DCX

Chr XX-linked

doublecortin

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

NCBI Gene: 1641 ENSG00000077279 UniProt: O43602 OMIM: 300121

The protein regulates microtubule organization and stability to direct neuronal migration during cortical development, interacting with LIS1 for proper microtubule function. Mutations cause X-linked inheritance disorders with sex-specific phenotypes: lissencephaly in males and subcortical band heterotopia (double cortex syndrome) in females, both associated with epilepsy and cognitive disability. The pathogenic mechanism involves disrupted neuronal migration and abnormal cortical layering due to impaired microtubule function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismX-linkedLOEUF 0.622 OMIM phenotypes

Clinical Summary— DCX

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Gene-Disease Validity (ClinGen)

lissencephaly spectrum disorders · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

127 unique Pathogenic / Likely Pathogenic· 101 VUS of 307 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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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

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.304

Z-score 2.50

OE 0.24 (0.11–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.70Z-score

OE missense 0.44 (0.36–0.53)

79 obs / 181.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.24 (0.11–0.62)

0≤0.351.4

Missense OE?0.44 (0.36–0.53)

0≤0.61.4

Synonymous OE?0.78

0≤1.21.6

LoF obs/exp: 3 / 12.6Missense obs/exp: 79 / 181.5Syn Z: 1.42

ClinVar Variant Classifications

307 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic87

Likely Pathogenic40

VUS101

Likely Benign41

Benign12

Conflicting13

Pathogenic

Likely Pathogenic

101

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	51	33	3	0	87
Likely Pathogenic	6	34	0	0	40
VUS	2	90	6	3	101
Likely Benign	0	5	9	27	41
Benign	1	0	9	2	12
Conflicting	—				13
Total	60	162	27	32	294

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

View in ClinVar →

113 pathogenic / likely-pathogenic (of 124) ClinVar copy-number / structural variants overlap DCX — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →