DOK3

Chr 5

docking protein 3

Also known as: DOKL

NCBI Gene: 79930 ENSG00000146094 UniProt: Q7L591

DOK3 encodes an adaptor protein that serves as a scaffolding platform for assembling signaling complexes and acts as a negative regulator of JNK signaling in B-cells. This gene is not well-established as a cause of pediatric neurological disease, with current evidence primarily linking it to colorectal adenocarcinoma rather than neurodevelopmental disorders. The gene shows low constraint against loss-of-function variants (pLI 0.0009, LOEUF 0.796), suggesting that complete loss of DOK3 function may be well-tolerated in humans.

ResearchSummary from RefSeq, UniProt

Predicted to enable signaling adaptor activity. Predicted to be involved in Ras protein signal transduction. Located in plasma membrane. Implicated in colorectal adenocarcinoma. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.001

Z-score 2.20

OE 0.44 (0.26–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.36Z-score

OE missense 0.94 (0.85–1.04)

292 obs / 310.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.26–0.80)

0≤0.351.4

Missense OE?0.94 (0.85–1.04)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 8 / 18.1Missense obs/exp: 292 / 310.1Syn Z: 0.28

Background carrier burden — how many people carry a rare variant somewhere in DOK3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

826 rare PASS variants

Rare truncating (LoF)

1 in 740

116 rare PASS variants

Rare synonymous (reference)

1 in 110

349 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DOK3. 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 60	1 in 720
South Asian	~43k	1 in 44	1 in 1,400
Remaining (unassigned)	~30k	1 in 53	1 in 1,800
European (Finnish)	~27k	1 in 110	1 in 650
Admixed American	~22k	1 in 53	1 in 2,300
African / African American	~21k	1 in 44	1 in 1,100
East Asian	~20k	1 in 61	1 in 2,700
Ashkenazi Jewish	~13k	1 in 180	none seen
Middle Eastern	~2,884	1 in 40	≈ 1 in 2,800

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.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