DLX5 (distal-less homeobox 5)

Gene

• Entrez ID: 1749
• Gene name: Distal-less homeobox 5
• Gene symbol: DLX5
• Synonyms (NCBI Gene): SHFM1, SHFM1D
• Chromosome: 7
• Chromosome location: 7q21.3
• 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs387906737	T>G	Pathogenic	Missense variant, coding sequence variant
rs398122527	C>A	Pathogenic	Missense variant, coding sequence variant
rs587777842	C>A	Pathogenic	Coding sequence variant, upstream transcript variant, genic upstream transcript variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000320	hsa-miR-141-3p	Luciferase reporter assay	19454767
MIRT000204	hsa-miR-200a-3p	Luciferase reporter assay	19454767
MIRT006041	hsa-miR-203a-3p	Immunoblot, In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	21159887
MIRT006041	hsa-miR-203a-3p	Immunoblot, In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	21159887
MIRT006041	hsa-miR-203a-3p	Immunoblot, In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	21159887
MIRT018111	hsa-miR-335-5p	Microarray	18185580
MIRT038077	hsa-miR-423-5p	CLASH	23622248
MIRT006041	hsa-miR-203a-3p	Luciferase reporter assay, qRT-PCR, Western blot	28025541
MIRT756262	hsa-miR-135a-5p	Luciferase reporter assay, Western blotting, qRT-PCR	38760791

Transcription factors

Transcription factor	Regulation	Reference
MECP2	Unknown	19195802
POU5F1	Repression	17068183

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IEA
GO:0000785	Component	Chromatin	ISA
GO:0000785	Component	Chromatin	ISS
GO:0000976	Function	Transcription cis-regulatory region binding	IDA	19497851
GO:0000976	Function	Transcription cis-regulatory region binding	IEA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	ISS
GO:0001501	Process	Skeletal system development	TAS	7907794
GO:0001503	Process	Ossification	IEA
GO:0001649	Process	Osteoblast differentiation	IEA
GO:0001649	Process	Osteoblast differentiation	ISS
GO:0001958	Process	Endochondral ossification	IEA
GO:0001958	Process	Endochondral ossification	ISS
GO:0003677	Function	DNA binding	IEA
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0007399	Process	Nervous system development	TAS	7907794
GO:0007409	Process	Axonogenesis	IEA
GO:0007411	Process	Axon guidance	IEA
GO:0008283	Process	Cell population proliferation	IDA	19497851
GO:0010628	Process	Positive regulation of gene expression	IEA
GO:0021889	Process	Olfactory bulb interneuron differentiation	IEA
GO:0030154	Process	Cell differentiation	IBA
GO:0030326	Process	Embryonic limb morphogenesis	IEA
GO:0030509	Process	BMP signaling pathway	IEA
GO:0030509	Process	BMP signaling pathway	ISS
GO:0030855	Process	Epithelial cell differentiation	IEA
GO:0042472	Process	Inner ear morphogenesis	IEA
GO:0043583	Process	Ear development	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IDA	19497851
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0048646	Process	Anatomical structure formation involved in morphogenesis	IEA
GO:0048706	Process	Embryonic skeletal system development	IBA
GO:0050679	Process	Positive regulation of epithelial cell proliferation	IEA
GO:0060021	Process	Roof of mouth development	IEA
GO:0060166	Process	Olfactory pit development	IEA
GO:0060322	Process	Head development	IEA
GO:0060325	Process	Face morphogenesis	IEA
GO:0060349	Process	Bone morphogenesis	IEA
GO:0071837	Function	HMG box domain binding	IEA
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	IEA
GO:0097376	Process	Interneuron axon guidance	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 600028
• HGNC: 2918
• e!Ensembl: ENSG00000105880

Protein

• UniProt ID: P56178
• Protein name: Homeobox protein DLX-5
• Protein function: Transcriptional factor involved in bone development. Acts as an immediate early BMP-responsive transcriptional activator essential for osteoblast differentiation. Stimulates ALPL promoter activity in a RUNX2-independent manner during osteoblast
• PDB: 2DJN, 4RDU
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF12413	DLL_N	32 → 118	Homeobox protein distal-less-like N terminal	Family
  PF00046	Homeodomain	138 → 194	Homeodomain	Domain

