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

Summary

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

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_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Novel homozygous KREMEN1 mutation causes ectodermal dysplasia.
Title: Novel homozygous KREMEN1 mutation causes ectodermal dysplasia.
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.
Novel SARS-CoV-2 receptors: ASGR1 and KREMEN1.
Title: Novel SARS-CoV-2 receptors: ASGR1 and KREMEN1.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

HSC0WE122 (e-PCR)
- UniSTS:66329

D22S1113 (e-PCR)
- UniSTS:15402

D22S1150 (e-PCR)
- UniSTS:51248

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

D22S991E (e-PCR)
- UniSTS:90419

G65395 (e-PCR)
- UniSTS:166451

G65396 (e-PCR)
- UniSTS:166452

G65397 (e-PCR)
- UniSTS:166453

G65333 (e-PCR)
- UniSTS:166462

G65332 (e-PCR)
- UniSTS:166466

D1S1425 (e-PCR)
- UniSTS:149621

D11S3114 (e-PCR)
- UniSTS:152207

D1S3693 (e-PCR)
- UniSTS:474271

AFM284VA9 (e-PCR)
- UniSTS:51359

NoName (e-PCR)
- UniSTS:480987

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

EC 2.3.2.27

NP_114434.3

EC 2.3.2.27

XP_011528731.1

EC 2.3.2.27

XP_011528732.1

EC 2.3.2.27

XP_011528733.1

EC 2.3.2.27

XP_016884478.1

EC 2.3.2.27

XP_054181978.1

EC 2.3.2.27

XP_054181979.1

EC 2.3.2.27

XP_054181980.1

EC 2.3.2.27

XP_054181981.1

EC 2.3.2.27

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

NG_052986.1 RefSeqGene

Range

4958..100256

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

NC_000022.11 Reference GRCh38.p14 Primary Assembly

Range

29073035..29168333

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_060946.1 Alternate T2T-CHM13v2.0

Range

29534263..29631831

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

B0QY46, B0QY47, B1AJR5, Q5TIB9, Q6P3X6, Q96MU8, Q9BY70, Q9UGS5, Q9UGU1
XM_054326004.1 → XP_054181979.1 kremen protein 1 isoform X2

UniProtKB/Swiss-Prot

B0QY46, B0QY47, B1AJR5, Q5TIB9, Q6P3X6, Q96MU8, Q9BY70, Q9UGS5, Q9UGU1
XM_054326006.1 → XP_054181981.1 kremen protein 1 isoform X4
XM_054326005.1 → XP_054181980.1 kremen protein 1 isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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.