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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DLX4
distal-less homeobox 4
Chromosome 17 · 17q21.33
NCBI Gene: 1748Ensembl: ENSG00000108813.12HGNC: HGNC:2917UniProt: Q92988
59PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription repressor activity, RNA polymerase II-specificprotein bindingsequence-specific DNA bindingorofacial cleft 15cleft lipcleft palatecleft lip/palate
✦AI Summary

DLX4 is a homeobox transcription factor located on chromosome 17-q22 that functions as a sequence-specific DNA-binding regulator of gene expression 1. Primary functions include controlling hematopoietic lineage commitment and developmental processes. DLX4 promotes megakaryocyte differentiation while suppressing erythroid development through IL-1β and NF-κB signaling activation 2. During embryonic development, DLX4 participates in palatogenesis and craniofacial development 3. DLX4 also enhances reprogramming of human dental pulp cells into induced pluripotent stem cells, functionally replacing c-MYC in combination with OCT3/4, SOX2, and KLF4 4. In normal physiology, DLX4 expression is cycle-dependent in the endometrium, with higher levels during the proliferative phase, suggesting roles in epithelial-mesenchymal cell interactions 5. Disease relevance includes associations with fetal growth restriction, where elevated placental DLX4 expression correlates with developmental abnormalities 6. In cancer, BP1 (a DLX4 isoform) overexpression in endometrial carcinoma promotes cell proliferation and migration while predicting poor prognosis 7. Nuclear DLX4 immunoreactivity is reduced in breast carcinomas compared to normal tissue 8. Non-syndromic orofacial clefts associate with DLX4 mutations, though population variants show limited independent association 3.

Sources cited
1
DLX4 promotes megakaryocyte differentiation and suppresses erythroid development via IL-1β and NF-κB signaling
PMID: 26208636
2
DLX4 promotes generation of induced pluripotent stem cells from dental pulp cells, replacing c-MYC function
PMID: 25471527
3
DLX4 expression is increased 3-fold in placentae with idiopathic fetal growth restriction
PMID: 17062780
4
DLX4 nuclear immunoreactivity is decreased in breast carcinomas compared to non-malignant tissue
PMID: 12820413
5
DLX4 shows cycle-dependent expression in endometrium with higher levels during proliferative phase
PMID: 9665637
6
BP1 isoform of DLX4 is overexpressed in endometrial cancer and promotes cell proliferation, migration, and poor prognosis
PMID: 31100338
7
DLX4 is a novel Distal-less family homeobox gene located on chromosome 17q21-q22, first identified from placental cDNA library
PMID: 9073066
8
DLX4 mutations cause syndromic cleft lip/palate; DLX4 polymorphisms show limited association with nonsyndromic orofacial clefts in Chinese Han population
PMID: 29738288
Disease Associationsⓘ21
orofacial cleft 15Open Targets
0.44Moderate
cleft lipOpen Targets
0.38Weak
cleft palateOpen Targets
0.37Weak
cleft lip/palateOpen Targets
0.37Weak
hair colorOpen Targets
0.33Weak
autoimmune disorder of musculoskeletal systemOpen Targets
0.26Weak
KeloidOpen Targets
0.24Weak
neoplasmOpen Targets
0.11Weak
nonpapillary renal cell carcinomaOpen Targets
0.09Suggestive
prostate carcinomaOpen Targets
0.08Suggestive
chronic myelogenous leukemiaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
MODYOpen Targets
0.08Suggestive
infectionOpen Targets
0.08Suggestive
parasitic infectionOpen Targets
0.07Suggestive
acute myeloid leukemiaOpen Targets
0.07Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.06Suggestive
hyperproinsulinemiaOpen Targets
0.06Suggestive
ovarian cancerOpen Targets
0.05Suggestive
Kaposi's sarcomaOpen Targets
0.05Suggestive
Non-syndromic orofacial cleft 15UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DLX6Shared pathway50%DLX2Shared pathway50%PPDPFLShared pathway50%ETV3LShared pathway50%ERFLShared pathway50%NKX1-2Shared pathway50%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
46%
Brain
31%
Ovary
5%
Liver
5%
Heart
0%
Gene Interaction Network
Click a node to explore
DLX4DLX6DLX2PPDPFLETV3LERFLNKX1-2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q92988
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.06LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.68 [0.45–1.06]
RankingsWhere DLX4 stands among ~20K protein-coding genes
  • #7,761of 20,598
    Most Researched59
  • #10,595of 17,882
    Most Constrained (LOEUF)1.06
Genes detectedDLX4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The homeobox gene DLX4 regulates erythro-megakaryocytic differentiation by stimulating IL-1β and NF-κB signaling.
PMID: 26208636
J Cell Sci · 2015
1.00
2
The homeobox gene DLX4 promotes generation of human induced pluripotent stem cells.
PMID: 25471527
Sci Rep · 2014
0.90
3
Homeobox gene DLX4 expression is increased in idiopathic human fetal growth restriction.
PMID: 17062780
Mol Hum Reprod · 2006
0.80
4
Expression and localization of homeodomain proteins DLX4/HB9 in normal and malignant human breast tissues.
PMID: 12820413
Anticancer Res · 2003
0.70
5
Homeobox genes DLX4 and HB24 are expressed in regions of epithelial-mesenchymal cell interaction in the adult human endometrium.
PMID: 9665637
Mol Hum Reprod · 1998
0.60