Affinage

PROP1

Homeobox protein prophet of Pit-1 · UniProt O75360

Length
226 aa
Mass
25.0 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PROP1 is a paired-like homeodomain transcription factor that serves as the master regulator of anterior pituitary development, governing the specification, migration, and differentiation of progenitors that give rise to all hormone-producing cell types of the anterior and intermediate pituitary lobes (PMID:26812162, PMID:9462743). PROP1 binds DNA via its homeodomain—including the PRDQ9 response element and inverted TAAT motifs (the latter as a heterodimer with HESX1)—to repress HESX1 and activate POU1F1, and it drives an epithelial-to-mesenchymal transition (EMT)-like program in pituitary stem cells by directly activating Zeb2, Notch2, and Gli2, enabling progenitor exit from Rathke's pouch (PMID:27351100, PMID:18996108, PMID:19879326). PROP1 also controls a downstream retinoic acid signaling axis via Aldh1a2 that is required for normal pituitary organogenesis (PMID:31913463). Loss-of-function mutations in PROP1 cause combined pituitary hormone deficiency by trapping progenitors in the perilumenal zone and blocking their differentiation, while persistent expression delays terminal differentiation and predisposes to pituitary adenomas (PMID:9462743, PMID:15591534, PMID:11371507).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1998 High

    Positional cloning of the Ames dwarf locus identified PROP1 as a pituitary-specific paired-like homeodomain transcription factor upstream of POU1F1, resolving the genetic basis for combined pituitary hormone deficiency affecting somatotropes, lactotropes, thyrotropes, and gonadotropes.

    Evidence Positional cloning of mouse Prop1, identification of human PROP1 mutations, in vitro DNA-binding and transactivation assays, genetic epistasis with Snell/Jackson dwarfism

    PMID:9462743 PMID:9824293

    Open questions at the time
    • Direct chromatin occupancy at the POU1F1 locus not yet shown
    • Mechanism by which PROP1 specifies gonadotropes (non-PIT1 lineage) unknown
    • In vivo target genes beyond POU1F1 unidentified
  2. 2000 High

    Structure–function studies of disease-associated homeodomain mutations (F88S, R73C) established that the hydrophobic core of helix 1 and the conserved Arg73 residue are essential for DNA binding and transactivation, and that even C-terminal truncations (W194X) unexpectedly impair DNA binding, revealing contributions of the transactivation domain to protein–DNA interaction.

    Evidence EMSA and luciferase reporter assays with site-directed and patient-derived PROP1 mutants in TSA-201 cells

    PMID:10946881 PMID:15531542 PMID:15941866

    Open questions at the time
    • No crystal structure of PROP1 homeodomain–DNA complex
    • C-terminal contribution to DNA binding not structurally explained
  3. 2001 High

    Gain-of-function experiments revealed that timely silencing of Prop1 is essential for terminal differentiation; persistent expression delayed gonadotrope and thyrotrope maturation and increased pituitary tumor susceptibility, establishing PROP1 as a factor whose temporal window of action must be tightly controlled.

    Evidence Transgenic mouse constitutive Prop1 overexpression with longitudinal hormonal, histological, and tumor analysis

    PMID:11371507

    Open questions at the time
    • Mechanism of Prop1 silencing unknown
    • Whether tumorigenesis requires cooperating mutations not addressed
  4. 2004 High

    Loss-of-function studies demonstrated that Prop1 is required for progenitor cells to physically exit the perilumenal zone of Rathke's pouch and seed the anterior lobe; without Prop1, cells remain trapped, leading to progressive hypoplasia through impaired migration rather than impaired proliferation.

    Evidence BrdU pulse-labeling, TUNEL assay, volumetric analysis in Prop1-deficient Ames dwarf mice from embryo to adult; genetic epistasis with Lhx4

    PMID:12183375 PMID:15591534

    Open questions at the time
    • Molecular mechanism linking Prop1 to cell migration not identified
    • Whether Prop1 acts cell-autonomously in migration not resolved
  5. 2008 High

    Double-mutant analysis of Prop1 and Hes1 revealed that Prop1 controls an EMT-like process: Prop1-mutant cells retain high N-cadherin and lack the EMT marker Slug, and epistasis with Hes1 separates the adhesion-loss and migrational-cue functions, placing Prop1 in a cell-exit regulatory module.

