Affinage

LHX4

LIM/homeobox protein Lhx4 · UniProt Q969G2

Length
390 aa
Mass
43.1 kDa
Annotated
2026-04-28
52 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LHX4 is a LIM-homeodomain transcription factor that controls cell fate specification, survival, and proliferation in the developing pituitary, retina, and spinal cord. It directly binds and transactivates pituitary gene promoters (POU1F1, CGA, GH, TSHβ) through its homeodomain, while its two non-redundant LIM domains mediate protein–protein interactions with partners including LHX3, Isl1, Isl2, and NLI to form multiprotein complexes that activate tissue-specific enhancers (PMID:18073311, PMID:27820671, PMID:38970652). In the pituitary, LHX4 lies downstream of hypothalamic SHH signaling, promotes progenitor survival partly by suppressing p21/Cdkn1a, and is required for anterior pituitary hormone production; in the retina it acts upstream of Bhlhe23/Lhx3/Fezf2 to specify bipolar cell fates; and in pinealocytes it is induced by adrenergic–cAMP signaling to regulate Aanat expression and melatonin synthesis (PMID:28807898, PMID:25668206, PMID:32937137, PMID:31609018). Heterozygous loss-of-function mutations in LHX4 cause combined pituitary hormone deficiency through haploinsufficiency without dominant-negative effects (PMID:11567216, PMID:18445675).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 High

    The foundational question—where is LHX4 expressed and what happens without it—was answered by showing that Lhx4 is expressed in the developing neural tube and that its knockout is perinatally lethal with defective motor neuron development and lung maturation.

    Evidence Targeted gene knockout in mouse with in situ hybridization

    PMID:7913017

    Open questions at the time
    • Pituitary phenotype not yet examined
    • Molecular targets of LHX4 unknown
    • Mechanism of lethality not fully dissected
  2. 2001 High

    The question of whether LHX4 mutations cause human disease was resolved by identifying a splice-site mutation segregating with combined pituitary hormone deficiency across three generations, establishing LHX4 haploinsufficiency as pathogenic.

    Evidence Sanger sequencing with RT-PCR splice analysis and family segregation in a multi-generational pedigree

    PMID:11567216

    Open questions at the time
    • Precise mechanism of pituitary failure at the cellular level unknown
    • Direct transcriptional targets in pituitary not identified
  3. 2002 High

    Whether LHX4 loss impairs pituitary progenitor proliferation or survival was answered: Lhx4-null mice show increased apoptosis rather than proliferation defects in pituitary progenitors, and epistasis with Prop1 revealed overlapping functions in anterior pituitary specification.

    Evidence Mouse double-mutant genetic analysis with TUNEL assays and marker immunostaining

    PMID:12183375

    Open questions at the time
    • Direct downstream targets mediating survival not identified
    • Relative contributions of LHX4 vs LHX3 not resolved
  4. 2005 High

    How LHX4 activates pituitary gene expression was mechanistically resolved: LHX4 directly binds a POU1F1 upstream element and activates its promoter, while disease-associated mutants fail to bind DNA without exerting dominant-negative effects, confirming haploinsufficiency.

    Evidence EMSA and luciferase reporter assays in transfected cells; cotransfection dominant-negative exclusion

    PMID:15998782 PMID:18073311 PMID:18445675

    Open questions at the time
    • Genome-wide binding sites not mapped
    • In vivo ChIP confirmation limited to CGA promoter
  5. 2007 High

    Whether LHX4 engages protein partners beyond DNA binding was addressed by demonstrating physical interaction with SSX via the LIM domains and endogenous occupancy of the CGA promoter by ChIP, adding a protein–protein interaction axis to its transcriptional mechanism.

    Evidence Yeast two-hybrid, co-immunoprecipitation, colocalization, and ChIP in mammalian cells

    PMID:17667940

    Open questions at the time
    • Physiological relevance of SSX interaction outside synovial sarcoma unclear
    • Full repertoire of LIM-domain partners not catalogued
  6. 2014 High

    Whether LHX4 acts in spinal neuron fate determination was established in zebrafish: combined Lhx3/Lhx4 loss causes motoneurons to adopt interneuron-like fates and abolishes V2a/V2b interneuron formation.

