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DLX5 (distal-less homeobox 5)

Written2012-03Jinfei Xu, Joseph R Testa
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
Updated2014-03Yorick Gitton, Giovanni Levi
Evolution des Regulations Endocriniennes, CNRS, UMR7221, Museum National d'Histoire Naturelle, Paris, France

Abstract DLX5 belongs to the six-member family of DLX genes characterized by a homeobox related to that found in the insect Distal-less (Dll) gene. The six DLX genes are organized as three bigenic pairs with a tail-to-tail orientation (Zerucha et al., 2000) and located on chromosomes where HOX clusters are also found (DLX5/DLX6; 7q21.3, syntenic to the HOXA cluster), (DLX1/DLX2; 2q32, syntenic to the HOXD cluster; Simeone et al., 1994) and (DLX3/DLX4; 17q21.33, syntenic to the HOXB cluster). During embryonic development DLX genes are involved in the control of appendage and craniofacial morphogenesis and in the differentiation of reproductive organs; in the adult they play a role in bone homeostasis and in the maintenance of tissue integrity.

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Identity

Alias_namesdistal-less homeo box 5
Other aliasSHFM1D
HGNC (Hugo) DLX5
LocusID (NCBI) 1749
Atlas_Id 44295
Location 7q21.3  [Link to chromosome band 7q21]
Location_base_pair Starts at 97020390 and ends at 97024831 bp from pter ( according to hg19-Feb_2009)  [Mapping DLX5.png]
Local_order -DLX6-DLX5-ACN9-
 
  Local order of DLX5 and flanking genes DLX6 and ACN9 is shown, with centromere at left and telomere (qter) at right. Arrows indicate transcriptional orientation of individual genes. DLX6 gene range: 96635290 - 96640352; DLX5 gene range: 96649702 - 96654143; ACN9 gene range: 96745905 - 96811075 (Hillier et al., 2003).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

 
  Exon 1: 1 - 563; exon 2: 2463 - 2647; exon 3: 3767 - 4442.
Description The DLX5 gene is composed of 3 exons spanning a genomic region of 4442 bp.

Genomic features
Mutations: Breakpoint analyses of genomic deletions and chromosomal rearrangements in the congenital split-hand/split-foot malformation (SHFM type 1D, OMIM #220600), have shown that positional effect and disrupted regulatory elements controlling DLX5/DLX6 activity are involved in the pathogenesis of this developmental disorder (see further "dysmorphologies"). In-depth sequencing of the candidate regions has shown that the expression of DLX6 depends upon the activity of conserved regulatory elements shared with DLX5, and located both within the DLX5/DLX6 intergenic territory and outside of the locus (Lango Allen et al., 2014). Furthermore these enhancers have been identified in all examined species - including in mouse where transgenic analyses have allowed the functional characterization of their tissue-specificity.
Moreover, recent analyses of genomic integrity in SHFM1D probands have unravelled two new intragenic, non-synonymous mutations within the open reading frame of DLX5.
Imprinting: The status of parental imprinting of the DLX5/DLX6 locus has recently gained strong interest as these genes have been considered to be putative methylation targets of the methyl-CpG binding protein-2 (MECP2), and thus might be indirectly involved in the aetiology of the Rett syndrome, a severe X-linked neurodevelopmental disorder afflicting girls with MECP2 mutation (see further "Rett syndrome").

Transcription The DLX5 coding sequence consists of 870 bp from the start of the first codon to the stop codon (Simeone et al., 1994).
Pseudogene None known.

