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Aliases for SPRY4 Gene

Aliases for SPRY4 Gene

  • Sprouty Homolog 4 (Drosophila) 2 3
  • HH17 3 6
  • Protein Sprouty Homolog 4 3
  • Spry-4 4

External Ids for SPRY4 Gene

Summaries for SPRY4 Gene

Entrez Gene Summary for SPRY4 Gene

  • This gene encodes a member of a family of cysteine- and proline-rich proteins. The encoded protein is an inhibitor of the receptor-transduced mitogen-activated protein kinase (MAPK) signaling pathway. Activity of this protein impairs the formation of active GTP-RAS. Nucleotide variation in this gene has been associated with hypogonadotropic hypogonadism 17 with or without anosmia. Alternative splicing results in a multiple transcript variants. [provided by RefSeq, Jun 2014]

GeneCards Summary for SPRY4 Gene

SPRY4 (Sprouty Homolog 4 (Drosophila)) is a Protein Coding gene. Diseases associated with SPRY4 include hypogonadotropic hypogonadism 17 with or without anosmia and testicular germ cell tumor. Among its related pathways are Jak-STAT signaling pathway. An important paralog of this gene is SPRY3.

UniProtKB/Swiss-Prot for SPRY4 Gene

  • Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras. Probably impairs the formation of GTP-Ras. Inhibits Ras-independent, but not Ras-dependent, activation of RAF1.

Gene Wiki entry for SPRY4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SPRY4 Gene

Genomics for SPRY4 Gene

Genomic Location for SPRY4 Gene

142,310,427 bp from pter
142,326,455 bp from pter
16,029 bases
Minus strand

Genomic View for SPRY4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SPRY4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPRY4 Gene

Regulatory Elements for SPRY4 Gene

Proteins for SPRY4 Gene

  • Protein details for SPRY4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Protein sprouty homolog 4
    Protein Accession:
    Secondary Accessions:
    • A4FVB2
    • A4FVB3
    • Q6QIX2
    • Q9C003

    Protein attributes for SPRY4 Gene

    299 amino acids
    Molecular mass:
    32541 Da
    Quaternary structure:
    • Interacts with the C-terminus of TESK1. Interacts with RAF1.
    • Sequence=AAK00652.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for SPRY4 Gene

    Alternative splice isoforms for SPRY4 Gene


neXtProt entry for SPRY4 Gene

Proteomics data for SPRY4 Gene at MOPED

Post-translational modifications for SPRY4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SPRY4 Gene

No data available for DME Specific Peptides for SPRY4 Gene

Domains for SPRY4 Gene

Protein Domains for SPRY4 Gene



  • The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles:
    • Q9C004
  • Contains 1 SPR (sprouty) domain.:
    • Q9C004
  • Belongs to the sprouty family.:
    • Q9C004
genes like me logo Genes that share domains with SPRY4: view

No data available for Gene Families for SPRY4 Gene

Function for SPRY4 Gene

Molecular function for SPRY4 Gene

UniProtKB/Swiss-Prot Function: Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras. Probably impairs the formation of GTP-Ras. Inhibits Ras-independent, but not Ras-dependent, activation of RAF1.

Gene Ontology (GO) - Molecular Function for SPRY4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 12027893
genes like me logo Genes that share ontologies with SPRY4: view
genes like me logo Genes that share phenotypes with SPRY4: view

Animal Models for SPRY4 Gene

MGI Knock Outs for SPRY4:

miRNA for SPRY4 Gene

miRTarBase miRNAs that target SPRY4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for SPRY4 Gene

Localization for SPRY4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPRY4 Gene

Cytoplasm. Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side.

Subcellular locations from

Jensen Localization Image for SPRY4 Gene COMPARTMENTS Subcellular localization image for SPRY4 gene
Compartment Confidence
plasma membrane 5
cytosol 3
nucleus 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for SPRY4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA --
GO:0005794 Golgi apparatus IDA --
GO:0005886 plasma membrane --
GO:0005925 focal adhesion IDA 21423176
GO:0016020 membrane --
genes like me logo Genes that share ontologies with SPRY4: view

Pathways for SPRY4 Gene

SuperPathways for SPRY4 Gene

Superpath Contained pathways
1 Jak-STAT signaling pathway
genes like me logo Genes that share pathways with SPRY4: view

Pathways by source for SPRY4 Gene

1 KEGG pathway for SPRY4 Gene

Gene Ontology (GO) - Biological Process for SPRY4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007275 multicellular organismal development IEA --
GO:0009966 regulation of signal transduction --
GO:0043407 negative regulation of MAP kinase activity IEA --
genes like me logo Genes that share ontologies with SPRY4: view

Compounds for SPRY4 Gene

(1) HMDB Compounds for SPRY4 Gene

Compound Synonyms Cas Number PubMed IDs
Guanosine triphosphate
  • 5'-GTP
genes like me logo Genes that share compounds with SPRY4: view

Transcripts for SPRY4 Gene

Unigene Clusters for SPRY4 Gene

Sprouty homolog 4 (Drosophila):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SPRY4 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b · 4c · 4d
SP1: - - -
SP3: - - - -
SP4: - -

Relevant External Links for SPRY4 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for SPRY4 Gene

mRNA expression in normal human tissues for SPRY4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for SPRY4 Gene

SOURCE GeneReport for Unigene cluster for SPRY4 Gene Hs.323308

genes like me logo Genes that share expressions with SPRY4: view

Orthologs for SPRY4 Gene

This gene was present in the common ancestor of animals.