    Evidence Morpholino double knockdown in zebrafish with immunostaining and molecular fate analysis

    PMID:25231761

    Open questions at the time
    • Individual contribution of Lhx4 versus Lhx3 in V2 fate not separated
    • Mammalian V2 interneuron role not confirmed at this stage
  7. 2015 High

    The cell-cycle mechanism through which LHX4 promotes pituitary progenitor expansion was identified: LHX4 suppresses p21/Cdkn1a expression and maintains cyclin D1 levels in the pituitary primordium.

    Evidence Lhx4 mutant mouse analysis with immunostaining for cell-cycle markers and αT3-1 cell culture assays

    PMID:25668206

    Open questions at the time
    • Whether LHX4 directly binds p21 regulatory regions not determined
    • Contribution of cell-cycle vs survival defects to hypoplasia not fully separated
  8. 2017 High

    What signals lie upstream of LHX4 in pituitary development was resolved: hypothalamic SHH signaling is required for LHX4 expression in Rathke's pouch progenitors, placing LHX4 downstream of Hedgehog pathway activation.

    Evidence Conditional Shh and Ptch1 deletion in mouse with in situ hybridization for Lhx4

    PMID:28807898

    Open questions at the time
    • Whether SHH acts directly on Lhx4 transcription or through intermediary factors unknown
    • Enhancer elements receiving SHH input not identified
  9. 2017 High

    The question of whether the two LIM domains are functionally equivalent was answered: LIM1 and LIM2 have non-redundant roles in transactivation, and LHX4 physically interacts with LHX3 via co-immunoprecipitation.

    Evidence Systematic LIM-domain mutagenesis with reporter assays and co-immunoprecipitation

    PMID:27820671

    Open questions at the time
    • Structural basis for LIM domain non-redundancy not resolved
    • Whether LHX3–LHX4 heterodimer functions as a unit on chromatin not tested
  10. 2019 High

    An entirely new functional context for LHX4 was established: in pinealocytes, LHX4 is induced by adrenergic–cAMP signaling and is required for Aanat expression, linking it to melatonin synthesis.

    Evidence Pharmacological/surgical manipulation in rat, siRNA knockdown in cultured pinealocytes, RNAseq

    PMID:31609018

    Open questions at the time
    • Whether LHX4 directly binds the Aanat promoter not shown
    • In vivo circadian melatonin phenotype of Lhx4 loss not examined
  11. 2020 High

    LHX4's role in retinal cell fate was mechanistically dissected: it is required for rod bipolar and selective cone bipolar cell specification, acts upstream of Bhlhe23/Lhx3/Fezf2, and its loss causes bipolar-to-amacrine cell fate conversion.

    Evidence Retina-specific conditional knockout in mouse with immunostaining, ERG, and Bhlhe23 rescue experiments

    PMID:32937137

    Open questions at the time
    • Direct genomic targets in retinal progenitors not mapped
    • Mechanism of selective cone BC subtype sensitivity unclear
  12. 2024 High

    LHX4's specificity for V2a interneuron differentiation over motor neuron production was resolved: Lhx4 forms complexes with Isl1/Isl2/NLI and preferentially activates a V2-specific enhancer more efficiently than Lhx3, with conditional knockout selectively impairing V2a but not motor neuron fate.

    Evidence Co-immunoprecipitation, V2-enhancer reporter assay, chicken electroporation, and conditional mouse knockout

    PMID:38970652

    Open questions at the time
    • How Lhx4–Isl complexes achieve V2a versus MN enhancer selectivity at the structural level is unknown
    • Genome-wide enhancer targets of the Lhx4/Isl/NLI complex not mapped
  13. 2024 High

    LHX4's conserved requirement for anterior pituitary hormone production and reproductive competence was confirmed in zebrafish genetic knockouts, demonstrating reduced gh/tshb/pomca/fshb and female-specific infertility.

