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DCX doublecortin [ Homo sapiens (human) ]

Gene ID: 1641, updated on 7-Apr-2024

Summary

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Official Symbol
DCXprovided by HGNC
Official Full Name
doublecortinprovided by HGNC
Primary source
HGNC:HGNC:2714
See related
Ensembl:ENSG00000077279 MIM:300121; AllianceGenome:HGNC:2714
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
DC; DBCN; LISX; SCLH; XLIS
Summary
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]
Expression
Biased expression in brain (RPKM 4.3) and endometrium (RPKM 1.0) See more
Orthologs
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Genomic context

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Location:
Xq23
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (111293779..111412192, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (109741985..109860408, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (110537007..110655420, complement)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene glutamate dehydrogenase 1 pseudogene 9 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:110489468-110490667 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:110498437-110498970 Neighboring gene calpain 6 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:110654454-110654986 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:110654987-110655518 Neighboring gene RNA, U6 small nuclear 496, pseudogene Neighboring gene high mobility group box 1 pseudogene 12

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Novel lissencephaly-associated DCX variants in the C-terminal DCX domain affect microtubule binding and dynamics. Lin JR, et al. Epilepsia, 2022 May. PMID 35213059
  2. Doublecortin undergo nucleocytoplasmic transport via the RanGTPase signaling to promote glioma progression. Ayanlaja AA, et al. Cell Commun Signal, 2020 Feb 12. PMID 32050972, Free PMC Article
  3. Pathogenic E2K mutation of doublecortin X (DCX) alters microtubule stabilisation and actin filament association. Moslehi M, et al. Biochem Biophys Res Commun, 2019 Jun 4. PMID 30979500
  4. Doublecortin X (DCX) serine 28 phosphorylation is a regulatory switch, modulating association of DCX with microtubules and actin filaments. Moslehi M, et al. Biochim Biophys Acta Mol Cell Res, 2019 Apr. PMID 30625347
  5. A dominant dendrite phenotype caused by the disease-associated G253D mutation in doublecortin (DCX) is not due to its endocytosis defect. Yap CC, et al. J Biol Chem, 2018 Dec 7. PMID 30291144, Free PMC Article

See all (110) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Novel lissencephaly-associated DCX variants in the C-terminal DCX domain affect microtubule binding and dynamics.
    Title: Novel lissencephaly-associated DCX variants in the C-terminal DCX domain affect microtubule binding and dynamics.
  2. Doublecortin undergo nucleocytoplasmic transport via the RanGTPase signaling to promote glioma progression.
    Title: Doublecortin undergo nucleocytoplasmic transport via the RanGTPase signaling to promote glioma progression.
  3. Study shows the DCX E2K mutant protein retains the ability to interact with and bundle microtubules (MT)s, but these MTs show a reduced sensitivity to nocodazole-induced depolymerization as well as slower alpha-tubulin exchange rates. Also shows increased association of DCX E2K mutant with the actin filament (F-ACT) network.
    Title: Pathogenic E2K mutation of doublecortin X (DCX) alters microtubule stabilisation and actin filament association.
  4. this is the first report revealing that cir-CCDC66 modulates DCX expression through sponging miR-488-3p and thus participates in the onset of Hirschsprung's disease.
    Title: Circular RNA CCDC66 targets DCX to regulate cell proliferation and migration by sponging miR-488-3p in Hirschsprung's disease.
  5. Phosphorylation of dublecortin X (DCX) serine 28 (S28) plays a critical role in DCX association with the cytoskeleton in human neuroblastoma cells.
    Title: Doublecortin X (DCX) serine 28 phosphorylation is a regulatory switch, modulating association of DCX with microtubules and actin filaments.
  6. Doublecortin can associate with AP-2 without being bound to microtubules. A DCX-G35D mutation causes a dominant-negative dendrite growth phenotype that is not due to a defect in neurofascin endocytosis.
    Title: A dominant dendrite phenotype caused by the disease-associated G253D mutation in doublecortin (DCX) is not due to its endocytosis defect.
  7. exchange rates for the C-terminal truncated DCX protein were resistant to the impact of taxol-induced stabilization
    Title: Dynamic microtubule association of Doublecortin X (DCX) is regulated by its C-terminus.
  8. Age-associated expression of the proliferation and immature neuron markers MKI67 and DCX, respectively, was unrelated, suggesting that neurogenesis-associated processes are independently altered at these points in the development from stem cell to neuron.
    Title: Evidence for reduced neurogenesis in the aging human hippocampus despite stable stem cell markers.
  9. specifically recognizes compacted GDP-like microtubule lattice
    Title: Doublecortin Is Excluded from Growing Microtubule Ends and Recognizes the GDP-Microtubule Lattice.
  10. this suggests that the microtubule-interacting doublecortin domain observed in cryo-electron micrographs is the C-terminal domain rather than the N-terminal one.
    Title: Crystal Structures of the Human Doublecortin C- and N-terminal Domains in Complex with Specific Antibodies.
Submit: New GeneRIF Correction See all GeneRIFs (51)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Lissencephaly type 1 due to doublecortin gene mutation
MedGen: C4551968 OMIM: 300067 GeneReviews: DCX-Related Disorders
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Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2012-07-06)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2012-07-06)

ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat induces hyperphosphorylation of neuronal migration protein doublecortin in neuronal cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ51296

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables microtubule binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables microtubule binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in axoneme assembly IEA
Inferred from Electronic Annotation
more info
  
involved_in central nervous system development TAS
Traceable Author Statement
more info
 PubMed 
involved_in intracellular signal transduction IEA
Inferred from Electronic Annotation
more info
  
involved_in nervous system development TAS
Traceable Author Statement
more info
 PubMed 
involved_in neuron migration IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in retina development in camera-type eye IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytoskeleton TAS
Traceable Author Statement
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in microtubule IEA
Inferred from Electronic Annotation
more info
  
part_of microtubule associated complex TAS
Traceable Author Statement
more info
 PubMed 
located_in neuron projection IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
neuronal migration protein doublecortin
Names
doublecortex
doublin
lis-X
lissencephalin-X

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011750.1 RefSeqGene

    Range
    4987..123400
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000555.3 → NP_000546.2  neuronal migration protein doublecortin isoform a

    See identical proteins and their annotated locations for NP_000546.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AJ003112, AL031117, AL450490, AW163329
    UniProtKB/TrEMBL
    B4DM53
    Related
    ENSP00000350776.6, ENST00000358070.10
    Conserved Domains (3) summary
    cd16112
    Location:132 → 220
    DCX1_DCX; Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX)
    cd17069
    Location:257 → 340
    DCX2; Dublecortin-like domain 2
    cl40450
    Location:365 → 419
    KLF8_12_N; N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins

  2. NM_001195553.2 → NP_001182482.1  neuronal migration protein doublecortin isoform d

    See identical proteins and their annotated locations for NP_001182482.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) has an alternate 5' exon, resulting in a downstream AUG start codon, and an additional segment and additional 3 nts in two different 3' CDS regions respectively, as compared to variant 1. The resulting isoform (d) has a shorter N-terminus, and has an extra segment and an extra aa in two different C-terminal regions respectively, compared to isoform a.
    Source sequence(s)
    AK290455, AL031117, DA497601
    Consensus CDS
    CCDS83483.1
    UniProtKB/TrEMBL
    A0A9S7N7F7, A8K340
    Related
    ENSP00000490614.1, ENST00000636035.2
    Conserved Domains (3) summary
    cd16112
    Location:51 → 139
    DCX1_DCX; Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX)
    cd17069
    Location:176 → 259
    DCX2; Dublecortin-like domain 2
    cl40450
    Location:284 → 343
    KLF8_12_N; N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins

  3. NM_001369370.1 → NP_001356299.1  neuronal migration protein doublecortin isoform d

    Status: REVIEWED

    Source sequence(s)
    AL031117, AL450490
    Consensus CDS
    CCDS83483.1
    UniProtKB/TrEMBL
    A0A9S7N7F7, A8K340
    Related
    ENSP00000490357.1, ENST00000637453.1
    Conserved Domains (3) summary
    cd16112
    Location:51 → 139
    DCX1_DCX; Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX)
    cd17069
    Location:176 → 259
    DCX2; Dublecortin-like domain 2
    cl40450
    Location:284 → 343
    KLF8_12_N; N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins

  4. NM_001369371.1 → NP_001356300.1  neuronal migration protein doublecortin isoform b

    Status: REVIEWED

    Source sequence(s)
    AL031117, AL450490
    Consensus CDS
    CCDS14558.1
    UniProtKB/Swiss-Prot
    A6NFY6, A9Z1V8, D3DUY8, D3DUY9, D3DUZ0, O43602, O43911, Q5JYZ5
    UniProtKB/TrEMBL
    A0A9S7N7F7
    Conserved Domains (3) summary
    cd16112
    Location:51 → 139
    DCX1_DCX; Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX)
    cd17069
    Location:176 → 259
    DCX2; Dublecortin-like domain 2
    cl40450
    Location:284 → 343
    KLF8_12_N; N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins

  5. NM_001369372.1 → NP_001356301.1  neuronal migration protein doublecortin isoform e

    Status: REVIEWED

    Source sequence(s)
    AL031117, AL450490
    Consensus CDS
    CCDS94654.1
    UniProtKB/TrEMBL
    A0A1B0GUE1, A0A1B0GWD1, E7EU50
    Related
    ENSP00000490878.1, ENST00000637570.1
    Conserved Domains (3) summary
    cd16112
    Location:51 → 139
    DCX1_DCX; Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX)
    cd17069
    Location:176 → 259
    DCX2; Dublecortin-like domain 2
    cl40450
    Location:284 → 338
    KLF8_12_N; N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins

  6. NM_001369373.1 → NP_001356302.1  neuronal migration protein doublecortin isoform f

    Status: REVIEWED

    Source sequence(s)
    AL031117, AL450490
    Consensus CDS
    CCDS94653.1
    UniProtKB/TrEMBL
    A0A1B0GUE1, A0A804CF28, E7EU50
    Related
    ENSP00000361061.3, ENST00000371993.7
    Conserved Domains (2) summary
    cd16112
    Location:51 → 139
    DCX1_DCX; Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX)
    cd17069
    Location:176 → 259
    DCX2; Dublecortin-like domain 2

  7. NM_001369374.1 → NP_001356303.1  neuronal migration protein doublecortin isoform f

    Status: REVIEWED

    Source sequence(s)
    AL031117, AL450490
    Consensus CDS
    CCDS94653.1
    UniProtKB/TrEMBL
    A0A1B0GUE1, A0A804CF28, E7EU50
    Conserved Domains (2) summary
    cd16112
    Location:51 → 139
    DCX1_DCX; Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX)
    cd17069
    Location:176 → 259
    DCX2; Dublecortin-like domain 2

  8. NM_001410715.1 → NP_001397644.1  neuronal migration protein doublecortin isoform g

    Status: REVIEWED

    Source sequence(s)
    AL031117, AL450490
    Consensus CDS
    CCDS94652.1
    UniProtKB/TrEMBL
    A0A7P0T9C5
    Related
    ENSP00000505501.1, ENST00000680476.1

  9. NM_178151.3 → NP_835364.1  neuronal migration protein doublecortin isoform c

    See identical proteins and their annotated locations for NP_835364.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has an alternate 5' exon, resulting in a downstream AUG start codon, as compared to variant 1. The resulting isoform (c) has a shorter N-terminus compared to isoform a. Variants 3 and 4 encode the same isoform.
    Source sequence(s)
    AF034634, AL031117, AL450490, AW163329, DC375659
    Consensus CDS
    CCDS14557.1
    UniProtKB/TrEMBL
    A0A1B0GUE1, E7EU50
    Conserved Domains (3) summary
    cd16112
    Location:51 → 139
    DCX1_DCX; Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX)
    cd17069
    Location:176 → 259
    DCX2; Dublecortin-like domain 2
    cl40450
    Location:284 → 338
    KLF8_12_N; N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins

  10. NM_178152.3 → NP_835365.1  neuronal migration protein doublecortin isoform b

    See identical proteins and their annotated locations for NP_835365.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has an alternate 5' exon, resulting in a downstream AUG start codon, and has an additional segment in the 3' coding region, as compared to variant 1. The resulting isoform (b) has a shorter N-terminus and an extra internal segment compared to isoform a.
    Source sequence(s)
    AF040254, AL031117, AW163329, DA497601
    Consensus CDS
    CCDS14558.1
    UniProtKB/Swiss-Prot
    A6NFY6, A9Z1V8, D3DUY8, D3DUY9, D3DUZ0, O43602, O43911, Q5JYZ5
    UniProtKB/TrEMBL
    A0A9S7N7F7
    Related
    ENSP00000489635.1, ENST00000635795.1
    Conserved Domains (3) summary
    cd16112
    Location:51 → 139
    DCX1_DCX; Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX)
    cd17069
    Location:176 → 259
    DCX2; Dublecortin-like domain 2
    cl40450
    Location:284 → 343
    KLF8_12_N; N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins

  11. NM_178153.3 → NP_835366.1  neuronal migration protein doublecortin isoform c

    See identical proteins and their annotated locations for NP_835366.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has an alternate 5' exon, resulting in a downstream AUG start codon, as compared to variant 1. The resulting isoform (c) has a shorter N-terminus compared to isoform a. Variants 3 and 4 encode the same isoform.
    Source sequence(s)
    AL031117, AW163329, BC027925, DA497601
    Consensus CDS
    CCDS14557.1
    UniProtKB/TrEMBL
    A0A1B0GUE1, E7EU50
    Related
    ENSP00000419861.1, ENST00000488120.2
    Conserved Domains (3) summary
    cd16112
    Location:51 → 139
    DCX1_DCX; Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX)
    cd17069
    Location:176 → 259
    DCX2; Dublecortin-like domain 2
    cl40450
    Location:284 → 338
    KLF8_12_N; N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    111293779..111412192 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    109741985..109860408 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O43602.4 GenPept UniProtKB/Swiss-Prot:O43602

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