This gene encodes a member of the GRB2/Sem5/Drk family and functions as a cytoplasmic signaling protein which contains an SH2 domain flanked by two SH3 domains. The SH2 domain interacts with ligand-activated receptors for stem cell factor and erythropoietin, and facilitates the formation of a stable complex with the BCR-ABL oncoprotein. This protein also associates with the Ras... See more...

Aliases for GRAP Gene

Aliases for GRAP Gene

  • GRB2 Related Adaptor Protein 2 3 5
  • GRB2-Related Adapter Protein 3 4
  • Growth Factor Receptor-Bound Protein 2-Related Adaptor Protein 3
  • DFNB114 3
  • GRAP 5

External Ids for GRAP Gene

Previous GeneCards Identifiers for GRAP Gene

  • GC17M019170
  • GC17M020585
  • GC17M018867
  • GC17M019124
  • GC17M018864
  • GC17M018923
  • GC17M018491
  • GC17M019021
  • GC17M019022
  • GC17M019077
  • GC17M019098
  • GC17M019111
  • GC17M019481
  • GC17M019025
  • GC17M019883
  • GC17M020248

Summaries for GRAP Gene

Entrez Gene Summary for GRAP Gene

  • This gene encodes a member of the GRB2/Sem5/Drk family and functions as a cytoplasmic signaling protein which contains an SH2 domain flanked by two SH3 domains. The SH2 domain interacts with ligand-activated receptors for stem cell factor and erythropoietin, and facilitates the formation of a stable complex with the BCR-ABL oncoprotein. This protein also associates with the Ras guanine nucleotide exchange factor SOS1 (son of sevenless homolog 1) through its N-terminal SH3 domain. In general, it couples signals from receptor and cytoplasmic tyrosine kinases to the Ras signaling pathway. [provided by RefSeq, Jul 2012]

GeneCards Summary for GRAP Gene

GRAP (GRB2 Related Adaptor Protein) is a Protein Coding gene. Diseases associated with GRAP include Deafness, Autosomal Recessive 114 and Autosomal Recessive Non-Syndromic Sensorineural Deafness Type Dfnb. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include SH3/SH2 adaptor activity. An important paralog of this gene is GRB2.

UniProtKB/Swiss-Prot Summary for GRAP Gene

  • Couples signals from receptor and cytoplasmic tyrosine kinases to the Ras signaling pathway. Plays a role in the inner ear and in hearing (PubMed:30610177).

Gene Wiki entry for GRAP Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GRAP Gene

Genomics for GRAP Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for GRAP Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17J019046 Promoter/Enhancer 0.8 EPDnew Ensembl dbSUPER 250.7 +0.8 810 2.4 GRAP lnc-SLC5A10-1 FAM83G
GH17J019048 Promoter/Enhancer 0.5 Ensembl dbSUPER 250.7 -1.9 -1890 0.2 GRAP LOC112268188 GRAPL
GH17J019645 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 5 -602.2 -602150 7.8 SP1 ZNF207 ZNF654 ZNF600 JUND ZNF580 ATF2 POLR2A CEBPA ZNF223 ENSG00000264932 ALDH3A2 ENSG00000275982 ENSG00000262769 piR-36817 MAPK7 TVP23B ENSG00000262202 SLC47A1P2 FOXO3B
GH17J019061 Promoter/Enhancer 1.5 Ensembl ENCODE dbSUPER 0.4 -16.0 -15990 4.8 ZNF207 NCOR1 ZNF600 ZNF580 KLF9 POLR2A CEBPA ZNF10 NFIC ZIC2 SNORD3B-1 SNORD3B-2 lnc-GRAP-1 lnc-SLC5A10-3 FOXO3B DRG2 MAPK7 ENSG00000262202 FLII GRAP
GH17J019109 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 0.2 -64.8 -64790 4 SP1 IKZF1 NCOR1 POLR2A NFIC NONO BCL11A SMAD5 ZNF639 ZNF341 ENSG00000262202 HSALNG0115095 SNORD3D EPN2 MAPK7 SMCR8 FOXO3B AKAP10 TOP3A ENSG00000228157
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GRAP on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GRAP

Top Transcription factor binding sites by QIAGEN in the GRAP gene promoter:
  • aMEF-2
  • AREB6
  • GATA-1
  • HTF
  • ITF-2
  • MEF-2A
  • Sox9
  • SRY
  • Tal-1beta

Genomic Locations for GRAP Gene

Latest Assembly
chr17:19,020,656-19,047,011
(GRCh38/hg38)
Size:
26,356 bases
Orientation:
Minus strand

Previous Assembly
chr17:18,923,969-18,950,270
(GRCh37/hg19 by Entrez Gene)
Size:
26,302 bases
Orientation:
Minus strand

chr17:18,923,986-18,950,950
(GRCh37/hg19 by Ensembl)
Size:
26,965 bases
Orientation:
Minus strand

Genomic View for GRAP Gene

Genes around GRAP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GRAP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GRAP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GRAP Gene

Proteins for GRAP Gene

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

    Protein Symbol:
    Q13588-GRAP_HUMAN
    Recommended name:
    GRB2-related adapter protein
    Protein Accession:
    Q13588