Protein

 
  DLL_N: homeobox protein distal-less-like N terminal; Homeodomain: homeobox DNA binding domain.
Description The DLX5 protein consists of 289 amino acids with a calculated molecular weight of 31,5 kDa. The protein contains two motifs, one dubbed homeobox protein distal-less-like N terminal and a second known as a homeodomain.
Localisation Nucleus.
Function Transcription factor important in the control of bone formation in embryonic development (Hassan et al., 2004).
Transcription from DLX5 yields three splice variants, which range from 1062 b to 1688 b (major isoform) due to alternative splicing sites throughout the precursor transcript. The shortest (Dlx5-002) is not processed. The other two share exon 1 which encodes an N-terminal DLL domain, and exon 2 which encodes a part of the homeodomain.
The shorter transcript (DLX5-003) encodes a predicted 191 AA-long, 20.9 kDa isoform with both N-terminal DLL domain and a homeodomain. It should be observed that in vitro 35S-primed expression from full-length murine Dlx5 yields only one isoform at 32 kDa (Zhang et al., 1997). The latter study provided evidence for an incompatibility between Dlx5 DNA binding to its target homeodomain-responsive element (TAATTA) and heterodimerization with its partner Msx factor. It further showed that both events were mutually antagonistic, suggesting a regulatory role during Dlx/Msx-controlled morphogenetic processes such as branchial arch and limb formation.
During bone formation, Dlx5 (pI 9.3) transactivation activity is enhanced through serine phosphorylation in the nucleus by p38 MAP-kinase upon BMP2 signaling (Ulsamer et al., 2008). Dlx5 has further been shown to be subjected to threonine phosphorylation by PKA during BMP2-induced osteoblast differentiation, which increases Dlx5 nuclear levels by improving its stability (Han et al., 2011).
 
  NCBI/COBALT alignment of DLX homeoproteins. Note the disposition according to the DLX 1/4/6 versus DLX 2/3/5 clades. Indicated by a yellow box is the ultraconserved glutamine featured by most homeoproteins at position 50 of the homeodomain.
Homology None reported to date.

Mutations

Germinal A novel DLX5 mutation (c.A533C: p.Q178P) was identified in a family with autosomal recessive split hand and foot malformation (Shamseldin et al., 2012).
Recently, a second rare familial case of SHFM1 has been demonstrated to result, with highest probability, from intragenic missense mutations of a critical glutamine residue in the third helix of the DLX5 homeodomain - Q186H (Wang et al., 2014). The encoded mutant DLX5 has been demonstrated to fail at transactivating a bona fide MYC target. Such an observation is not unexpected as this mutation affects Q50, the most conserved residue of all homeoproteins (see diagram above), which numerous biochemical studies have demonstrated to be responsible for the specificity of the DNA recognition at the TAATT homeo-element (for review, Galliot et al., 1999).
Somatic A DLX5 mutation (c.C119G: p.S40C) was observed in an ovarian carcinoma (Cancer Genome Atlas Research Network, 2011).
Overexpression of DLX5 has been reported in several types of human malignancy including lung cancer (Kato et al., 2008; Xu and Testa, 2009), T-cell lymphoma (Tan et al., 2008), and ovarian cancer (Tan et al., 2010), etc.

Implicated in

Note
  
Entity Lung cancer
Note The DLX5 gene was reported to be overexpressed in the great majority of human non-small cell lung cancers examined by Kato et al., 2008. Furthermore, immunohistochemical studies revealed that positive immunostaining for DLX5 correlated with tumor size and poorer prognosis.
A DLX5 transcript isoform has been shown to be strongly overexpressed in a large panel of primary lung cancer samples, providing a reliable prognosis marker (Kato et al., 2008). In this study, the detected isoform (1.8 kb on Northern blot using a probe spanning exon 3 and 3'UTR) was claimed to be found only in the placenta, among 23 normal adult tissues. It should be observed that other studies have reported numerous expression sites in adult human, including bone (osteoblasts and marrow), ear, tooth, fat and brain. With regards to function, down-regulation of DLX5 through RNA interference compromised the growth or survival of two lung cancer cell lines, suggesting that controling DLX5 expression levels might be clinically relevant (Kato et al., 2008).
  
  
Entity Lymphoma
Note DLX5 was found to be highly expressed in 3 of 7 (42%) patient-derived T-cell lymphomas compared with that observed in nonmalignant lymph node samples (Tan et al., 2008). In addition, these investigators found repeated upregulation of Dlx5 in T-cell lymphomas from transgenic mice in which the Lck promoter was used to drive expression of a constitutively active form of Akt2 in the thymus. Dlx5 was overexpressed due to a novel chromosome inversion that placed the T-cell receptor beta (Tcrb) enhancer region near the Dlx5 locus.
  