    Evidence Prop1/Hes1 double-mutant mouse analysis with immunohistochemistry for N-cadherin, Slug, and differentiation markers

    PMID:18996108

    Open questions at the time
    • Direct regulation of N-cadherin or Slug by Prop1 not demonstrated
    • Hes1–Prop1 protein interaction not tested
  6. 2009 Medium

    PROP1 was localized to SOX2-positive adult pituitary stem/progenitor cells and shown to heterodimerize with HESX1 on inverted TAAT motifs, altering HESX1 DNA-binding specificity, providing a molecular mechanism for the developmental transition from HESX1-dominated repression to PROP1-driven activation.

    Evidence EMSA with recombinant HESX1/PROP1; co-immunofluorescence for PROP1, SOX2, PIT1 in rat pituitary; sphere-formation assays from GPS cells

    PMID:19283075 PMID:19442651 PMID:19879326

    Open questions at the time
    • HESX1–PROP1 heterodimer not validated in vivo by ChIP
    • Whether heterodimer binding alters target gene selection genome-wide unknown
    • Functional role of PROP1 in adult stem cells beyond marker expression not established
  7. 2010 Medium

    Identification of TLE1 and TLE3 as corepressors that physically interact with PROP1 and repress its transcriptional activity independently of HESX1 added a new layer of regulation, showing that PROP1 activity is modulated by Groucho-family corepressors.

    Evidence Cell culture co-repression assays, protein–protein interaction studies, transgenic mouse HESX1/TLE3 expression in pituitary

    PMID:20181723

    Open questions at the time
    • Direct binding domains mediating PROP1–TLE interaction not mapped
    • In vivo relevance of PROP1–TLE interaction at endogenous loci not shown
  8. 2016 High

    Genome-wide ChIP-seq and transcriptomics resolved the direct PROP1 transcriptional program: PROP1 binds and activates EMT inducers (Zeb2, Notch2, Gli2), represses Hesx1, and activates Pou1f1; lineage tracing confirmed that all anterior and intermediate lobe hormone-producing cells descend from Prop1-expressing progenitors, establishing PROP1 as a pan-pituitary progenitor regulator.

    Evidence ChIP-seq and RNA-seq in Prop1-mutant mice and stem cells; inducible Prop1 cell lines; Prop1-cre lineage tracing with Rosa reporter

    PMID:26812162 PMID:27351100

    Open questions at the time
    • Relative contributions of Zeb2 vs. Notch2 vs. Gli2 to EMT not dissected
    • Whether PROP1 directly or indirectly activates all bound loci not resolved for each target
  9. 2018 Medium

    Upstream regulation of Prop1 was mapped: retinoic acid via RARα activates Prop1 through a cis-regulatory element, while SOX2 and multiple pituitary transcription factors regulate the Prop1 promoter, placing Prop1 within a RA–SOX2 regulatory network.

    Evidence Ex vivo Rathke's pouch organ culture with RA; luciferase reporter assays with serial 5′-truncations; CHO cell reporter screens with 40 transcription factors

    PMID:26640231 PMID:29356182

    Open questions at the time
    • In vivo RARα ChIP at the Prop1 locus not performed
    • Relative importance of individual upstream factors not ranked by genetic epistasis
  10. 2020 High

    A Prop1→Aldh1a2→RA signaling axis was established as a downstream effector pathway: Prop1-mutant mice show reduced Aldh1a2, and conditional Aldh1a2 deletion or dominant-negative RA signaling partially phenocopies the Prop1 mutant pituitary dysmorphology, connecting PROP1 to a retinoic acid feed-forward loop.

    Evidence Conditional Aldh1a2 knockout and dominant-negative RA receptor mouse models compared to Prop1-mutant phenotype

    PMID:31913463

    Open questions at the time
    • Whether Prop1 directly binds the Aldh1a2 locus not shown
    • Partial phenocopy suggests additional Prop1-dependent pathways remain unidentified
    • RA feedback onto Prop1 expression in vivo not formally tested in this context

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for PROP1–DNA and PROP1–HESX1 interactions, the mechanism by which PROP1 is silenced after progenitor commitment, the cell-autonomous vs. non-autonomous contributions of PROP1 to progenitor migration, and the full spectrum of direct PROP1 targets that mediate its EMT and differentiation programs.
  • No crystal or cryo-EM structure of PROP1 or its complexes
  • Mechanism of Prop1 transcriptional silencing unknown
  • Cell-autonomous requirement for Prop1 in migration not formally demonstrated by mosaic or clonal analysis

