DCX

Chr XX-linked

doublecortin

Also known as: DBCN, DC, LISX, SCLH, XLIS

This gene encodes a member of the doublecortin family. The protein encoded by this gene is a cytoplasmic protein and contains two doublecortin domains, which bind microtubules. In the developing cortex, cortical neurons must migrate over long distances to reach the site of their final differentiation. The encoded protein appears to direct neuronal migration by regulating the organization and stability of microtubules. In addition, the encoded protein interacts with LIS1, the regulatory gamma subunit of platelet activating factor acetylhydrolase, and this interaction is important to proper microtubule function in the developing cortex. Mutations in this gene cause abnormal migration of neurons during development and disrupt the layering of the cortex, leading to epilepsy, cognitive disability, subcortical band heterotopia ("double cortex" syndrome) in females and lissencephaly ("smooth brain" syndrome) in males. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Lissencephaly, X-linkedMIM #300067
X-linked
Subcortical laminal heterotopia, X-linkedMIM #300067
X-linked
UniProtSubcortical band heterotopia X-linked

Clinical highlights

Gene-disease validity (ClinGen)
lissencephaly spectrum disorders · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
237
Pubs (1 yr)
P/LP submissions
P/LP missense
0.62
LOEUF
LOF
Mechanism· G2P
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GeneReview available — DCX
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.62LOEUF
pLI 0.304
Z-score 2.50
OE 0.24 (0.110.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
2.70Z-score
OE missense 0.44 (0.360.53)
79 obs / 181.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.24 (0.110.62)
00.351.4
Missense OE?0.44 (0.360.53)
00.61.4
Synonymous OE?0.78
01.21.6
LoF obs/exp: 3 / 12.6Missense obs/exp: 79 / 181.5Syn Z: 1.42

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DCX · protein map & ClinVar variants

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