  
Entity Breast cancer
Note Both DLX5 and DLX6 were found to be upregulated during metastasis formation after intravenous injection of MDA-MB-231 breast cancer cells. The in vitro treatment of MDA-MB-231 cells with endothelin 1, a peptide associated with breast cancer invasive phenotype, resulted in a switch from DLX2 to DLX5 expression. Mutually exclusive expression of DLX2 and DLX5 was found in both MDA-MB-231 cells and human breast cancer specimens. This evidence suggested that DLX genes are involved in human breast cancer progression, and that expression of DLX2 and DLX5 genes might serve as prognostic markers (Morini et al., 2010).
  
  
Entity Astrocytoma
Note Transcriptional profiling in search for prognosis markers has identified DLX5 as an upregulated candidate for high-grade astrocytomas (Phillips et al., 2006).
  
  
Entity Various cancers
Note DLX5 mRNA is abundantly expressed in many cancer cell lines derived from malignant tissues of breast, brain, lung, skin, and ovarian cancer patients, whereas expression of DLX5 was low or undetectable in tumor cells from patients with leukemia or with colorectal, prostate, and kidney cancers (Tan et al., 2010).
  
  
Entity Dysmorphologies
Note Split hand-foot malformation (SHFM) type 1 with sensory-neural hearing loss (SHFM1D; MIM:220600). This malformative syndrome affects hands and feet alike, resulting in moderate to severe median ray deficiency with syndactily. Among the described six non-syndromic SHFM loci, one spans the DLX5/DLX6 bigenic cluster (Scherer et al., 1994; Crackower et al., 1996). However, numerous reported mutations spare DLX5 or DLX6 open reading frames, suggesting it may rather be their common regulatory elements which is impacted (Robledo et al., 2002; Lo Iacono et al., 2008). However recently, one rare familial case of SHFM1 has been demonstrated to result, with highest probability, from an intragenic missense mutation of the DLX5 homeodomain (Q178P; Shamseldin et al., 2012). In the latter case, a causal link between defective DLX5/DLX6 expression and the pathogenic mechanism impairing limb development remains to be elucidated (Lango Allen et al., 2014).
On a further note, SHFM cases have often been reported to include hearing loss, a trait consistent with a developmental role demonstrated for Dlx5/Dlx6 during ear formation in mouse embryogenesis (Acampora et al., 1999; Merlo et al., 2002; Robledo and Lufkin, 2006; Chatterjee et al., 2010; Frenz et al., 2010). Moreover, both genes are major targets of two regulator genes whose deficiencies are responsible for a related pathogenic condition, the auriculo-condylar syndrome (ACS, Rieder et al., 2012; Brown et al., 2010).
Anorectal malformation associated with SHFM has been reported in a family with a missense mutation in the P63 gene, a known direct upstream regulator of DLX5/DLX6 during morphogenesis (Su et al., 2013). Whether DLX5/DLX6 expression is dysregulated in this condition, and whether this trait can be functionaly associated with the phenotype, remains to be elucidated.
  
  
Entity Rett syndrome
Note DLX5 and DLX6 (OMIM 600028) have been controversial candidates for neurodevelopmental defects progressively afflicting young girls suffering of Rett syndrome (OMIM 312750). This late onset disorder features fatal motor abnormalities, seizures, autism and mental retardation. While the genomic sequence of the DLX5/DXL6 locus remains unaffected in all reported cases, it is a direct target of the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2), which has been strongly associated to this syndrome by linkage analysis (Horike et al., 2005). While still debated (Horike et al., 2005; Schüle et al., 2007; LaSalle, 2007; Miyano et al., 2008), initial MeCP2 deficiency is considered as causing defective neurogenesis through dysregulated expression of DLX5/DLX6, due to altered chromatin state at this target locus (Horike et al., 2005; Lilja et al., 2013). Mouse mutagenesis has substantiated this hypothesis by pinpointing GABA (γ-aminobutyric acid)-releasing neurons as a major cellular target expressing Dlx5 and Dlx6, whose deficiency impairs neurogenesis in MeCP2 null mutant (Chao et al., 2010).
  
