DLX4 (distal-less homeobox 4)

Gene

• Entrez ID: 1748
• Gene name: Distal-less homeobox 4
• Gene symbol: DLX4
• Synonyms (NCBI Gene): BP1, DLX7, DLX8, DLX9, OFC15
• Chromosome: 17
• Chromosome location: 17q21.33
• Summary: Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx gene family contain a homeobox that is related to that of Distal-less (Dll), a gene expressed

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs869025279	G>-,GG	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT039137	hsa-miR-769-3p	CLASH	23622248
MIRT573291	hsa-miR-6819-3p	PAR-CLIP	20371350
MIRT573290	hsa-miR-6877-3p	PAR-CLIP	20371350
MIRT573289	hsa-miR-95-5p	PAR-CLIP	20371350
MIRT573288	hsa-miR-2114-3p	PAR-CLIP	20371350
MIRT573286	hsa-miR-6823-3p	PAR-CLIP	20371350
MIRT573287	hsa-miR-183-3p	PAR-CLIP	20371350
MIRT573285	hsa-miR-4452	PAR-CLIP	20371350
MIRT439166	hsa-let-7c-5p	3'LIFE	25074381
MIRT439166	hsa-let-7c-5p	3'LIFE	25074381
MIRT573291	hsa-miR-6819-3p	PAR-CLIP	20371350
MIRT573290	hsa-miR-6877-3p	PAR-CLIP	20371350
MIRT573289	hsa-miR-95-5p	PAR-CLIP	20371350
MIRT573288	hsa-miR-2114-3p	PAR-CLIP	20371350
MIRT573286	hsa-miR-6823-3p	PAR-CLIP	20371350
MIRT573287	hsa-miR-183-3p	PAR-CLIP	20371350
MIRT573285	hsa-miR-4452	PAR-CLIP	20371350
MIRT939000	hsa-miR-1178	CLIP-seq
MIRT939001	hsa-miR-185	CLIP-seq
MIRT939002	hsa-miR-3140-3p	CLIP-seq
MIRT939003	hsa-miR-3150b-3p	CLIP-seq
MIRT939004	hsa-miR-3185	CLIP-seq
MIRT939005	hsa-miR-323-5p	CLIP-seq
MIRT939006	hsa-miR-4270	CLIP-seq
MIRT939007	hsa-miR-4306	CLIP-seq
MIRT939008	hsa-miR-4436b-5p	CLIP-seq
MIRT939009	hsa-miR-4441	CLIP-seq
MIRT939010	hsa-miR-4447	CLIP-seq
MIRT939011	hsa-miR-4472	CLIP-seq
MIRT939012	hsa-miR-4481	CLIP-seq
MIRT939013	hsa-miR-4644	CLIP-seq
MIRT939014	hsa-miR-4745-5p	CLIP-seq
MIRT939015	hsa-miR-4784	CLIP-seq
MIRT939016	hsa-miR-876-3p	CLIP-seq
MIRT939017	hsa-miR-1275	CLIP-seq
MIRT939004	hsa-miR-3185	CLIP-seq
MIRT939018	hsa-miR-3688-5p	CLIP-seq
MIRT939010	hsa-miR-4447	CLIP-seq
MIRT939011	hsa-miR-4472	CLIP-seq
MIRT939012	hsa-miR-4481	CLIP-seq
MIRT939019	hsa-miR-4525	CLIP-seq
MIRT939020	hsa-miR-4665-5p	CLIP-seq
MIRT939021	hsa-miR-4723-5p	CLIP-seq
MIRT939014	hsa-miR-4745-5p	CLIP-seq
MIRT939022	hsa-miR-625	CLIP-seq
MIRT1977814	hsa-miR-3675-5p	CLIP-seq
MIRT1977815	hsa-miR-661	CLIP-seq
MIRT2213127	hsa-miR-1286	CLIP-seq
MIRT2213128	hsa-miR-1343	CLIP-seq
MIRT2213129	hsa-miR-3144-5p	CLIP-seq
MIRT2213130	hsa-miR-3191	CLIP-seq
MIRT2213131	hsa-miR-378g	CLIP-seq
MIRT2213132	hsa-miR-4314	CLIP-seq
MIRT2213133	hsa-miR-4476	CLIP-seq
MIRT2213134	hsa-miR-4652-5p	CLIP-seq
MIRT2213135	hsa-miR-4667-5p	CLIP-seq
MIRT2213136	hsa-miR-4700-5p	CLIP-seq
MIRT2213137	hsa-miR-4722-5p	CLIP-seq
MIRT2213138	hsa-miR-508-5p	CLIP-seq
MIRT2213139	hsa-miR-637	CLIP-seq
MIRT2213140	hsa-miR-766	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	11909945
GO:0000785	Component	Chromatin	ISA
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	IDA	11909945
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:0001227	Function	DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA	11909945
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	NAS	11069021
GO:0003700	Function	DNA-binding transcription factor activity	TAS	8975708
GO:0005515	Function	Protein binding	IPI	17474147, 21297662
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	NAS	11069021
GO:0005654	Component	Nucleoplasm	IDA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	NAS	11069021
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0030154	Process	Cell differentiation	IBA
GO:0043565	Function	Sequence-specific DNA binding	IDA	9073066
GO:0048706	Process	Embryonic skeletal system development	IBA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 601911
• HGNC: 2917
• e!Ensembl: ENSG00000108813