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 7 GO:0140110 transcription regulator activity 7
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-74160 Gene expression (Transcription) 5
Partners
HES1HESX1LHX4POU1F1SOX2TLE1TLE3

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PROP1 encodes a paired-like homeodomain transcription factor expressed specifically in embryonic pituitary that is necessary for Pit1 (POU1F1) expression; human PROP1 mutations reduce DNA-binding and transcriptional activation ability, establishing PROP1 as an upstream regulator of the PIT1 lineage and as required for ontogenesis of somatotropes, lactotropes, caudomedial thyrotropes, and gonadotropes. Positional cloning of mouse Prop1 (Ames dwarf gene), followed by identification of human PROP1 mutations via sequencing; functional assessment of mutant proteins by DNA-binding and transcriptional activation assays; genetic epistasis (Ames dwarf epistatic to Snell/Jackson dwarfism) Nature genetics High 9462743
1998 Human PROP1 protein requires the homeodomain for DNA binding; an R73C missense mutation (conserved in >95% of homeodomain proteins) impairs function, and a splice-site mutation abolishes correct splicing of PROP1 transcripts, as demonstrated by in vitro splicing assays. Human cDNA cloning, exon/intron mapping, in vitro splicing assays, sequencing of CPHD families FEBS letters High 9824293
2000 The F88S mutation in the first helix of the PROP1 homeodomain abolishes DNA binding to the PRDQ9 Prop1 response element (gel shift assay) and reduces transcriptional activation of a luciferase reporter to ~34% of wild-type, demonstrating that the hydrophobic core of helix 1 is essential for DNA-binding and transactivation. Site-directed mutagenesis of murine Prop1 cDNA; electrophoretic mobility shift assay (EMSA); luciferase reporter transfection in TSA-201 cells The Journal of clinical endocrinology and metabolism High 10946881
2001 Constitutive (persistent) expression of Prop1 in transgenic mice delays terminal differentiation of gonadotropes and thyrotropes, impairs thyrotrope function, and increases susceptibility to pituitary adenomas and Rathke's cleft cysts, demonstrating that timely silencing of Prop1 is required for normal anterior pituitary differentiation. Transgenic mouse overexpression of Prop1 with longitudinal phenotypic analysis (hormone measurements, histology, tumor assessment) Human molecular genetics High 11371507
2002 Lhx4 and Prop1 have overlapping but mechanistically distinct functions in early pituitary development: Lhx4 mutants show increased cell death and temporal shift in Lhx3 activation, whereas Prop1 mutants exhibit normal proliferation/survival but defective dorsal-ventral patterning; double mutants fail to specify all anterior pituitary cell types except corticotropes (delayed), establishing genetic epistasis between these factors. Analysis of single and double mutant mice (Lhx4 KO × Prop1 df); immunohistochemistry, cell death assays, molecular marker analysis Development (Cambridge, England) High 12183375
2004 Prop1 is required for anterior pituitary progenitors to leave the perilumenal region of Rathke's pouch, migrate to the anterior lobe, and differentiate; Prop1-deficient cells are retained in the perilumenal area and fail to differentiate. After birth, mutant pituitaries show enhanced apoptosis and reduced proliferation because the anterior lobe is not seeded with progenitors. Longitudinal volumetric studies, BrdU pulse-labeling for cell migration and proliferation tracking, TUNEL apoptosis assay in normal and Prop1-deficient (Ames dwarf) mice from embryogenesis to adulthood Molecular endocrinology (Baltimore, Md.) High 15591534
