Affinage

SHOX

Short stature homeobox protein · UniProt O15266

Length
292 aa
Mass
32.2 kDa
Annotated
2026-06-10
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SHOX encodes a paired-related homeodomain transcription factor that governs chondrocyte differentiation and skeletal growth, residing in the pseudoautosomal region PAR1 where it escapes X-inactivation to give dosage-sensitive expression relevant to stature (PMID:9259282). The protein localizes exclusively to the nucleus via a non-classic basic AKCRK motif in the homeodomain recognition helix, and functions as a cell-type-specific transcriptional activator whose disease-associated mutations impair DNA binding, dimerization, nuclear entry, or a separable transactivation function (PMID:11751690, PMID:15173321, PMID:15931687). SHOX directly activates a chondrogenic target program, binding and transactivating the NPPB/BNP promoter, cooperating with SOX5/SOX6/SOX9 at the Agc1 (aggrecan) enhancer through a homeodomain–HMG-domain interaction, regulating FGFR3 and the extracellular-matrix gene Ctgf, and acting as a repressor of Nkx2.5 in sinoatrial node development — a role rescued by human SHOX in Shox2 knock-in mice (PMID:17881654, PMID:21262861, PMID:21273290, PMID:21454626, PMID:24887312). In hypertrophic growth-plate chondrocytes, where endogenous SHOX is concentrated, it drives cell-cycle arrest and an intrinsic apoptotic program proceeding through oxidative stress, lysosomal membrane rupture, cathepsin B release, and caspase activation (PMID:15145945, PMID:24186869). SHOX expression is itself tightly controlled by dual promoters with uAUG-mediated translational repression, alternative splicing coupled to NMD, downstream and upstream limb-specific enhancers requiring HOX binding sites, WRN-helicase resolution of locus G-quadruplexes, and retinoic acid levels set by the genetic modifier CYP26C1 (PMID:12960152, PMID:17200153, PMID:21448463, PMID:27861128, PMID:30250174, PMID:36114168). Loss of SHOX function causes Leri-Weill dyschondrosteosis and idiopathic short stature, as established by recurrent coding and non-coding deletions and functionally null mutations (PMID:11751690, PMID:17200153, PMID:30250174).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1997 Medium

    Established the identity and genomic context of SHOX, linking a homeodomain transcription factor in PAR1 that escapes X-inactivation to dosage-sensitive control of stature.

    Evidence Positional cloning, osteogenic expression analysis, and X-inactivation assay

    PMID:9259282

    Open questions at the time
    • No target genes or biochemical activity defined
    • Functional reconstitution absent
  2. 2001 High

    Showed SHOX is a nuclear, cell-type-restricted transcriptional activator and that Leri-Weill truncations abolish target activation, tying the protein's transactivation to disease.

    Evidence Luciferase reporter assays, immunofluorescence, and truncation mutant analysis across multiple cell lines

    PMID:11751690

    Open questions at the time
    • Direct target genes not yet identified
    • Basis of cell-type specificity unresolved
  3. 2003 High

    Defined translational and promoter-level control: a P2 promoter yields efficiently translated mRNA whereas P1 transcripts are repressed by upstream AUG codons.

    Evidence Reporter and in vitro translation assays with uAUG mutagenesis, validated in Xenopus embryos

    PMID:12960152

    Open questions at the time
    • Physiological trigger selecting promoter/translation usage unknown
  4. 2004 High

    Connected SHOX to growth-plate biology by showing it drives cell-cycle arrest and apoptosis in chondrocytes and is concentrated in hypertrophic chondrocytes.

    Evidence Stable transfection, flow cytometry, apoptosis assays, cell-cycle regulator Westerns, and growth-plate IHC, with disease-mutant comparison

    PMID:15145945

    Open questions at the time
    • Molecular pathway from SHOX to apoptosis not yet defined
    • Direct apoptotic target genes unknown
  5. 2004 High

    Mapped the nuclear localization signal to the AKCRK motif in the recognition helix and showed a disease mutation (R173C) blocks nuclear entry, explaining one mutational mechanism.

    Evidence Deletion mapping, NLS-reporter fusions, immunofluorescence, and rescue mutagenesis

    PMID:15173321

    Open questions at the time
    • Import receptor mediating non-classic NLS recognition unidentified
  6. 2005 High

    Systematically resolved how homeodomain mutations cause haploinsufficiency — via lost DNA binding, dimerization, or nuclear entry — and isolated a transactivation-specific defect (R153L).