Protein

• UniProt ID: Q92988
• Protein name: Homeobox protein DLX-4 (Beta protein 1) (Homeobox protein DLX-7) (Homeobox protein DLX-8)
• Protein function: May play a role in determining the production of hemoglobin S. May act as a repressor. During embryonic development, plays a role in palatogenesis.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00046	Homeodomain	118 → 174	Homeodomain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in leukemia cells and placenta. Also expressed in kidney and fetal liver. {ECO:0000269|PubMed:11069021, ECO:0000269|PubMed:11909945}.
• Sequence:

  MTSLPCPLPGRDASKAVFPDLAPVPSVAAAYPLGLSPTTAASPNLSYSRPYGHLLSYPYT
  EPANPGDSYLSCQQPAALSQPLCGPAEHPQELEADSEKPRLSPEPSERRPQAPAKKLRKP
  RTIYSSLQLQHLNQRFQHTQYLALPERAQLAAQLGLTQTQVKIWFQNKRSKYKKLLKQNS
  GGQEGDFPGRTFSVSPCSPPLPSLWDLPKAGTLPTSGYGNSFGAWYQHHSSDVLASPQMM
  

• Sequence length: 240

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)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CLEFT PALATE WITH CLEFT LIP	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DLX4-related disorder	Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Orofacial cleft 15	Uncertain significance; Benign; Likely benign	ClinVar CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Amyloidosis	Amyloidosis	BEFREE	17003054		★☆☆☆☆ Found in Text Mining only
Anemia Sickle Cell	Sickle cell anemia	Pubtator	11909945, 1346253	Associate	★☆☆☆☆ Found in Text Mining only
Angelman Syndrome	Angelman syndrome	Pubtator	32327713	Associate	★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	24021960		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	24021960		★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	BEFREE	17015815		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	24821083	Associate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	21359847	Associate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	24821083	Stimulate	★☆☆☆☆ Found in Text Mining only
beta Thalassemia	Beta thalassemia	Pubtator	15327529	Associate	★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	BEFREE	11572994, 15762851, 17230047, 28360522, 28628769, 8917544		★☆☆☆☆ Found in Text Mining only
Bipolar I disorder	Bipolar Disorder	BEFREE	24522887		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	12820413, 17854498, 17999690, 18992636, 19119308, 23222298, 24947980, 25823567, 26524685, 27449292, 29575937, 30131852		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	12817998, 17854498, 18992636, 20877436, 23091415, 24947980	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	19119308	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	15161049	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Ductal Breast	Ductal carcinoma of breast	Pubtator	17854498	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	33048956	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	31739630, 35983409	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	26067154		★☆☆☆☆ Found in Text Mining only
Cardiovascular Abnormalities	Cardiovascular abnormalities	Pubtator	32327713	Associate	★☆☆☆☆ Found in Text Mining only
Choriocarcinoma	Choriocarcinoma	BEFREE	9481790		★☆☆☆☆ Found in Text Mining only
Cleft Lip with or without Cleft Palate	Cleft Lip With Or Without Cleft Palate	BEFREE	29738288		★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	32327713	Associate	★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	25823567		★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital euryblepharon	Congenital Euryblepharon	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dental Caries	Dental caries	Pubtator	34311721	Associate	★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	17230047, 28628769		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	21359847, 33931204	Associate	★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	BEFREE	28574650, 9502204		★☆☆☆☆ Found in Text Mining only
Eating Disorders	Eating Disorders	BEFREE	28241886		★☆☆☆☆ Found in Text Mining only
Endometrial Carcinoma	Endometrial carcinoma	BEFREE	31100338		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	26824476, 37156729	Associate	★☆☆☆☆ Found in Text Mining only
Familial Alzheimer Disease (FAD)	Alzheimer disease	BEFREE	9751187		★☆☆☆☆ Found in Text Mining only
Gestational Trophoblastic Disease	Gestational trophoblastic disease	Pubtator	39632297	Associate	★☆☆☆☆ Found in Text Mining only
Hemoglobin C Disease	Hemoglobin c disease	Pubtator	15551156	Associate	★☆☆☆☆ Found in Text Mining only
Hereditary Breast and Ovarian Cancer Syndrome	Hereditary breast and ovarian cancer syndrome	Pubtator	20877436, 23222298	Associate	★☆☆☆☆ Found in Text Mining only
Hydrocephalus	Hydrocephalus	Pubtator	30342661	Associate	★☆☆☆☆ Found in Text Mining only
