DKK2

dickkopf WNT signaling pathway inhibitor 2

Basic information

Region (hg38): 4:106921801-107283806

Links

ENSG00000155011 ∙ NCBI:27123 ∙ OMIM:605415 ∙ HGNC:2892 ∙ Uniprot:Q9UBU2 ∙ 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 DKK2 gene.

• Inborn genetic diseases (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DKK2 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			9			9
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	10	0	0

Variants in DKK2

This is a list of pathogenic ClinVar variants found in the DKK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-106923995-A-T		not specified	Uncertain significance (Sep 21, 2021)
4-106924040-C-T		not specified	Uncertain significance (May 11, 2022)
4-106924082-G-A		not specified	Uncertain significance (Oct 29, 2021)
4-106924168-C-G		not specified	Uncertain significance (Sep 12, 2023)
4-106924560-T-A		not specified	Uncertain significance (Nov 14, 2023)
4-106924601-T-C		not specified	Uncertain significance (Sep 22, 2023)
4-106925861-C-T		not specified	Uncertain significance (Jun 29, 2022)
4-106925871-T-C		not specified	Uncertain significance (Jan 26, 2022)
4-106925880-A-G		not specified	Uncertain significance (Apr 15, 2022)
4-106925949-C-T		not specified	Uncertain significance (Jul 06, 2021)
4-107035572-C-T		not specified	Uncertain significance (Jan 23, 2023)
4-107035585-C-T		not specified	Uncertain significance (Jun 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DKK2	protein_coding	protein_coding	ENST00000285311	4	362005

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.753	0.246	125730	0	3	125733	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.415	139	153	0.906	0.00000836	1689
Missense in Polyphen		58	69.617	0.83313		752
Synonymous	0.215	56	58.1	0.964	0.00000296	503
Loss of Function	2.88	2	13.4	0.150	8.22e-7	140

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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: Wnt signaling pathway - Homo sapiens (human);BMP Signaling Pathway in Eyelid Development;Wnt Signaling Pathway;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;Negative regulation of TCF-dependent signaling by WNT ligand antagonists;Wnt Canonical;TCF dependent signaling in response to WNT;Wnt Mammals;Presenilin action in Notch and Wnt signaling (Consensus)

Recessive Scores

• pRec: 0.144

Intolerance Scores

• loftool: 0.167
• rvis_EVS: 0.08
• rvis_percentile_EVS: 60.09

Haploinsufficiency Scores

• pHI: 0.450
• hipred: Y
• hipred_score: 0.776
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.161

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dkk2
• Phenotype: immune system phenotype; skeleton phenotype; vision/eye phenotype; hematopoietic system phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: dkk2
• Affected structure: neuromast
• Phenotype tag: abnormal
• Phenotype quality: increased area

Gene ontology

• Biological process: multicellular organism development;Wnt signaling pathway;negative regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;extracellular negative regulation of signal transduction
• Cellular component: extracellular space
• Molecular function: co-receptor binding;receptor antagonist activity