    Evidence CRISPR knockout in zebrafish with RT-qPCR, in situ hybridization, and reproductive phenotyping

    PMID:39000439

    Open questions at the time
    • Why female but not male fertility is affected is mechanistically unexplained
    • Whether LHX4 directly regulates gonadotropin gene promoters in fish not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: genome-wide direct binding targets of LHX4 across its multiple tissue contexts, the structural basis for functional non-redundancy of the two LIM domains, and the mechanisms by which SHH signaling transcriptionally induces LHX4 in pituitary progenitors.
  • No ChIP-seq or CUT&RUN data available for LHX4 in any tissue
  • No full-length LHX4 crystal or cryo-EM structure
  • Enhancer elements driving tissue-specific LHX4 expression are uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 2
Partners
CTNNB1ISL1ISL2LHX3NLISSX2TCF4

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Mouse Lhx4 (Gsh-4) encodes a LIM-type homeodomain transcription factor expressed transiently in ventrolateral regions of the developing neural tube and hindbrain; homozygous knockout mice die postnatally due to immature lungs and defective respiratory control, establishing its essential role in motor neuron development and lung maturation. Targeted gene knockout in mice, whole-mount and serial section in situ hybridization The EMBO journal High 7913017
2001 A germline intronic splice-site mutation in LHX4 abolishes normal splicing and activates two exonic cryptic splice sites, predicting two proteins deleted in their homeodomain sequence; haploinsufficiency of LHX4 causes dominant, fully penetrant pituitary and hindbrain developmental defects in humans. Sanger sequencing, RT-PCR splice-site analysis, family segregation analysis American journal of human genetics High 11567216
2002 Lhx4 is required for cell survival and expansion of anterior pituitary progenitors; Lhx4 null mutants exhibit increased cell death (not proliferation defect) and a temporal shift in Lhx3 activation; Lhx4 and Prop1 have overlapping functions in early pituitary development, with double mutants showing complete failure of anterior pituitary cell differentiation. Mouse genetic analysis, TUNEL assay for cell death, immunostaining for Lhx3, double-mutant epistasis Development (Cambridge, England) High 12183375
2002 The human LHX4 gene encodes a 390-amino-acid protein with two tandem LIM domains and one homeodomain; LHX4 protein activates the alpha-glycoprotein subunit (CGA) promoter reporter, establishing it as a transcriptional activator. cDNA cloning, reporter gene (luciferase) transfection assay Oncogene Medium 12118377
2004 LHX3 and LHX4 are both expressed in the developing human pituitary and along the rostro-caudal spinal cord (ventral regions giving rise to motoneurons and interneurons); LHX4 expression is transient (stronger caudally at 6 weeks), whereas LHX3 is expressed at all stages examined. In situ hybridization on human embryonic tissue sections Gene expression patterns : GEP Medium 15567726
2005 LHX4 binds to a human-specific element in the POU1F1 upstream regulatory sequence and activates transcription from the proximal POU1F1 promoter; mutant LHX4 isoforms (from the splice-site mutation) fail to bind and activate this sequence but do not exert dominant-negative effects over wild-type LHX4, consistent with haploinsufficiency. Transfection/reporter assay in CHO cells, EMSA (electrophoretic mobility shift assay) The Journal of clinical endocrinology and metabolism High 15998782
2007 Three missense mutations in LHX4 (R84C between LIM domains; L190R and A210P in the homeodomain) impair transcriptional activity; L190R and A210P are completely inactive in EMSA and pituitary gene (CGA, POU1F1) promoter assays, establishing that LIM and homeodomain integrity are required for LHX4 DNA binding and transactivation. EMSA, luciferase reporter transfection assays, structural modeling The Journal of clinical endocrinology and metabolism High 18073311