    Evidence EMSA, co-immunoprecipitation, immunofluorescence, and reporter assays across nine patient mutations

    PMID:15931687

    Open questions at the time
    • Transactivation cofactors at R153L-affected step not identified
  7. 2006 Medium

    Placed Shox in limb patterning, showing its expression is bounded by FGF/BMP and retinoic acid signals and that overexpression lengthens skeletal elements.

    Evidence In situ hybridization, retroviral overexpression, and micromass culture in chicken

    PMID:16904661

    Open questions at the time
    • Direct transcriptional targets mediating elongation not defined
    • Mammalian relevance not addressed
  8. 2007 High

    Identified NPPB/BNP as a direct SHOX target, providing the first validated transcriptional target with growth-plate co-expression.

    Evidence Promoter-deletion luciferase assays, ChIP, disease-mutant comparison, and IHC

    PMID:17881654

    Open questions at the time
    • Role of BNP induction in chondrocyte fate not functionally tested
  9. 2007 High

    Demonstrated that downstream conserved non-coding elements act as limb enhancers and that their deletion phenocopies coding mutations, defining non-coding disease mechanisms.

    Evidence In ovo electroporation enhancer assays and mapping of patient deletions

    PMID:17200153

    Open questions at the time
    • Trans-factors binding the enhancers not identified
  10. 2009 Medium

    Extended the regulatory landscape upstream, showing tissue-specific upstream enhancers active in limb but not cornea.

    Evidence In ovo electroporation enhancer assays in two tissues

    PMID:19997128

    Open questions at the time
    • Endogenous contribution and bound factors undetermined
  11. 2011 High

    Revealed how SHOX is integrated into the chondrogenic network, physically partnering with SOX5/SOX6 and cooperating with SOX9 to activate the Agc1 enhancer.

    Evidence Yeast two-hybrid, reciprocal Co-IP, domain mapping, Agc1 reporter, IHC, and disease-mutant panel

    PMID:21262861

    Open questions at the time
    • Genome-wide co-occupancy with SOX factors not mapped
  12. 2011 High

    Established FGFR3 as a directly bound SHOX target, linking SHOX to a key growth-plate signaling receptor in mesomelic segments.

    Evidence Microarray, reporter assay, ChIP-seq, EMSA, and chicken micromass overexpression

    PMID:21273290

    Open questions at the time
    • Activation versus repression context dependence not fully resolved
  13. 2011 High

    Showed SHOX represses Nkx2.5 and is functionally interchangeable with Shox2 in sinoatrial node development, defining a repressor activity and conserved function outside the skeleton.

    Evidence Nkx2.5 reporter repression assay and SHOX/Shox2 knock-in mouse rescue

    PMID:21454626

    Open questions at the time
    • Whether native human SHOX functions in cardiac tissue physiologically untested
  14. 2011 Medium

    Added post-transcriptional control by alternative splicing coupled to NMD, including a tissue-specific exon 2a that triggers decay.

    Evidence RT-PCR, RNA-Seq, minigene/NMD reporter, and tissue profiling

    PMID:21448463

    Open questions at the time
    • Regulatory inputs controlling splice-choice not identified
  15. 2013 High

    Dissected the SHOX apoptotic pathway as oxidative stress → lysosomal rupture → cathepsin B release → mitochondrial permeabilization → caspase activation, with disease mutants failing at the first step.

    Evidence ROS, lysosomal integrity, cathepsin B, mitochondrial potential, and caspase assays with WT vs mutant SHOX in U2OS

    PMID:24186869

    Open questions at the time
    • SHOX transcriptional targets that initiate oxidative stress unknown
  16. 2014 Medium

    Identified Ctgf as a SHOX-regulated extracellular matrix gene in vivo, broadening the target repertoire to ECM organization.

    Evidence Col2a1-SHOX transgenic mouse with confirmation in human cells and chicken micromass

    PMID:24887312

    Open questions at the time
    • Direct versus indirect regulation of Ctgf not distinguished
  17. 2014 Medium

    Confirmed an evolutionarily conserved requirement for shox in skeletal calcification through loss-of-function in zebrafish.

    Evidence Morpholino knockdown with mRNA rescue and skeletal staining

    PMID:25483930

    Open questions at the time
    • Morpholino-only knockdown without genetic mutant
  18. 2016 High

    Defined CYP26C1 as a genetic modifier acting through retinoic acid, where reduced RA catabolism lowers SHOX expression and worsens skeletal phenotypes.

