DKK4

dickkopf WNT signaling pathway inhibitor 4

Basic information

Region (hg38): 8:42374062-42377229

Links

ENSG00000104371 ∙ NCBI:27121 ∙ OMIM:605417 ∙ HGNC:2894 ∙ Uniprot:Q9UBT3 ∙ 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 DKK4 gene.

• Inborn genetic diseases (15 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DKK4 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			14	1		15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	14	1	0

Variants in DKK4

This is a list of pathogenic ClinVar variants found in the DKK4 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-42374108-T-C		not specified	Uncertain significance (Nov 02, 2023)
8-42374123-A-C		not specified	Uncertain significance (Jan 20, 2023)
8-42374147-G-A		not specified	Uncertain significance (Feb 11, 2022)
8-42374170-C-T		not specified	Uncertain significance (Aug 17, 2021)
8-42374238-T-G		not specified	Uncertain significance (Jul 21, 2022)
8-42374246-A-G		not specified	Uncertain significance (Feb 28, 2024)
8-42374287-G-A		not specified	Uncertain significance (May 26, 2022)
8-42374299-C-T		not specified	Uncertain significance (Jul 11, 2023)
8-42374300-G-T		not specified	Uncertain significance (May 03, 2023)
8-42374327-C-A		not specified	Uncertain significance (Nov 30, 2022)
8-42374826-C-T		not specified	Likely benign (May 25, 2022)
8-42375760-G-A		not specified	Uncertain significance (Jul 20, 2021)
8-42375772-C-T		not specified	Likely benign (Apr 25, 2023)
8-42375773-G-A		not specified	Uncertain significance (Jan 19, 2022)
8-42375806-C-A		not specified	Uncertain significance (Sep 27, 2022)
8-42375817-A-C		not specified	Uncertain significance (Sep 01, 2021)
8-42377024-C-T		not specified	Uncertain significance (Nov 01, 2022)
8-42377033-C-T		not specified	Uncertain significance (Aug 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DKK4	protein_coding	protein_coding	ENST00000220812	4	3165

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000767	0.784	125710	0	37	125747	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.226	125	132	0.945	0.00000769	1453
Missense in Polyphen		48	44.641	1.0753		508
Synonymous	0.683	44	50.2	0.877	0.00000267	447
Loss of Function	1.05	6	9.48	0.633	4.85e-7	107

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000539	0.000539
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000151	0.000149
Middle Eastern	0.000217	0.000217
South Asian	0.0000981	0.0000980
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);Hair Follicle Development- Induction (Part 1 of 3);Extracellular vesicle-mediated signaling in recipient cells;EDA Signalling in Hair Follicle Development;Wnt Signaling Pathway;Signaling by WNT;Signal Transduction;Negative regulation of TCF-dependent signaling by WNT ligand antagonists;Wnt Canonical;Regulation of nuclear beta catenin signaling and target gene transcription;TCF dependent signaling in response to WNT;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.522
• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.0690
• hipred: N
• hipred_score: 0.123
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0572

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dkk4
• Phenotype: normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

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