This gene encodes a high-affinity dickkopf homolog 1 (DKK1) transmembrane receptor. A similar protein in mouse functions interacts with with DKK1 to block wingless (WNT)/beta-catenin signaling. The encoded protein forms a ternary membrane complex with DKK1 and the WNT receptor lipoprotein receptor-related protein 6 (LRP6), and induces rapid endocytosis and removal of LRP6 from ... See more...

Aliases for KREMEN2 Gene

Aliases for KREMEN2 Gene

  • Kringle Containing Transmembrane Protein 2 2 3 5
  • KRM2 2 3 4
  • Kringle-Containing Protein Marking The Eye And The Nose 3 4
  • Kringle Domain-Containing Transmembrane Protein 2 3 4
  • Dickkopf Receptor 2 3 4
  • Kremen Protein 2 3 4
  • MGC10791 2
  • KREMEN2 5

External Ids for KREMEN2 Gene

Previous GeneCards Identifiers for KREMEN2 Gene

  • GC16P003034
  • GC16P003014
  • GC16P002954
  • GC16P002986
  • GC16P002963
  • GC16P003829
  • GC16P003880
  • GC16P004055

Summaries for KREMEN2 Gene

Entrez Gene Summary for KREMEN2 Gene

  • This gene encodes a high-affinity dickkopf homolog 1 (DKK1) transmembrane receptor. A similar protein in mouse functions interacts with with DKK1 to block wingless (WNT)/beta-catenin signaling. The encoded protein forms a ternary membrane complex with DKK1 and the WNT receptor lipoprotein receptor-related protein 6 (LRP6), and induces rapid endocytosis and removal of LRP6 from the plasma membrane. It contains extracellular kringle, WSC, and CUB domains. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

GeneCards Summary for KREMEN2 Gene

KREMEN2 (Kringle Containing Transmembrane Protein 2) is a Protein Coding gene. Diseases associated with KREMEN2 include Cone-Rod Dystrophy 2. Among its related pathways are Signaling by GPCR and S45 mutants of beta-catenin arent phosphorylated. An important paralog of this gene is KREMEN1.

UniProtKB/Swiss-Prot Summary for KREMEN2 Gene

  • Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6. Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow normal limb patterning and can also negatively regulate bone formation.

Additional gene information for KREMEN2 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KREMEN2 Gene

Genomics for KREMEN2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KREMEN2 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 KREMEN2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KREMEN2

Top Transcription factor binding sites by QIAGEN in the KREMEN2 gene promoter:
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • NRSF form 1
  • NRSF form 2

Genomic Locations for KREMEN2 Gene

Genomic Locations for KREMEN2 Gene
chr16:2,964,216-2,968,383
(GRCh38/hg38)
Size:
4,168 bases
Orientation:
Plus strand
chr16:3,013,945-3,018,384
(GRCh37/hg19)
Size:
4,440 bases
Orientation:
Plus strand

Genomic View for KREMEN2 Gene

Genes around KREMEN2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KREMEN2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KREMEN2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KREMEN2 Gene

Proteins for KREMEN2 Gene

  • Protein details for KREMEN2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8NCW0-KREM2_HUMAN
    Recommended name:
    Kremen protein 2
    Protein Accession:
    Q8NCW0
    Secondary Accessions:
    • B4DXF6
    • I3L2S2
    • Q8N2J4
    • Q8NCW1
    • Q96GL8
    • Q9BTP9

    Protein attributes for KREMEN2 Gene

    Size:
    462 amino acids
    Molecular mass:
    48849 Da
    Quaternary structure:
    • Interacts with ERLEC1. Forms a ternary complex with DKK1 and LRP6.

    Alternative splice isoforms for KREMEN2 Gene

neXtProt entry for KREMEN2 Gene

Post-translational modifications for KREMEN2 Gene

  • Glycosylation at Asn49, Asn222, Asn244, and Asn351
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for KREMEN2 Gene

Domains & Families for KREMEN2 Gene

Gene Families for KREMEN2 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for KREMEN2 Gene

InterPro:
Blocks:
  • Kringle
  • CUB domain
  • Carbohydrate-binding WSC
ProtoNet:

Suggested Antigen Peptide Sequences for KREMEN2 Gene

GenScript: Design optimal peptide antigens:
  • Kringle-containing protein marking the eye and the nose (KREM2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8NCW0

UniProtKB/Swiss-Prot:

KREM2_HUMAN :
  • Binding to ERLEC1 is mediated by the oligosaccharides linked to the kringle domain.
Domain:
  • Binding to ERLEC1 is mediated by the oligosaccharides linked to the kringle domain.
genes like me logo Genes that share domains with KREMEN2: view

Function for KREMEN2 Gene

Molecular function for KREMEN2 Gene

UniProtKB/Swiss-Prot Function:
Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6. Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow normal limb patterning and can also negatively regulate bone formation.

