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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LHX6
LIM homeobox 6
Chromosome 9 · 9q33.2
NCBI Gene: 26468Ensembl: ENSG00000106852.16HGNC: HGNC:21735UniProt: Q9UPM6
41PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sequence-specific double-stranded DNA bindingprotein bindingnucleusRNA polymerase II transcription regulatory region sequence-specific DNA bindingAlzheimer diseaseneurodegenerative diseaselysosomal storage diseasemultiple sclerosis
✦AI Summary

LHX6 is a LIM homeodomain transcription factor serving as a master regulator of GABAergic interneuron development and specification 1. In the telencephalon, LHX6 acts as a cell fate mediator essential for cortical interneuron specification and migration of GABAergic precursors from the subpallium to the cerebral cortex 1. Beyond neural development, LHX6 functions in craniofacial morphogenesis by negatively regulating the cell cycle inhibitor p57Kip2 to promote palatal cell proliferation 2. LHX6 is regulated by developmental signaling pathways including sonic hedgehog, fibroblast growth factors, and Wnt/β-catenin 1. In the hypothalamus, LHX6 shows divergent functions from telencephalic contexts: it is necessary for neuronal survival and specification of GABAergic subsets through interaction with Dlx1/2, Nkx2-2, and Nkx2-1, but these neurons lack long-distance migration and express distinct neuropeptide profiles 3. Mechanistically, LHX6 regulates mitochondrial homeostasis via PINK1/Parkin-mediated mitophagy and MAPK signaling in palatal mesenchymal cells 4. Clinically, LHX6 functions as a tumor suppressor: its epigenetic downregulation through promoter hypermethylation promotes pancreatic and cervical cancer progression by deregulating tumor-suppressive genes and enhancing proliferative signaling 56. Conversely, LHX6+ interneuron lineages represent cells of origin for FOXR2-driven CNS neuroblastoma 7.

Sources cited
1
LHX6 functions as a transcription factor and cell fate mediator in neurogenesis and is regulated by sonic hedgehog, FGF, and Wnt/β-catenin signaling
PMID: 26148970
2
LHX6 is necessary for hypothalamic GABAergic neuron survival and specification through interaction with Dlx1/2, Nkx2-2, and Nkx2-1
PMID: 33479483
3
LHX6 and LHX8 promote palate development by negatively regulating p57Kip2 through direct and indirect mechanisms involving FOX transcription factors
PMID: 26071365
4
LHX6 regulates mitochondrial homeostasis in palatal mesenchymal cells via PINK1/Parkin-mediated mitophagy and MAPK signaling pathway
PMID: 39438838
5
LHX6 is epigenetically silenced through promoter hypermethylation in pancreatic cancer, and re-expression inhibits proliferation by upregulating tumor-suppressive genes
PMID: 32248980
6
LHX6 isoforms containing exon 12 promote cervical cancer proliferation via MAPK signaling pathway activation
PMID: 35384355
7
LHX6+/DLX+ interneuron lineages from the medial ganglionic eminence are cells of origin for FOXR2-driven CNS neuroblastoma
PMID: 39495206
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.28Weak
lysosomal storage diseaseOpen Targets
0.28Weak
multiple sclerosisOpen Targets
0.28Weak
neurodegenerative diseaseOpen Targets
0.28Weak
Parkinson diseaseOpen Targets
0.28Weak
lung cancerOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.08Suggestive
cervical cancerOpen Targets
0.08Suggestive
lung adenocarcinomaOpen Targets
0.07Suggestive
Generalized epilepsy with febrile seizures-plusOpen Targets
0.07Suggestive
autosomal dominant epilepsy with auditory featuresOpen Targets
0.07Suggestive
generalised epilepsyOpen Targets
0.06Suggestive
juvenile myoclonic epilepsyOpen Targets
0.06Suggestive
temporal lobe epilepsyOpen Targets
0.06Suggestive
genetic developmental and epileptic encephalopathyOpen Targets
0.05Suggestive
developmental and epileptic encephalopathy, 9Open Targets
0.05Suggestive
schizophreniaOpen Targets
0.05Suggestive
benign familial infantile epilepsyOpen Targets
0.05Suggestive
Febrile seizure (within the age range of 3 months to 6 years)Open Targets
0.05Suggestive
undetermined early-onset epileptic encephalopathyOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PDE1CProtein interaction89%RAB2AProtein interaction83%NPYProtein interaction83%LDB1Protein interaction80%SSBP2Protein interaction80%SSBP3Protein interaction80%
Tissue Expression6 tissues
Heart
100%
Brain
45%
Lung
39%
Ovary
33%
Liver
5%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
LHX6PDE1CRAB2ANPYLDB1SSBP2SSBP3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9UPM6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.59Moderately Constrained
pLIⓘ
0.68Intermediate
Observed/Expected LoF0.37 [0.24–0.59]
RankingsWhere LHX6 stands among ~20K protein-coding genes
  • #10,029of 20,598
    Most Researched41
  • #4,036of 17,882
    Most Constrained (LOEUF)0.59 · top quartile
Genes detectedLHX6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Lhx6 and Lhx8: cell fate regulators and beyond.
PMID: 26148970
FASEB J · 2015
1.00
2
PMID: 39637134
0.90
3
Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons.
PMID: 33479483
Commun Biol · 2021
0.80
4
Downregulation of tumor-suppressor gene LHX6 in cancer: a systematic review.
PMID: 29533904
Rom J Intern Med · 2018
0.70
5
Lhx6 deficiency causes human embryonic palatal mesenchymal cell mitophagy dysfunction in cleft palate.
PMID: 39438838
Mol Med · 2024
0.60