    Evidence Enzymatic assays, RA treatment of human chondrocytes, zebrafish single/double knockdown epistasis, and family co-segregation

    PMID:27861128

    Open questions at the time
    • Transcription factors transducing RA signal onto SHOX promoter unidentified
  19. 2018 High

    Localized a 563 bp downstream limb enhancer whose HOX binding sites are required and whose loss in PAR1 deletions causes LWD, refining the regulatory disease map.

    Evidence Transgenic mouse and cell reporter assays, HOX-site mutagenesis, and deletion mapping in patients

    PMID:30250174

    Open questions at the time
    • Specific HOX factors binding the core not identified
  20. 2020 Medium

    Showed 5'UTR variants reduce SHOX expression post-transcriptionally or via aberrant splicing, expanding mechanisms of haploinsufficiency.

    Evidence Luciferase reporter, mRNA quantification, and minigene splicing assays

    PMID:32647378

    Open questions at the time
    • Endogenous quantitative impact on stature not measured
  21. 2022 High

    Linked WRN helicase to SHOX transcription by resolving locus G-quadruplexes, with SHOX overexpression rescuing WRN-null skeletal defects, placing SHOX downstream of WRN in bone growth.

    Evidence In vitro G-quadruplex unwinding assay and zebrafish wrn-/-, shox-/- epistasis with genetic rescue

    PMID:36114168

    Open questions at the time
    • Whether WRN-SHOX axis operates in human growth plate not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SHOX selects between activator and repressor modes, and the full identity of its cofactor-dependent target program in human hypertrophic chondrocytes, remains unresolved.
  • No genome-wide SHOX occupancy map in human chondrocytes
  • Switch between transactivation and repression not mechanistically defined
  • Apoptosis-initiating target genes unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-5357801 Programmed Cell Death 2
Partners
SOX5SOX6SOX9

