DCX

doublecortin, the group of Doublecortin superfamily

Basic information

Region (hg38): X:111293779-111412429

Links

ENSG00000077279 ∙ NCBI:1641 ∙ OMIM:300121 ∙ HGNC:2714 ∙ Uniprot:O43602 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lissencephaly spectrum disorders (Definitive), mode of inheritance: XL
• lissencephaly type 1 due to doublecortin gene mutation (Strong), mode of inheritance: XL
• lissencephaly type 1 due to doublecortin gene mutation (Supportive), mode of inheritance: XL
• subcortical band heterotopia (Supportive), mode of inheritance: AR
• lissencephaly type 1 due to doublecortin gene mutation (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lissencephaly, X-linked, 1	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	9489699; 9489700; 9817918; 10430413; 10915612; 11175293; 12034802; 12552055; 19673952; 19050731; 19619967; 19673952; 20301364; 20726879; 21488284; 22408144; 25140959

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DCX gene.

• not_provided (173 variants)
• Ectopic_tissue (90 variants)
• Lissencephaly_type_1_due_to_doublecortin_gene_mutation (61 variants)
• Inborn_genetic_diseases (34 variants)
• not_specified (17 variants)
• Subcortical_laminar_heterotopia,_X-linked (16 variants)
• Abnormal_cortical_gyration (9 variants)
• DCX-related_disorder (9 variants)
• Lissencephaly (4 variants)
• Neurodevelopmental_disorder (2 variants)
• Abnormal_cerebral_morphology (2 variants)
• Intellectual_disability (2 variants)
• Fucosidosis (1 variants)
• Subcortical_band_heterotopia (1 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Genetic_developmental_and_epileptic_encephalopathy (1 variants)
• Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DCX gene is commonly pathogenic or not. These statistics are base on transcript: NM_001195553.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	27	2	34
missense	48	53	87	2		190
nonsense	20	1	1			22
start loss	2					2
frameshift	35	3			1	39
splice donor/acceptor (+/-2bp)	6	4				10
Total	111	61	93	29	3

Highest pathogenic variant AF is 0.000020694833

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DCX	protein_coding	protein_coding	ENST00000338081	7	118597

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.70	79	181	0.435	0.0000146	2932
Missense in Polyphen		10	59.029	0.16941		862
Synonymous	1.42	53	67.9	0.780	0.00000532	861
Loss of Function	2.50	3	12.6	0.238	0.00000109	198

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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, signaling pathways that promote neuronal migration. {ECO:0000269|PubMed:22359282}.
• Disease: DISEASE: Lissencephaly, X-linked 1 (LISX1) [MIM:300067]: A classic lissencephaly characterized by mental retardation and seizures that are more severe in male patients. Affected boys show an abnormally thick cortex with absent or severely reduced gyri. Clinical manifestations include feeding problems, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe phenotype referred to as 'doublecortex'. {ECO:0000269|PubMed:11468322, ECO:0000269|PubMed:12552055, ECO:0000269|PubMed:27292316, ECO:0000269|PubMed:9489699, ECO:0000269|PubMed:9489700, ECO:0000269|PubMed:9668176, ECO:0000269|PubMed:9817918}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Subcortical band heterotopia X-linked (SBHX) [MIM:300067]: SBHX is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal. {ECO:0000269|PubMed:10369164, ECO:0000269|PubMed:10441340, ECO:0000269|PubMed:10807542, ECO:0000269|PubMed:11175293, ECO:0000269|PubMed:11601509, ECO:0000269|PubMed:12390976, ECO:0000269|PubMed:9618162, ECO:0000269|PubMed:9989615}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving DCX is found in lissencephaly. Translocation t(X;2)(q22.3;p25.1).
• Pathway: Developmental Biology;Neurofascin interactions;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.800

Intolerance Scores

• loftool: 0.0265
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: neuron migration;nervous system development;central nervous system development;axoneme assembly;intracellular signal transduction;photoreceptor cell development;retina development in camera-type eye
• Cellular component: cytosol;cytoskeleton;microtubule;microtubule associated complex;axoneme;neuron projection
• Molecular function: protein binding;microtubule binding;protein kinase binding