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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DCX
doublecortin
Chromosome X · Xq23
NCBI Gene: 1641Ensembl: ENSG00000077279.21HGNC: HGNC:2714UniProt: A0A1B0GWD1
117PubMed Papers
22Diseases
0Drugs
168Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolmicrotubule bindingprotein bindingprotein kinase bindinglissencephaly type 1 due to doublecortin gene mutationsubcortical band heterotopiaNon-syndromic cerebral malformation due to abnormal neuronal migrationAbnormal cortical gyration
✦AI Summary

DCX (doublecortin) is a microtubule-associated protein essential for cortical development and neuronal migration. During brain development, DCX regulates nucleokinesis—the nuclear translocation required for proper neuronal positioning—through its interaction with microtubules 1. DCX mutations cause type 1 lissencephaly and subcortical band heterotopia by impairing this migration process 12. Recent structural studies reveal DCX promotes α-tubulin polyglutamylation and restricts neurite branching, highlighting its role in maintaining the tubulin code 3. Beyond developmental roles, DCX serves as a marker of neuronal maturation. In adults, while DCX traditionally marks newly generated neurons in hippocampal neurogenesis in rodents and macaques, it displays atypical expression patterns in humans, appearing across diverse neuronal populations rather than defining immature cell types 4. DCX+ neural progenitors from the central nervous system can infiltrate peripheral tissues; notably, they migrate into prostate tumors where they promote neurogenesis and tumor progression, suggesting unexpected roles in cancer biology 5. Clinically, DCX expression responds to therapeutic interventions—exercise-induced cathepsin B enhances DCX expression in hippocampal progenitor cells, correlating with improved memory function 6. DCX genetic variants associate with neurodevelopmental disorders affecting intellectual disability and social behavior, potentially converging with COMT and FMR1 in Wnt signaling and axon morphogenesis pathways 7.

Sources cited
1
DCX protein interacts with microtubules and is critical for nucleokinesis during neuronal migration; DCX mutations cause type 1 lissencephaly
PMID: 11429281
2
DCX is a microtubule-associated protein involved in neuronal migration regulation and lissencephaly pathogenesis
PMID: 24278775
3
DCX promotes α-tubulin polyglutamylation and restricts neurite branching; DCX-KO neurons show reduced nuclear movement velocities and increased neurites
PMID: 39966472
4
DCX expression in humans marks diverse neuronal populations rather than defining immature neurons, contrasting with rodent and macaque neurogenesis patterns
PMID: 34798047
5
DCX+ neural progenitors infiltrate prostate tumors and promote neurogenesis and tumor progression
PMID: 31092925
6
Exercise-induced cathepsin B enhances DCX expression in adult hippocampal progenitor cells and correlates with memory function
PMID: 27345423
7
DCX genetic variants link to intellectual disability and social behavior disorders through pathways involving Wnt signaling and axon morphogenesis
PMID: 35590332
Disease Associationsⓘ22
lissencephaly type 1 due to doublecortin gene mutationOpen Targets
0.86Strong
subcortical band heterotopiaOpen Targets
0.67Moderate
Non-syndromic cerebral malformation due to abnormal neuronal migrationOpen Targets
0.56Moderate
Abnormal cortical gyrationOpen Targets
0.52Moderate
genetic disorderOpen Targets
0.52Moderate
lissencephaly spectrum disordersOpen Targets
0.46Moderate
LissencephalyOpen Targets
0.46Moderate
Neurodevelopmental disorderOpen Targets
0.37Weak
Abnormal cerebral morphologyOpen Targets
0.36Weak
Abnormality of the nervous systemOpen Targets
0.34Weak
fucosidosisOpen Targets
0.27Weak
Intellectual disabilityOpen Targets
0.15Weak
genetic developmental and epileptic encephalopathyOpen Targets
0.12Weak
SeizureOpen Targets
0.11Weak
gliomaOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.08Suggestive
Nijmegen breakage syndromeOpen Targets
0.08Suggestive
temporal lobe epilepsyOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.07Suggestive
Lissencephaly, X-linked 1UniProt