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 SHOX (alias PHOG) encodes a homeodomain-containing transcription factor expressed at highest levels in osteogenic cells; the gene resides in the pseudoautosomal region PAR1 of the sex chromosomes and escapes X inactivation, establishing dosage-sensitive expression relevant to stature. Positional cloning, expression analysis in osteogenic cells, X-inactivation assay Human molecular genetics Medium 9259282
2001 SHOX protein localizes exclusively to the nucleus in multiple cell lines (U2Os, HEK293, COS7, NIH 3T3), and functions as a cell-type-specific transcriptional activator: transactivation of luciferase reporter constructs was detected only in the osteogenic U2Os line. C-terminally truncated SHOX proteins (as found in Leri-Weill syndrome patients) are inactive for target gene activation. Stable cell-line transfection, luciferase reporter assays, nuclear localization by immunofluorescence, truncation mutant analysis Human molecular genetics High 11751690
2003 SHOX expression is regulated by a combination of transcriptional and translational control: an alternative internal promoter (P2) within exon 2 drives efficiently translated mRNA, while the upstream promoter (P1) produces mRNA with seven upstream AUG codons (uAUGs) that strongly inhibit translation. Site-directed mutagenesis of these uAUGs fully restores translation efficiency in cell lines and Xenopus embryos. Transient transfection of mono- and bicistronic reporters, in vitro translation assays, direct mRNA transfection, site-directed mutagenesis, Xenopus embryo injection The Journal of biological chemistry High 12960152
2004 SHOX expression in osteogenic cell lines, primary oral fibroblasts, and primary chondrocytes induces cell cycle arrest and apoptosis, associated with altered expression of pRB, p53, p21(Cip1) and p27(Kip1). A disease-associated SHOX mutant (from Leri-Weill patients) does not exhibit these activities. Endogenous SHOX protein is predominantly expressed in hypertrophic/apoptotic chondrocytes of the human growth plate. Stable transfection in cell lines and primary cells, flow cytometry (cell cycle), apoptosis assays, Western blotting of cell cycle regulators, immunohistochemistry of human growth plate The Journal of biological chemistry High 15145945
2004 The nuclear localization signal (NLS) of SHOX was mapped to a non-classic basic motif AKCRK in the recognition helix of the homeodomain. Fusion of this pentapeptide to a cytoplasmic reporter protein is sufficient to drive nuclear translocation. A disease-associated missense mutation R173C (C517T) abolishes nuclear entry; insertion of the NLS sequence adjacent to the mutant site restores translocation. Deletion mapping, NLS-reporter fusion constructs, immunofluorescence, mutagenesis of R173C, NLS rescue experiment Journal of cell science High 15173321
2005 Nine homeodomain missense mutations found in ISS/LWD patients impair SHOX function through loss of DNA binding, reduced dimerization ability, and/or impaired nuclear translocation. One mutation (R153L) retains DNA binding, dimerization, and nuclear entry but is defective in transcriptional activation, defining a separable transactivation function. Electrophoretic mobility shift assay (DNA binding), co-immunoprecipitation (dimerization), immunofluorescence (nuclear translocation), luciferase reporter assay (transactivation), mutagenesis panel Human mutation High 15931687
2006 In chicken limb buds, Shox expression is restricted to the central/proximal regions; it is repressed distally by FGF and BMP signals from the apical ectodermal ridge and proximally by retinoic acid signaling. Viral overexpression of Shox in chicken limbs consistently increases the length of skeletal elements, and micromass cultures show an initial increase in cartilage nodule number but failure to enlarge. In situ hybridization, retroviral overexpression in chicken embryos, micromass cultures, skeletal staining Developmental biology Medium 16904661
2007 NPPB (encoding BNP, natriuretic peptide B) is a direct transcriptional target of SHOX. SHOX transactivates the endogenous NPPB promoter in luciferase assays; chromatin immunoprecipitation (ChIP) confirmed SHOX binding to the NPPB promoter in vivo. Two LWD-associated SHOX mutants fail to activate the promoter. BNP and SHOX are co-expressed in late proliferative and hypertrophic chondrocytes of the human growth plate. Luciferase reporter assay with serial NPPB promoter deletions, chromatin immunoprecipitation (ChIP), mutant SHOX functional comparison, immunohistochemistry Human molecular genetics High 17881654
2007 Conserved non-coding elements (CNEs) located ~48–215 kb downstream of SHOX function as cis-regulatory enhancers active in the developing chicken limb bud; in ovo electroporation of GFP reporter constructs driven by individual CNEs demonstrated enhancer activity in three of eight tested elements. Deletion of this region in patients produces an LWD phenotype identical to SHOX coding mutations. In ovo electroporation enhancer assay in chicken limb bud (GFP reporter), comparative genomics, SNP/FISH mapping of patient deletions Human molecular genetics High 17200153
2009 Three conserved non-coding elements upstream of SHOX have enhancer activity in the developing chicken limb bud (in ovo electroporation assay) but not in the developing cornea, defining tissue-specific upstream regulatory elements for SHOX. In ovo electroporation enhancer assay in chicken limb bud and cornea, comparative genomic analysis European journal of human genetics Medium 19997128