    Protein attributes for GRAP Gene

    Size:
    217 amino acids
    Molecular mass:
    25337 Da
    Quaternary structure:
    • Associates through its SH2 domain with ligand-activated receptors for stem cell factor (KIT) and erythropoietin (EPOR). Also forms a stable complex with the Bcr-Abl oncoprotein. GRAP is associated with the Ras guanine nucleotide exchange factor SOS1, primarily through its N-terminal SH3 domain. Interacts with phosphorylated LAT upon TCR activation. Interacts with SHB.

neXtProt entry for GRAP Gene

Post-translational modifications for GRAP Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GRAP Gene

No data available for DME Specific Peptides for GRAP Gene

Domains & Families for GRAP Gene

Gene Families for GRAP Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for GRAP Gene

InterPro:
Blocks:
  • SH2 domain signature
  • SH3 domain signature

Suggested Antigen Peptide Sequences for GRAP Gene

GenScript: Design optimal peptide antigens:
  • GRB2-related adapter protein (GRAP_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q13588

UniProtKB/Swiss-Prot:

GRAP_HUMAN :
  • Belongs to the GRB2/sem-5/DRK family.
Family:
  • Belongs to the GRB2/sem-5/DRK family.
genes like me logo Genes that share domains with GRAP: view

Function for GRAP Gene

Molecular function for GRAP Gene

UniProtKB/Swiss-Prot Function:
Couples signals from receptor and cytoplasmic tyrosine kinases to the Ras signaling pathway. Plays a role in the inner ear and in hearing (PubMed:30610177).

Gene Ontology (GO) - Molecular Function for GRAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA,IPI 25036101
genes like me logo Genes that share ontologies with GRAP: view
genes like me logo Genes that share phenotypes with GRAP: view

Human Phenotype Ontology for GRAP Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GRAP Gene

MGI Knock Outs for GRAP:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GRAP

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Transcription Factor Targets and HOMER Transcription for GRAP Gene

Localization for GRAP Gene

Subcellular locations from UniProtKB/Swiss-Prot for GRAP Gene

Membrane. Peripheral membrane protein. Cell junction, synapse. Note=Localizes at the presynaptic terminal. {ECO:0000250 UniProtKB:Q08012}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GRAP gene
Compartment Confidence
cytosol 5
nucleus 3
plasma membrane 2
cytoskeleton 2
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GRAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm TAS 8647802
GO:0005829 cytosol TAS --
GO:0016020 membrane IEA --
GO:0030054 cell junction IEA --
GO:0045202 synapse IEA --
genes like me logo Genes that share ontologies with GRAP: view

Pathways & Interactions for GRAP Gene

PathCards logo

SuperPathways for GRAP Gene

SuperPathway Contained pathways
1 Signaling by GPCR
2 RET signaling
genes like me logo Genes that share pathways with GRAP: view

Pathways by source for GRAP Gene

2 Reactome pathways for GRAP Gene

SIGNOR curated interactions for GRAP Gene

Is activated by:

Gene Ontology (GO) - Biological Process for GRAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007265 Ras protein signal transduction TAS 8647802
GO:0007267 cell-cell signaling TAS 8647802
GO:0007605 sensory perception of sound IDA 30610177
genes like me logo Genes that share ontologies with GRAP: view

Drugs & Compounds for GRAP Gene

(4) Drugs for GRAP Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Guanosine diphosphate Experimental Pharma 0
Guanosine monophosphate Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0
genes like me logo Genes that share compounds with GRAP: view

Transcripts for GRAP Gene

mRNA/cDNA for GRAP Gene

2 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GRAP

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

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c · 6d
SP1:
SP2: -
SP3: - -
SP4: - - -

Relevant External Links for GRAP Gene

GeneLoc Exon Structure for
GRAP

Expression for GRAP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GRAP Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Lymph (Hematopoietic System)

mRNA differential expression in normal tissues according to GTEx for GRAP Gene

This gene is overexpressed in Spleen (x7.7) and Whole Blood (x5.0).

Protein differential expression in normal tissues from HIPED for GRAP Gene

This gene is overexpressed in Peripheral blood mononuclear cells (22.5), Tlymphocyte (20.6), and Monocytes (6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GRAP Gene



Protein tissue co-expression partners for GRAP Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GRAP

SOURCE GeneReport for Unigene cluster for GRAP Gene:

Hs.567416

Evidence on tissue expression from TISSUES for GRAP Gene

  • Blood(4.4)
  • Nervous system(4.2)
  • Spleen(2)
genes like me logo Genes that share expression patterns with GRAP: view

Primer products for research

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for GRAP Gene

Orthologs for GRAP Gene

This gene was present in the common ancestor of animals.

