DKK1
dickkopf WNT signaling pathway inhibitor 1
Basic information
Region (hg38): 10:52314281-52318042
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (29 variants)
- not_provided (9 variants)
- DKK1-related_disorder (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DKK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000012242.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | |||||
| missense | 27 | 32 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 27 | 8 | 1 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DKK1 | protein_coding | protein_coding | ENST00000373970 | 4 | 3747 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.174 | 0.814 | 125741 | 0 | 7 | 125748 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.176 | 145 | 151 | 0.960 | 0.00000708 | 1714 |
| Missense in Polyphen | 42 | 52.213 | 0.8044 | 606 | ||
| Synonymous | 0.488 | 54 | 58.8 | 0.919 | 0.00000262 | 533 |
| Loss of Function | 2.17 | 3 | 10.7 | 0.282 | 5.38e-7 | 132 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000619 | 0.0000615 |
| Ashkenazi Jewish | 0.000116 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000190 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000981 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6 (PubMed:22000856). DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease (PubMed:17143291). Inhibits the pro-apoptotic function of KREMEN1 in a Wnt-independent manner, and has anti- apoptotic activity (By similarity). {ECO:0000250|UniProtKB:O54908, ECO:0000269|PubMed:22000856, ECO:0000303|PubMed:17143291}.;
- Pathway
- Wnt signaling pathway - Homo sapiens (human);WNT-Ncore;Cardiac Progenitor Differentiation;Primary Focal Segmental Glomerulosclerosis FSGS;Differentiation Pathway;Endoderm Differentiation;Mesodermal Commitment Pathway;POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation;Wnt-beta-catenin Signaling Pathway in Leukemia;VEGFA-VEGFR2 Signaling Pathway;EDA Signalling in Hair Follicle Development;Role of Osx and miRNAs in tooth development;Wnt Signaling Pathway;Developmental Biology;Signaling by WNT;Signal Transduction;wnt signaling pathway;segmentation clock;multi-step regulation of transcription by pitx2;wnt lrp6 signalling;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation;Negative regulation of TCF-dependent signaling by WNT ligand antagonists;Direct p53 effectors;Transcriptional regulation of pluripotent stem cells;Wnt;Wnt Canonical;Wnt signaling network;Regulation of nuclear beta catenin signaling and target gene transcription;Validated targets of C-MYC transcriptional repression;TCF dependent signaling in response to WNT;Wnt Mammals;Presenilin action in Notch and Wnt signaling
(Consensus)
Recessive Scores
- pRec
- 0.592
Intolerance Scores
- loftool
- 0.397
- rvis_EVS
- 0.42
- rvis_percentile_EVS
- 76.81
Haploinsufficiency Scores
- pHI
- 0.248
- hipred
- Y
- hipred_score
- 0.734
- ghis
- 0.418
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dkk1
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; taste/olfaction phenotype; growth/size/body region phenotype; embryo phenotype; renal/urinary system phenotype; skeleton phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype;
Zebrafish Information Network
- Gene name
- dkk1b
- Affected structure
- head
- Phenotype tag
- abnormal
- Phenotype quality
- truncated
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;cell morphogenesis involved in differentiation;endoderm formation;mesoderm formation;hair follicle development;regulation of receptor internalization;learning or memory;regulation of signaling receptor activity;positive regulation of gene expression;positive regulation of cell death;negative regulation of Wnt signaling pathway;negative regulation of ossification;embryonic limb morphogenesis;negative regulation of BMP signaling pathway;forebrain development;negative regulation of protein binding;response to retinoic acid;negative regulation of peptidyl-serine phosphorylation;negative regulation of mesodermal cell fate specification;regulation of endodermal cell fate specification;negative regulation of apoptotic process;positive regulation of JUN kinase activity;positive regulation of Wnt signaling pathway, calcium modulating pathway;negative regulation of skeletal muscle tissue development;regulation of synapse organization;regulation of synaptic transmission, glutamatergic;limb development;face morphogenesis;negative regulation of pathway-restricted SMAD protein phosphorylation;motor learning;positive regulation of heart induction by negative regulation of canonical Wnt signaling pathway;negative regulation of canonical Wnt signaling pathway;Wnt signaling pathway involved in somitogenesis;modulation of age-related behavioral decline;synapse pruning;extracellular negative regulation of signal transduction;positive regulation of neuron death;negative regulation of canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment;positive regulation of tau-protein kinase activity;regulation of dopaminergic neuron differentiation;negative regulation of Wnt-Frizzled-LRP5/6 complex assembly;positive regulation of midbrain dopaminergic neuron differentiation;positive regulation of Wnt signaling pathway, planar cell polarity pathway;negative regulation of cardiac muscle cell differentiation
- Cellular component
- extracellular region;extracellular space;plasma membrane;early endosome membrane
- Molecular function
- protein binding;growth factor activity;co-receptor binding;receptor antagonist activity;low-density lipoprotein particle receptor binding