2011 SHOX physically interacts with the chondrogenic transcription factors SOX5 and SOX6, identified by yeast two-hybrid screen and confirmed by co-immunoprecipitation in human cells. The SHOX homeodomain and SOX6 HMG domain mediate the interaction. Disease-associated SHOX missense mutations disrupt the interaction. SHOX cooperates with SOX5/SOX6 and SOX9 to activate the upstream Agc1 (aggrecan) enhancer; SHOX mutations impair this cooperative activation. Yeast two-hybrid screen, co-immunoprecipitation, domain mapping, luciferase reporter assay (Agc1 enhancer), immunohistochemistry of human fetal growth plate, disease-mutant panel Human molecular genetics High 21262861
2011 SHOX activates FGFR3 promoter in luciferase reporter assays; ChIP-sequencing and EMSA demonstrated direct binding of SHOX to multiple upstream sequences of FGFR3. In chicken micromass cultures, viral overexpression of Shox negatively regulates Fgfr3 (quantitative RT-PCR and in situ hybridization), suggesting that SHOX represses FGFR3 in the mesomelic limb segments. Microarray analysis, luciferase reporter assay, ChIP-sequencing, EMSA, viral overexpression in chicken micromass cultures, qRT-PCR, in situ hybridization Human molecular genetics High 21273290
2011 Human SHOX and mouse Shox2 share functional redundancy in sinoatrial node (SAN) development: both show similar transcriptional repressive activity on the Nkx2.5 promoter in cell culture. In SHOX/Shox2 knock-in mice (Shox2 replaced by human SHOX), SAN formation and pacemaking function are fully restored, demonstrating that SHOX can repress Nkx2.5-driven SAN differentiation pathways. Luciferase reporter assay (Nkx2.5 promoter repression), SHOX/Shox2 knock-in mouse model, physiological/histological/molecular analysis of SAN The Journal of biological chemistry High 21454626
2011 Alternative splicing coupled with nonsense-mediated RNA decay (NMD) regulates SHOX expression levels in a tissue- and time-specific manner. Inclusion of novel exon 2a introduces a premature stop codon leading to NMD; four novel exons (2a, 7-1, 7-2, 7-3) were identified. Exon 7 variants are exclusively expressed in fetal neural tissues. RT-PCR, RNA-Seq, functional analysis of exon 2a by minigene/NMD reporter, tissue expression profiling PloS one Medium 21448463
2013 SHOX triggers apoptosis via oxidative stress leading to lysosomal membrane rupture, release of active cathepsin B to the cytosol, mitochondrial membrane permeabilization, and caspase activation (intrinsic apoptotic pathway). LWD-associated mutants SHOX R153L and SHOX L185X (C-terminal truncation) do not induce oxidative stress or any of these downstream apoptotic events. ROS measurement, lysosomal integrity assays, cathepsin B activity assay, mitochondrial membrane potential assay, caspase activity assay, stable transfection of wild-type vs. mutant SHOX in U2OS cells Human molecular genetics High 24186869
2014 In a Col2a1-SHOX transgenic mouse, human SHOXa regulates extracellular matrix gene expression during early limb development, including transcriptional activation of Ctgf (connective tissue growth factor). This was confirmed in human NHDF and U2OS cells and chicken micromass culture. Transgenic mouse (Col2a1-SHOX), quantitative and in situ hybridization analyses, confirmation in human cell lines and chicken micromass culture PloS one Medium 24887312
2014 Zebrafish shox loss-of-function (morpholino knockdown) delays embryonic growth and markedly impairs calcification of the anterior vertebral column and craniofacial bones. The growth delay phenotype is rescued by co-overexpression of morpholino-resistant Shox mRNA, confirming specificity. Antisense morpholino knockdown in zebrafish, skeletal staining, mRNA rescue experiment Developmental dynamics Medium 25483930
2016 CYP26C1 (a retinoic acid catabolizing enzyme) is a genetic modifier of SHOX deficiency. CYP26C1 variants reduce its catabolic activity, elevating retinoic acid levels, which significantly decrease SHOX expression in human primary chondrocytes and zebrafish embryos. In zebrafish, individual morpholino knockdown of either shox or cyp26c1 shortens pectoral fins; combined knockdown produces a more severe phenotype, establishing epistasis. CYP26C1 enzymatic activity assay, SHOX expression in human primary chondrocytes with retinoic acid treatment, zebrafish morpholino knockdown (single and double), pectoral fin length measurement, family genetic co-segregation EMBO molecular medicine High 27861128
2018 A 563 bp enhancer downstream of SHOX drives specific expression in the zeugopodal limb regions where SHOX is required; a primary cell luciferase assay confirmed enhancer activity, and putative HOX binding sites within the conserved 100 bp core are required for its activity. This enhancer is removed in most non-coding PAR1 deletions that cause LWD. Transgenic mouse enhancer assay, luciferase reporter assay, HOX binding site mutagenesis, deletion mapping against LWD patient cohort Scientific reports High 30250174
2020 5'UTR variants (c.-51G>A, c.-19G>A, c.-9del) reduce SHOX expression and contribute to haploinsufficiency. Luciferase assays showed c.-51G>A and c.-9del reduce activity at the post-transcriptional level; a minigene splicing assay demonstrated that c.-19G>A creates an aberrant branch site causing mis-splicing of SHOX mRNA. Luciferase reporter assay (5'UTR variants), luciferase mRNA quantification, minigene exon-trapping splicing assay European journal of human genetics Medium 32647378
2022 WRN helicase domain directly regulates SHOX transcription by unwinding G-quadruplex structures in the SHOX locus. WRN-null zebrafish (wrn-/-) show impaired bone growth and shorter stature; shox-/- zebrafish exhibit the same phenotype; genetic overexpression of SHOX/shox rescues bone developmental deficiency in WRN/wrn-null animals both in vitro and in vivo. Zebrafish genetic knockout (wrn-/-, shox-/-), G-quadruplex unwinding assay (helicase assay), genetic rescue by SHOX overexpression in vitro and in vivo Nature communications High 36114168

