DKK4

Chr 8

dickkopf Wnt signaling pathway inhibitor 4

Also known as: DKK-4

NCBI Gene: 27121 ENSG00000104371 UniProt: Q9UBT3 OMIM: 605417

This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. Activity of this protein is modulated by binding to the Wnt co-receptor and the co-factor kremen 2. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.25

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.25LOEUF

pLI 0.001

Z-score 1.05

OE 0.63 (0.35–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.23Z-score

OE missense 0.94 (0.82–1.10)

125 obs / 132.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.63 (0.35–1.25)

0≤0.351.4

Missense OE?0.94 (0.82–1.10)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 6 / 9.5Missense obs/exp: 125 / 132.3Syn Z: 0.68

Background carrier burden — how many people carry a rare variant somewhere in DKK4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

299 rare PASS variants

Rare truncating (LoF)

1 in 2,000

67 rare PASS variants

Rare synonymous (reference)

1 in 600

97 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DKK4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 350	1 in 2,000
South Asian	~43k	1 in 130	1 in 3,600
Remaining (unassigned)	~30k	1 in 130	1 in 2,000
European (Finnish)	~27k	1 in 370	≈ 1 in 8,900
Admixed American	~22k	1 in 190	1 in 1,400
African / African American	~21k	1 in 100	1 in 1,600
East Asian	~20k	1 in 200	1 in 2,000
Ashkenazi Jewish	~13k	1 in 1,000	none seen
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.