Subcortical band heterotopia X-linkedUniProt
Pathogenic Variants168
NM_001195553.2(DCX):c.557G>T (p.Arg186Leu)Pathogenic
Ectopic tissue|not provided|Lissencephaly type 1 due to doublecortin gene mutation
★★☆☆2026→ Residue 186
NM_001195553.2(DCX):c.115C>T (p.Arg39Ter)Pathogenic
Ectopic tissue|Inborn genetic diseases|not provided|Lissencephaly type 1 due to doublecortin gene mutation
★★☆☆2026→ Residue 39
NM_001195553.2(DCX):c.587G>A (p.Arg196His)Pathogenic
Subcortical laminar heterotopia, X-linked|Lissencephaly type 1 due to doublecortin gene mutation|Ectopic tissue|not provided|Abnormal cerebral morphology|Inborn genetic diseases
★★☆☆2025→ Residue 196
NM_001195553.2(DCX):c.505C>T (p.Gln169Ter)Pathogenic
not provided|Lissencephaly type 1 due to doublecortin gene mutation
★★☆☆2025→ Residue 169
NM_001195553.2(DCX):c.907C>T (p.Arg303Ter)Pathogenic
Ectopic tissue|not provided|Lissencephaly|Lissencephaly type 1 due to doublecortin gene mutation|Inborn genetic diseases
★★☆☆2025→ Residue 303
NM_001195553.2(DCX):c.586C>T (p.Arg196Cys)Pathogenic
Ectopic tissue|not provided|Lissencephaly type 1 due to doublecortin gene mutation
★★☆☆2025→ Residue 196
NM_001195553.2(DCX):c.703C>T (p.Gln235Ter)Pathogenic
not provided
★★☆☆2025→ Residue 235
NM_001195553.2(DCX):c.532C>T (p.Arg178Cys)Pathogenic
Ectopic tissue|not provided|Lissencephaly type 1 due to doublecortin gene mutation
★★☆☆2025→ Residue 178
NM_001195553.2(DCX):c.536C>G (p.Pro179Arg)Pathogenic
not provided|Lissencephaly type 1 due to doublecortin gene mutation
★★☆☆2025→ Residue 179
NM_001195553.2(DCX):c.233G>A (p.Arg78His)Pathogenic
Subcortical laminar heterotopia, X-linked|not provided
★★☆☆2025→ Residue 78
NM_001195553.2(DCX):c.478del (p.Gln160fs)Pathogenic
Lissencephaly type 1 due to doublecortin gene mutation
★★☆☆2025→ Residue 160
NM_001195553.2(DCX):c.814C>T (p.Arg272Ter)Pathogenic
Ectopic tissue|not provided|Lissencephaly type 1 due to doublecortin gene mutation|Inborn genetic diseases
★★☆☆2025→ Residue 272
NM_001195553.2(DCX):c.574C>T (p.Arg192Trp)Pathogenic
Subcortical laminar heterotopia, X-linked|Lissencephaly type 1 due to doublecortin gene mutation|Ectopic tissue|not provided
★★☆☆2024→ Residue 192
NM_001195553.2(DCX):c.611C>A (p.Ala204Asp)Pathogenic
Ectopic tissue|not provided
★★☆☆2024→ Residue 204
NM_001195553.2(DCX):c.681dup (p.Leu228fs)Pathogenic
Abnormal cortical gyration|not provided
★★☆☆2024→ Residue 228
NM_001195553.2(DCX):c.556C>T (p.Arg186Cys)Pathogenic
Ectopic tissue|not provided
★★☆☆2024→ Residue 186
NM_001195553.2(DCX):c.232C>T (p.Arg78Cys)Pathogenic
Ectopic tissue|not provided
★★☆☆2024→ Residue 78
NM_001195553.2(DCX):c.176G>A (p.Arg59His)Pathogenic
Ectopic tissue|not provided|Lissencephaly type 1 due to doublecortin gene mutation
★★☆☆2024→ Residue 59
NM_001195553.2(DCX):c.536C>A (p.Pro179His)Likely pathogenic
Lissencephaly type 1 due to doublecortin gene mutation
★★☆☆2024→ Residue 179
NM_001195553.2(DCX):c.706-2A>GPathogenic
not provided
★★☆☆2023
View on ClinVar ↗
Related Genes
TUBA1BProtein interaction100%MAPKAPK3Protein interaction97%TUBB2BProtein interaction95%CAMK4Protein interaction93%PSKH2Protein interaction90%PPP1R9BProtein interaction90%
Tissue Expression6 tissues
Brain
100%
Heart
0%
Bone Marrow
0%
Ovary
0%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
DCXTUBA1BMAPKAPK3TUBB2BCAMK4PSKH2PPP1R9B
PROTEIN STRUCTURE
Preparing viewer…
PDB5IO9 · 1.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.44Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.19 [0.09–0.44]
RankingsWhere DCX stands among ~20K protein-coding genes
  • #4,036of 20,598
    Most Researched117 · top quartile
  • #442of 5,498
    Most Pathogenic Variants168 · top 10%
  • #2,379of 17,882
    Most Constrained (LOEUF)0.44 · top quartile
Genes detectedDCX
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells.
PMID: 34798047
Neuron · 2022
1.00
2
Progenitors from the central nervous system drive neurogenesis in cancer.
PMID: 31092925
Nature · 2019
0.90
3
PMID: 20301364
0.80
4
Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function.
PMID: 27345423
Cell Metab · 2016
0.70
5
LIS1 and DCX: Implications for Brain Development and Human Disease in Relation to Microtubules.
PMID: 24278775
Scientifica (Cairo) · 2013
0.60