Hyperlipidemia, Familial Combined	Hyperlipidemia	BEFREE	2004437		★☆☆☆☆ Found in Text Mining only
Hyperlipoproteinemia Type IIb	Hyperlipoproteinemia	BEFREE	2004437		★☆☆☆☆ Found in Text Mining only
Hypoplasia of the maxilla	Hypoplasia of the maxilla	HPO_DG			★☆☆☆☆ Found in Text Mining only
Inflammatory Breast Carcinoma	Breast Cancer	BEFREE	30131852		★☆☆☆☆ Found in Text Mining only
Language Development Disorders	Language development disorders	Pubtator	21359847	Associate	★☆☆☆☆ Found in Text Mining only
Learning Disabilities	Learning disorders	Pubtator	36807331	Associate	★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	11069021		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	23091415, 26753961, 9096378	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	26753961	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	26325005, 26753961		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	25823567		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	LHGDN	18420035		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	18992636, 24947980	Associate	★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 1	Major Affective Disorder	BEFREE	15762851		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 2	Major Affective Disorder	BEFREE	15762851		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 4	Major Affective Disorder	BEFREE	15762851		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 6	Major Affective Disorder	BEFREE	15762851		★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	17230047, 28241886		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	17854498, 17999690, 18992636, 19119308, 23222298, 24947980, 25823567, 26524685, 27449292, 29575937, 30131852		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of endometrium	Endometrial Cancer	BEFREE	31100338		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	26067154		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	29575937, 31100338		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	25823567		★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	12820413, 15830137, 24947980, 27449292		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	17999690		★☆☆☆☆ Found in Text Mining only
Manic	Manic Disorder	BEFREE	10743849, 17064428, 30274650		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	17230047, 28628769		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	30342661	Associate	★☆☆☆☆ Found in Text Mining only
Mood Disorders	Mood Disorder	BEFREE	26995248		★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	26485746		★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	26086097		★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	32281175	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	12820413, 17999690, 18992636, 23222298, 24947980, 25823567, 27449292		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental disorder	Pubtator	32327713	Associate	★☆☆☆☆ Found in Text Mining only
Oestrogen receptor positive breast cancer	Oestrogen Receptor Positive Breast Cancer	BEFREE	27449292		★☆☆☆☆ Found in Text Mining only
OROFACIAL CLEFT 15	Orofacial Cleft	GENOMICS_ENGLAND_DG	25954033		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
OROFACIAL CLEFT 15	Orofacial Cleft	CLINVAR_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
OROFACIAL CLEFT 15	Orofacial Cleft	CTD_human_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Oropharyngeal Dysphagia	Oropharyngeal Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	26067154		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	21297662, 23091415	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Intraepithelial Neoplasia	Prostatic intraepithelial neoplasia	Pubtator	18931648	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	LHGDN	18931648		★☆☆☆☆ Found in Text Mining only
Recurrent otitis media	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Schizoaffective Disorder	Schizoaffective Disorder	BEFREE	12802785		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	Pubtator	26824476, 36807331	Associate	★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	21359847	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	22143938		★☆☆☆☆ Found in Text Mining only
Thyroid Cancer Papillary	Papillary thyroid cancer	Pubtator	36609218	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Carcinoma Anaplastic	Thyroid cancer	Pubtator	36609218	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	36609218	Associate	★☆☆☆☆ Found in Text Mining only
Tricho-dento-osseous syndrome (disorder)	Trichodentoosseous syndrome	BEFREE	10466415, 9467018		★☆☆☆☆ Found in Text Mining only
Unipolar Depression	Mental Depression	BEFREE	28241886		★☆☆☆☆ Found in Text Mining only
Velopharyngeal Insufficiency	Velopharyngeal Insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only