This gene encodes a multidomain protein that functions as a scaffold protein to mediate the mitogen-activated protein kinase pathways downstream from Ras. This gene product is induced by vitamin D and inhibits apoptosis in certain cancer cells. It may also play a role in ternary complex assembly of synaptic proteins at the postsynaptic membrane and coupling of signal transducti... See more...

Aliases for CNKSR2 Gene

Aliases for CNKSR2 Gene

  • Connector Enhancer Of Kinase Suppressor Of Ras 2 2 3 3 4 5
  • CNK2 2 3 4
  • KSR2 2 3 4
  • CNK Homolog Protein 2 3 4
  • KIAA0902 2 4
  • Membrane-Associated Guanylate Kinase-Interacting Protein 3
  • Connector Enhancer Of KSR 2 4
  • Connector Enhancer Of KSR2 3
  • MAGUIN 3
  • MRXSHG 3
  • CNKSR2 5

External Ids for CNKSR2 Gene

Previous GeneCards Identifiers for CNKSR2 Gene

  • GC0XP020754
  • GC0XP021152
  • GC0XP021302
  • GC0XP019116

Summaries for CNKSR2 Gene

Entrez Gene Summary for CNKSR2 Gene

  • This gene encodes a multidomain protein that functions as a scaffold protein to mediate the mitogen-activated protein kinase pathways downstream from Ras. This gene product is induced by vitamin D and inhibits apoptosis in certain cancer cells. It may also play a role in ternary complex assembly of synaptic proteins at the postsynaptic membrane and coupling of signal transduction to membrane/cytoskeletal remodeling. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

GeneCards Summary for CNKSR2 Gene

CNKSR2 (Connector Enhancer Of Kinase Suppressor Of Ras 2) is a Protein Coding gene. Diseases associated with CNKSR2 include Mental Retardation, X-Linked, Syndromic, Houge Type and Alacrima, Achalasia, And Mental Retardation Syndrome. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include identical protein binding. An important paralog of this gene is CNKSR3.

UniProtKB/Swiss-Prot Summary for CNKSR2 Gene

  • May function as an adapter protein or regulator of Ras signaling pathways.

Gene Wiki entry for CNKSR2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CNKSR2 Gene

Genomics for CNKSR2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CNKSR2 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
GH0XJ021373 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE CraniofacialAtlas 250.7 +2.3 2300 4.2 EZH2 BHLHE40 POLR2A CTCF TAF1 IKZF1 L3MBTL2 RAD21 SIN3A SCRT2 CNKSR2 5MWI_A-182 ENSG00000283380 LOC105373146 YY2 HSALNG0136941 RARRES2P3 KLHL34
GH0XJ021408 Enhancer 0.3 Ensembl ENCODE 13 +35.7 35700 0.6 CNKSR2 RARRES2P3 HSALNG0136941 5MWI_A-182 KLHL34
GH0XJ021395 Enhancer 0.2 Ensembl 13.1 +23.0 23000 1.2 CNKSR2 5MWI_A-182 RARRES2P3 HSALNG0136941 KLHL34
GH0XJ021438 Enhancer 0.4 ENCODE 0.2 +66.8 66751 1.9 SPI1 ELF1 ZBTB40 HSALNG0136942 CNKSR2 piR-60885-168 KLHL34
GH0XJ021378 Enhancer 0.2 Ensembl 0.4 +6.3 6300 0.6 5MWI_A-182 CNKSR2 RARRES2P3 HSALNG0136941 KLHL34
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CNKSR2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CNKSR2

Top Transcription factor binding sites by QIAGEN in the CNKSR2 gene promoter:
  • Cdc5
  • FOXJ2
  • FOXJ2 (long isoform)
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • Nkx3-1 v3
  • Nkx3-1 v4
  • Pbx1a
  • Sox9

Genomic Locations for CNKSR2 Gene

Latest Assembly
chrX:21,372,801-21,654,695
(GRCh38/hg38)
Size:
281,895 bases
Orientation:
Plus strand

Previous Assembly
chrX:21,392,536-21,672,807
(GRCh37/hg19 by Entrez Gene)
Size:
280,272 bases
Orientation:
Plus strand

chrX:21,392,536-21,672,813
(GRCh37/hg19 by Ensembl)
Size:
280,278 bases
Orientation:
Plus strand

Genomic View for CNKSR2 Gene

Genes around CNKSR2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CNKSR2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CNKSR2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CNKSR2 Gene

Proteins for CNKSR2 Gene

  • Protein details for CNKSR2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WXI2-CNKR2_HUMAN
    Recommended name:
    Connector enhancer of kinase suppressor of ras 2
    Protein Accession:
    Q8WXI2
    Secondary Accessions:
    • B4DGR4
    • B7ZLJ1
    • B9EG83
    • E7ESA4
    • O94976
    • Q5JPK4
    • Q5JPN0
    • Q8WXI1

    Protein attributes for CNKSR2 Gene

    Size:
    1034 amino acids
    Molecular mass:
    117535 Da
    Quaternary structure:
    • Interacts with RAF1, RAB2L and RAL GTPase proteins.

