SPRED1 sprouty-related, EVH1 domain containing 1 [Homo sapiens] - Gene

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Summary

Official Symbol: SPRED1provided by HGNC
Official Full Name: sprouty-related, EVH1 domain containing 1provided by HGNC
Primary source: HGNC:20249
See related: Ensembl:ENSG00000166068; HPRD:11601; MIM:609291; Vega:OTTHUMG00000172377
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NFLS; hSpred1; spred-1; FLJ33903
Summary: 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]

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Genomic context

Location :: 15q14

Sequence :: Chromosome: 15; NC_000015.9 (38545052..38649450)

See SPRED1 in Epigenomics, MapViewer

Chromosome 15 - NC_000015.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Interaction of FGFRL1 with Spred1 increases the proportion of the receptor at the plasma membrane.
Title: Interaction of the receptor FGFRL1 with the negative regulator Spred1.
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
Title: Identification of five novel SPRED1 germline mutations in Legius syndrome.
SPRED1 is a likely substrate of SHP2, whose tyrosine dephosphorylation is required to attenuate the inhibitory action of SPRED1 in the Ras/ERK pathway.
Title: 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.
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.
Title: Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.
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.
Title: SPRED 1 mutations in a neurofibromatosis clinic.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
no evidence of leukemogenic SPRED1 involement in juvenile myelomonocytic leukemia
Title: Does SPRED1 contribute to leukemogenesis in juvenile myelomonocytic leukemia (JMML)?
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.
Title: Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome.
Observational study of gene-disease association. (HuGE Navigator)
Title: Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome.
Unrelated mild NF1 patients were screened for mutations of the SPRED1-3 and the SPRY1-4 genes. SPRED1 mutations were identified in 6 cases.
Title: SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype.

Submit: New GeneRIF Correction See all (17)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Legius syndrome is characterized by multiple caf au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1 (NF1). Additional clinical manifestations reported commonly include intertriginous freckling, lipomas, macrocephaly, and learning disabilities / ADHD / developmental delays. Current knowledge of the natural history of Legius syndrome is based on the clinical manifestations of fewer than 200 individuals with a molecularly confirmed diagnosis; better delineation of the clinical manifestations and natural history of Legius syndrome will likely occur as more affected individuals are identified.

Diagnosis Testing

The diagnosis of Legius syndrome is difficult to make on clinical grounds alone. Detection of a mutation in SPRED1, the only gene known to be associated with Legius syndrome, is necessary to confirm the diagnosis. Such testing is clinically available.

Genetic Counseling

Legius syndrome is inherited in an autosomal dominant manner. Each child of an individual with Legius syndrome has a 50% chance of inheriting the mutation. Although uncommonly requested, prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutation of an affected family member has been identified.

References

PMID: 20945555

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Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
Q7Z699	P10721	KIT	HPRD	PubMed
Q7Z699	P62136	PPP1CA	HPRD	PubMed
BioGRID:127800	BioGRID:107460	CDKN1A	BioGRID	PubMed	Two-hybrid
BioGRID:127800	BioGRID:119699	DNAJB11	BioGRID	PubMed	Two-hybrid
BioGRID:127800	BioGRID:122742	FAM118B	BioGRID	PubMed	Two-hybrid
BioGRID:127800	BioGRID:120728	NAGK	BioGRID	PubMed	Two-hybrid
BioGRID:127800	BioGRID:120779	OSGEP	BioGRID	PubMed	Two-hybrid
BioGRID:127800	BioGRID:111493	PPP1CA	BioGRID	PubMed	Two-hybrid
BioGRID:127800	BioGRID:107529	RCC1	BioGRID	PubMed	Two-hybrid
BioGRID:127800	BioGRID:112875	TESK1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:127800	BioGRID:114374	TSC22D1	BioGRID	PubMed	Two-hybrid
BioGRID:127800	BioGRID:120248	TTC19	BioGRID	PubMed	Two-hybrid
BioGRID:127800	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western

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General gene information

Markers

REN61523 (e-PCR)
- UniSTS:386323

RH104263 (e-PCR)
- UniSTS:98588

NoName (e-PCR)
- UniSTS:490015

SPRED1__5300 (e-PCR)
- UniSTS:463907

WI-14940 (e-PCR)
- UniSTS:5676

STS-AA026390 (e-PCR)
- UniSTS:3929

RH36905 (e-PCR)
- UniSTS:87932

Spred1 (e-PCR), detects polymorphism
- UniSTS:528299

NoName (e-PCR)
- UniSTS:483534

Genotypes

See SPRED1 SNP Geneview Report
See SPRED1 SNP Genotype Report
See SPRED1 SNP Variation Viewer Report

Homology

Homologs of the SPRED1 gene: The SPRED1 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, and mosquito.
Map Viewer (Mouse, Rat)

Pathways from BioSystems

Jak-STAT signaling pathway, organism-specific biosystem (from KEGG)
Jak-STAT signaling pathway, organism-specific biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
Jak-STAT signaling pathway, conserved biosystem (from KEGG)
Jak-STAT signaling pathway, conserved biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
Kit Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
Kit Receptor Signaling Pathway, organism-specific biosystemKit is a receptor protein tyrosine kinase, which is a receptor for stem cell factor or kit ligand. Signaling through Kit is important for formation of red cells, lymphocytes, mast cells and platelets...
Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem
Signaling events mediated by Stem cell factor receptor (c-Kit)

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
phosphatase binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
stem cell factor receptor binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
inactivation of MAPK activity	ISS Inferred from Sequence or Structural Similarity more info
multicellular organismal development	IEA Inferred from Electronic Annotation more info
negative regulation of phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
regulation of signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
caveola	IEA Inferred from Electronic Annotation more info
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
NOT nucleolus	IDA Inferred from Direct Assay more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed

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General protein information

Preferred Names: sprouty-related, EVH1 domain-containing protein 1

Names: sprouty-related, EVH1 domain-containing protein 1; suppressor of Ras/MAPK activation

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008980.1 RefSeqGene

Range

5001..109399

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_152594.2 → NP_689807.1 sprouty-related, EVH1 domain-containing protein 1

Status: REVIEWED

Source sequence(s)

AC069381, AY299089, DA405650

Consensus CDS

CCDS32193.1

UniProtKB/Swiss-Prot

Q7Z699

Related

ENSP00000299084, OTTHUMP00000248269, ENST00000299084, OTTHUMT00000418217

Conserved Domains (2) summary

pfam05210
Location:332 – 424
Blast Score: 371

Sprouty; Sprouty protein (Spry)

cl00273
Location:15 – 120
Blast Score: 196

PH-like; Pleckstrin homology-like domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000015.9 Reference GRCh37.p5 Primary Assembly

Range

38545052..38649450

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000147.1 Alternate HuRef

Range

15389475..15493873

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC069381.8 (85537..190472)	None
genomic	AL833561.1	None
genomic	CH471125.1	EAW92368.1
mRNA	AK091222.1	BAC03614.1
mRNA	AK095219.1	None
mRNA	AY299089.1	AAP59414.1
mRNA	BC018015.1	AAH18015.1
mRNA	BC137480.1	AAI37481.1
mRNA	BC137481.1	AAI37482.1
mRNA	BX538234.1	None
mRNA	DA405650.1	None