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Title: Dlx5  
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Subject: DLX gene family, MSX1, Transcription factors, NeuroD, EMX homeogene
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Distal-less homeobox 5

PDB rendering based on 2djn.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; SHFM1D
External IDs GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Homeobox protein DLX-5 is a protein that in humans is encoded by the distal-less homeobox 5 gene, or DLX5 gene.[1][2]


This gene encodes a member of a homeobox transcription factor gene family similar to the Drosophila distal-less (Dll) gene. The encoded protein may play a role in bone development and fracture healing. Current research holds that the homeobox gene family is important in appendage development. DLX5 and DLX6 can be seen to work in conjunction and are both necessary for proper craniofacial, axial, and appendicular skeleton development. 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.[2]

DLX5 also acts as the early BMP-responsive transcriptional activator needed for osteoblast differentiation by stimulating the up-regulation of a variety of promoters (ALPL promoter, SP7 promoter, MYC promoter).[3]

Clinical significance

Mutations in the DLX5 gene have been shown to be involved in the hand and foot malformation syndrome.[4] SHFM is a heterogenous limb defect in which the development of the central digital rays is hindered, leading to missing central digits and claw-like distal extremities. Other defects associated with DLX5 include sensorineural hearing loss, mental retardation, ectodermal and craniofacial findings, and orofacial clefting.

In mice, the targeted disruption of DLX1, DLX2, DLX1/2, or DLX5 orthologs yields craniofacial, bone, and vestibular defects. If DLX5 is disrupted in conjunction with DLX6, bone, inner ear, and severe craniofacial defects are prevalent. Research utilizing Dlx5/6-nulls suggests that these genes have both unique and redundant functions.[5]

Developmental Stage

DLX5 begins to express DLX5 protein in the facial and branchial arch mesenchyme, otic vesicles, and frontonasal ectoderm at around day 8.5-9. By day 12.5, DLX5 protein begins to be expressed in the brain, bones, and all remaining skeletal structures. Expression in the brain and skeleton begins to decrease by day 17.[3]


DLX5 has been shown to interact with DLX1,[5] DLX2,[6] DLX6,[5] MSX1[6] and MSX2.[6]


  1. ^ Simeone A, Acampora D, Pannese M, D'Esposito M, Stornaiuolo A, Gulisano M, Mallamaci A, Kastury K, Druck T, Huebner K, et al. (Apr 1994). "Cloning and characterization of two members of the vertebrate Dlx gene family". Proc Natl Acad Sci U S A 91 (6): 2250–4.  
  2. ^ a b "Entrez Gene: DLX5 distal-less homeobox 5". 
  3. ^ a b "Homeobox protein DLX-5". 
  4. ^ Shamseldin HE, Faden MA, Alashram W, Alkuraya FS (November 2011). "Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation". J Med Genet 49 (1): 16–20.  
  5. ^ a b c Robledo RF, Rajan L, Li X, Lufkin T (2002). "The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development". Genes Dev. 16 (9): 1089–101.  
  6. ^ a b c Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C (May 1997). "Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism". Mol. Cell. Biol. 17 (5): 2920–32.  

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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