    Three dimensional structures from OCA and Proteopedia for CNKSR2 Gene

    Alternative splice isoforms for CNKSR2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CNKSR2 Gene

Post-translational modifications for CNKSR2 Gene

No data available for DME Specific Peptides for CNKSR2 Gene

Domains & Families for CNKSR2 Gene

Protein Domains for CNKSR2 Gene

InterPro:
Blocks:
  • Sterile alpha motif SAM
  • PDZ/DHR/GLGF domain
  • Pleckstrin-like
  • Protein of unknown function DUF1170

Suggested Antigen Peptide Sequences for CNKSR2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ61239, highly similar to Connector enhancer of kinase suppressor of ras 2 (B4DGR4_HUMAN)
  • CNK homolog protein 2 (CNKR2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8WXI2

UniProtKB/Swiss-Prot:

CNKR2_HUMAN :
  • Belongs to the CNKSR family.
Family:
  • Belongs to the CNKSR family.
genes like me logo Genes that share domains with CNKSR2: view

Function for CNKSR2 Gene

Molecular function for CNKSR2 Gene

UniProtKB/Swiss-Prot Function:
May function as an adapter protein or regulator of Ras signaling pathways.

Phenotypes From GWAS Catalog for CNKSR2 Gene

Gene Ontology (GO) - Molecular Function for CNKSR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA,IPI 18287031
GO:0019901 protein kinase binding IDA 14597674
GO:0042802 identical protein binding IEA --
genes like me logo Genes that share ontologies with CNKSR2: view
genes like me logo Genes that share phenotypes with CNKSR2: view

Human Phenotype Ontology for CNKSR2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CNKSR2

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for CNKSR2 Gene

Localization for CNKSR2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CNKSR2 Gene

Cytoplasm. Membrane. Peripheral membrane protein.

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 CNKSR2 gene
Compartment Confidence
plasma membrane 5
extracellular 4
nucleus 2
cytosol 2
golgi apparatus 2
cytoskeleton 1
mitochondrion 1
endosome 1

Subcellular locations from the

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

Gene Ontology (GO) - Cellular Components for CNKSR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005886 plasma membrane IDA 14597674
GO:0014069 postsynaptic density IEA --
GO:0016020 membrane IEA --
GO:0043005 neuron projection IEA --
genes like me logo Genes that share ontologies with CNKSR2: view

Pathways & Interactions for CNKSR2 Gene

PathCards logo

SuperPathways for CNKSR2 Gene

SuperPathway Contained pathways
1 RET signaling
2 Paradoxical activation of RAF signaling by kinase inactive BRAF
3 Developmental Biology
4 Cytokine Signaling in Immune system
5 HIV Life Cycle
.45
genes like me logo Genes that share pathways with CNKSR2: view

Pathways by source for CNKSR2 Gene

SIGNOR curated interactions for CNKSR2 Gene

Activates:

Gene Ontology (GO) - Biological Process for CNKSR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0009966 regulation of signal transduction IEA --
GO:0035556 intracellular signal transduction IDA 14597674
GO:0099173 postsynapse organization IEA --
genes like me logo Genes that share ontologies with CNKSR2: view

Drugs & Compounds for CNKSR2 Gene

No Compound Related Data Available

Transcripts for CNKSR2 Gene

mRNA/cDNA for CNKSR2 Gene

8 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
40 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 CNKSR2

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for CNKSR2 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22
SP1:
SP2: -
SP3:
SP4: -

Relevant External Links for CNKSR2 Gene

GeneLoc Exon Structure for
CNKSR2

Expression for CNKSR2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CNKSR2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CNKSR2 Gene

This gene is overexpressed in Brain - Cerebellar Hemisphere (x7.1), Brain - Frontal Cortex (BA9) (x5.6), Brain - Cerebellum (x5.6), Brain - Nucleus accumbens (basal ganglia) (x4.5), Brain - Anterior cingulate cortex (BA24) (x4.5), and Brain - Cortex (x4.0).

Protein differential expression in normal tissues from HIPED for CNKSR2 Gene

This gene is overexpressed in Bone marrow mesenchymal stem cell (68.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CNKSR2 Gene



Protein tissue co-expression partners for CNKSR2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CNKSR2

SOURCE GeneReport for Unigene cluster for CNKSR2 Gene:

Hs.555917

Evidence on tissue expression from TISSUES for CNKSR2 Gene

  • Nervous system(4.9)
  • Liver(4.1)
genes like me logo Genes that share expression patterns with CNKSR2: 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 CNKSR2 Gene

Orthologs for CNKSR2 Gene

This gene was present in the common ancestor of animals.