  
Entity Osteoporosis
Note Mouse mutational studies have demonstrated a role for Dlx5 and Dlx6 as a major determinant of chondrogenesis and chondrocyte hypertrophy in the endochondral skeleton, throughout embryogenesis and adulthood (Samee et al., 2007; Samee et al., 2008; Samee et al., 2009). These observations pave the way for a better understanding of human osteoporosis, in particular in patients with dysfunctional regulation of bone-remodeling hormonal levels (Prall et al., 2013).
  
  
Entity Reproductive tract
Note Dlx5 and Dlx6 are involved in the development and function of the reproductive tract. The dual mouse mutant for Dlx5 and Dlx6 displays abnormal urethra formation (Suzuki et al., 2007), reduced testicular steroidogenesis with feminization (Nishida et al., 2008), and early ovarian follicular depletion (Bouhali et al., 2011). A human mutation in a genomic region including DLX5 and DLX6 has been associated to a case of familial premature ovarian failure (Caburet et al., 2012).
  
  
Entity Teratology
Note With regards to pharmacologically-induced teratogenesis, dysregulation of DLX5/DLX6 gene expression has been demonstrated to be a major step during craniofacial embryopathy induced by two compounds:
i) retinoic acid, a vitamin A derivative found in the RoAccutane ® drug, which indirectly prevents the induction of DLX5/DLX6 in human (Lammer et al., 1985; Coberly et al., 1996) and in all animal models investigated (Vieux-Rochas et al., 2007), which share a wide range of jaw and ear malformations;
ii) the food contaminant ochratoxin A, a fungal toxin demonstrated to prevent Dlx5 activation in exposed mouse embryos, which later develop craniofacial malformations (Wei and Sulik, 1993; Napoletano et al., 2010). Although a causal link between Dlx5, Dlx6 and the toxin remains to be functionally demonstrated, this observation may account for teratogenesis observed in human embryos maternally exposed to the toxin (Hope and Hope, 2012; Thrasher et al., 2012).
  

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Cancer Res. 2010 Nov 15;70(22):9197-206. Epub 2010 Nov 2.
PMID 21045156
 
A novel recurrent chromosomal inversion implicates the homeobox gene Dlx5 in T-cell lymphomas from Lck-Akt2 transgenic mice.
Tan Y, Timakhov RA, Rao M, Altomare DA, Xu J, Liu Z, Gao Q, Jhanwar SC, Di Cristofano A, Wiest DL, Knepper JE, Testa JR.
Cancer Res. 2008 Mar 1;68(5):1296-302.
PMID 18316591
 
A water-damaged home and health of occupants: a case study.
Thrasher JD, Gray MR, Kilburn KH, Dennis DP, Yu A.
J Environ Public Health. 2012;2012:312836. doi: 10.1155/2012/312836. Epub 2011 Dec 15.
PMID 22220187
 
BMP-2 induces Osterix expression through up-regulation of Dlx5 and its phosphorylation by p38.
Ulsamer A, Ortuno MJ, Ruiz S, Susperregui AR, Osses N, Rosa JL, Ventura F.
J Biol Chem. 2008 Feb 15;283(7):3816-26. Epub 2007 Dec 3.
PMID 18056716
 
Molecular dynamics of retinoic acid-induced craniofacial malformations: implications for the origin of gnathostome jaws.
Vieux-Rochas M, Coen L, Sato T, Kurihara Y, Gitton Y, Barbieri O, Le Blay K, Merlo G, Ekker M, Kurihara H, Janvier P, Levi G.
PLoS One. 2007 Jun 6;2(6):e510.
PMID 17551590
 
Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation.
Wang X, Xin Q, Li L, Li J, Zhang C, Qiu R, Qian C, Zhao H, Liu Y, Shan S, Dang J, Bian X, Shao C, Gong Y, Liu Q.
Eur J Hum Genet. 2014 Feb 5. doi: 10.1038/ejhg.2014.7. [Epub ahead of print]
PMID 24496061
 
Pathogenesis of craniofacial and body wall malformations induced by ochratoxin A in mice.
Wei X, Sulik KK.
Am J Med Genet. 1993 Nov 1;47(6):862-71.
PMID 8279484
 