2004 Prop1 is required directly or indirectly for normal Notch2 expression in the developing pituitary; Notch2 is nearly absent in Prop1-mutant pituitaries but unaltered in other panhypopituitary mutants, implicating Notch signaling downstream of Prop1 in pituitary progenitor maintenance and cell specification. Comparative gene expression analysis in Prop1 mutant and other panhypopituitary mutant mice; transgenic Prop1 overexpression; in situ hybridization Developmental biology Medium 14732396
2005 In the W194X PROP1 mutant (truncated in the transactivation domain), transactivation capacity is reduced to 34.4% of wild type; unexpectedly, DNA-binding properties are also altered, indicating that the C-terminal end of PROP1 contributes to protein-DNA interaction in addition to transactivation. Transfection transactivation assays; DNA-binding experiments with mutant PROP1 The Journal of clinical endocrinology and metabolism Medium 15941866
2008 Prop1 and Hes1 have overlapping functions in maintaining pituitary progenitors within Rathke's pouch and in controlling cell movement; in Prop1 mutants, N-cadherin expression remains high and cells are trapped in Rathke's pouch; Slug (an EMT marker) is absent from the dorsal anterior lobe. Loss of both Prop1 and Hes1 allows N-cadherin downregulation and cell exit but abolishes migrational cues, producing ectopic foci. Prop1/Hes1 double-mutant mouse analysis; immunohistochemistry for N-cadherin, Slug, and differentiation markers; analysis of ectopic differentiation Developmental biology High 18996108
2009 PROP1 is expressed in adult pituitary stem/progenitor cells (GPS cells: GFRa2/Prop1/Stem) that co-express Sox2, Sox9, Oct4, and GFRa2; these cells can form non-endocrine spheroids in culture and differentiate into hormone-producing cells or neurons, placing PROP1 in a postnatal pituitary stem cell niche with neuroectoderm potential. Immunohistochemistry, co-immunofluorescence, in vitro sphere formation, BrdU label retention, telomere length analysis in rodent and human pituitary PloS one Medium 19283075
2009 HESX1 forms a heterodimer with PROP1 on an inverted TAAT motif; in the presence of PROP1, HESX1 shifts from monomer binding on a TAATT motif to heterodimer binding on the inverted TAAT motif, suggesting that newly appearing PROP1 alters the DNA-binding specificity of HESX1 to advance pituitary development. Random oligonucleotide binding selection, electrophoretic mobility shift assay (EMSA) with recombinant HESX1 and PROP1 Molecular and cellular endocrinology Medium 19879326
2009 PROP1 is expressed in SOX2-positive stem/progenitor cells throughout rat pituitary development; PROP1-positive cells coexist transiently with PIT1 but not with hormones, consistent with PROP1 acting in the progenitor-to-committed cell transition for PIT1-lineage specification. Immunohistochemistry and co-immunofluorescence for PROP1, SOX2, and PIT1 in rat embryonic and postnatal pituitary Biochemical and biophysical research communications Medium 19442651
2010 TLE1 and TLE3 are corepressors that physically interact with PROP1 and repress PROP1 transcriptional activity independently of HESX1; HESX1 also interacts with TLE3 (in addition to the known TLE1 interaction) and represses PROP1 with similar efficiency when paired with either corepressor. In transgenic mice, HESX1 expression in thyrotrophs/gonadotrophs suppresses their terminal differentiation. Cell culture co-repression assays; protein-protein interaction studies; transgenic mouse expression of TLE3 and HESX1 in pituitary thyrotrophs/gonadotrophs Molecular endocrinology (Baltimore, Md.) Medium 20181723