Orthologs for CNKSR2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CNKSR2 29 30
  • 96.36 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CNKSR2 29 30
  • 95.04 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CNKSR2 29 30
  • 94.91 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Cnksr2 29
  • 94.02 (n)
Oppossum
(Monodelphis domestica)
Mammalia CNKSR2 30
  • 94 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Cnksr2 29 16 30
  • 93.77 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CNKSR2 30
  • 88 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CNKSR2 29 30
  • 81.88 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CNKSR2 30
  • 91 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia cnksr2 29
  • 78.71 (n)
Zebrafish
(Danio rerio)
Actinopterygii cnksr2b 30
  • 71 (a)
OneToMany
cnksr2a 29 30
  • 68.82 (n)
OneToMany
Dr.26298 29
Fruit Fly
(Drosophila melanogaster)
Insecta cnk 30
  • 17 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea cnk-1 30
  • 19 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 39 (a)
OneToOne
Species where no ortholog for CNKSR2 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)
  • 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 CNKSR2 Gene

ENSEMBL:
Gene Tree for CNKSR2 (if available)
TreeFam:
Gene Tree for CNKSR2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CNKSR2: view image
Alliance of Genome Resources:
Additional Orthologs for CNKSR2

Paralogs for CNKSR2 Gene

Paralogs for CNKSR2 Gene

(2) SIMAP similar genes for CNKSR2 Gene using alignment to 2 proteins:

  • CNKR2_HUMAN
  • L8E9Q3_HUMAN
genes like me logo Genes that share paralogs with CNKSR2: view

Variants for CNKSR2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CNKSR2 Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
1013357 Pathogenic: not provided 21,532,043(+) AG/A
NM_014927.5(CNKSR2):c.1280del (p.Arg427fs)
FRAMESHIFT
1013358 Likely Benign: not provided 21,609,173(+) A/T
NM_014927.5(CNKSR2):c.2248A>T (p.Thr750Ser)
MISSENSE
1030443 Uncertain Significance: Intellectual disability, X-linked, syndromic, Houge type 21,563,291(+) A/G
NM_014927.5(CNKSR2):c.1447A>G (p.Met483Val)
MISSENSE
1030444 Uncertain Significance: Intellectual disability, X-linked, syndromic, Houge type 21,595,038(+) G/A
NM_014927.5(CNKSR2):c.1895G>A (p.Arg632His)
MISSENSE
1030445 Uncertain Significance: Intellectual disability, X-linked, syndromic, Houge type 21,648,887(+) G/C
NM_014927.5(CNKSR2):c.2749G>C (p.Glu917Gln)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CNKSR2 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 CNKSR2 Gene

Variant ID Type Subtype PubMed ID
esv3309065 CNV mobile element insertion 20981092
esv3334033 CNV insertion 20981092
nsv476176 CNV novel sequence insertion 20440878
nsv510819 CNV deletion 20534489
nsv6830 CNV insertion 18451855

Variation tolerance for CNKSR2 Gene

Residual Variation Intolerance Score: 3.25% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.38; 42.19% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CNKSR2 Gene

Human Gene Mutation Database (HGMD)
CNKSR2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CNKSR2
Leiden Open Variation Database (LOVD)
CNKSR2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CNKSR2 Gene

Disorders for CNKSR2 Gene

MalaCards: The human disease database

(12) MalaCards diseases for CNKSR2 Gene - From: OMI, CVR, ORP, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

CNKR2_HUMAN
  • Mental retardation, X-linked, syndromic, Houge type (MRXSHG) [MIM:301008]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSHG is characterized by delayed development, intellectual disability, speech and language delay, and early-onset seizures. Carrier females may be mildly affected. {ECO:0000269 PubMed:25223753, ECO:0000269 PubMed:28098945}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for CNKSR2

genes like me logo Genes that share disorders with CNKSR2: view

No data available for Genatlas for CNKSR2 Gene

Publications for CNKSR2 Gene

  1. Absent CNKSR2 causes seizures and intellectual, attention, and language deficits. (PMID: 25223753) Vaags AK … Minassian BA (Annals of neurology 2014) 3 4 72
  2. The DNA sequence of the human X chromosome. (PMID: 15772651) Ross MT … Bentley DR (Nature 2005) 3 4
  3. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  5. Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf. (PMID: 14597674) Lanigan TM … Guan KL (FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2003) 3 4

Products for CNKSR2 Gene

Sources for CNKSR2 Gene