DKK3

dickkopf WNT signaling pathway inhibitor 3

Basic information

Region (hg38): 11:11956207-12009769

Links

ENSG00000050165

∙ NCBI:27122 ∙ OMIM:605416 ∙ HGNC:2893 ∙ Uniprot:Q9UBP4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DKK3 gene.

not_specified (37 variants)
not_provided (3 variants)
Autosomal_dominant_polycystic_liver_disease (3 variants)
Autosomal_dominant_polycystic_kidney_disease (2 variants)
Marfanoid_habitus_and_intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DKK3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001018057.2. 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				1 clinvar		1
missense		1 clinvar	39 clinvar	1 clinvar	2 clinvar	43
nonsense						0
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	2	41	2	2

Highest pathogenic variant AF is 0.000033454555

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DKK3	protein_coding	protein_coding	ENST00000396505	7	46664

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000410	0.842	125701	0	47	125748	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.802	170	202	0.841	0.0000108	2268
Missense in Polyphen		47	56.952	0.82525		703
Synonymous	-0.295	90	86.5	1.04	0.00000508	690
Loss of Function	1.41	11	17.4	0.634	0.00000101	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000481	0.000481
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000163	0.000163
South Asian	0.000261	0.000261
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

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. 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 (By similarity). {ECO:0000250}.;
Pathway: Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds;Wnt Canonical;Wnt Mammals (Consensus)

Recessive Scores

pRec: 0.288

Intolerance Scores

loftool: 0.848
rvis_EVS: 0.73
rvis_percentile_EVS: 86.17

Haploinsufficiency Scores

pHI: 0.309
hipred: N
hipred_score: 0.242
ghis: 0.432

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.128

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Dkk3
Phenotype: homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; immune system phenotype;

Zebrafish Information Network

Gene name: dkk3a
Affected structure: post-vent region
Phenotype tag: abnormal
Phenotype quality: decreased length

Gene ontology

Biological process: anatomical structure morphogenesis;Wnt signaling pathway;regulation of transforming growth factor beta receptor signaling pathway;adrenal gland development;negative regulation of aldosterone biosynthetic process;negative regulation of transcription, DNA-templated;negative regulation of canonical Wnt signaling pathway;extracellular negative regulation of signal transduction;negative regulation of anti-Mullerian hormone signaling pathway;negative regulation of cortisol biosynthetic process
Cellular component: extracellular space
Molecular function: co-receptor binding;receptor antagonist activity