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Human molecular genetics 344 10749976
1998 SHOX mutations in dyschondrosteosis (Leri-Weill syndrome). Nature genetics 276 9590292
1998 Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis. Nature genetics 251 9590293
1997 PHOG, a candidate gene for involvement in the short stature of Turner syndrome. Human molecular genetics 228 9259282
2006 Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency. Journal of medical genetics 179 17182655
2011 Short stature due to SHOX deficiency: genotype, phenotype, and therapy. Hormone research in paediatrics 168 21325865
2002 Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature. The Journal of clinical endocrinology and metabolism 155 11889216
2001 Phenotypes Associated with SHOX Deficiency. The Journal of clinical endocrinology and metabolism 146 11739418
2006 High incidence of SHOX anomalies in individuals with short stature. Journal of medical genetics 107 16597678
2005 A novel class of Pseudoautosomal region 1 deletions downstream of SHOX is associated with Leri-Weill dyschondrosteosis. American journal of human genetics 104 16175500
2006 The pseudoautosomal regions, SHOX and disease. Current opinion in genetics & development 103 16650979
2016 A Track Record on SHOX: From Basic Research to Complex Models and Therapy. Endocrine reviews 101 27355317
2009 Enhancer deletions of the SHOX gene as a frequent cause of short stature: the essential role of a 250 kb downstream regulatory domain. Journal of medical genetics 101 19578035
1998 SHOT, a SHOX-related homeobox gene, is implicated in craniofacial, brain, heart, and limb development. Proceedings of the National Academy of Sciences of the United States of America 100 9482898
2007 Long-range conserved non-coding SHOX sequences regulate expression in developing chicken limb and are associated with short stature phenotypes in human patients. Human molecular genetics 94 17200153
2001 SHOX haploinsufficiency and overdosage: impact of gonadal function status. Journal of medical genetics 93 11134233
2004 The short stature homeodomain protein SHOX induces cellular growth arrest and apoptosis and is expressed in human growth plate chondrocytes. The Journal of biological chemistry 86 15145945
2007 SHOX mutations in idiopathic short stature and Leri-Weill dyschondrosteosis: frequency and phenotypic variability. Clinical endocrinology 84 17201812
2001 The Leri-Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator. Human molecular genetics 83 11751690
2002 Complete SHOX deficiency causes Langer mesomelic dysplasia. American journal of medical genetics 81 12116254
2000 Identification of short stature caused by SHOX defects and therapeutic effect of recombinant human growth hormone. The Journal of clinical endocrinology and metabolism 77 10634394
2016 SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature. Molecular syndromology 72 27194967
2004 Expression of SHOX in human fetal and childhood growth plate. The Journal of clinical endocrinology and metabolism 70 15292358
2004 SHOX haploinsufficiency and Leri-Weill dyschondrosteosis: prevalence and growth failure in relation to mutation, sex, and degree of wrist deformity. The Journal of clinical endocrinology and metabolism 60 15356038
2010 SHOX duplications found in some cases with type I Mayer-Rokitansky-Kuster-Hauser syndrome. Genetics in medicine : official journal of the American College of Medical Genetics 57 20847698
2009 Berkeley PHOG: PhyloFacts orthology group prediction web server. Nucleic acids research 53 19435885
2012 IGF1, IGF1R and SHOX mutation analysis in short children born small for gestational age and short children with normal birth size (idiopathic short stature). Hormone research in paediatrics 51 22572840
2000 SHOX: growth, Léri-Weill and Turner syndromes. Trends in endocrinology and metabolism: TEM 51 10878753
2012 Genotypes and phenotypes of children with SHOX deficiency in France. The Journal of clinical endocrinology and metabolism 49 22518848
2006 The Aspergillus nidulans xprG (phoG) gene encodes a putative transcriptional activator involved in the response to nutrient limitation. Fungal genetics and biology : FG & B 47 16464624
2003 Transcriptional and translational regulation of the Leri-Weill and Turner syndrome homeobox gene SHOX. The Journal of biological chemistry 47 12960152
2011 SHOX interacts with the chondrogenic transcription factors SOX5 and SOX6 to activate the aggrecan enhancer. Human molecular genetics 46 21262861
2009 Clinical and molecular characterization of duplications encompassing the human SHOX gene reveal a variable effect on stature. American journal of medical genetics. Part A 44 19533800
2007 BNP is a transcriptional target of the short stature homeobox gene SHOX. Human molecular genetics 44 17881654
2013 The sitting height/height ratio for age in healthy and short individuals and its potential role in selecting short children for SHOX analysis. Hormone research in paediatrics 43 24296787
