The protein encoded by this gene is an atypical member of the family of growth factor receptor protein tyrosine kinases, differing from other members at a number of conserved residues in the activation and nucleotide binding domains. This gene product belongs to a subfamily whose members do not appear to be regulated by phosphorylation in the activation segment. It has been sug... See more...

Aliases for RYK Gene

Aliases for RYK Gene

  • Receptor Like Tyrosine Kinase 2 3 5
  • JTK5A Protein Tyrosine Kinase 2 3
  • Tyrosine-Protein Kinase RYK 3 4
  • EC 2.7.10.1 4 50
  • D3S3195 2 3
  • JTK5A 3 4
  • JTK5 2 3
  • RYK1 2 3
  • RYK Receptor-Like Tyrosine Kinase 2
  • Hydroxyaryl-Protein Kinase 3
  • EC 2.7.10 50
  • RYK 5

External Ids for RYK Gene

Previous HGNC Symbols for RYK Gene

  • JTK5A

Previous GeneCards Identifiers for RYK Gene

  • GC03P130793
  • GC03M134620
  • GC03M135157
  • GC03M135197
  • GC03M135196
  • GC03M135358
  • GC03M133794
  • GC03M131254

Summaries for RYK Gene

Entrez Gene Summary for RYK Gene

  • The protein encoded by this gene is an atypical member of the family of growth factor receptor protein tyrosine kinases, differing from other members at a number of conserved residues in the activation and nucleotide binding domains. This gene product belongs to a subfamily whose members do not appear to be regulated by phosphorylation in the activation segment. It has been suggested that mediation of biological activity by recruitment of a signaling-competent auxiliary protein may occur through an as yet uncharacterized mechanism. The encoded protein has a leucine-rich extracellular domain with a WIF-type Wnt binding region, a single transmembrane domain, and an intracellular tyrosine kinase domain. This protein is involved in stimulating Wnt signaling pathways such as the regulation of axon pathfinding. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2012]

GeneCards Summary for RYK Gene

RYK (Receptor Like Tyrosine Kinase) is a Protein Coding gene. Diseases associated with RYK include Atypical Chronic Myeloid Leukemia and Exudative Vitreoretinopathy 1. Among its related pathways are Nanog in Mammalian ESC Pluripotency and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is ROS1.

UniProtKB/Swiss-Prot Summary for RYK Gene

  • May be a coreceptor along with FZD8 of Wnt proteins, such as WNT1, WNT3, WNT3A and WNT5A. Involved in neuron differentiation, axon guidance, corpus callosum establishment and neurite outgrowth. In response to WNT3 stimulation, receptor C-terminal cleavage occurs in its transmembrane region and allows the C-terminal intracellular product to translocate from the cytoplasm to the nucleus where it plays a crucial role in neuronal development.

Gene Wiki entry for RYK Gene

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

Genomics for RYK Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RYK Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

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

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

Top Transcription factor binding sites by QIAGEN in the RYK gene promoter:
  • AML1a
  • AP-1
  • ATF-2
  • c-Jun
  • GATA-1
  • GATA-2
  • HOXA3

Genomic Locations for RYK Gene

Latest Assembly
chr3:134,065,303-134,250,859
(GRCh38/hg38)
Size:
185,557 bases
Orientation:
Minus strand

Previous Assembly
chr3:133,875,977-133,969,701
(GRCh37/hg19 by Entrez Gene)
Size:
93,725 bases
Orientation:
Minus strand

chr3:133,784,147-133,969,689
(GRCh37/hg19 by Ensembl)
Size:
185,543 bases
Orientation:
Minus strand

Genomic View for RYK Gene

Genes around RYK on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for RYK Gene

Proteins for RYK Gene

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

    Protein Symbol:
    P34925-RYK_HUMAN
    Recommended name:
    Tyrosine-protein kinase RYK
    Protein Accession:
    P34925
    Secondary Accessions:
    • A0A087WUK1
    • A0A096LNL3
    • Q04696

    Protein attributes for RYK Gene

    Size:
    607 amino acids
    Molecular mass:
    67815 Da
    Quaternary structure:
    • Interacts with DVL1 (via PDZ domain).
    SequenceCaution:
    • Sequence=AAB26341.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA65406.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RYK Gene

    Alternative splice isoforms for RYK Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RYK Gene

Selected DME Specific Peptides for RYK Gene

P34925:
  • WMALESL
  • SDVWAFGVT

Post-translational modifications for RYK Gene

  • Proteolytically cleaved, in part by presenilin, in response to WNT3 stimulation. Cleavage occurs during neuronal differentiation.
  • Glycosylation at Asn139, Asn174, Asn178, Asn182, and Asn209
  • Modification sites at PhosphoSitePlus

