DLX5 distal-less homeobox 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DLX5provided by HGNC
Official Full Name: distal-less homeobox 5provided by HGNC
Primary source: HGNC:HGNC:2918
See related: Ensembl:ENSG00000105880 MIM:600028
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: SHFM1D
Summary: This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. The encoded protein may play a role in bone development and fracture healing. Mutation in this gene, which is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7, may be associated with split-hand/split-foot malformation. [provided by RefSeq, Jul 2008]
Expression: Biased expression in endometrium (RPKM 4.3), placenta (RPKM 4.0) and 9 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 7q21.3

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	7	NC_000007.14 (97020390..97024831, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (96649702..96654143, complement)

Chromosome 7 - NC_000007.14 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 Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Our results in mice suggest that long-range DLX5 enhancer elements located in the human SLC25A13 gene may underlie the sensorineural hearing loss that is sometimes associated with SHFM1.
Title: Deletion of a Long-Range <i>Dlx5</i> Enhancer Disrupts Inner Ear Development in Mice.
These results indicate activation of DLX5 and RUNX2 via its distal promoter represents a unique feature of GFs, and is important for ECM regulation. Down-regulation of these transcription factors in PAFs could be associated with their property to degrade collagen, which may impact on the process of periodontitis.
Title: Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.
these findings indicate that, in MSCs, DLX5 is a master regulator of osteogenesis. Furthermore, tanshinone IIA may be valuable for stem cell-based therapies of certain bone diseases.
Title: Distal-less homeobox 5 is a master regulator of the osteogenesis of human mesenchymal stem cells.
As a result of disturbed imprinting, the upregulated DLX5 affects trophoblast proliferation in preeclampsia.
Title: Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker.
These data indicate that certain missense mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and they likely destabilize the formation of functional complexes.
Title: Dlx5 Homeodomain:DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome.
In cells grown on titanium support, DLX5 and RUNX1 were respectively upregulated (+3.12-fold) and downregulated (-2.14-fold)
Title: Expression of SP7, RUNX1, DLX5, and CTNNB1 in human mesenchymal stem cells cultured on xenogeneic bone substitute as compared with machined titanium.
Absent expression of the osteoblast-specific maternally imprinted genes, DLX5 and DLX6, causes split hand/split foot malformation type I.
Title: Absent expression of the osteoblast-specific maternally imprinted genes, DLX5 and DLX6, causes split hand/split foot malformation type I.
Heterozygous DLX5 nonsense mutation c.G115T(p.E39X) associated with isolated split-hand/foot malformation with reduced penetrance and variable expressivity in two unrelated Polish families.
Title: Heterozygous DLX5 nonsense mutation associated with isolated split-hand/foot malformation with reduced penetrance and variable expressivity in two unrelated families.
A novel heterozygous mutation in exon 3 of DLX5 found in the family members with SHFM1 phenotype.
Title: Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation.
Genome sequencing of the deletion breakpoints showed that the DLX5 and DLX6 genes are disomic but the putative DYNC1I1 exon 15 and 17 enhancers are deleted.
Title: Next generation sequencing of chromosomal rearrangements in patients with split-hand/split-foot malformation provides evidence for DYNC1I1 exonic enhancers of DLX5/6 expression in humans.

Submit: New GeneRIF Correction See all GeneRIFs (32)

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
Split-hand/foot malformation 1 with sensorineural hearing loss MedGen: C1857344 OMIM: 220600 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated (2012-05-14) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated (2012-05-14) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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MECP2 and Associated Rett Syndrome, organism-specific biosystem (from WikiPathways)
MECP2 and Associated Rett Syndrome, organism-specific biosystemMecp2 is in many mammals an important regulator of neuronal function and development. It affects all cell types, especially neurons but also astrocytes, oligodendrocytes, and glial cells. Mecp2 plays...
Neural Crest Differentiation, organism-specific biosystem (from WikiPathways)
Neural Crest Differentiation, organism-specific biosystemGene regulatory network model of cranial neural crest cell (CNCC) development, adaped from PMID: 19575671. Most interactions in the model are proposed to regulate transcription of core factors involv...
Signaling pathways regulating pluripotency of stem cells, organism-specific biosystem (from KEGG)
Signaling pathways regulating pluripotency of stem cells, organism-specific biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
Signaling pathways regulating pluripotency of stem cells, conserved biosystem (from KEGG)
Signaling pathways regulating pluripotency of stem cells, conserved biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Dlx5 (e-PCR), detects polymorphism
- UniSTS:498467