2011 Functional redundancy between human SHOX and mouse Shox2 genes in the regulation of sinoatrial node formation and pacemaking function. The Journal of biological chemistry 43 21454626
2005 The phenotype of short stature homeobox gene (SHOX) deficiency in childhood: contrasting children with Leri-Weill dyschondrosteosis and Turner syndrome. The Journal of pediatrics 43 16227037
2011 Identification of the first PAR1 deletion encompassing upstream SHOX enhancers in a family with idiopathic short stature. European journal of human genetics : EJHG 41 22071895
2011 FGFR3 is a target of the homeobox transcription factor SHOX in limb development. Human molecular genetics 39 21273290
2011 Alternative splicing and nonsense-mediated RNA decay contribute to the regulation of SHOX expression. PloS one 39 21448463
2009 Enhancer elements upstream of the SHOX gene are active in the developing limb. European journal of human genetics : EJHG 39 19997128
2006 PAR1 deletions downstream of SHOX are the most frequent defect in a Spanish cohort of Léri-Weill dyschondrosteosis (LWD) probands. Human mutation 39 16941489
2001 Analysis of short stature homeobox-containing gene ( SHOX) and auxological phenotype in dyschondrosteosis and isolated Madelung deformity. Human genetics 37 11735031
2011 SHOX gene defects and selected dysmorphic signs in patients of idiopathic short stature and Léri-Weill dyschondrosteosis. Gene 36 22020182
2006 Expression of the short stature homeobox gene Shox is restricted by proximal and distal signals in chick limb buds and affects the length of skeletal elements. Developmental biology 35 16904661
2005 Alteration of DNA binding, dimerization, and nuclear translocation of SHOX homeodomain mutations identified in idiopathic short stature and Leri-Weill dyschondrosteosis. Human mutation 35 15931687
2007 SHOX at a glance: from gene to protein. Archives of physiology and biochemistry 33 17922307
2015 Rare pseudoautosomal copy-number variations involving SHOX and/or its flanking regions in individuals with and without short stature. Journal of human genetics 32 26040210
2000 Mutations in short stature homeobox containing gene (SHOX) in dyschondrosteosis but not in hypochondroplasia. Human genetics 32 11030412
2011 The role of the SHOX gene in the pathophysiology of Turner syndrome. Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion 31 21925981
2006 Identification and characterization of different SHOX gene deletions in patients with Leri-Weill dyschondrosteosys by MLPA assay. Journal of human genetics 30 17091221
2016 Microduplications at the pseudoautosomal SHOX locus in autism spectrum disorders and related neurodevelopmental conditions. Journal of medical genetics 29 27073233
2004 Impairment of SHOX nuclear localization as a cause for Léri-Weill syndrome. Journal of cell science 28 15173321
2014 Skeletal Deformity Associated with SHOX Deficiency. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology 27 25110390
2013 SHOX triggers the lysosomal pathway of apoptosis via oxidative stress. Human molecular genetics 27 24186869
2005 Microdeletion in the SHOX 3' region associated with skeletal phenotypes of Langer mesomelic dysplasia in a 45,X/46,X,r(X) infant and Leri-Weill dyschondrosteosis in her 46,XX mother: implication for the SHOX enhancer. American journal of medical genetics. Part A 26 16007631
1999 SHOX: pseudoautosomal homeobox containing gene for short stature and dyschondrosteosis. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 26 10549307
2016 Large Deletions at the SHOX Locus in the Pseudoautosomal Region Are Associated with Skeletal Atavism in Shetland Ponies. G3 (Bethesda, Md.) 25 27207956
2013 Prepubertal girls with Turner syndrome and children with isolated SHOX deficiency have similar bone geometry at the radius. The Journal of clinical endocrinology and metabolism 25 23666967
2006 Short stature and dysmorphology associated with defects in the SHOX gene. Hormones (Athens, Greece) 25 16807223
2002 Pseudodominant inheritance of Langer mesomelic dysplasia caused by a SHOX homeobox missense mutation. American journal of medical genetics 25 12116253
2016 Systematic molecular analyses of SHOX in Japanese patients with idiopathic short stature and Leri-Weill dyschondrosteosis. Journal of human genetics 24 26984564
2002 Trisomy of the short stature homeobox-containing gene (SHOX), resulting from a duplication-deletion of the X chromosome. Clinical endocrinology 24 12035792
2001 Growth hormone and gonadotropin-releasing hormone analog therapy in haploinsufficiency of SHOX. Endocrine journal 24 11523902
1999 Loss of the SHOX gene associated with Leri-Weill dyschondrosteosis in a 45,X male. Journal of medical genetics 24 10507731
2015 Duplications upstream and downstream of SHOX identified as novel causes of Leri-Weill dyschondrosteosis or idiopathic short stature. American journal of medical genetics. Part A 23 26698168
2011 Functional analysis of conserved non-coding regions around the short stature hox gene (shox) in whole zebrafish embryos. PloS one 23 21731768