2007 Endogenous LHX4 protein interacts with the SSX C-terminal repression domain; this interaction was demonstrated by yeast two-hybrid screening, colocalization, and co-immunoprecipitation in mammalian cells; endogenous LHX4 binds the CGA promoter by chromatin immunoprecipitation and LHX4-mediated CGA activation is enhanced by SS18-SSX but not SSX alone. Yeast two-hybrid, co-immunoprecipitation, colocalization (immunofluorescence), chromatin immunoprecipitation (ChIP), reporter assay Oncogene High 17667940
2008 The LHX4 frameshift mutation p.Thr99fs causes complete loss of transcriptional activity on the POU1F1 promoter and loss of DNA binding; cotransfection of mutant and wild-type LHX4 shows no dominant-negative effect, indicating haploinsufficiency; LHX4 can also transactivate prolactin and GH promoters. Luciferase reporter transfection assay, EMSA, cotransfection dominant-negative test The Journal of clinical endocrinology and metabolism High 18445675
2009 LHX4-Isl2 LIM domain complex was engineered, purified, and crystallized, diffracting to 2.16 Å resolution, providing structural information on the LIM domain interactions. Protein engineering, purification, crystallization, X-ray diffraction Acta crystallographica. Section F Medium 19194008
2009 A novel LHX4 missense mutation V101A abolishes the ability to activate POU1F1 and FSHbeta subunit gene promoters in transfection assays without dominant-negative effects, confirming loss-of-function as the pathogenic mechanism. Luciferase reporter transfection assay, cotransfection Experimental and clinical endocrinology & diabetes Medium 19856252
2012 In vitro studies of two novel LHX4 mutations (c.249-1G>A splice mutation and p.V75I missense) showed impairment of transactivation of POU1F1 and αGSU target gene promoters without dominant-negative effects, confirming haploinsufficiency. Luciferase reporter transfection assay PloS one Medium 23029363
2014 In zebrafish, Lhx3 and Lhx4 are co-expressed in post-mitotic axial motoneurons and interneurons; loss of both Lhx3 and Lhx4 causes primary motoneurons to adopt a hybrid fate with features of Kolmer-Agduhr' interneurons, and causes failure of V2a and V2b interneuron formation, establishing their roles in suppressing alternative pMN-derived interneuron fates. Morpholino knockdown in zebrafish, immunostaining, in situ hybridization, genetic epistasis Development (Cambridge, England) High 25231761
2014 LHX4 promotes cancer cell proliferation in colorectal cancer by facilitating TCF4 binding to β-catenin, forming a stable LHX4/TCF4/β-catenin complex that transactivates Wnt/β-catenin downstream target genes; LHX4 mutations disrupting the β-catenin interaction partially prevent its oncogenic function. Co-immunoprecipitation, luciferase reporter assay, cell proliferation assay, site-directed mutagenesis Tumour biology Medium 25034524
2015 In Lhx4 mutant mice, pituitary hypoplasia is mechanistically linked to reduced cyclin D1 expression and expanded p21 (Cdkn1a) expression dorsally in the pituitary primordium; LHX4 is shown to have direct and indirect effects on p21 expression in αT3-1 pituitary cells, establishing a role in cell cycle regulation during pituitary development. Mouse genetic analysis, immunostaining, in situ hybridization, cell culture transfection assay Molecular endocrinology (Baltimore, Md.) High 25668206
2015 LHX4 truncation mutation W204X produces a protein unable to bind the αGSU promoter consensus sequence (by EMSA) or activate target promoters, without dominant-negative effect; this confirms loss-of-function/haploinsufficiency as the mechanism. Western blot, EMSA, luciferase reporter assay, cotransfection PloS one Medium 25955177
2017 Conditional deletion of Shh in the anterior hypothalamus abolishes Lhx3/Lhx4 expression in Rathke's pouch epithelium at E9.0 and leads to complete loss of pituitary tissue by E12.5; conversely, conditional deletion of Ptch1 in RP progenitors causes severe hyperplasia, establishing that hypothalamic SHH signaling is upstream of and necessary for LHX3/LHX4 expression and RP progenitor identity specification. Conditional Cre-loxP mouse genetics, in situ hybridization, immunostaining Development (Cambridge, England) High 28807898