Other Protein References for RYK Gene

Domains & Families for RYK Gene

Gene Families for RYK Gene

Protein Domains for RYK Gene

InterPro:
Blocks:
  • Tyrosine protein kinase, active site
  • WIF domain

Suggested Antigen Peptide Sequences for RYK Gene

GenScript: Design optimal peptide antigens:
  • RYK protein (Q8WTZ8_HUMAN)
  • Tyrosine-protein kinase RYK (RYK_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P34925

UniProtKB/Swiss-Prot:

RYK_HUMAN :
  • The extracellular WIF domain is responsible for Wnt binding.
  • Belongs to the protein kinase superfamily. Tyr protein kinase family.
Domain:
  • The extracellular WIF domain is responsible for Wnt binding.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family.
genes like me logo Genes that share domains with RYK: view

Function for RYK Gene

Molecular function for RYK Gene

UniProtKB/Swiss-Prot Function:
May be a coreceptor along with FZD8 of Wnt proteins, such as WNT1, WNT3, WNT3A and WNT5A. Involved in neuron differentiation, axon guidance, corpus callosum establishment and neurite outgrowth. In response to WNT3 stimulation, receptor C-terminal cleavage occurs in its transmembrane region and allows the C-terminal intracellular product to translocate from the cytoplasm to the nucleus where it plays a crucial role in neuronal development.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};.
GENATLAS Biochemistry:
related to receptor tyrosine kinase

Enzyme Numbers (IUBMB) for RYK Gene

Phenotypes From GWAS Catalog for RYK Gene

Gene Ontology (GO) - Molecular Function for RYK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA --
GO:0004713 NOT protein tyrosine kinase activity IEA,IDA 10454588
GO:0004714 NOT transmembrane receptor protein tyrosine kinase activity IBA 21873635
GO:0004888 transmembrane signaling receptor activity IDA 10454588
genes like me logo Genes that share ontologies with RYK: view
genes like me logo Genes that share phenotypes with RYK: view

Animal Models for RYK Gene

MGI Knock Outs for RYK:
  • Ryk Ryk<tm1Stac>

Inhibitory RNAs for research

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

Clone products for research

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RYK Gene

Localization for RYK Gene

Subcellular locations from UniProtKB/Swiss-Prot for RYK Gene

Membrane. Single-pass type I membrane protein. Nucleus. Cytoplasm. Note=In cells that have undergone neuronal differentiation, the C-terminal cleaved part is translocated from the cytoplasm to the nucleus. {ECO:0000250}.

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 RYK gene
Compartment Confidence
nucleus 5
plasma membrane 4
extracellular 2
cytoskeleton 2
cytosol 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Golgi apparatus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RYK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus NAS 20004982
GO:0005737 cytoplasm ISS --
GO:0005886 plasma membrane IEA,TAS --
GO:0005887 integral component of plasma membrane TAS,IBA 21873635
GO:0016020 membrane ISS --
genes like me logo Genes that share ontologies with RYK: view

Pathways & Interactions for RYK Gene

PathCards logo

SuperPathways for RYK Gene

SuperPathway Contained pathways
1 GPCR Pathway
.73
.73
.62
.59
.58
.58
.55
.38
2 ERK Signaling
.61
.61
.58
.51
.49
3 Nanog in Mammalian ESC Pluripotency
.61
.61
.59
.48
4 Actin Nucleation by ARP-WASP Complex
.66
.66
.41
5 Activation of cAMP-Dependent PKA
.77
.71
genes like me logo Genes that share pathways with RYK: view

Pathways by source for RYK Gene

2 KEGG pathways for RYK Gene
28 Qiagen pathways for RYK Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin Nucleation and Branching
  • Actin Nucleation by ARP-WASP Complex
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR

SIGNOR curated interactions for RYK Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for RYK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 NOT protein phosphorylation IEA,IDA 10454588
GO:0007165 signal transduction TAS 8386829
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway IBA 21873635
GO:0007275 multicellular organism development IBA 21873635
GO:0007409 axonogenesis IEA,TAS 24431302
genes like me logo Genes that share ontologies with RYK: view

Drugs & Compounds for RYK Gene

(2) Drugs for RYK Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
ATP Investigational Nutra 0

(1) Additional Compounds for RYK Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
58-64-0
genes like me logo Genes that share compounds with RYK: view

Transcripts for RYK Gene

mRNA/cDNA for RYK Gene

2 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
9 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 RYK

Clone products for research

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

No ASD Table

Relevant External Links for RYK Gene

GeneLoc Exon Structure for
RYK

Expression for RYK Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for RYK Gene

This gene is overexpressed in Ovary (43.8), Adipocyte (18.9), and CD8 Tcells (6.3).

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



Protein tissue co-expression partners for RYK Gene

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

SOURCE GeneReport for Unigene cluster for RYK Gene:

Hs.654562

mRNA Expression by UniProt/SwissProt for RYK Gene:

P34925-RYK_HUMAN
Tissue specificity: Observed in all the tissues examined.

