• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
DCX (HGNC:2714) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
doublecortin
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
SCLH, DC, LISX, DBCN, XLIS
%HI
1.65(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.3(Read more about gnomAD pLI score)
LOEUF
0.62(Read more about gnomAD LOEUF score)
Cytoband
Xq23
Genomic Coordinates
GRCh37/hg19: chrX:110537007-110655420 NCBI Ensembl UCSC
GRCh38/hg38: chrX:111293779-111412192 NCBI Ensembl UCSC
MANE Select Transcript
NM_001195553.2 ENST00000636035.2 (Read more about MANE Select)
Function
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, sign... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-35994
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
07/06/2012

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • lissencephaly type 1 due to doublecortin gene mutation Monarch
HI Evidence:
  • PUBMED: PMID: 9489700
    Gleeson et al (1998) described 3 unrelated (sporadic) females with subcortical band heterotopia (see loss phenotype description below) with disruption of the DCX gene. Patient 1 has a 2 basepair AG insertion at position 36, resulting in a frameshift and protein termination at amino acid 24. Patient 2 has a 2 basepair CT deletion at position 684, resulting in a frameshift and protein termination at amino acid 240. Patient 3 has a 2 basepair CT deletion at position 691, resulting in a frameshift and protein termination at amino acid 240. Patient 3 was the only one with parental testing, and the mutation is de novo. In the same paper, Gleeson et al also describe 4 families with different missense mutations in the DCX gene. In each of these families, males carrying the mutation have lissencephaly and females with the mutation have subcortical band heterotopia.
HI Evidence Comments:
Males with X-linked lissencephaly (XLIS) caused by mutations in DCX display a phenotype essentially indistinguishable from lissencephaly caused by LIS1 mutations. Affected females heterozygous for DCX mutations show a milder phenotype, presumably representing a mosaic state caused by random inactivation of either the mutant or normal X chromosome. The brains of affected females show a population of neurons that behaves normally and a population that migrates approximately halfway to the cortex and then arrests in the subcortical white matter, producing a band of neurons called subcortical band heterotopia or "doublecortex" (DC). The majority of patients with DC are female, presumably representing mutations in the X-linked locus.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)