DCLK3

Chr 3

doublecortin like kinase 3

Also known as: CLR, DCAMKL3, DCDC3C, DCK3

NCBI Gene: 85443 ENSG00000163673 UniProt: Q9C098 OMIM: 613167

Encodes a serine/threonine kinase that regulates protein localization to the nucleus through phosphorylation. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy. The gene shows moderate constraint against loss-of-function variants, affecting neurological development when disrupted.

OMIM ResearchSummary from RefSeq

Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in intracellular signal transduction. Predicted to act upstream of or within negative regulation of protein localization to nucleus and peptidyl-serine phosphorylation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating 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.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.56

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.137

Z-score 2.93

OE 0.27 (0.14–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.80Z-score

OE missense 0.88 (0.80–0.97)

317 obs / 359.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.14–0.56)

0≤0.351.4

Missense OE?0.88 (0.80–0.97)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 5 / 18.7Missense obs/exp: 317 / 359.6Syn Z: -0.90

Background carrier burden — how many people carry a rare variant somewhere in DCLK3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 52

987 rare PASS variants

Rare truncating (LoF)

1 in 2,300

78 rare PASS variants

Rare synonymous (reference)

1 in 90

465 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DCLK3. 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 70	1 in 2,300
South Asian	~43k	1 in 43	1 in 980
Remaining (unassigned)	~30k	1 in 54	1 in 1,900
European (Finnish)	~27k	1 in 210	1 in 3,200
Admixed American	~22k	1 in 46	1 in 2,600
African / African American	~21k	1 in 51	1 in 1,700
East Asian	~20k	1 in 56	≈ 1 in 7,800
Ashkenazi Jewish	~13k	1 in 180	1 in 1,200
Middle Eastern	~2,884	1 in 57	≈ 1 in 2,600

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): 3 of 5 coding exons well covered in gnomAD exomes; exon 1 poorly covered; exon 2 marginal. Genomes: all 5.? see exons ↓