DLX5 (distal-less homeobox 5) promotes tumor cell proliferation by transcriptionally regulating MYC.
Xu J, Testa JR.
J Biol Chem. 2009 Jul 31;284(31):20593-601. Epub 2009 Jun 4.
PMID 19497851
 
A highly conserved enhancer in the Dlx5/Dlx6 intergenic region is the site of cross-regulatory interactions between Dlx genes in the embryonic forebrain.
Zerucha T, Stuhmer T, Hatch G, Park BK, Long Q, Yu G, Gambarotta A, Schultz JR, Rubenstein JL, Ekker M.
J Neurosci. 2000 Jan 15;20(2):709-21.
PMID 10632600
 
Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism.
Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C.
Mol Cell Biol. 1997 May;17(5):2920-32.
PMID 9111364
 

Citation

This paper should be referenced as such :
Y Gitton, G Levi
DLX5 (distal-less homeobox 5)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(11):810-816.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/DLX5ID44295ch7q21.html
History of this paper:
Xu, J ; Testa, JR. DLX5 (distal-less homeobox 5). Atlas Genet Cytogenet Oncol Haematol. 2012;16(8):526-528.
http://documents.irevues.inist.fr/bitstream/handle/2042/47484/03-2012-DLX5ID44295ch7q21.pdf