2014 miR-593 and miR-511 directly target the 3'-UTR of the PROP1 gene and attenuate PROP1 protein expression, as demonstrated by reporter assays and western blot in transfected HEK293T cells. miRNA microarray, luciferase 3'-UTR reporter assay, western blot in HEK293T cells transfected with miR-593 or miR-511 International journal of molecular medicine Low 25434367
2016 PROP1 drives an epithelial-to-mesenchymal transition (EMT)-like process in pituitary stem cells required for cell migration and differentiation; genome-wide ChIP analysis shows PROP1 binds genes expressed in epithelial cells (e.g., Claudin 23) and EMT inducer genes (Zeb2, Notch2, Gli2). Zeb2 activation is identified as a key downstream step. PROP1 also represses Hesx1 and activates Pou1f1. Genome-wide ChIP-seq (PROP1 DNA binding), RNA-seq in Prop1-mutant mice and isolated stem cells, engineered mouse cell lines with inducible Prop1 expression eLife High 27351100
2016 Lineage tracing with a Prop1-cre mouse demonstrates that all hormone-secreting cell types of both the anterior and intermediate pituitary lobes are descended from Prop1-expressing progenitors, establishing PROP1 as a marker of a pan-pituitary progenitor rather than only the PIT1 lineage. Prop1-cre transgenic mouse generation; Cre-mediated lineage tracing (Rosa reporter); immunofluorescence for all pituitary hormone cell types Endocrinology High 26812162
2018 Retinoic acid (RA) signaling regulates Prop1 expression in the pituitary primordium via RARα; ex vivo Rathke's pouch organ culture and in vitro reporter assays show RA increases Prop1 mRNA, and a RARα cis-regulatory element was identified in the 5'-upstream region of mouse Prop1. Ex vivo Rathke's pouch organ culture with RA treatment; in vitro luciferase reporter assay with serial 5'-truncation constructs; in situ hybridization for Raldh genes and RA receptors Journal of neuroendocrinology Medium 29356182
2020 RA signaling is active during pituitary organogenesis and depends on Prop1; Prop1-mutant mice show reduced Aldh1a2 (retinaldehyde dehydrogenase) expression. Conditional deletion of Aldh1a2 or dominant-negative RA signaling during pituitary organogenesis partially phenocopies Prop1 mutants (embryonic dysmorphology, reduced thyrotropin), establishing a Prop1→Aldh1a2→RA signaling axis in pituitary stem cell differentiation. Conditional Aldh1a2 knockout; dominant-negative RA receptor mouse model; phenotypic comparison with Prop1-mutant mice; gene expression analysis Endocrinology High 31913463
2015 Reporter assays in CHO cells identify 8 transcription factors (MSX2, PAX6, PIT1, PITX1, PITX2, RPF1, SOX8, SOX11) as direct regulators of Prop1 expression through the 3 kb upstream promoter region; an additional 10 factors show synergy with SOX2. SOX2 itself has both inhibitory and activating functions on Prop1 through proximal and distal upstream regions, respectively. Luciferase reporter assays with serial truncated 5'-upstream Prop1 constructs transfected with 40 candidate transcription factors in CHO cells The Journal of reproduction and development Medium 26640231
2004 The R73C mutation reduces PROP1 transactivation capacity to 11.5% of wild type and abolishes binding to a high-affinity DNA sequence in vitro, confirming R73 in the homeodomain as critical for both DNA binding and transcriptional activation. In vitro transactivation assay; DNA-binding experiment with R73C mutant PROP1 in a large consanguineous family study The Journal of clinical endocrinology and metabolism Medium 15531542

