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    KREMEN1 kringle containing transmembrane protein 1 [ Homo sapiens (human) ]

    Gene ID: 83999, updated on 27-Dec-2024

    Summary

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    Official Symbol
    KREMEN1provided by HGNC
    Official Full Name
    kringle containing transmembrane protein 1provided by HGNC
    Primary source
    HGNC:HGNC:17550
    See related
    Ensembl:ENSG00000183762 MIM:609898; AllianceGenome:HGNC:17550
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    KRM1; ECTD13; KREMEN
    Summary
    This gene encodes a high-affinity dickkopf homolog 1 (DKK1) transmembrane receptor that functionally cooperates with DKK1 to block wingless (WNT)/beta-catenin signaling. The encoded protein is a component of a membrane complex that modulates canonical WNT signaling through lipoprotein receptor-related protein 6 (LRP6). It contains extracellular kringle, WSC, and CUB domains. Mutations in this gene result in ectodermal dysplasia. This protein has also been found to be a functional receptor for Coxsackievirus A10 and may be an alternative entry receptor for SARS-CoV-2. [provided by RefSeq, Nov 2021]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in SARS-CoV-2 infection.
    Expression
    Ubiquitous expression in skin (RPKM 9.8), esophagus (RPKM 9.6) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See KREMEN1 in Genome Data Viewer
    Location:
    22q12.1
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (29073035..29168333)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (29534263..29631831)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (29469023..29564321)

    Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107985549 Neighboring gene Sharpr-MPRA regulatory region 13625 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:29275395-29275496 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13582 Neighboring gene Sharpr-MPRA regulatory region 4838 Neighboring gene Sharpr-MPRA regulatory region 5766 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29298674-29299487 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:29299851-29301050 Neighboring gene zinc and ring finger 3 Neighboring gene NANOG hESC enhancer GRCh37_chr22:29335494-29335995 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29371305-29371805 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr22:29378648-29379847 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29384398-29385198 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr22:29396251-29396817 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:29396818-29397383 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29399041-29399852 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29399853-29400662 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29400663-29401473 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29406873-29407710 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_63211 Neighboring gene ZNRF3 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 3696 Neighboring gene Sharpr-MPRA regulatory region 8961 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29458189-29458956 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13583 Neighboring gene chromosome 22 open reading frame 31 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:29524988-29525196 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29536985-29537486 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29537487-29537986 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29541773-29542473 Neighboring gene RNA, U6 small nuclear 810, pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29547849-29548632 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18809 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18810 Neighboring gene uncharacterized LOC101929638 Neighboring gene CRISPRi-validated cis-regulatory element chr22.1165 Neighboring gene Sharpr-MPRA regulatory region 4816 Neighboring gene RNA, U6 small nuclear 1219, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13584 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13585 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13586 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13587 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29610708-29611288 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29611289-29611868 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29611869-29612448 Neighboring gene uncharacterized LOC124905099 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29612449-29613028 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29613609-29614188 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29614189-29614768 Neighboring gene EMI domain containing 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Genetic analysis and effect of triiodothyronine and prednisone trial on bone turnover in a patient with craniotubular hyperostosis. López JM, et al. Bone, 2008 Aug. PMID 18538647
    2. Host proviral and antiviral factors for SARS-CoV-2. Lv L, et al. Virus Genes, 2021 Dec. PMID 34510331, Free PMC Article
    3. Novel homozygous KREMEN1 mutation causes ectodermal dysplasia. Lee Y, et al. Oral Dis, 2022 Apr. PMID 34028942, Free PMC Article
    4. Molecular basis of Coxsackievirus A10 entry using the two-in-one attachment and uncoating receptor KRM1. Cui Y, et al. Proc Natl Acad Sci U S A, 2020 Aug 4. PMID 32690697, Free PMC Article
    5. Replication of 15 loci involved in human plasma protein N-glycosylation in 4802 samples from four cohorts. Sharapov SZ, et al. Glycobiology, 2021 Feb 9. PMID 32521004, Free PMC Article

    See all (35) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Novel homozygous KREMEN1 mutation causes ectodermal dysplasia.
      Title: Novel homozygous KREMEN1 mutation causes ectodermal dysplasia.
    2. Replication of 15 loci involved in human plasma protein N-glycosylation in 4802 samples from four cohorts.
      Title: Replication of 15 loci involved in human plasma protein N-glycosylation in 4802 samples from four cohorts.
    3. Novel SARS-CoV-2 receptors: ASGR1 and KREMEN1.
      Title: Novel SARS-CoV-2 receptors: ASGR1 and KREMEN1.
    4. Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2.
      Title: Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2.
    5. Molecular basis of Coxsackievirus A10 entry using the two-in-one attachment and uncoating receptor KRM1.
      Title: Molecular basis of Coxsackievirus A10 entry using the two-in-one attachment and uncoating receptor KRM1.
    6. MiR-137 repressed KREMEN1 expression in neuronal cells.
      Title: Knockdown of lncRNA SNHG1 attenuated Aβ(25-35)-inudced neuronal injury via regulating KREMEN1 by acting as a ceRNA of miR-137 in neuronal cells.
    7. CV-A10 mature virus alone and in complex with KRM1 as well as of the CV-A10 A-particle.
      Title: Hand-foot-and-mouth disease virus receptor KREMEN1 binds the canyon of Coxsackie Virus A10.
    8. Thai family study that has identified the second and third mutations found in KREMEN1 confirms that KREMEN1 is a human disease gene for autosomal recessive ectodermal dysplasia 13, hair/tooth type. Agenesis of permanent maxillary lateral incisors and mandibular anterior teeth could be a unique manifestation of KREMEN1 mutations.
      Title: Novel compound heterozygous mutations in KREMEN1 confirm it as a disease gene for ectodermal dysplasia.
    9. Dkk4 CRD2 mediates high-affinity binding to both the E1E2 region of low-density lipoprotein receptor-related protein 6 (LRP6 E1E2) and the Kremen1 (Krm1) extracellular domain.
      Title: Structural and functional analysis of Dickkopf 4 (Dkk4): New insights into Dkk evolution and regulation of Wnt signaling by Dkk and Kremen proteins.
    10. Structure of the dual-mode Wnt regulator Kremen1 and insight into ternary complex formation with LRP6 and DKK1 have been presented.
      Title: Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf.
    Submit: New GeneRIF Correction See all GeneRIFs (20)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Ectodermal dysplasia 13, hair/tooth type
    MedGen: C4479322 OMIM: 617392 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.
    EBI GWAS Catalog
    Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ31863

