DCX

Chr XX-linked

doublecortin

NCBI Gene: 1641ENSG00000077279UniProt: O43602

Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. May act by competing with the putative neuronal protein kinase DCLK1 in binding to a target protein. May in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. May be part with PAFAH1B1/LIS-1 of overlapping, but distinct, signaling pathways that promote neuronal migration

Primary Disease Associations & Inheritance

Lissencephaly, X-linkedMIM #300067
X-linked
Subcortical laminal heterotopia, X-linkedMIM #300067
X-linked
UniProtSubcortical band heterotopia X-linked
407
ClinVar variants
240
Pathogenic / LP
0.30
pLI score
1
Active trials
Clinical Summary— DCX
🧬
Gene-Disease Validity (ClinGen)
lissencephaly spectrum disorders · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
240 Pathogenic / Likely Pathogenic· 107 VUS of 407 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.62LOEUF
pLI 0.304
Z-score 2.50
OE 0.24 (0.11–0.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.24 (0.11–0.62)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.44 (0.36–0.53)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.78
0≤1.21.6
LoF obs/exp: 3 / 12.6Missense obs/exp: 79 / 181.5Syn Z: 1.42

ClinVar Variant Classifications

407 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic195
Likely Pathogenic45
VUS107
Likely Benign39
Benign12
Conflicting9
195
Pathogenic
45
Likely Pathogenic
107
VUS
39
Likely Benign
12
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
36
36
123
0
195
Likely Pathogenic
5
34
6
0
45
VUS
1
85
18
3
107
Likely Benign
0
3
9
27
39
Benign
1
0
9
2
12
Conflicting
—9
Total4315816532407

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

View 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.

Gene2Phenotype Curations

DCX-related lissencephaly

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

DCX-related subcortical band heterotopia

definitive
Monoallelic X HeterozygousLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
DOUBLECORTIN; DCX
MIM #300121 · *

Lissencephaly, X-linked

MIM #300067

Molecular basis of disorder known

X-linked

Subcortical laminal heterotopia, X-linked

MIM #300067

Molecular basis of disorder known

X-linked
📖
GeneReview available — DCX
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
X-Linked Epilepsies: A Narrative Review.
Bernardo P et al.·Int J Mol Sci
2024Review
Neuronal migration.
Lambert de Rouvroit C et al.·Mech Dev
2001Review
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
PC12 Cell Line: Cell Types, Coating of Culture Vessels, Differentiation and Other Culture Conditions.
Wiatrak B et al.·Cells
2020
Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma.
Islam S et al.·Sci Transl Med
2024Cohort
Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain.
Simard S et al.·J Psychiatry Neurosci
2024
Doublecortin reinforces microtubules to promote growth cone advance in soft environments.
Dema A et al.·Curr Biol
2024
Gray matter heterotopia.
Barkovich AJ et al.·Neurology
2000
Characterization of the Epileptogenic Phenotype and Response to Antiseizure Medications in Lissencephaly Patients.
Proepper CR et al.·Neuropediatrics
2024Cohort
DCX(+) cells cripple systemic spleen immunity and promote tumor progression.
Ren D et al.·Brain Behav Immun
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Post Traumatic Stress DisorderComplex Posttraumatic Stress DisorderStress

Building Resilience at Schools: Emotional and Biological Assessment and Treatment of Traumatic Stress

RECRUITING
NCT05701111Phase NAStanford UniversityStarted 2024-02-23
Start with the Heart StudentsStart with the Heart TeachersCue Centered Therapy Counselors

External Resources

Links to major genomics databases and tools