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nature genetics 382 9462743
1998 The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. The Journal of clinical endocrinology and metabolism 151 9745452
1998 Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg-->Cys at codon 120 (R120C). The Journal of clinical endocrinology and metabolism 143 9768691
2004 Role of PROP1 in pituitary gland growth. Molecular endocrinology (Baltimore, Md.) 141 15591534
1999 "Hot spot" in the PROP1 gene responsible for combined pituitary hormone deficiency. The Journal of clinical endocrinology and metabolism 141 10323394
2009 A GRFa2/Prop1/stem (GPS) cell niche in the pituitary. PloS one 137 19283075
2002 Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia. Development (Cambridge, England) 122 12183375
1999 Longitudinal hormonal and pituitary imaging changes in two females with combined pituitary hormone deficiency due to deletion of A301,G302 in the PROP1 gene. The Journal of clinical endocrinology and metabolism 118 10084575
2002 Pituitary magnetic resonance imaging and function in patients with growth hormone deficiency with and without mutations in GHRH-R, GH-1, or PROP-1 genes. The Journal of clinical endocrinology and metabolism 101 12414875
2004 Developmental regulation of Notch signaling genes in the embryonic pituitary: Prop1 deficiency affects Notch2 expression. Developmental biology 97 14732396
1998 Human Prop-1: cloning, mapping, genomic structure. Mutations in familial combined pituitary hormone deficiency. FEBS letters 96 9824293
2001 Persistent Prop1 expression delays gonadotrope differentiation and enhances pituitary tumor susceptibility. Human molecular genetics 95 11371507
2004 PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis. The Journal of clinical endocrinology and metabolism 93 15472232
1998 Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency. The Journal of clinical endocrinology and metabolism 92 9661653
2001 PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency. The Journal of clinical endocrinology and metabolism 89 11549703
1999 Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene. The Journal of clinical endocrinology and metabolism 80 9920061
2000 Adrenocorticotropin deficiency in combined pituitary hormone deficiency patients homozygous for a novel PROP1 deletion. The Journal of clinical endocrinology and metabolism 78 11134108
2009 PROP1 coexists with SOX2 and induces PIT1-commitment cells. Biochemical and biophysical research communications 74 19442651
2001 Longitudinal imaging reveals pituitary enlargement preceding hypoplasia in two brothers with combined pituitary hormone deficiency attributable to PROP1 mutation. The Journal of clinical endocrinology and metabolism 71 11549674
2005 Mutations within the transcription factor PROP1 are rare in a cohort of patients with sporadic combined pituitary hormone deficiency (CPHD). Clinical endocrinology 70 15963055
2005 Mutation analysis of POUF-1, PROP-1 and HESX-1 show low frequency of mutations in children with sporadic forms of combined pituitary hormone deficiency and septo-optic dysplasia. Clinical endocrinology 63 15670191
2016 PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells. eLife 62 27351100
2004 Pituitary magnetic resonance imaging in 15 patients with Prop1 gene mutations: pituitary enlargement may originate from the intermediate lobe. The Journal of clinical endocrinology and metabolism 61 15126542
2002 A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty. Clinical endocrinology 53 12153609
2016 All Hormone-Producing Cell Types of the Pituitary Intermediate and Anterior Lobes Derive From Prop1-Expressing Progenitors. Endocrinology 52 26812162
2000 Combined pituitary hormone deficiency caused by a novel mutation of a highly conserved residue (F88S) in the homeodomain of PROP-1. The Journal of clinical endocrinology and metabolism 50 10946881
2002 The spectrum of hypopituitarism caused by PROP1 mutations. Best practice & research. Clinical endocrinology & metabolism 48 12464226
2008 Premature differentiation and aberrant movement of pituitary cells lacking both Hes1 and Prop1. Developmental biology 46 18996108
2005 Auxological and endocrine phenotype in a population-based cohort of patients with PROP1 gene defects. European journal of endocrinology 46 16131601
2000 MR imaging of the pituitary gland in children and young adults with congenital combined pituitary hormone deficiency associated with PROP1 mutations. AJR. American journal of roentgenology 46 10658742
2005 An uncommon phenotype with familial central hypogonadism caused by a novel PROP1 gene mutant truncated in the transactivation domain. The Journal of clinical endocrinology and metabolism 43 15941866
1999 Combined pituitary hormone deficiency: role of Pit-1 and Prop-1. Acta paediatrica (Oslo, Norway : 1992). Supplement 43 10626543
1998 A mutational hot spot in the Prop-1 gene in Russian children with combined pituitary hormone deficiency. Pituitary 41 11081182
2000 Molecular analysis of LHX3 and PROP-1 in pituitary hormone deficiency patients with posterior pituitary ectopia. The Journal of clinical endocrinology and metabolism 39 10946868