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transmembrane signaling receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cell communication TAS
    Traceable Author Statement
    more info
    		  
    involved_in limb development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of axon regeneration IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of canonical Wnt signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of ossification IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of canonical Wnt signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in neuronal cell body IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    kremen protein 1
    Names
    dickkopf receptor
    kringle domain-containing transmembrane protein 1
    kringle-coding gene marking the eye and the nose
    kringle-containing protein marking the eye and the nose
    NP_001034659.2
    NP_114434.3
    XP_011528731.1
    XP_011528732.1
    XP_011528733.1
    XP_016884478.1
    XP_054181978.1
    XP_054181979.1
    XP_054181980.1
    XP_054181981.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_052986.1 RefSeqGene

      Range
      4958..100256
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001039570.3 → NP_001034659.2  kremen protein 1 isoform 3 precursor

      See identical proteins and their annotated locations for NP_001034659.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 3' UTR and 3' coding region, compared to variant 2. The resulting isoform has a distinct C-terminus and is shorter than isoform 2.
      Source sequence(s)
      AL021393, Z95116
      Consensus CDS
      CCDS43000.2
      UniProtKB/Swiss-Prot
      B0QY46, B0QY47, B1AJR5, Q5TIB9, Q6P3X6, Q96MU8, Q9BY70, Q9UGS5, Q9UGU1
      Related
      ENSP00000383189.4, ENST00000400335.9
      Conserved Domains (3) summary
      cd00041
      Location:216 → 322
      CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
      cd00108
      Location:33 → 116
      KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...
      pfam01822
      Location:121 → 202
      WSC; WSC domain

    2. NM_032045.5 → NP_114434.3  kremen protein 1 isoform 2 precursor

      See identical proteins and their annotated locations for NP_114434.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the shorter transcript but encodes the longer isoform (2).
      Source sequence(s)
      AK056425, AL021393, Z95116
      Consensus CDS
      CCDS13849.1
      UniProtKB/Swiss-Prot
      B0QY46, B0QY47, B1AJR5, Q5TIB9, Q6P3X6, Q96MU8, Q9BY70, Q9UGS5, Q9UGU1
      Related
      ENSP00000331242.5, ENST00000327813.9
      Conserved Domains (3) summary
      cd00041
      Location:216 → 322
      CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
      cd00108
      Location:33 → 116
      KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...
      pfam01822
      Location:121 → 202
      WSC; WSC domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

      Range
      29073035..29168333
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011530429.3 → XP_011528731.1  kremen protein 1 isoform X1

      See identical proteins and their annotated locations for XP_011528731.1

      UniProtKB/Swiss-Prot
      B0QY46, B0QY47, B1AJR5, Q5TIB9, Q6P3X6, Q96MU8, Q9BY70, Q9UGS5, Q9UGU1
      Conserved Domains (3) summary
      cd00041
      Location:216 → 322
      CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
      cd00108
      Location:33 → 116
      KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...
      pfam01822
      Location:121 → 202
      WSC; WSC domain

    2. XM_011530430.3 → XP_011528732.1  kremen protein 1 isoform X2

      UniProtKB/Swiss-Prot
      B0QY46, B0QY47, B1AJR5, Q5TIB9, Q6P3X6, Q96MU8, Q9BY70, Q9UGS5, Q9UGU1
      Conserved Domains (2) summary
      cd00041
      Location:123 → 229
      CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
      cd00108
      Location:33 → 116
      KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...

    3. XM_017028989.2 → XP_016884478.1  kremen protein 1 isoform X4

    4. XM_011530431.3 → XP_011528733.1  kremen protein 1 isoform X3

      Conserved Domains (2) summary
      cd00041
      Location:111 → 217
      CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
      pfam01822
      Location:16 → 97
      WSC; WSC domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060946.1 Alternate T2T-CHM13v2.0

      Range
      29534263..29631831
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054326003.1 → XP_054181978.1  kremen protein 1 isoform X1

      UniProtKB/Swiss-Prot
      B0QY46, B0QY47, B1AJR5, Q5TIB9, Q6P3X6, Q96MU8, Q9BY70, Q9UGS5, Q9UGU1

    2. XM_054326004.1 → XP_054181979.1  kremen protein 1 isoform X2

      UniProtKB/Swiss-Prot
      B0QY46, B0QY47, B1AJR5, Q5TIB9, Q6P3X6, Q96MU8, Q9BY70, Q9UGS5, Q9UGU1

    3. XM_054326006.1 → XP_054181981.1  kremen protein 1 isoform X4

    4. XM_054326005.1 → XP_054181980.1  kremen protein 1 isoform X3

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_153379.2: Suppressed sequence

      Description
      NM_153379.2: This RefSeq was temporarily suppressed because currently there is not sufficient data to support this transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96MU8.3 GenPept UniProtKB/Swiss-Prot:Q96MU8

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