GeneBe

KREMEN1

protein-coding

kringle containing transmembrane protein 1

Gene 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]

Previous symbols:
  • KREMEN

MANE transcript

NM_001039570.3

Inheritance

AR

ClinVar variants

P:2U:85B:30

Top phenotype

Ectodermal dysplasia 13, hair/tooth type

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr22:29,073,035-29,168,333

External References & Databases

Ensembl (ENSG00000183762)OMIM (609898)HGNC:17550GenCCUniProt (Q96MU8)AlphaFoldClinVar (KREMEN1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~95.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ectodermal dysplasia 13, hair/tooth typeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0044305

Submitter: PanelApp Australia

ectodermal dysplasia 13, hair/tooth typeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0044305

Submitter: Ambry Genetics

ectodermal dysplasia 13, hair/tooth typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044305

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Ectodermal dysplasia 13, hair/tooth typeAR

Manifestation: Craniofacial; Dental; Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 27049303Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KREMEN1 variants in ClinVar

6 Conditions Cataloged
Inborn genetic diseasesTotal: 78
not providedTotal: 45
Ectodermal dysplasia 13, hair/tooth typeTotal: 7
not specifiedTotal: 3
KREMEN1-related disorderTotal: 3
Infantile cerebellar-retinal degenerationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039570.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
14
clinvar
6
clinvar
 21
missense
1
clinvar
76
clinvar
8
clinvar
2
clinvar
 87
nonsense
1
clinvar
 1
start loss
0
frameshift
1
clinvar
2
clinvar
 3
splice donor/acceptor (+/-2bp)
5
clinvar
 5
Total2085228117

Highest pathogenic variant AF is 0.0000065664194

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001039570.3RefSeqNP_001034659.29MANE Select
ENST00000400335.9EnsemblENSP00000383189.49MANE Select
NM_032045.5RefSeqNP_114434.310Standard
ENST00000327813.10EnsemblENSP00000331242.510Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
kremen1Danio rerio

Structure: hair cell

Quality: has extra parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • WNT-Ncore
  • Wnt Signaling Pathway
  • Signaling by WNT
  • Signal Transduction
  • Negative regulation of TCF-dependent signaling by WNT ligand antagonists

Biological Process

  • apoptotic process
  • cell communication
  • Wnt signaling pathway
  • negative regulation of ossification
  • limb development

Molecular Function

  • protein binding

Cellular Component

  • plasma membrane
  • membrane
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000327813
Coding exons
10
Length
95256
Individuals with no LoFs
124772
Homozygous LoFs
0
Heterozygous LoFs
37
Defined
124809
p
0.000148
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.7782392750.8680.00001593191
Missense (PolyPhen)98115.430.848981331
Synonymous0.702981070.9140.00000700977
Loss of Function2.76720.50.3428.67e-7257

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000200.00019rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.000890.00089rare
Finnish00.0absent
European (Non-Finnish)0.000140.00014rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
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. In the absence of DKK1, potentiates Wnt-beta-catenin signaling by maintaining LRP5 or LRP6 at the cell membrane. Can trigger apoptosis in a Wnt-independent manner and this apoptotic activity is inhibited upon binding of the ligand DKK1. 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. Modulates cell fate decisions in the developing cochlea with an inhibitory role in hair cell fate specification. {ECO:0000250|UniProtKB:Q90Y90, ECO:0000250|UniProtKB:Q99N43}.;
Disease
DISEASE: Ectodermal dysplasia 13, hair/tooth type (ECTD13) [MIM:617392]: A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD13 is an autosomal recessive form characterized by severe oligodontia accompanied by anomalies of hair and skin. {ECO:0000269|PubMed:27049303}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.135

Intolerance Scores

LoFtool
0.554
RVIS EVS
0.4
RVIS percentile EVS
76.36

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.486

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.