2000 Central hypocortisolism as part of combined pituitary hormone deficiency due to mutations of PROP-1 gene. European journal of endocrinology 38 11022176
2006 PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency. Clinical endocrinology 34 16984240
2003 Clinical characteristics and molecular analysis of PIT1, PROP1,LHX3, and HESX1 in combined pituitary hormone deficiency patients with abnormal pituitary MR imaging. Hormone research 34 14646405
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
2008 Molecular analysis of novel PROP1 mutations associated with combined pituitary hormone deficiency (CPHD). Clinical endocrinology 32 19128366
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
2021 The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons. eLife 31 34165428
2005 Role of prophet of Pit1 (PROP1) in gonadotrope differentiation and puberty. Endocrinology 31 16384867
2012 Short communication: A missense mutation in the PROP1 (prophet of Pit 1) gene affects male fertility and milk production traits in the US Holstein population. Journal of dairy science 30 23245960
2004 A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies. The Journal of clinical endocrinology and metabolism 30 15531542
2013 A critical functional missense mutation (H173R) in the bovine PROP1 gene significantly affects growth traits in cattle. Gene 27 24029076
2006 Combined pituitary hormone deficiency (CPHD) due to a complete PROP1 deletion. Clinical endocrinology 27 16918947
2013 High prevalence of PROP1 defects in Lithuania: phenotypic findings in an ethnically homogenous cohort of patients with multiple pituitary hormone deficiency. The Journal of clinical endocrinology and metabolism 26 24178788
2015 Genesis of two most prevalent PROP1 gene variants causing combined pituitary hormone deficiency in 21 populations. European journal of human genetics : EJHG 25 26059845
2010 Corepressors TLE1 and TLE3 interact with HESX1 and PROP1. Molecular endocrinology (Baltimore, Md.) 25 20181723
2020 PROP1-Dependent Retinoic Acid Signaling Regulates Developmental Pituitary Morphogenesis and Hormone Expression. Endocrinology 23 31913463
2011 PROP1 and CTNNB1 expression in adamantinomatous craniopharyngiomas with or without β-catenin mutations. Clinics (Sao Paulo, Brazil) 23 22086512
1999 Combined pituitary hormone deficiency in an inbred Brazilian kindred associated with a mutation in the PROP-1 gene. Molecular genetics and metabolism 23 10329025
2014 Molecular analysis of PROP1, POU1F1, LHX3, and HESX1 in Turkish patients with combined pituitary hormone deficiency: a multicenter study. Endocrine 22 25500790
2004 Prolonged jaundice and hypothyroidism as the presenting symptoms in a neonate with a novel Prop1 gene mutation (Q83X). European journal of endocrinology 22 15012608
2013 Rapid transition of NESTIN-expressing dividing cells from PROP1-positive to PIT1-positive advances prenatal pituitary development. Journal of neuroendocrinology 21 23855824
2006 [Standardization of DNA extraction with NaCl from oral mucosa cells: application in PROP1 gene study]. Arquivos brasileiros de endocrinologia e metabologia 21 16544023
2006 High prevalence of PROP1 gene mutations in Hungarian patients with childhood-onset combined anterior pituitary hormone deficiency. Endocrine 20 17526936
2016 Identification of Novel PROP1 and POU1F1 Mutations in Patients with Combined Pituitary Hormone Deficiency. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18 27756091
2011 Mutations and pituitary morphology in a series of 82 patients with PROP1 gene defects. Hormone research in paediatrics 18 22024773
2002 Pseudotumor of the pituitary due to PROP-1 deletion. Journal of pediatric endocrinology & metabolism : JPEM 18 11822586
2007 Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene. Mammalian genome : official journal of the International Mammalian Genome Society 17 17557180
2010 Identification of SNPs within the sheep PROP1 gene and their effects on wool traits. Molecular biology reports 16 21104025
2008 Pituitary changes in Prop1 transgenic mice: hormone producing tumors and signet-ring type gonadotropes. Acta histochemica et cytochemica 16 18636109
2004 A novel PROP1 gene mutation (157delA) in Japanese siblings with combined anterior pituitary hormone deficiency. Clinical endocrinology 16 15521968
2003 Two new PROP1 gene mutations responsible for compound pituitary hormone deficiency. Clinical genetics 16 12859410
2003 PROP-1 gene mutation (R120C) causing combined pituitary hormone deficiencies with variable clinical course in eight siblings of one Jewish Moroccan family. Hormone research 16 14614227
2002 Familial combined pituitary hormone deficiency caused by PROP-1 gene mutation. Growth patterns and MRI studies in untreated subjects. Hormone research 16 12006708
2013 Three-dimensional studies of Prop1-expressing cells in the rat pituitary just before birth. Cell and tissue research 15 24026438
2018 Retinoic acid signalling is a candidate regulator of the expression of pituitary-specific transcription factor Prop1 in the developing rodent pituitary. Journal of neuroendocrinology 14 29356182
2005 Short-term caloric restriction does not modify the in vivo insulin signaling pathway leading to Akt activation in skeletal muscle of Ames dwarf (Prop1(df)/Prop1(df)) mice. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 14 16308835