Orthologs for GRAP Gene

Organism Taxonomy Gene Similarity Type Details
Dog
(Canis familiaris)
Mammalia GRAP 29
  • 90.78 (n)
Cow
(Bos Taurus)
Mammalia GRAP 29
  • 89.25 (n)
Mouse
(Mus musculus)
Mammalia Grap 29 16 30
  • 87.4 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Grap 29
  • 86.18 (n)
Oppossum
(Monodelphis domestica)
Mammalia -- 30
  • 86 (a)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 71 (a)
OneToMany
Chicken
(Gallus gallus)
Aves GRAP 29 30
  • 77.31 (n)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 67 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100127598 29
  • 70.09 (n)
Zebrafish
(Danio rerio)
Actinopterygii grapa 29 30
  • 63.38 (n)
ManyToMany
grapb 30
  • 59 (a)
ManyToMany
Fruit Fly
(Drosophila melanogaster)
Insecta drk 30 31
  • 55 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea sem-5 30 31
  • 48 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.8309 30
  • 48 (a)
OneToMany
Species where no ortholog for GRAP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • Chimpanzee (Pan troglodytes)
  • 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 Vase (Ciona intestinalis)
  • 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)

Evolution for GRAP Gene

ENSEMBL:
Gene Tree for GRAP (if available)
TreeFam:
Gene Tree for GRAP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GRAP: view image
Alliance of Genome Resources:
Additional Orthologs for GRAP

Paralogs for GRAP Gene

Paralogs for GRAP Gene

(22) SIMAP similar genes for GRAP Gene using alignment to 4 proteins:

  • GRAP_HUMAN
  • A8MW78_HUMAN
  • I3L2P9_HUMAN
  • J3QRP9_HUMAN

Pseudogenes.org Pseudogenes for GRAP Gene

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

Variants for GRAP Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GRAP Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
rs201111642 Likely Benign: not provided 19,041,812(-) G/A
NM_006613.4(GRAP):c.171C>T (p.Pro57=)
SYNONYMOUS
rs370564476 Likely Pathogenic: Deafness, autosomal recessive 114. Deafness, autosomal recessive, 114 (DFNB114) [MIM:618456] 19,024,372(-) T/Ap.Gln104Leu
NM_006613.4(GRAP):c.311A>T (p.Gln104Leu)
MISSENSE_VARIANT,INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for GRAP Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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

Variant ID Type Subtype PubMed ID
dgv1700e59 CNV duplication 20981092
dgv3116n100 CNV gain 25217958
dgv895e212 CNV loss 25503493
esv25927 CNV gain+loss 19812545
esv2758678 CNV gain+loss 17122850
esv33572 CNV gain 17666407
esv3387737 CNV duplication 20981092
esv3398141 CNV duplication 20981092
esv3444578 CNV duplication 20981092
esv3892975 CNV loss 25118596
esv3892976 CNV loss 25118596
nsv428336 CNV gain+loss 18775914
nsv574554 CNV loss 21841781
nsv7291 OTHER inversion 18451855
nsv833391 CNV loss 17160897
nsv9504 CNV gain+loss 18304495
nsv953842 CNV deletion 24416366
nsv960071 CNV duplication 23825009
nsv962282 CNV duplication 23825009
nsv962450 CNV duplication 23825009
nsv978383 CNV duplication 23825009

Variation tolerance for GRAP Gene

Gene Damage Index Score: 0.44; 9.66% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GRAP Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GRAP
Leiden Open Variation Database (LOVD)
GRAP

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GRAP Gene

Disorders for GRAP Gene

MalaCards: The human disease database

(4) MalaCards diseases for GRAP Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
deafness, autosomal recessive 114
  • dfnb114
autosomal recessive non-syndromic sensorineural deafness type dfnb
  • autosomal recessive isolated neurosensory deafness type dfnb
mucocele of salivary gland
  • mucous retention cyst of salivary gland
sensorineural hearing loss
  • central hearing loss
- elite association - COSMIC cancer census association via MalaCards
Search GRAP in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

GRAP_HUMAN
  • Deafness, autosomal recessive, 114 (DFNB114) [MIM:618456]: A form of non-syndromic deafness characterized by congenital profound sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269 PubMed:30610177}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for GRAP

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with GRAP: view

No data available for Genatlas for GRAP Gene

Publications for GRAP Gene

  1. Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine kinases to the Ras pathway. (PMID: 8647802) Feng GS … Ni J (The Journal of biological chemistry 1996) 2 3 4 22
  2. Dysfunction of GRAP, encoding the GRB2-related adaptor protein, is linked to sensorineural hearing loss. (PMID: 30610177) Li C … Tekin M (Proceedings of the National Academy of Sciences of the United States of America 2019) 3 4 72
  3. The role of a lymphoid-restricted, Grb2-like SH3-SH2-SH3 protein in T cell receptor signaling. (PMID: 8995379) Trüb T … Shoelson SE (The Journal of biological chemistry 1997) 2 3 22
  4. Quantitative mass spectrometry of diabetic kidney tubules identifies GRAP as a novel regulator of TGF-beta signaling. (PMID: 19836472) Cummins TD … Powell DW (Biochimica et biophysica acta 2010) 3 22
  5. CD28 and Grb-2, relative to Gads or Grap, preferentially co-operate with Vav1 in the activation of NFAT/AP-1 transcription. (PMID: 18295596) Schneider H … Rudd CE (Biochemical and biophysical research communications 2008) 3 22

Products for GRAP Gene

Sources for GRAP Gene