quote |
| SPRED1 Knockout A-549 Cell Line | EDJ-KQ46286 | Human | 161742 | Details Get a Quote |
| SPRED1 Knockout HCT 116 Cell Line | EDJ-KQ46287 | Human | 161742 | Details Get a Quote |
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