DCX doublecortin [Homo sapiens (human)] - Gene

Summary

Official Symbol: DCXprovided by HGNC
Official Full Name: doublecortinprovided by HGNC
Primary source: HGNC:HGNC:2714
See related: Ensembl:ENSG00000077279 MIM:300121
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: mouse all

Genomic context

Location:: Xq23

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	X	NC_000023.11 (111293779..111412205, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (110537007..110655460, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
specifically recognizes compacted GDP-like microtubule lattice
Title: Doublecortin Is Excluded from Growing Microtubule Ends and Recognizes the GDP-Microtubule Lattice.
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.
From this family, we conclude that a DCX mutation causes a pleiotropic phenotype in the female even if X chromosome inactivation pattern is not skewed, and the novel missense mutation in DCX produced relatively mild dysfunction of the doublecortin protein.
Title: Novel DCX mutation-caused lissencephaly in a boy and very mild heterotopia in his mother.
We identified a novel DCX mutation c.785A > G, p.Asp262Gly in a family with X-linked lissencephaly and subcortical band heterotopia
Title: A novel DCX missense mutation in a family with X-linked lissencephaly and subcortical band heterotopia syndrome inherited from a low-level somatic mosaic mother: Genetic and functional studies.
In high-risk metastatic Neuroblastoma, TH and DCX mRNA quantification could be used for the assessment of response to treatment and for early detection of progressive disease or relapses.
Title: TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients.
Results point to a critical role of doublecortin in the formation of the neuromuscular junctions.
Title: A critical and previously unsuspected role for doublecortin at the neuromuscular junction in mouse and human.

Submit: New GeneRIF Correction See all GeneRIFs (47)

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, X-linked MedGen: C4551968 OMIM: 300067 GeneReviews: DCX-Related Disorders	Compare labs

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)

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 BioSystems

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Axon guidance, organism-specific biosystem (from REACTOME)
Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
L1CAM interactions, organism-specific biosystem (from REACTOME)
L1CAM interactions, organism-specific biosystemThe L1 family of cell adhesion molecules (L1CAMs) are a subfamily of the immunoglobulin superfamily of transmembrane receptors, comprised of four structurally related proteins: L1, Close Homolog of L...
Lissencephaly gene (LIS1) in neuronal migration and development, organism-specific biosystem (from Pathway Interaction Database)
Lissencephaly gene (LIS1) in neuronal migration and development, organism-specific biosystem
Lissencephaly gene (LIS1) in neuronal migration and development
Neurofascin interactions, organism-specific biosystem (from REACTOME)
Neurofascin interactions, organism-specific biosystemNeurofascin is an L1 family immunoglobulin cell adhesion molecule involved in axon subcellular targeting and synapse formation during neural development. There are a range of different isoforms ident...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH15935 (e-PCR)
- UniSTS:5647

DXS1188 (e-PCR)
- UniSTS:21121

AL008939 (e-PCR)
- UniSTS:64916

REN20181 (e-PCR)
- UniSTS:344981

AFM340za9 (e-PCR)
- UniSTS:28842

RH47363 (e-PCR)
- UniSTS:42666

DXS7357 (e-PCR)
- UniSTS:54445

SHGC-34529 (e-PCR)
- UniSTS:83140

SHGC-58209 (e-PCR)
- UniSTS:13257

NoName (e-PCR)
- UniSTS:11003

Homology

Homologs of the DCX gene: The DCX gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and frog.
Orthologs from Annotation Pipeline: 285 organisms have orthologs with human gene DCX
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
microtubule binding	IDA Inferred from Direct Assay more info	PubMed
microtubule binding	IMP Inferred from Mutant Phenotype more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
axoneme assembly	IBA Inferred from Biological aspect of Ancestor more info	PubMed
central nervous system development	TAS Traceable Author Statement more info	PubMed
intracellular signal transduction	IEA Inferred from Electronic Annotation more info
nervous system development	TAS Traceable Author Statement more info	PubMed
neuron migration	IDA Inferred from Direct Assay more info	PubMed
photoreceptor cell development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
retina development in camera-type eye	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
axoneme	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoskeleton	TAS Traceable Author Statement more info	PubMed
cytosol	TAS Traceable Author Statement more info
microtubule	IEA Inferred from Electronic Annotation more info
microtubule associated complex	TAS Traceable Author Statement more info	PubMed
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

NG_011750.1 RefSeqGene

Range

4987..123400

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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/Swiss-Prot

O43602

Conserved Domains (1) summary

smart00537
Location:129 → 219

DCX; Domain in the Doublecortin (DCX) gene product
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

A8K340

Related

ENSP00000490614.1, ENST00000636035.1

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

Status: REVIEWED

Source sequence(s)

AL031117, AL450490

Related

ENSP00000490357.1, ENST00000637453.1

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

Status: REVIEWED

Source sequence(s)

AL031117, AL450490

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

Status: REVIEWED

Source sequence(s)

AL031117, AL450490

Related

ENSP00000490878.1, ENST00000637570.1

Conserved Domains (3) summary

pfam10428
Location:276 → 352

SOG2; RAM signalling pathway protein

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

Status: REVIEWED

Source sequence(s)

AL031117, AL450490

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

Status: REVIEWED

Source sequence(s)

AL031117, AL450490

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
NM_178151.2 → 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, AW163329, DC375659

Consensus CDS

CCDS14557.1

UniProtKB/Swiss-Prot

O43602

UniProtKB/TrEMBL

H3BLV5

Related

ENSP00000361061.2, ENST00000371993.6

Conserved Domains (1) summary

smart00537
Location:48 → 138

DCX; Domain in the Doublecortin (DCX) gene product
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

O43602

Related

ENSP00000489635.1, ENST00000635795.1

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
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/Swiss-Prot

O43602

UniProtKB/TrEMBL

H3BLV5

Related

ENSP00000419861.1, ENST00000488120.2

Conserved Domains (1) summary

smart00537
Location:48 → 138

DCX; Domain in the Doublecortin (DCX) gene product