DCX doublecortin [Homo sapiens (human)] - Gene

Summary

Go to the top of the page Help

Official Symbol: DCXprovided by HGNC
Official Full Name: doublecortinprovided by HGNC
Primary source: HGNC:2714
Locus tag: RP5-914P14.1
See related: Ensembl:ENSG00000077279; HPRD:02127; MIM:300121; Vega:OTTHUMG00000022204
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, mental retardation, 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]

Genomic context

Go to the top of the page Help

Location :: Xq22.3-q23

Sequence :: Chromosome: X; NC_000023.10 (110537007..110655460, complement)

See DCX in Epigenomics, MapViewer

Chromosome X - NC_000023.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions What's a GeneRIF?

This finding points to the possible implication of mosaic deletions in the DCX gene in unexplained forms of subcortical band heterotopia (SBH) and may allow for detection of SBH prenatally.
Title: Mosaic DCX deletion causes subcortical band heterotopia in males.
DCX binds to polymerization intermediates at growing microtubule ends, in support of a mechanism for stabilizing 13-protofilament microtubules.
Title: Doublecortin recognizes the 13-protofilament microtubule cooperatively and tracks microtubule ends.
Data report a negative correlation between DCX mRNA expression and white matter neuron density in schizophrenia, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life.
Title: Developmental patterns of doublecortin expression and white matter neuron density in the postnatal primate prefrontal cortex and schizophrenia.
Up-regulation of doublecortin is associated with brain damage in children with acute lymphoblastic leukemia
Title: Expression of liquoral neuroprotection markers in children with acute lymphoblastic leukemia.
DCX synthesis induces apoptosis in brain tumor stem cells (BTSC) through a novel JNK1/neurabin II/DCX/PP1/caspase-3 pathway.
Title: Effect of doublecortin on self-renewal and differentiation in brain tumor stem cells.
study describes male siblings with Lennox-Gastaut syndrome and pachygyria with a novel missense mutation in the DCX gene
Title: Familial Lennox-Gastaut syndrome in male siblings with a novel DCX mutation and anterior pachygyria.
The DCX binding on the microtubules surface indirectly stabilizes conserved tubulin-tubulin lateral contacts in the microtubules lumen, operating independently of the nucleotide bound to tubulin.
Title: Template-free 13-protofilament microtubule-MAP assembly visualized at 8 A resolution.
variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, have roles in memory and general cognitive abilities
Title: Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities.
Evidence for a role for miR-128 in neuroblastoma progression and aggressiveness through reelin and DCX expression is reported.
Title: MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness.
intragenic deletions and duplications of the DCX gene account for a significant number of patients with isolated lissencephaly sequence and subcortical band heterotopia, where no molecular defect had previously been identified.
Title: Intragenic deletions and duplications of the LIS1 and DCX genes: a major disease-causing mechanism in lissencephaly and subcortical band heterotopia.

Submit: New GeneRIF Correction See all (28)

Phenotypes

Go to the top of the page Help

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

Review eQTL and phenotype association data in this region using PheGenI

DCX-related disorders include the neuronal migration disorders classic lissencephaly (formerly also known as lissencephaly type 1), usually in males; and subcortical band heterotopia (SBH, also called double cortex), primarily in females. Males with classic DCX-related lissencephaly typically have severe and global developmental delay, infantile-onset seizures (infantile spasms, West syndrome, focal and generalized seizures), and severe intellectual disability. In individuals with SBH, cognitive abilities range from normal to learning disabilities and/or severe intellectual disability. The majority of individuals with SBH present with focal or generalized seizures. Behavior problems may also be observed. In DCX-related lissencephaly and SBH the severity of the clinical manifestation correlates with the degree of the underlying brain malformation.

Diagnosis Testing

The diagnosis of a DCX-related disorder is considered in the presence of characteristic MRI findings (frontally pronounced or generalized classic lissencephaly and/or SBH) in combination with neurologic features (in particular developmental delay, epileptic seizures, cognitive impairment) and/or a family history compatible with X-linked inheritance. The diagnosis is confirmed by molecular genetic testing. The DCX-related lissencephaly presents as classic lissencephaly and is characterized by absent gyri (agyria) or reduced gyration (pachygyria) with thickened cortex. Molecular genetic testing of DCX should include sequence analysis including all coding exons and exon-intron boundaries in combination with a specific method (e.g., MLPA) to identify exonic deletions or duplications.

Genetic Counseling

DCX-related disorders are inherited in an X-linked dominant manner. About 25% of males with DCX-related lissencephaly have a de novo DCX mutation. Approximately 10% of unaffected mothers of children with a DCX mutation were reported to have somatic mosaicism or germline mosaicism. A woman who is heterozygous for a DCX mutation has a 50% chance of transmitting the mutation in each pregnancy. Hemizygous male offspring usually manifest DCX-related classic lissencephaly; while heterozygous female offspring may be asymptomatic mutation carriers or more frequently manifest a wide phenotypic spectrum of SBH. If the disease-causing mutation has been identified in the family, carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are available.