External links

Nomenclature
HGNC (Hugo)DLX5   2918
Cards
AtlasDLX5ID44295ch7q21
Entrez_Gene (NCBI)DLX5  1749  distal-less homeobox 5
AliasesSHFM1D
GeneCards (Weizmann)DLX5
Ensembl hg19 (Hinxton)ENSG00000105880 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000105880 [Gene_View]  chr7:97020390-97024831 [Contig_View]  DLX5 [Vega]
ICGC DataPortalENSG00000105880
TCGA cBioPortalDLX5
AceView (NCBI)DLX5
Genatlas (Paris)DLX5
WikiGenes1749
SOURCE (Princeton)DLX5
Genetics Home Reference (NIH)DLX5
Genomic and cartography
GoldenPath hg38 (UCSC)DLX5  -     chr7:97020390-97024831 -  7q21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)DLX5  -     7q21.3   [Description]    (hg19-Feb_2009)
EnsemblDLX5 - 7q21.3 [CytoView hg19]  DLX5 - 7q21.3 [CytoView hg38]
Mapping of homologs : NCBIDLX5 [Mapview hg19]  DLX5 [Mapview hg38]
OMIM220600   600028   
Gene and transcription
Genbank (Entrez)AA129308 AK023493 AK297614 BC006226 BT006903
RefSeq transcript (Entrez)NM_005221
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)DLX5
Cluster EST : UnigeneHs.99348 [ NCBI ]
CGAP (NCI)Hs.99348
Alternative Splicing GalleryENSG00000105880
Gene ExpressionDLX5 [ NCBI-GEO ]   DLX5 [ EBI - ARRAY_EXPRESS ]   DLX5 [ SEEK ]   DLX5 [ MEM ]
Gene Expression Viewer (FireBrowse)DLX5 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1749
GTEX Portal (Tissue expression)DLX5
Human Protein AtlasENSG00000105880-DLX5 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP56178   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP56178  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP56178
Splice isoforms : SwissVarP56178
PhosPhoSitePlusP56178
Domaine pattern : Prosite (Expaxy)HOMEOBOX_1 (PS00027)    HOMEOBOX_2 (PS50071)   
Domains : Interpro (EBI)Distal-less_N    Homeobox-like    Homeobox_CS    Homeobox_dom    Homeobox_metazoa    HTH_motif   
Domain families : Pfam (Sanger)DLL_N (PF12413)    Homeobox (PF00046)   
Domain families : Pfam (NCBI)pfam12413    pfam00046   
Domain families : Smart (EMBL)HOX (SM00389)  
Conserved Domain (NCBI)DLX5
DMDM Disease mutations1749
Blocks (Seattle)DLX5
PDB (SRS)2DJN    4RDU   
PDB (PDBSum)2DJN    4RDU   
PDB (IMB)2DJN    4RDU   
PDB (RSDB)2DJN    4RDU   
Structural Biology KnowledgeBase2DJN    4RDU   
SCOP (Structural Classification of Proteins)2DJN    4RDU   
CATH (Classification of proteins structures)2DJN    4RDU   
SuperfamilyP56178
Human Protein Atlas [tissue]ENSG00000105880-DLX5 [tissue]
Peptide AtlasP56178
HPRD02492
IPIIPI00008192   
Protein Interaction databases
DIP (DOE-UCLA)P56178
IntAct (EBI)P56178
FunCoupENSG00000105880
BioGRIDDLX5
STRING (EMBL)DLX5
ZODIACDLX5
Ontologies - Pathways
QuickGOP56178
Ontology : AmiGOnuclear chromatin  RNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  skeletal system development  osteoblast differentiation  endochondral ossification  cytoplasm  transcription from RNA polymerase II promoter  nervous system development  cell proliferation  olfactory bulb interneuron differentiation  embryonic limb morphogenesis  BMP signaling pathway  epithelial cell differentiation  inner ear morphogenesis  transcription regulatory region DNA binding  positive regulation of transcription, DNA-templated  anatomical structure formation involved in morphogenesis  positive regulation of epithelial cell proliferation  palate development  olfactory pit development  face morphogenesis  cellular response to BMP stimulus  HMG box domain binding  positive regulation of canonical Wnt signaling pathway  interneuron axon guidance  positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus  
Ontology : EGO-EBInuclear chromatin  RNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  skeletal system development  osteoblast differentiation  endochondral ossification  cytoplasm  transcription from RNA polymerase II promoter  nervous system development  cell proliferation  olfactory bulb interneuron differentiation  embryonic limb morphogenesis  BMP signaling pathway  epithelial cell differentiation  inner ear morphogenesis  transcription regulatory region DNA binding  positive regulation of transcription, DNA-templated  anatomical structure formation involved in morphogenesis  positive regulation of epithelial cell proliferation  palate development  olfactory pit development  face morphogenesis  cellular response to BMP stimulus  HMG box domain binding  positive regulation of canonical Wnt signaling pathway  interneuron axon guidance  positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus  
NDEx NetworkDLX5
Atlas of Cancer Signalling NetworkDLX5
Wikipedia pathwaysDLX5
Orthology - Evolution
OrthoDB1749
GeneTree (enSembl)ENSG00000105880
Phylogenetic Trees/Animal Genes : TreeFamDLX5
HOVERGENP56178
HOGENOMP56178
Homologs : HomoloGeneDLX5
Homology/Alignments : Family Browser (UCSC)DLX5
Gene fusions - Rearrangements
Tumor Fusion PortalDLX5
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerDLX5 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)DLX5
dbVarDLX5
ClinVarDLX5
1000_GenomesDLX5 
Exome Variant ServerDLX5
ExAC (Exome Aggregation Consortium)ENSG00000105880
GNOMAD BrowserENSG00000105880
Genetic variants : HAPMAP1749
Genomic Variants (DGV)DLX5 [DGVbeta]
DECIPHERDLX5 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisDLX5 
Mutations
ICGC Data PortalDLX5 
TCGA Data PortalDLX5 
Broad Tumor PortalDLX5
OASIS PortalDLX5 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICDLX5  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDDLX5
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch DLX5
DgiDB (Drug Gene Interaction Database)DLX5
DoCM (Curated mutations)DLX5 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)DLX5 (select a term)
intoGenDLX5
NCG5 (London)DLX5
Cancer3DDLX5(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM220600    600028   
Orphanet2261    10993   
DisGeNETDLX5
MedgenDLX5
Genetic Testing Registry DLX5
NextProtP56178 [Medical]
TSGene1749
GENETestsDLX5
Target ValidationDLX5
Huge Navigator DLX5 [HugePedia]
snp3D : Map Gene to Disease1749
BioCentury BCIQDLX5
ClinGenDLX5 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1749
Chemical/Pharm GKB GenePA27373
Clinical trialDLX5
Miscellaneous
canSAR (ICR)DLX5 (select the gene name)
Probes
Litterature
PubMed46 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineDLX5
EVEXDLX5
GoPubMedDLX5
iHOPDLX5
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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