Evidence on tissue expression from TISSUES for RYK Gene

  • Skin(2.5)
  • Nervous system(2.5)
  • Heart(2.5)
  • Kidney(2.4)
  • Muscle(2.4)
  • Intestine(2.2)
  • Lung(2.2)
  • Spleen(2.1)
  • Liver(2.1)
  • Thyroid gland(2)
genes like me logo Genes that share expression patterns with RYK: view

Primer products for research

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for RYK Gene

Orthologs for RYK Gene

This gene was present in the common ancestor of animals.

Orthologs for RYK Gene

Organism Taxonomy Gene Similarity Type Details
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 100 (a)
OneToMany
-- 30
  • 89 (a)
OneToMany
Chimpanzee
(Pan troglodytes)
Mammalia RYK 29 30
  • 96.31 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia RYK 29 30
  • 95.34 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia RYK 29 30
  • 94.44 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ryk 29
  • 90.71 (n)
Mouse
(Mus musculus)
Mammalia Ryk 29 16 30
  • 90.53 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia RYK 30
  • 85 (a)
OneToOne
Chicken
(Gallus gallus)
Aves RYK 29 30
  • 82.48 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia RYK 30
  • 86 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia ryk 29
  • 73.4 (n)
Str.16124 29
Zebrafish
(Danio rerio)
Actinopterygii ryk 29 30
  • 74.51 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Drl-2 29 30 31
  • 49.85 (n)
OneToMany
dnt 30 31
  • 37 (a)
OneToMany
drl 30 31
  • 33 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006405 29
  • 48.86 (n)
Worm
(Caenorhabditis elegans)
Secernentea lin-18 29 30 31
  • 45.2 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 57 (a)
OneToOne
Species where no ortholog for RYK was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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 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 RYK Gene

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

Paralogs for RYK Gene

Pseudogenes.org Pseudogenes for RYK Gene

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

Variants for RYK Gene

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

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
767934 Benign: not provided 134,250,594(-) G/.
NM_002958.4(RYK):c.61= (p.Leu21=)
NO_SEQUENCE_ALTERATION
767935 Benign: not provided 134,250,645(-) C/.
NM_002958.4(RYK):c.10= (p.Ala4=)
NO_SEQUENCE_ALTERATION
rs1000514707 Likely Benign: not provided 134,209,732(-) G/A
NM_001005861.2(RYK):c.552C>T (p.Thr184=)
SYNONYMOUS
rs116254638 Benign: not provided 134,175,954(-) T/C
NM_001005861.2(RYK):c.1400A>G (p.Lys467Arg)
MISSENSE
rs116266774 Benign: not provided 134,222,543(-) G/C
NM_001005861.2(RYK):c.233-4C>G
INTRON

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

Variant ID Type Subtype PubMed ID
esv23490 CNV loss 19812545
nsv1074626 CNV deletion 25765185
nsv1142373 CNV tandem duplication 24896259
nsv1145001 CNV deletion 24896259
nsv475801 CNV novel sequence insertion 20440878

Variation tolerance for RYK Gene

Gene Damage Index Score: 9.00; 87.40% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RYK Gene

Human Gene Mutation Database (HGMD)
RYK
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RYK
Leiden Open Variation Database (LOVD)
RYK

SNP Genotyping and Copy Number Assays for research

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

Disorders for RYK Gene

MalaCards: The human disease database

(4) MalaCards diseases for RYK Gene - From: COP and GCD

Disorder Aliases PubMed IDs
atypical chronic myeloid leukemia
  • acml
exudative vitreoretinopathy 1
  • evr1
robinow syndrome
  • acral dysostosis with facial and genital abnormalities
norrie disease
  • nd
- elite association - COSMIC cancer census association via MalaCards
Search RYK in MalaCards View complete list of genes associated with diseases

Additional Disease Information for RYK

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 RYK: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RYK Gene

Publications for RYK Gene

  1. Molecular cloning and chromosomal localisation of the human homologue of a receptor related to tyrosine kinases (RYK). (PMID: 8386829) Stacker SA … Wilks AF (Oncogene 1993) 2 3 4 22
  2. A mutation in RYK is a genetic factor for nonsyndromic cleft lip and palate. (PMID: 16681403) Watanabe A … Yoshiura K (The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 2006) 3 22 40
  3. Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia. (PMID: 20634891) Jugessur A … Murray JC (PloS one 2010) 3 40
  4. Testing reported associations of genetic risk factors for oral clefts in a large Irish study population. (PMID: 19937600) Carter TC … Mills JL (Birth defects research. Part A, Clinical and molecular teratology 2010) 3 40
  5. Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. (PMID: 15454084) Lu W … Baltimore D (Cell 2004) 3 4

Products for RYK Gene

Sources for RYK Gene