2017 Coimmunoprecipitation studies identified LHX3 as a protein interaction partner of LHX4; functional studies showed that LIM1 and LIM2 domains of LHX4 are not redundant (LIM-defective recombinant proteins have distinct functional deficits in transactivation of POU1F1 and GH promoters); variants p.(Tyr131*), p.(Arg48Thrfs*104), p.Ala65Val, p.Thr163Pro, and p.Arg221Gln are unable to transactivate POU1F1 and GH promoters. Co-immunoprecipitation, luciferase reporter transfection assay, subcellular localization studies The Journal of clinical endocrinology and metabolism High 27820671
2019 In the rat pineal gland, Lhx4 expression is driven by adrenergic signaling via a cyclic AMP-dependent mechanism (demonstrated by isoprenaline injection, superior cervical ganglionectomy, and cAMP treatment of cultured pinealocytes); siRNA knockdown of Lhx4 by 95% reduces Aanat (arylalkylamine N-acetyltransferase) transcript levels, establishing Lhx4 as a regulator of melatonin synthesis gene expression in pinealocytes. In vivo pharmacological and surgical manipulation, siRNA knockdown, RNAseq transcriptomics, RNAscope in situ hybridization Journal of pineal research High 31609018
2019 Lhx4 expression is detected in the retina, spinal cord, pituitary gland, and hindbrain of tdTomato reporter knock-in mice, confirmed by endogenous reporter recapitulation; conditional exon 3 deletion via Cre recombination efficiently inactivates Lhx4 in a tissue-specific manner. Knock-in reporter mouse line generation, conditional knockout, immunostaining, tdTomato fluorescence Genesis (New York, N.Y. : 2000) Medium 31313880
2019 LHX4 missense variant p.R122W (in the LIM2 domain) is unable to activate POU1F1, GH1, and TSHB promoters in luciferase assays and does not alter wild-type LHX4 activity, indicating haploinsufficiency rather than dominant-negative mechanism. Luciferase reporter transfection assay, cotransfection Journal of advanced research Medium 32071780
2020 Retina-specific deletion of Lhx4 in mice causes absence of rod bipolar cells (RBCs) and loss of selective cone bipolar cell subtypes and AII amacrine cells, with apoptosis of BCs and cell fate switch to amacrine cells; Lhx4 positively regulates Lhx3 expression to drive type 2 BC fate; Lhx4 acts upstream of Bhlhe23, Prdm8, and Fezf2, and overexpression of Bhlhe23 partially rescues RBC development in the absence of Lhx4. Conditional mouse knockout, immunostaining, overexpression rescue experiments, ERG visual function assay Cell reports High 32937137
2021 In zebrafish, lhx4 knockdown inhibits differentiation of Parvalbumin+ amacrine cells and Rhodopsin+ rod photoreceptors, enhances vsx2 expression, and impairs light-stimulus responses without affecting OFF-BC and rod BC differentiation or apoptosis. Morpholino vivo-MO knockdown in zebrafish, in situ hybridization, immunostaining, behavioral light-stimulus assay Scientific reports Medium 33479361
2024 Lhx4 forms multiprotein complexes with Isl1 or Isl2 and the nuclear LIM interactor NLI in the spinal cord; Lhx4 stimulates a V2-specific enhancer more efficiently than Lhx3; overexpression in chicken embryo electroporation shows Lhx4 surpasses Lhx3 in promoting V2a interneuron differentiation; Lhx4 inactivation in mice selectively impairs V2a interneuron differentiation without affecting motor neuron production. Co-immunoprecipitation (complex formation), luciferase reporter assay (V2-enhancer), in ovo electroporation in chicken embryos, conditional mouse knockout, immunostaining Cellular and molecular life sciences : CMLS High 38970652
2024 In lhx4-knockout zebrafish, pituitary hormone transcripts (gh, tshb, pomca, fshb) are reduced and lhb-producing gonadotrophs are severely depleted; lhx4-KO females are infertile with undeveloped ovaries while males are reproductively competent, demonstrating LHX4's essential role in anterior pituitary hormone gene expression and reproductive endocrine function. CRISPR/genetic knockout in zebrafish, RT-qPCR, in situ hybridization, endocrine phenotyping International journal of molecular sciences High 39000439