Orthologs for SPRY4 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia SPRY4 36
  • 98.86 (n)
  • 98.45 (a)
SPRY4 37
  • 98 (a)
(Bos Taurus)
Mammalia SPRY4 36
  • 91.08 (n)
  • 94.65 (a)
SPRY4 37
  • 95 (a)
(Canis familiaris)
Mammalia SPRY4 36
  • 90.9 (n)
  • 92.7 (a)
SPRY4 37
  • 91 (a)
(Mus musculus)
Mammalia Spry4 36
  • 88.63 (n)
  • 92.98 (a)
Spry4 16
Spry4 37
  • 92 (a)
(Monodelphis domestica)
Mammalia SPRY4 37
  • 80 (a)
(Ornithorhynchus anatinus)
Mammalia SPRY4 37
  • 77 (a)
(Rattus norvegicus)
Mammalia Spry4 36
  • 88.96 (n)
  • 93.31 (a)
(Gallus gallus)
Aves LOC100858637 36
  • 78.11 (n)
  • 76.77 (a)
SPRY4 37
  • 76 (a)
SPRY4 37
  • 76 (a)
(Anolis carolinensis)
Reptilia SPRY4 37
  • 73 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia spry4 36
  • 70.73 (n)
  • 75.93 (a)
(Danio rerio)
Actinopterygii spry4 36
  • 65.41 (n)
  • 63.92 (a)
spry4 37
  • 56 (a)
fruit fly
(Drosophila melanogaster)
Insecta sty 37
  • 14 (a)
Species with no ortholog for SPRY4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SPRY4 Gene

Gene Tree for SPRY4 (if available)
Gene Tree for SPRY4 (if available)

Paralogs for SPRY4 Gene

Paralogs for SPRY4 Gene

Selected SIMAP similar genes for SPRY4 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with SPRY4: view

Variants for SPRY4 Gene

Sequence variations from dbSNP and Humsavar for SPRY4 Gene

SNP ID Clin Chr 05 pos Sequence Context AA Info Type MAF
rs3797053 -- 142,311,254(-) GCTTC(C/T)GCGAG utr-variant-3-prime
rs3839201 -- 142,311,199(-) AAGAT(-/T)GGGCA utr-variant-3-prime
rs4912844 -- 142,311,806(+) GGGGA(A/C)AAAAG utr-variant-3-prime
rs6862653 -- 142,322,193(+) GACAT(A/G)TGAGG intron-variant
rs6874376 -- 142,310,959(+) CAGGA(C/T)GCTTC utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for SPRY4 Gene

Variant ID Type Subtype PubMed ID
nsv830509 CNV Gain 17160897

Relevant External Links for SPRY4 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

Disorders for SPRY4 Gene

(1) OMIM Diseases for SPRY4 Gene (607984)


  • Hypogonadotropic hypogonadism 17 with or without anosmia (HH17) [MIM:615266]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269 PubMed:23643382}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in SPRY4 also have a heterozygous mutation in another HH-associated gene including DUSP6 and FGFR1 (PubMed:23643382). {ECO:0000269 PubMed:23643382}.

(1) University of Copenhagen DISEASES for SPRY4 Gene

Relevant External Links for SPRY4

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with SPRY4: view

Publications for SPRY4 Gene

  1. Genomic structure and promoter characterization of the human Sprouty4 gene, a novel regulator of lung morphogenesis. (PMID: 14977631) Ding W. … Warburton D. (Am. J. Physiol. 2004) 3 4 23
  2. Human sprouty 4, a new ras antagonist on 5q31, interacts with the dual specificity kinase TESK1. (PMID: 12027893) Leeksma O.C. … de Vries C.J.M. (Eur. J. Biochem. 2002) 3 4
  3. Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1. (PMID: 12717443) Sasaki A. … Yoshimura A. (Nat. Cell Biol. 2003) 3 4
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T. … Sugano S. (Nat. Genet. 2004) 3 4
  5. A genome-wide association study of testicular germ cell tumor. (PMID: 19483681) Rapley E.A. … Stratton M.R. (Nat. Genet. 2009) 3 49

Products for SPRY4 Gene

Sources for SPRY4 Gene

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