• Sequence:

  MTGVFDRRVPSIRSGDFQAPFQTSAAMHHPSQESPTLPESSATDSDYYSPTGGAPHGYCS
  PTSASYGKALNPYQYQYHGVNGSAGSYPAKAYADYSYASSYHQYGGAYNRVPSATNQPEK
  EVTEPEVRMVNGKPKKVRKPRTIYSSFQLAALQRRFQKTQYLALPERAELAASLGLTQTQ
  VKIWFQNKRSKIKKIMKNGEMPPEHSPSSSDPMACNSPQSPAVWEPQGSSRSLSHHPHAH
  PPTSNQSPASSYLENSASWYTSAASSINSHLPPPGSLQHPLALASGTLY

• Sequence length: 289

Pathways

KEGG:

Signaling pathways regulating pluripotency of stem cells

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
DLX5-related disorder	Likely pathogenic	rs2485521415, rs2485516681	RCV003402777 RCV003901803	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Split hand-foot malformation 1	Pathogenic; Likely pathogenic	rs587777842, rs2485520889, rs398122527	RCV000144533 RCV003228726 RCV000144532	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Split hand-foot malformation 1 with sensorineural hearing loss	Pathogenic	rs387906737	RCV000022921	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BONE DISEASES, DEVELOPMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL CLEFT HAND	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL MALFORMATION SYNDROMES PREDOMINANTLY INVOLVING LIMBS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRANIOFACIAL ABNORMALITIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ECTRODACTYLY	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTROESOPHAGEAL REFLUX DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KLIPPEL-TRENAUNAY-WEBER SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, HIP	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RUBINSTEIN-TAYBI SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPLIT HAND FOOT DEFORMITY 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPLIT HAND-FOOT MALFORMATION	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPLIT HAND-SPLIT FOOT-DEAFNESS SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPLIT-HAND-FOOT MALFORMATION WITH SENSORINEURAL HEARING LOSS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPLIT-HAND/FOOT MALFORMATION 1	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPLIT-HAND/FOOT MALFORMATION 1 WITH SENSORINEURAL HEARING LOSS, AUTOSOMAL RECESSIVE	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VATER ASSOCIATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	26830138		★☆☆☆☆ Found in Text Mining only
Aniridia	Aniridia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	19195802		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	17562589, 19195802		★☆☆☆☆ Found in Text Mining only
Bone Diseases, Developmental	Bone Disease	CTD_human_DG	10433909		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	21108812		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	26829219, 28747748	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	18413826, 26829219, 30901718		★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	21045156		★☆☆☆☆ Found in Text Mining only
Choroid Plexus Papilloma	Choroid Plexus Papilloma	BEFREE	29692624		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	24485021	Associate	★☆☆☆☆ Found in Text Mining only
Congenital chromosomal disease	Congenital Chromosomal Disease	BEFREE	26839112, 27821526		★☆☆☆☆ Found in Text Mining only
Congenital Foot Deformity	Congenital deformity of foot	BEFREE	17230488, 17898012, 22121204, 23169702, 26829219, 8733122		★☆☆☆☆ Found in Text Mining only
Craniosynostosis	Craniosynostosis	BEFREE	22547067		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	24635637		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	26829219, 27622494	Associate	★☆☆☆☆ Found in Text Mining only
Ectrodactyly	Ectrodactyly	BEFREE	12112878, 22342398, 25196357		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ectrodactyly	Ectrodactyly	ORPHANET_DG	24496061		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ectrodactyly	Ectrodactyly	Pubtator	24496061, 25231166, 26829219, 27291887	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Endometriosis	Endometriosis	BEFREE	29692624		★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	40244296	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	27863244, 32513296	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	27863244	Associate	★☆☆☆☆ Found in Text Mining only
Glomerulosclerosis (disorder)	Glomerulosclerosis	BEFREE	31297803		★☆☆☆☆ Found in Text Mining only
Hypertrophy	Hypertrophy	Pubtator	32650430	Associate	★☆☆☆☆ Found in Text Mining only
