Property Summary

NCBI Gene PubMed Count 45
PubMed Score 72.53
PubTator Score 50.76

Knowledge Summary


No data available


  Disease (6)


  Differential Expression (20)

Disease log2 FC p
astrocytic glioma -1.500 1.9e-03
ependymoma -1.100 4.0e-02
osteosarcoma 1.671 1.1e-02
glioblastoma 2.200 1.9e-03
medulloblastoma -1.600 4.0e-06
atypical teratoid / rhabdoid tumor 1.900 2.8e-03
medulloblastoma, large-cell -2.500 8.1e-04
tuberculosis and treatment for 3 months 1.200 9.2e-03
intraductal papillary-mucinous adenoma (... 1.200 1.9e-02
ulcerative colitis 1.100 1.2e-05
Breast cancer 3.900 4.0e-02
pediatric high grade glioma 1.600 4.8e-03
pilocytic astrocytoma 1.800 3.6e-06
aldosterone-producing adenoma -1.211 9.4e-03
Polycystic Ovary Syndrome -1.021 1.7e-03
lung carcinoma -1.200 9.9e-22
Pick disease -1.200 3.8e-05
gastric carcinoma 1.100 8.3e-03
acute myeloid leukemia -2.000 2.2e-02
ovarian cancer 2.500 4.8e-05


Accession Q7Z699 B2RPJ8 Q05D53 Q8N256 Spred-1
Symbols NFLS


PANTHER Protein Class (1)



  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 OMIM Phenotype (1)

Protein-protein Interaction (2)

Gene RIF (29)

26635368 Data suggest SPRED1 EVH1 domain interacts with NF1 GRD domain [N-term. 16AA/C-term. 20AA of GTPase-activating protein-related domain]; SPRED1 EVH1 and NF1 GRD mutations observed in Legius syndrome reduce binding affinity between EVH1/GRD domains.
26075267 Cosuppression of Sprouty and Sprouty-related negative regulators of FGF signalling in prostate cancer
25202123 Antisense-mediated knockdown (anti-miR) revealed that miR-206/21 coordinately promote RAS-ERK signaling and the corresponding cell phenotypes by inhibiting translation of the pathway suppressors RASA1 and SPRED1.
24469042 SPRED1 decreased expression correlated with genetic features of AML. Our study reveals a new mechanism which contributes to deregulate RAS MAPK pathway in the vast majority of paediatric AMLs
24334617 SPRED1 seems to play an important role in recruiting neurofibromin to the plasma membrane. (Review)
24014835 Microrna-126 was transported into recipient human coronary artery endothelial cells by endothelial microparticles and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1).
23823658 Older age and deletions of IKZF1 and SPRED1 were also associated with poor overall survival of pediatric B-cell precursor acute lymphoblastic leukemia.
23811937 Data indicate that upregulated miR-126 upon coxsackievirus B3 (CVB3) infection targets SPRED1, LRP6, and WRCH1 genes, mediating cross-talk between ERK1/2 and Wnt/beta-catenin pathways, and thus promoting viral replication.
23016555 Based on our current understanding of KIT and SPRED1 protein interactions, we propose that cafe-au-lait macules and freckling may be seen in some patients with piebaldism and does not necessarily represent coexistence of neurofibromatosis type 1.
22753041 Sixty-three mutations and deletions are definitely pathogenic or most likely pathogenic, eight SPRED1 mutations are probably benign rare variants, and 17 SPRED1 missense mutations are still unclassified. Review.
22751498 show that neurofibromin, the NF1 gene product, is a Spred1-interacting protein that is necessary for Spred1's inhibitory function
21649642 a cohort of 115 NF1-like patients were screened for SPRED1 gene mutations and six mutations were identified. 12 potentially pathogenic SPRED1 mutations have been detected in 200 such NF1-like patients
21616146 Interaction of FGFRL1 with Spred1 increases the proportion of the receptor at the plasma membrane.
21531714 SPRED1 is a likely substrate of SHP2, whose tyrosine dephosphorylation is required to attenuate the inhibitory action of SPRED1 in the Ras/ERK pathway.
21364986 Sprouty and Spred proteins are negative regulators of the ERK/Elk-1 pathway activation induced not only by growth-factors, but also by reactive lipidic mediators.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20339110 no evidence of leukemogenic SPRED1 involement in juvenile myelomonocytic leukemia
20179001 The frequency of SPRED1 mutations in patients meeting diagnostic criteria for neurofibromatosis 1 in a hospital-based clinic is 1% to 2%. The likelihood an individual is harboring a SPRED1 mutation increases with age.
19920235 A high SPRED1 mutation detection rate was found in NF1 mutation-negative families with an autosomal dominant phenotype of CALMs (cafe au lait macules)with or without freckling and no other NF1 features.
19920235 Observational study of gene-disease association. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19443465 Unrelated mild NF1 patients were screened for mutations of the SPRED1-3 and the SPRY1-4 genes. SPRED1 mutations were identified in 6 cases.
19366998 SPRED1 mutations occurred with a prevalence of 0.5% in NF1 patients and in 5% of NF1 patients displaying an NF1-like phenotype.
19120036 Linkage analysis of SPRED1 excluded its involvement in Cafe-au-lait spots in a patient with a severe form of Noonan syndrome.
18216281 enhanced TESK1 activity results in increased stress fibers (via phospho-cofilin), but this can be blocked by elevating Spred1
17704776 Studies show that the clinical features of the reported disorder resemble those of neurofibromatosis type 1 provide the first report of mutations of SPRED1 (SPROUTY)/SPRED family of genes) in human disease.
17672918 the apparent occurrence of an unusual TG 3' splice site in intron 1 is discussed
16652141 reduction of Spred expression in hepatocellular carcinoma (HCC) is one of the causes of the acquisition of malignant features. Thus, Spred could be not only a novel prognostic factor but also a new therapeutic target for human HCC
15683364 We show here that Spred-1 and Spred-2 appear to have distinct mechanisms whereby they induce their effects, as the Sprouty domain of Spred-1 is not required to block MAPK (mitogen-activated protein kinase) activation, while that of Spred-2 is required.