RH69322 (e-PCR)
- UniSTS:8489

Dlx5 (e-PCR), detects polymorphism
- UniSTS:471089

DLX5_2316 (e-PCR)
- UniSTS:280646

D7S527 (e-PCR), detects polymorphism
- UniSTS:28778

MARC_9717-9718:996688547:1 (e-PCR)
- UniSTS:269979

DLX6 (e-PCR)
- UniSTS:44196

Dlx5 (e-PCR), detects polymorphism
- UniSTS:506853

Homology

Homologs of the DLX5 gene: The DLX5 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 238 organisms have orthologs with human gene DLX5
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA-binding transcription activator activity, RNA polymerase II-specific	ISS Inferred from Sequence or Structural Similarity more info
DNA-binding transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	ISM Inferred from Sequence Model more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
HMG box domain binding	IEA Inferred from Electronic Annotation more info
RNA polymerase II proximal promoter sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
RNA polymerase II proximal promoter sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transcription regulatory region DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
BMP signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
anatomical structure formation involved in morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
anatomical structure formation involved in morphogenesis	IEA Inferred from Electronic Annotation more info
cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell proliferation	IDA Inferred from Direct Assay more info	PubMed
cellular response to BMP stimulus	ISS Inferred from Sequence or Structural Similarity more info
embryonic limb morphogenesis	IEA Inferred from Electronic Annotation more info
endochondral ossification	ISS Inferred from Sequence or Structural Similarity more info
epithelial cell differentiation	IEA Inferred from Electronic Annotation more info
face morphogenesis	IEA Inferred from Electronic Annotation more info
inner ear morphogenesis	IEA Inferred from Electronic Annotation more info
interneuron axon guidance	IEA Inferred from Electronic Annotation more info
nervous system development	TAS Traceable Author Statement more info	PubMed
olfactory bulb interneuron differentiation	IEA Inferred from Electronic Annotation more info
olfactory pit development	IEA Inferred from Electronic Annotation more info
osteoblast differentiation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
roof of mouth development	IEA Inferred from Electronic Annotation more info
skeletal system development	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
nuclear chromatin	ISS Inferred from Sequence or Structural Similarity more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: homeobox protein DLX-5

Names: distal-less homeo box 5; split hand/foot malformation type 1 with sensorineural hearing loss

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_009220.1 RefSeqGene

Range

5001..9436

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005221.6 → NP_005212.1 homeobox protein DLX-5

See identical proteins and their annotated locations for NP_005212.1

Status: REVIEWED

Source sequence(s)

BC006226, DB280023

Consensus CDS

CCDS5647.1

UniProtKB/Swiss-Prot

P56178

UniProtKB/TrEMBL

Q53Y73

Related

ENSP00000222598.4, ENST00000222598.5

Conserved Domains (2) summary

pfam00046
Location:140 → 193

Homeobox; Homeobox domain

pfam12413
Location:32 → 118

DLL_N; Homeobox protein distal-less-like N terminal

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000007.14 Reference GRCh38.p12 Primary Assembly

Range

97020390..97024831 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005250185.3 → XP_005250242.1 homeobox protein DLX-5 isoform X1

Conserved Domains (1) summary

pfam00046
Location:12 → 65

Homeobox; Homeobox domain
XM_017011803.1 → XP_016867292.1 homeobox protein DLX-5 isoform X1

Conserved Domains (1) summary

pfam00046
Location:12 → 65

Homeobox; Homeobox domain