DKK1

Chr 10

dickkopf Wnt signaling pathway inhibitor 1

Also known as: DKK-1, SK

This gene encodes a member of the dickkopf family of proteins. Members of this family are secreted proteins characterized by two cysteine-rich domains that mediate protein-protein interactions. The encoded protein binds to the LRP6 co-receptor and inhibits beta-catenin-dependent Wnt signaling. This gene plays a role in embryonic development and may be important in bone formation in adults. Elevated expression of this gene has been observed in numerous human cancers and this protein may promote proliferation, invasion and growth in cancer cell lines. [provided by RefSeq, Sep 2017]

OMIMResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
4
Active trials
307
Pubs (1 yr)
P/LP submissions
P/LP missense
0.73
LOEUF
Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.73LOEUF
pLI 0.174
Z-score 2.17
OE 0.28 (0.130.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.18Z-score
OE missense 0.96 (0.841.10)
145 obs / 151.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.28 (0.130.73)
00.351.4
Missense OE?0.96 (0.841.10)
00.61.4
Synonymous OE?0.92
01.21.6
LoF obs/exp: 3 / 10.7Missense obs/exp: 145 / 151.1Syn Z: 0.49

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DKK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.