AA Sequence

VPLRMCHRCGEACGCCGGKHKAAG                                                  421 - 444

Text Mined References (51)

PMID Year Title
26635368 2016 Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1.
26075267 2015 Cosuppression of Sprouty and Sprouty-related negative regulators of FGF signalling in prostate cancer: a working hypothesis.
25202123 2014 MicroRNAs 206 and 21 cooperate to promote RAS-extracellular signal-regulated kinase signaling by suppressing the translation of RASA1 and SPRED1.
24705354 2014 The palmitoyl acyltransferase HIP14 shares a high proportion of interactors with huntingtin: implications for a role in the pathogenesis of Huntington's disease.
24469042 2015 SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia.
24334617 2013 Legius syndrome, an Update. Molecular pathology of mutations in SPRED1.
24129315 2014 Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.
24014835 2013 Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles.
23823658 2014 Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 2011.
23811937 2013 MiR-126 promotes coxsackievirus replication by mediating cross-talk of ERK1/2 and Wnt/?-catenin signal pathways.
23646285 2013 Genome-wide association study of HLA-DQB1*06:02 negative essential hypersomnia.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23128233 2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
23016555 Association of Piebaldism, multiple café-au-lait macules, and intertriginous freckling: clinical evidence of a common pathway between KIT and sprouty-related, ena/vasodilator-stimulated phosphoprotein homology-1 domain containing protein 1 (SPRED1).
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22753041 2012 Review and update of SPRED1 mutations causing Legius syndrome.
22751498 2012 A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1.
22321011 Protein phosphatase 1? interacting proteins in the human brain.
21649642 2011 Identification of five novel SPRED1 germline mutations in Legius syndrome.
21616146 2011 Interaction of the receptor FGFRL1 with the negative regulator Spred1.
21531714 2011 Sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein (SPRED1), a tyrosine-protein phosphatase non-receptor type 11 (SHP2) substrate in the Ras/extracellular signal-regulated kinase (ERK) pathway.
21364986 2011 Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.
21089071 2011 Legius syndrome in fourteen families.
20736167 2010 Direct association of Sprouty-related protein with an EVH1 domain (SPRED) 1 or SPRED2 with DYRK1A modifies substrate/kinase interactions.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20339110 2010 Does SPRED1 contribute to leukemogenesis in juvenile myelomonocytic leukemia (JMML)?
20179001 2010 SPRED 1 mutations in a neurofibromatosis clinic.
20108422 2010 Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome.
19920235 2009 Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19443465 2009 SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype.
19389623 2009 Docking motif-guided mapping of the interactome of protein phosphatase-1.
19366998 2009 SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype.
19120036 2009 A severe form of Noonan syndrome and autosomal dominant café-au-lait spots - evidence for different genetic origins.
18216281 2008 Spred1 and TESK1--two new interaction partners of the kinase MARKK/TAO1 that link the microtubule and actin cytoskeleton.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17974561 2008 Tesk1 interacts with Spry2 to abrogate its inhibition of ERK phosphorylation downstream of receptor tyrosine kinase signaling.
17704776 2007 Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype.
17672918 2007 Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns.
16652141 2006 Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16115197 2005 The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1.
15683364 2005 Distinct requirements for the Sprouty domain for functional activity of Spred proteins.
15580519 2004 Expression and subcellular localization of Spred proteins in mouse and human tissues.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15465815 2004 Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells.
15231748 2004 Functional proteomics mapping of a human signaling pathway.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12646235 2003 Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11493923 2001 Spred is a Sprouty-related suppressor of Ras signalling.