Phenotypes From GWAS Catalog for KREMEN2 Gene

genes like me logo Genes that share phenotypes with KREMEN2: view

Animal Models for KREMEN2 Gene

MGI Knock Outs for KREMEN2:

Animal Model Products

  • Taconic Biosciences Mouse Models for KREMEN2

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KREMEN2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for KREMEN2 Gene

Localization for KREMEN2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KREMEN2 Gene

Membrane. Single-pass type I 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 KREMEN2 gene
Compartment Confidence
plasma membrane 4
endosome 4
extracellular 3
nucleus 3
cytoskeleton 1
endoplasmic reticulum 1
cytosol 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for KREMEN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0031901 early endosome membrane TAS --
genes like me logo Genes that share ontologies with KREMEN2: view

Pathways & Interactions for KREMEN2 Gene

genes like me logo Genes that share pathways with KREMEN2: view

SIGNOR curated interactions for KREMEN2 Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for KREMEN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016055 Wnt signaling pathway IEA --
GO:0030279 negative regulation of ossification IEA,ISS --
GO:0060173 limb development IEA,ISS --
GO:0090090 negative regulation of canonical Wnt signaling pathway TAS --
genes like me logo Genes that share ontologies with KREMEN2: view

Drugs & Compounds for KREMEN2 Gene

No Compound Related Data Available

Transcripts for KREMEN2 Gene

mRNA/cDNA for KREMEN2 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KREMEN2

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for KREMEN2 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8a · 8b ^ 9
SP1: - - -
SP2: - -
SP3:
SP4:

Relevant External Links for KREMEN2 Gene

GeneLoc Exon Structure for
KREMEN2

Expression for KREMEN2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KREMEN2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KREMEN2 Gene

This gene is overexpressed in Skin - Not Sun Exposed (Suprapubic) (x9.4), Skin - Sun Exposed (Lower leg) (x7.5), and Esophagus - Mucosa (x4.1).

Protein differential expression in normal tissues from HIPED for KREMEN2 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for KREMEN2 Gene



Protein tissue co-expression partners for KREMEN2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KREMEN2

SOURCE GeneReport for Unigene cluster for KREMEN2 Gene:

Hs.661128

Evidence on tissue expression from TISSUES for KREMEN2 Gene

  • Nervous system(4.3)
genes like me logo Genes that share expression patterns with KREMEN2: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for KREMEN2 Gene

Orthologs for KREMEN2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for KREMEN2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia KREMEN2 31
  • 99 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia KREMEN2 30 31
  • 90.15 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Kremen2 30
  • 84.27 (n)
Mouse
(Mus musculus)
Mammalia Kremen2 30 17 31
  • 84.12 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia KREMEN2 31
  • 76 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia KREMEN2 31
  • 72 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia KREMEN2 31
  • 47 (a)
OneToOne
Species where no ortholog for KREMEN2 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)
  • Chicken (Gallus gallus)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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)
  • Oppossum (Monodelphis domestica)
  • 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 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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for KREMEN2 Gene

ENSEMBL:
Gene Tree for KREMEN2 (if available)
TreeFam:
Gene Tree for KREMEN2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KREMEN2: view image

Paralogs for KREMEN2 Gene

Paralogs for KREMEN2 Gene

(3) SIMAP similar genes for KREMEN2 Gene using alignment to 1 proteins:

  • KREM2_HUMAN
genes like me logo Genes that share paralogs with KREMEN2: view

Variants for KREMEN2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KREMEN2 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
776964 Benign: not provided 2,967,373(+) C/T MISSENSE_VARIANT
rs1210829529 Uncertain Significance: Ependymoma 2,966,649(+) G/T MISSENSE_VARIANT,INTRON_VARIANT
rs11866302 - p.Ala408Pro

Additional dbSNP identifiers (rs#s) for KREMEN2 Gene

Structural Variations from Database of Genomic Variants (DGV) for KREMEN2 Gene

Variant ID Type Subtype PubMed ID
nsv433167 CNV loss 18776910
nsv509588 CNV insertion 20534489
nsv510673 CNV deletion 20534489
nsv571246 CNV loss 21841781
nsv827525 CNV gain 20364138
nsv952906 CNV deletion 24416366

Variation tolerance for KREMEN2 Gene

Gene Damage Index Score: 11.58; 93.06% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KREMEN2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
KREMEN2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KREMEN2 Gene

Disorders for KREMEN2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for KREMEN2 Gene - From: DISEASES

Disorder Aliases PubMed IDs
cone-rod dystrophy 2
  • cord2
- elite association - COSMIC cancer census association via MalaCards
genes like me logo Genes that share disorders with KREMEN2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KREMEN2 Gene

Publications for KREMEN2 Gene

  1. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  2. 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
  3. Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. (PMID: 12050670) Mao B … Niehrs C (Nature 2002) 2 3
  4. Kremen1-induced cell death is regulated by homo- and heterodimerization. (PMID: 31069116) Sumia I … Causeret F (Cell death discovery 2019) 3
  5. Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. (PMID: 28986522) Antoniali G … Tell G (Nature communications 2017) 3

Products for KREMEN2 Gene

Sources for KREMEN2 Gene