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Symbol LHX2 contributors: mct/npt/pgu - updated : 30-03-2018
HGNC name LIM homeobox 2
HGNC id 6594
Location 9q33.3      Physical location : 126.773.888 - 126.795.442
Synonym name LIM HOX gene 2
Synonym symbol(s) LH2, MGC138390
TYPE functioning gene
STRUCTURE 21.55 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status confirmed
Map cen - ASS1 - LHX2 - ABL1 - qter
Authors Wu (96)
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 2416 - 406 - 1999 10593900
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel   moderately
Digestiveintestinesmall intestine  moderately
Nervousbraindiencephalonhypothalamus highly Homo sapiens
 nerve   highly
Visualeyeanterior segmentconjunctiva   Homo sapiens
 eyeanterior segmentcornea   Homo sapiens
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
SystemCellPubmedSpeciesStageRna symbol
Nervousepithelial cell Homo sapiens
cell lineage
cell lines
physiological period embryo, fetal
Text nervous system, Rathke pouch, extensively expressed in the developing ventral diencephalon, including the infundibulum and the posterior lobe of the pituitary
  • two cysteine-rich (LIM) Zn2+ binding domains
  • an helix-turn-helix homeobox DNA-binding domain
  • C-terminal LIM domain that with the homeodomain were required for its growth-suppressive activity
    interspecies ortholog to rattus Lhx2 (99pc)
    ortholog to murine Lhx2 (99pc)
    CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • acting as a tissue specific transcriptional activator of the alpha subunit of glycoprotein hormones
  • involved in the control of cell differentiation in developing lymphoid and neural cell types
  • acting as a classic selector gene and essential intrinsic determinant of cortical identity
  • required for optic vesicle patterning and lens formation in part by regulating BMP signaling in an autocrine manner in the optic neuroepithelium and in a paracrine manner in the lens ectoderm
  • regulates a regional-fate decision by telencephalic progenitors during a critical period that ends as they differentiate from neuroepithelial cells to neuronogenic radial glia
  • essential role in the regulation of posterior pituitary development
  • unique role in the hippocampus during the phase of active neurogenesis
  • key regulator of the neuron-astrocyte cell fate switch in the developing hippocampus but it is an unexpected spatial selectivity within the telencephalon for this critical function
  • is able to suppress baseline activation as well as NFIA-induced activation of the GFAP promoter
  • LHX2 and LHX9 determine neuronal differentiation and compartition in the caudal forebrain by regulating Wnt signaling
  • regulates the development of the forebrain hem system
  • plays a critical role in human neural differentiation
  • LHX2 regulates the transcription of downstream intrinsic and extrinsic molecules that are essential for early neural differentiation
  • is a key regulator of retinal progenitor cells (RPCs) properties that contribute to the ordered production of multiple cell types during retinal tissue formation
  • essential roles for LHX2 in glial wedge (GW), hippocampal commissure, and corpus callosum formation, suggesting that defects in radial GW progenitors can give rise to agenesis of the corpus callosum (ACC)
  • LHX2 is a key intrinsic regulator of tanycyte differentiation, sustaining RAX-dependent activation of tanycyte-specific genes while also inhibiting expression of ependymal cell-specific genes
  • critical roles for LHX2 that acts as one of the terminal selector genes in controlling principal properties of neurons
  • regulates the cortex size by maintaining the cortical progenitor proliferation and delaying the initiation of neurogenesis
  • is required for maintenance of the corneal epithelial cell compartment and the limbal barrier
  • LHX2 not only directly regulates expression of NOTCH signaling pathway components, but also acts together with the gliogenic NOTCH pathway to drive Müller glia (MG) specification and differentiation
  • neuroretinal expression of LHX2 and neuroretina-derived FGF factors are crucial for lens fiber development
  • function for LHX2 in regulating dorsoventral patterning in the telencephalon
  • is capable of blocking proliferation of T-ALL-derived cells by both LMO2-dependent and -independent means
  • is a fundamental, temporally dynamic, always necessary, and often sufficient factor in a range of critical developmental phenomena
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development , nervous system
    text Rathke
    a component
    DNA binding
    small molecule metal binding,
  • Zn2+
  • protein
  • CBP/p300 interactive transactivator
  • SSBP3 inhibits LHX2 and LDB1 turnover, stimulates assembly of this DNA-binding complex, promotes its recruitment to the CGA promoter, and enhances CGA transcription
  • LHX2 binds to a conserved motif in the ROBO3 gene, suggesting that LHX2/LHX9 regulate directly the expression of ROBO3
  • interacting with PAX6 (LHX2 and PAX6 transcription factors operate in a concerted manner during retinal development to promote transcriptional activation of the SIX6 homeobox-gene in primitive and mature retinal progenitors)
  • able to suppress NFIA-induced astrogliogenesis robustly
  • highly specific point of interaction of LHX2 with the NOTCH pathway in suppressing the astrogliogenic effects of the NOTCH target NFIA
  • influences axon guidance and the topographical sorting of axons by regulating the expression of ROBO1 and ROBO2 guidance receptors, which are essential for these axons to establish correct connections in the cerebral cortex
  • histone modification and E2F1 binding are integral parts of the mechanism for LHX2 gene expression
  • LMO3 is a putative direct transcriptional target of GBX2 (GBX2 regulates the LIM transcriptional codes comprising LHX2, LHX9 and LMO3, which subsequently control the differential expression of ROBO1 and ROBO2 in the thalamus
  • regulates neural differentiation at two levels: first, it promotes expression of PAX6 by binding to its active enhancers, and second, it attenuates BMP and WNT signaling by promoting expression of the BMP and WNT antagonist CER1, to inhibit non-neural differentiation
  • LHX2 is required for the expression of transcription factor PAX6, axon guidance molecule EFNA5, and the receptor NMDAR1
  • LHX2 promotes tumor growth and metastasis by inducing autocrine and paracrine PDGFB signaling
  • is required for CTNNB1 function in maintaining cortical progenitor proliferation and controls the timing of cortical neurogenesis
  • confers neuronal competency for activity-dependent dendritic development in L4 neurons by inducing the expression of BTBD3
  • LHX2 binds a highly conserved putative enhancer of DMRTA2, suggesting an evolutionarily conserved regulatory relationship between these factors
  • overexpression of PAX6 can substitute for LHX2 in the regulation of the neuronal versus glial cell fate in the developing hippocampus
  • control of LHX2 function by LDB1 and RLIM underpins the coordinated differentiation of neurons and Müller glia in postnatal retina
  • cell & other
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation --low  
    maybe inactivated by the BCR-ABL translocation in chronic myelogenous leukemia
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • deletion of Lhx2 with Emx1-cre at embryonic day 10.5 (E10.5) altered the fates of progenitors, causing them to generate three-layer cortex, phenocopying olfactory cortex rather than lateral neocortex
  • Lhx2cKO mice produced reduced body hair and spontaneous epithelial defects in the cornea that included neovascularization, perforation with formation of scar tissue and opacification