References

PMID: 20301364

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Source	Pubs	Description
O43602	Q9BXS5	AP1M1	HPRD	PubMed
O43602	Q96CW1	AP2M1	HPRD	PubMed
O43602	Q00535	CDK5	HPRD	PubMed
O43602	O43602	DCX	HPRD	PubMed
O43602	O94856	NFASC	HPRD	PubMed
O43602	P43034	PAFAH1B1	HPRD	PubMed
O43602	P62136	PPP1CA	HPRD	PubMed
O43602	Q96SB3	PPP1R9B	HPRD	PubMed
O43602	Q9HCM9	TRIM39	HPRD	PubMed
O43602	Q93008	USP9X	HPRD	PubMed
BioGRID:108008	BioGRID:122379	ACD	BioGRID	PubMed	Two-hybrid
BioGRID:108008	BioGRID:106848	APP	BioGRID	PubMed	Reconstituted Complex
BioGRID:108008	BioGRID:108008	DCX	BioGRID	PubMed	Reconstituted Complex
BioGRID:108008	BioGRID:111085	PAFAH1B1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:108008	BioGRID:117417	POT1	BioGRID	PubMed	Two-hybrid
BioGRID:108008	BioGRID:111493	PPP1CA	BioGRID	PubMed	Affinity Capture-Western; Co-localization
BioGRID:108008	BioGRID:124202	PPP1R9B	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108008	BioGRID:112574	SPP1	BioGRID	PubMed	Two-hybrid
BioGRID:108008	BioGRID:112872	TERF1	BioGRID	PubMed	Two-hybrid
BioGRID:108008	BioGRID:117660	TINF2	BioGRID	PubMed	Two-hybrid
BioGRID:108008	BioGRID:113867	USP9X	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid

Pathways from BioSystems

Go to the top of the page Help

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...

General gene information

Go to the top of the page Help

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

Genotypes

See DCX SNP Geneview Report
See DCX SNP Genotype Report
See DCX SNP Variation Viewer Report

Homology

Homologs of the DCX gene: The DCX gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and chicken.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

FLJ51296

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
axon extension	IEA Inferred from Electronic Annotation more info
axon guidance	TAS Traceable Author Statement more info
brain development	IEA Inferred from Electronic Annotation more info
central nervous system development	TAS Traceable Author Statement more info	PubMed
central nervous system projection neuron axonogenesis	IEA Inferred from Electronic Annotation more info
dendrite morphogenesis	IEA Inferred from Electronic Annotation more info
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

Component	Evidence Code	Pubs
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

Go to the top of the page Help

Preferred Names: neuronal migration protein doublecortin

Names: neuronal migration protein doublecortin; lis-X; doublin; doublecortex; lissencephalin-X

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

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

4947..123400

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AJ003112, AL031117, AL450490, AW163329

Consensus CDS

CCDS14556.1

UniProtKB/Swiss-Prot

O43602

Related

ENSP00000337697, OTTHUMP00000216315, ENST00000338081, OTTHUMT00000357058

Conserved Domains (1) summary

cd01617
Location:134 – 216
Blast Score: 304

DCX; Ubiquitin-like domain of DCX
NM_001195553.1 → NP_001182482.1 neuronal migration protein doublecortin isoform d

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

UniProtKB/TrEMBL

A8K340

Conserved Domains (1) summary

cd01617
Location:53 – 135
Blast Score: 301

DCX; Ubiquitin-like domain of DCX
NM_178151.2 → NP_835364.1 neuronal migration protein doublecortin isoform c

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

Related

ENSP00000361061, ENST00000371993

Conserved Domains (1) summary

cd01617
Location:53 – 135
Blast Score: 301

DCX; Ubiquitin-like domain of DCX
NM_178152.2 → NP_835365.1 neuronal migration protein doublecortin isoform b

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

ENSP00000349385, ENST00000356915

Conserved Domains (1) summary

cd01617
Location:53 – 135
Blast Score: 301

DCX; Ubiquitin-like domain of DCX
NM_178153.2 → NP_835366.1 neuronal migration protein doublecortin isoform c

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

Conserved Domains (1) summary

cd01617
Location:53 – 135
Blast Score: 301

DCX; Ubiquitin-like domain of DCX

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000023.10 Reference GRCh37.p10 Primary Assembly

Range

110537007..110655460, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000155.1 Alternate HuRef

Range

100159414..100278099, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018934.1 Alternate CHM1_1.0

Range

110517064..110635502, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01043303.1	None
genomic	ABBA01043304.1	None
genomic	ABBA01043305.1	None
genomic	ABBA01043306.1	None
genomic	ABBA01043307.1	None
genomic	ABBA01043308.1	None
genomic	ABBA01043309.1	None
genomic	ABBA01043310.1	None
genomic	ABBA01043311.1	None
genomic	ABBA01043312.1	None
genomic	ABBA01043313.1	None
genomic	ABBA01043314.1	None
genomic	ABBA01043315.1	None
genomic	ABBA01043316.1	None
genomic	ABBA01043317.1 (4497..6354)	None
genomic	AJ005591.1 (53..300)	None
genomic	AJ005592.1	CAA06617.1
genomic	AL031117.1 (80188..155375)	None
genomic	AL450490.6 (101..43366)	None
genomic	AMYH01022840.1 (1408922..1430611)	None
genomic	AMYH01022841.1	None
genomic	CH471120.2	EAX02642.1
		EAX02643.1
		EAX02644.1
		EAX02645.1
		EAX02646.1
		EAX02647.1
		EAX02648.1
		EAX02649.1
mRNA	AF034634.1	AAC52037.1
mRNA	AF040254.1	AAC31797.1
mRNA	AF040255.1	AAC31696.1
mRNA	AJ003112.1	CAA05867.1
mRNA	AK002120.1	None
mRNA	AK290455.1	BAF83144.1
mRNA	AK297297.1	BAG59765.1
mRNA	AK299822.1	BAG61691.1
mRNA	AU120758.1	None
mRNA	AW163329.1	None
mRNA	BC027925.1	AAH27925.1
mRNA	DA497601.1	None
mRNA	DC375659.1	None
other-genetic	HQ447825.1	ADQ32309.1