Hypodontia	Hypodontia	BEFREE	31420900		★☆☆☆☆ Found in Text Mining only
Infantile Spasm	Infantile Spasms	BEFREE	19439424		★☆☆☆☆ Found in Text Mining only
Isolated split hand-split foot malformation	Isolated Split Hand-Split Foot Malformation	Orphanet			★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	LHGDN	18413826		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	BEFREE	19497851, 26829219		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	Pubtator	26829219	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	21108812		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	18413826, 19497851, 26829219, 30901718		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	21045156		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	18413826, 21045156		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	18316591, 18413826, 19497851, 21045156, 28122332		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural Tube Defect	BEFREE	30889190		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	26786290	Associate	★☆☆☆☆ Found in Text Mining only
Oligodactyly	Oligodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	32650430	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoporosis	Osteoporosis	BEFREE	26829219		★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	Pubtator	26829219	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Failure, Premature	Ovarian Failure	BEFREE	21505076		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	21045156		★☆☆☆☆ Found in Text Mining only
Periodontitis	Periodontitis	BEFREE	27645561		★☆☆☆☆ Found in Text Mining only
Periodontitis	Periodontitis	Pubtator	27645561	Associate	★☆☆☆☆ Found in Text Mining only
Premature Menopause	Premature Menopause	BEFREE	21505076		★☆☆☆☆ Found in Text Mining only
RAPP-HODGKIN SYNDROME	RAPP-HODGKIN SYNDROME	BEFREE	22342398		★☆☆☆☆ Found in Text Mining only
Renal fibrosis	Renal fibrosis	BEFREE	31297803		★☆☆☆☆ Found in Text Mining only
Rett Syndrome	Rett Syndrome	BEFREE	15608638, 15954098, 17363207, 17562589, 17701895, 26829219		★☆☆☆☆ Found in Text Mining only
Rett Syndrome	Rett Syndrome	LHGDN	15954098		★☆☆☆☆ Found in Text Mining only
Rett Syndrome	Rett syndrome	Pubtator	26829219	Associate	★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	BEFREE	17898012		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Split foot	Split Hand Foot Deformity	BEFREE	17230488, 17898012, 23169702		★☆☆☆☆ Found in Text Mining only
Split foot	Split Hand Foot Deformity	HPO_DG			★☆☆☆☆ Found in Text Mining only
Split hand foot deformity 1	Split hand foot deformity	BEFREE	12112878, 19401716, 22342398, 23169702, 25196357, 26839112		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Split hand foot deformity 1	Split hand foot deformity	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Split hand-split foot-deafness syndrome	Split Hand-Split Foot-Deafness Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Split-Hand-Foot Malformation With Sensorineural Hearing Loss	Split-Hand-Foot Malformation With Sensorineural Hearing Loss	GENOMICS_ENGLAND_DG	22121204, 27085093		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Split-Hand-Foot Malformation With Sensorineural Hearing Loss	Split-Hand-Foot Malformation With Sensorineural Hearing Loss	UNIPROT_DG	22121204		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Split-Hand-Foot Malformation With Sensorineural Hearing Loss	Split-Hand-Foot Malformation With Sensorineural Hearing Loss	ORPHANET_DG	22121204		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Split-Hand-Foot Malformation With Sensorineural Hearing Loss	Split-Hand-Foot Malformation With Sensorineural Hearing Loss	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Split-Hand-Foot Malformation With Sensorineural Hearing Loss	Split-Hand-Foot Malformation With Sensorineural Hearing Loss	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Syndactyly of fingers	Syndactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
T-Cell Lymphoma	T-Cell Lymphoma	BEFREE	18316591, 21045156, 28122332		★☆☆☆☆ Found in Text Mining only
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	BEFREE	19707792		★☆☆☆☆ Found in Text Mining only
Uranostaphyloschisis	Uranostaphyloschisis	BEFREE	19934017, 24699068		★☆☆☆☆ Found in Text Mining only
Uremia	Uremia	BEFREE	31297803		★☆☆☆☆ Found in Text Mining only
West Syndrome	West Syndrome	BEFREE	19439424		★☆☆☆☆ Found in Text Mining only