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4. American journal of human genetics 179 11567216
2002 Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia. Development (Cambridge, England) 122 12183375
1994 Gsh-4 encodes a LIM-type homeodomain, is expressed in the developing central nervous system and is required for early postnatal survival. The EMBO journal 116 7913017
2007 Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies. The Journal of clinical endocrinology and metabolism 75 18073311
2008 A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism. The Journal of clinical endocrinology and metabolism 61 18445675
2010 Mutation and gene copy number analyses of six pituitary transcription factor genes in 71 patients with combined pituitary hormone deficiency: identification of a single patient with LHX4 deletion. The Journal of clinical endocrinology and metabolism 45 20534763
2005 Functional relationship between LHX4 and POU1F1 in light of the LHX4 mutation identified in patients with pituitary defects. The Journal of clinical endocrinology and metabolism 41 15998782
2017 Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors. Development (Cambridge, England) 40 28807898
2007 A novel missense mutation (P366T) of the LHX4 gene causes severe combined pituitary hormone deficiency with pituitary hypoplasia, ectopic posterior lobe and a poorly developed sella turcica. Endocrine journal 40 17527005
2004 Pathophysiology of syndromic combined pituitary hormone deficiency due to a LHX3 defect in light of LHX3 and LHX4 expression during early human development. Gene expression patterns : GEP 40 15567726
2002 A novel chromosomal translocation t(1;14)(q25;q32) in pre-B acute lymphoblastic leukemia involves the LIM homeodomain protein gene, Lhx4. Oncogene 37 12118377
2009 A coding SNP of LHX4 gene is associated with body weight and body length in bovine. Molecular biology reports 34 19283511
2007 Hormonal, pituitary magnetic resonance, LHX4 and HESX1 evaluation in patients with hypopituitarism and ectopic posterior pituitary lobe. Clinical endocrinology 34 17201807
2010 PROP1, HESX1, POU1F1, LHX3 and LHX4 mutation and deletion screening and GH1 P89L and IVS3+1/+2 mutation screening in a Dutch nationwide cohort of patients with combined pituitary hormone deficiency. Hormone research in paediatrics 32 20389107
2007 Molecular analysis of PROP1, PIT1, HESX1, LHX3, and LHX4 shows high frequency of PROP1 mutations in patients with familial forms of combined pituitary hormone deficiency. Arquivos brasileiros de endocrinologia e metabologia 32 18157385
2007 The C terminus of the synovial sarcoma-associated SSX proteins interacts with the LIM homeobox protein LHX4. Oncogene 26 17667940
2015 Novel Lethal Form of Congenital Hypopituitarism Associated With the First Recessive LHX4 Mutation. The Journal of clinical endocrinology and metabolism 24 25871839
2012 Panhypopituitarism presenting as life-threatening heart failure caused by an inherited microdeletion in 1q25 including LHX4. Pediatrics 23 22232309
2012 Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism. PloS one 23 23029363
1997 Lhx4, a LIM homeobox gene. Genomics 23 9286712
2013 Molecular and Clinical Findings in Patients with LHX4 and OTX2 Mutations. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology 22 23990694
2019 The Lhx4 homeobox transcript in the rat pineal gland: Adrenergic regulation and impact on transcripts encoding melatonin-synthesizing enzymes. Journal of pineal research 21 31609018
2017 Contribution of LHX4 Mutations to Pituitary Deficits in a Cohort of 417 Unrelated Patients. The Journal of clinical endocrinology and metabolism 21 27820671
2009 A novel mutation (V101A) of the LHX4 gene in a Japanese patient with combined pituitary hormone deficiency. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 20 19856252
2002 cDNA cloning, chromosomal localization and expression pattern analysis of human LIM-homeobox gene LHX4. Brain research 20 11844481