2000 Expression of the pituitary transcription factor Ptx-1, but not that of the trans-activating factor prop-1, is reduced in human corticotroph adenomas and is associated with decreased alpha-subunit secretion. The Journal of clinical endocrinology and metabolism 14 10902805
2012 Frequency of mutations in PROP-1 gene in Turkish children with combined pituitary hormone deficiency. The Turkish journal of pediatrics 13 23692781
2011 Three-dimensional studies of Prop1-expressing cells in the rat pituitary primordium of Rathke's pouch. Cell and tissue research 13 22113335
2011 Genetic background of Prop1(df) mutants provides remarkable protection against hypothyroidism-induced hearing impairment. Journal of the Association for Research in Otolaryngology : JARO 13 22143287
2004 Ovulation induction and successful pregnancy outcome in two patients with Prop1 gene mutations. Fertility and sterility 13 15302300
2017 Molecular analysis of brazilian patients with combined pituitary hormone deficiency and orthotopic posterior pituitary lobe reveals eight different PROP1 alterations with three novel mutations. Clinical endocrinology 12 28734020
2011 Involvement of Prop1 homeobox gene in the early development of fish pituitary gland. General and comparative endocrinology 12 21362424
2008 Basic science and clinical research advances in the pituitary transcription factors: Pit-1 and Prop-1. Current opinion in endocrinology, diabetes, and obesity 12 18594277
2008 A novel missense (A79V) mutation of goat PROP1 gene and its association with production traits. Molecular biology reports 12 19031010
2001 Insufficient adrenarche in patients with combined pituitary hormone deficiency caused by a PROP-1 gene defect. Journal of pediatric endocrinology & metabolism : JPEM 12 11592567
2015 Novel Mutations in HESX1 and PROP1 Genes in Combined Pituitary Hormone Deficiency. Hormone research in paediatrics 11 26111865
2005 High level expression of Prop-1 gene in gonadotropic cell lines. The Journal of reproduction and development 11 16394624
2002 Adrenocorticotrope deficiency with clinical evidence for late onset in combined pituitary hormone deficiency caused by a homozygous 301-302delAG mutation of the PROP1 gene. Pituitary 11 12812307
2000 Cloning, characterization, and physical mapping of the canine Prop-1 gene (PROP1): exclusion as a candidate for combined pituitary hormone deficiency in German shepherd dogs. Cytogenetics and cell genetics 11 10773688
2003 Long-term follow-up of childhood-onset hypopituitarism in patients with the PROP-1 gene mutation. Hormone research 10 14530604
2018 Gene polymorphisms in PROP1 associated with growth traits in sheep. Gene 9 30316920
2014 Circulating microRNA profiles and the identification of miR-593 and miR-511 which directly target the PROP1 gene in children with combined pituitary hormone deficiency. International journal of molecular medicine 9 25434367
2013 Suprasellar mass mimicking a hypothalamic glioma in a patient with a complete PROP1 deletion. European journal of medical genetics 9 23831233
2010 A large deletion of PROP1 gene in patients with combined pituitary hormone deficiency from two unrelated Chinese pedigrees. Hormone research in paediatrics 9 20395664
2009 Pituitary enlargement in patients with PROP1 gene inactivating mutation represents cystic hyperplasia of the intermediate pituitary lobe. Histopathology and over 10 years follow-up of two patients. Journal of pediatric endocrinology & metabolism : JPEM 9 19774847
2006 Pituitary size fluctuation in long-term MR studies of PROP1 deficient patients: A persistent pathophysiological mechanism? Journal of endocrinological investigation 9 16794371
2015 Two coexisting heterozygous frameshift mutations in PROP1 are responsible for a different phenotype of combined pituitary hormone deficiency. Journal of applied genetics 8 26608600
2013 Isolated central hypothyroidism in young siblings as a manifestation of PROP1 deficiency: clinical impact of whole exome sequencing. Hormone research in paediatrics 8 23652424
2009 Pituitary homeodomain transcription factors HESX1 and PROP1 form a heterodimer on the inverted TAAT motif. Molecular and cellular endocrinology 8 19879326
2009 Ames dwarf (Prop1(df)/Prop1(df)) mice display increased sensitivity of the major GH-signaling pathways in liver and skeletal muscle. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 8 20022531
2006 Waxing and waning of a pituitary mass in a young woman with combined pituitary hormone deficiency (CPHD) due to a PROP-1 mutation. Pituitary 8 16703408
2006 Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT). Journal of pediatric endocrinology & metabolism : JPEM 8 16759034
2019 Identification of a Novel PROP1 Mutation in a Patient with Combined Pituitary Hormone Deficiency and Enlarged Pituitary. International journal of molecular sciences 7 30988269
2015 Search for regulatory factors of the pituitary-specific transcription factor PROP1 gene. The Journal of reproduction and development 7 26640231
1999 Gene analysis of PROP1 in dwarfism with combined pituitary hormone deficiency. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 7 10549300