2003 Familial growth and skeletal features associated with SHOX haploinsufficiency. Journal of pediatric endocrinology & metabolism : JPEM 22 14513875
2015 Profiling of conserved non-coding elements upstream of SHOX and functional characterisation of the SHOX cis-regulatory landscape. Scientific reports 21 26631348
1999 SHOX gene mutations and deletions in dyschondrosteosis or Leri-Weill syndrome. Acta paediatrica (Oslo, Norway : 1992). Supplement 21 10626546
2022 WRN promotes bone development and growth by unwinding SHOX-G-quadruplexes via its helicase activity in Werner Syndrome. Nature communications 20 36114168
2016 Retinoic acid catabolizing enzyme CYP26C1 is a genetic modifier in SHOX deficiency. EMBO molecular medicine 20 27861128
2015 The growth response to GH treatment is greater in patients with SHOX enhancer deletions compared to SHOX defects. European journal of endocrinology 20 26264720
2018 Identification of a limb enhancer that is removed by pathogenic deletions downstream of the SHOX gene. Scientific reports 19 30250174
2013 Comparative transgenic analysis of enhancers from the human SHOX and mouse Shox2 genomic regions. Human molecular genetics 19 23575226
2010 Usefulness of MLPA in the detection of SHOX deletions. European journal of medical genetics 19 20538086
2003 Deletion of the SHOX gene in patients with short stature of unknown cause. American journal of medical genetics. Part A 19 12784295
2013 Replacing Shox2 with human SHOX leads to congenital disc degeneration of the temporomandibular joint in mice. Cell and tissue research 18 24248941
2013 SHOX gene and conserved noncoding element deletions/duplications in Colombian patients with idiopathic short stature. Molecular genetics & genomic medicine 18 24689071
2010 Unexpected phenotype in a boy with trisomy of the SHOX gene. Journal of pediatric endocrinology & metabolism : JPEM 18 20432819
2002 SHOX nullizygosity and haploinsufficiency in a Japanese family: implication for the development of Turner skeletal features. The Journal of clinical endocrinology and metabolism 18 11889214
2012 Impaired GH secretion in patients with SHOX deficiency and efficacy of recombinant human GH therapy. Hormone research in paediatrics 17 23208451
2008 Identification and characterization of cryptic SHOX intragenic deletions in three Japanese patients with Léri-Weill dyschondrosteosis. Journal of human genetics 17 18322641
2007 Compound heterozygosity of SHOX-encompassing and downstream PAR1 deletions results in Langer mesomelic dysplasia (LMD). American journal of medical genetics. Part A 17 17394206
2002 The human SHOX mutation database. Human mutation 17 12402330
2020 Pathogenic/likely pathogenic variants in the SHOX, GHR and IGFALS genes among Indian children with idiopathic short stature. Journal of pediatric endocrinology & metabolism : JPEM 16 31834863
2015 Radiological Features in Patients with Short Stature Homeobox-Containing (SHOX) Gene Deficiency and Turner Syndrome before and after 2 Years of GH Treatment. Hormone research in paediatrics 16 25967354
2014 In vivo loss of function study reveals the short stature homeobox-containing (shox) gene plays indispensable roles in early embryonic growth and bone formation in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 16 25483930
2007 The novel human SHOX allelic variant database. Human mutation 16 17726696
2014 Identification of novel SHOX target genes in the developing limb using a transgenic mouse model. PloS one 15 24887312
2001 SHOX in short stature syndromes. Hormone research 15 11408757
2017 The Short-Stature Homeobox-Containing Gene (shox/SHOX) Is Required for the Regulation of Cell Proliferation and Bone Differentiation in Zebrafish Embryo and Human Mesenchymal Stem Cells. Frontiers in endocrinology 14 28642734
2013 Phenotypic characterization of patients with deletions in the 3'-flanking SHOX region. PeerJ 14 23638371
2013 Short stature before puberty: which children should be screened for SHOX deficiency? Hormone research in paediatrics 14 24051572
2009 SHOX gene is expressed in vertebral body growth plates in idiopathic and congenital scoliosis: implications for the etiology of scoliosis in Turner syndrome. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 14 19016538
2020 Rare and de novo duplications containing SHOX in clubfoot. Journal of medical genetics 13 32518174
2020 Variants in the 5'UTR reduce SHOX expression and contribute to SHOX haploinsufficiency. European journal of human genetics : EJHG 13 32647378
2016 Prevalence of SHOX haploinsufficiency among short statured children. Pediatric research 13 27814343
2014 Increased cortical area and thickness in the distal radius in subjects with SHOX-gene mutation. Bone 13 25220427
2013 Y-chromosome microdeletions are not associated with SHOX haploinsufficiency. Human reproduction (Oxford, England) 13 24008148

Missed literature

Know a paper Affinage missed for SHOX? Flag it for the maintainers and the community.

No submissions yet.