DKK3

dickkopf WNT signaling pathway inhibitor 3

Basic information

Region (hg38): 11:11956206-12009769

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.

• Inborn genetic diseases (15 variants)
• not provided (2 variants)
• Autosomal dominant polycystic kidney disease (1 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			15	1	2	18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	15	1	2

Variants in DKK3

This is a list of pathogenic ClinVar variants found in the DKK3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-11964497-G-A		not specified	Likely benign (Feb 05, 2024)
11-11964504-G-A		Autosomal dominant polycystic kidney disease	Uncertain significance (Sep 01, 2021)
11-11964510-T-TC		Autosomal dominant polycystic liver disease	Likely pathogenic (Sep 01, 2021)
11-11964559-C-T		not specified	Uncertain significance (Sep 29, 2023)
11-11964565-G-A		Autosomal dominant polycystic liver disease	Likely pathogenic (Sep 01, 2021)
11-11964577-T-C		not specified	Uncertain significance (Feb 05, 2024)
11-11964594-T-C		not specified	Uncertain significance (Nov 29, 2021)
11-11964597-T-C			Benign (Jun 26, 2018)
11-11964642-C-T		not specified	Likely benign (Dec 02, 2022)
11-11964657-G-A		not specified	Uncertain significance (Aug 02, 2021)
11-11964669-A-T		not specified	Uncertain significance (Nov 15, 2021)
11-11964685-G-C		not specified	Uncertain significance (Feb 06, 2023)
11-11965906-C-T		not specified	Uncertain significance (Jun 30, 2023)
11-11965933-C-T		not specified	Uncertain significance (Nov 14, 2023)
11-11965941-G-T		not specified	Uncertain significance (Jul 13, 2021)
11-11966980-G-A		Autosomal dominant polycystic liver disease	Uncertain significance (Sep 01, 2021)
11-11967016-T-C		Autosomal dominant polycystic kidney disease • not specified	Uncertain significance (Feb 06, 2023)
11-11967023-C-T		not specified	Uncertain significance (Jan 04, 2022)
11-11967089-G-A		not specified	Uncertain significance (Aug 30, 2021)
11-11968418-G-T		Marfanoid habitus and intellectual disability	Uncertain significance (-)
11-12002346-G-A		not specified	Uncertain significance (Apr 07, 2023)
11-12002352-G-C		not specified	Uncertain significance (Oct 03, 2022)
11-12002364-T-C		not specified	Uncertain significance (Feb 21, 2024)
11-12002374-T-C			Benign (May 09, 2018)
11-12002430-G-T		not specified	Uncertain significance (Mar 16, 2022)

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