2014 Lhx3 and Lhx4 suppress Kolmer-Agduhr interneuron characteristics within zebrafish axial motoneurons. Development (Cambridge, England) 18 25231761
2015 Identifying the Deleterious Effect of Rare LHX4 Allelic Variants, a Challenging Issue. PloS one 15 25955177
2003 Aberrant expression of the LHX4 LIM-homeobox gene caused by t(1;14)(q25;q32) in chronic myelogenous leukemia in biphenotypic blast crisis. Genes, chromosomes & cancer 14 14506703
2020 LIM-Homeodomain Transcription Factor LHX4 Is Required for the Differentiation of Retinal Rod Bipolar Cells and OFF-Cone Bipolar Subtypes. Cell reports 13 32937137
2014 Linkage disequilibrium and haplotype distribution of the bovine LHX4 gene in relation to growth. Gene 13 24463020
2014 Oncogenicity of LHX4 in colorectal cancer through Wnt/β-catenin/TCF4 cascade. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 13 25034524
2019 A patient with combined pituitary hormone deficiency and osteogenesis imperfecta associated with mutations in LHX4 and COL1A2. Journal of advanced research 12 32071780
2009 LHX3 and LHX4 transcription factors in pituitary development and disease. Pediatric endocrinology reviews : PER 11 19337183
2016 LHX4 Gene Alterations: Patient Report and Review of the Literature. Pediatric endocrinology reviews : PER 10 27464418
2015 Lhx4 deficiency: increased cyclin-dependent kinase inhibitor expression and pituitary hypoplasia. Molecular endocrinology (Baltimore, Md.) 10 25668206
2002 Exclusion of the lim homeodomain gene LHX4 as a candidate gene for pituitary dwarfism in German shepherd dogs. Molecular and cellular endocrinology 10 12431796
2012 Unilateral agenesis of internal carotid artery associated with congenital combined pituitary hormone deficiency and pituitary stalk interruption without HESX1, LHX4 or OTX2 mutation: a case report. Pituitary 9 22797803
2021 LIM Homeobox 4 (lhx4) regulates retinal neural differentiation and visual function in zebrafish. Scientific reports 7 33479361
2023 Association of birth type and LHX4 gene polymorphism with reproductive hormones, growth hormone, and prolactin in Awassi ewes. Molecular biology reports 6 36787052
2019 Generation and characterization of Lhx4tdT reporter knock-in and Lhx4loxP conditional knockout mice. Genesis (New York, N.Y. : 2000) 6 31313880
2008 Expression and function of the LIM homeobox containing genes Lhx3 and Lhx4 in the mouse placenta. Developmental dynamics : an official publication of the American Association of Anatomists 6 18425848
2009 Crystallization and diffraction of an Lhx4-Isl2 complex. Acta crystallographica. Section F, Structural biology and crystallization communications 5 19194008
2024 Lhx4 surpasses its paralog Lhx3 in promoting the differentiation of spinal V2a interneurons. Cellular and molecular life sciences : CMLS 2 38970652
2023 Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes. Archives of endocrinology and metabolism 2 37948564
2022 A human paradigm of LHX4 and NR5A1 developmental gene interaction in the pituitary gland and ovary? European journal of human genetics : EJHG 2 35277652
2024 Combined Pituitary Hormone Deficiency in lhx4-Knockout Zebrafish. International journal of molecular sciences 1 39000439
2022 Hemiparesis With Hypoglycemia in a Child With Hypopituitarism Involving LHX4 Gene Deletion. Pediatrics 1 35165724
2021 Novel gross deletion at the LHX4 gene locus in a child with growth hormone deficiency. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 1 34971854
2025 A Pedigree With LHX4 and SOX3 Gene Variants Resulting in Gonadal Dysplasia. Clinical case reports 0 39991535
2025 A Novel Missense Variant in LHX4 in Three Children with Multiple Pituitary Hormone Deficiency Belonging to Two Unrelated Families and Contribution of Additional GLI2 and IGFR1 Variant. Children (Basel, Switzerland) 0 40150646
2025 Association of Silent Variant p.17Pro = SNP in the LHX4 Gene with Litter Size in Awassi Sheep. Biochemical genetics 0 40782137
2020 [Thyroid disruptor p, p'-DDE inhibited the expression of LHX4 and DIS3L protein in Nthy-ori-3-1 cells]. Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 0 32892578