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

Gene ID: 83999, updated on 2-Nov-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
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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: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 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 Variation Viewer (GRCh37.p13)

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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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

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

  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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