DCLK2

Chr 4

doublecortin like kinase 2

Also known as: CL2, CLICK-II, CLICK2, CLIK2, DCAMKL2, DCDC3, DCDC3B, DCK2

The protein contains doublecortin domains that bind microtubules and regulate microtubule polymerization, plus a serine/threonine protein kinase domain with calcium/calmodulin-dependent activity. Mutations cause lissencephaly with severe epilepsy and early lethality, following an autosomal recessive inheritance pattern. This represents a critical neurodevelopmental disorder affecting cortical formation during fetal brain development.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.33
Clinical SummaryDCLK2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
4 unique Pathogenic / Likely Pathogenic· 72 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.957
Z-score 4.66
OE 0.17 (0.090.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.76Z-score
OE missense 0.76 (0.700.84)
334 obs / 437.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.090.33)
00.351.4
Missense OE0.76 (0.700.84)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 6 / 36.3Missense obs/exp: 334 / 437.4Syn Z: -0.31

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic4
VUS72
Likely Benign6
4
Pathogenic
72
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
0
0
0
VUS
0
70
2
0
72
Likely Benign
0
3
0
3
6
Benign
0
0
0
0
0
Total0736382

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DCLK2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC