POU1F1 (POU class 1 homeobox 1)

2014-02-01   Jean-Louis Franc , Denis Becquet , Anne-Marie François-Bellan 

CRN2M, UMR7286 Aix-Marseille Universite, CNRS, Faculte de Medecine, Bd P. Dramard, Marseille, France





The anterior pituitary-specific transcription factor POU1F1 was initially identified and cloned as a transactivator of prolactin (PRL), growth hormone (GH), and TSHβ-subunit genes (Bodner et al., 1988; Ingraham et al., 1988). Transcription produces 2 alternatively spliced mRNAs α (NM_000306.2) and β (NM_001122757.1).
Atlas Image
Structure of POU1F1 gene and its transcripts encoded on minus strand of chromosome 3.


The human POU1F1 gene is composed of 6 exons (Theill et al., 1992).


Two transcripts have been reported for this gene.


Atlas Image


The main protein isoform expressed in pituitary cells is POU1F1α. This isoform, also named PIT-1.b or PIT-1α, has 291 aa. The predicted protein corresponding to POU1F1β, also named PIT-1.a or PIT-1β, has 317 aa and acts as a repressor in pituitary cells (Theill et al., 1992; Jonsen et al., 2009). POU1F1 is structurally related to the POU family of transcriptional regulators, containing a characteristic POU domain divided into two regions, the POU-specific and homeo subdomains. The POUs-specific domain consists of 75 amino acids, comprises 4 α-helices, and contributes to the DNA binding specificity and protein / protein interactions (Ingraham et al., 1990; Jacobson et al., 1997). The homeodomain is composed of 60 amino and contains 3 α-helices. The N-terminal part of POU1F1 is involved in the transcriptional activity. POU1F1 binds as a dimer to most DNA response elements (for review see Phillips and Luisi, 2000).


The expression of POU1F1 is largely restricted in the pituitary gland in somato- thyreo- and lacto-trope cells, but this factor is also expressed in some extrapituitary tissues and cell lines, including the mammary gland (Gil-Puig et al., 2002).


The localization of POU1F1 is nuclear.


POU1F1 is a member of the POU family of transcription factors. This factor is required for terminal differentiation of the somatotrope, lactotrope and thyrotrope cell types (Ingraham et al., 1988; Cohen et al., 1996). This factor is also implicated in the cell growth and prevents the apoptotic cell death (Pellegrini et al., 2006).



In humans, mutation in the POU1F1 gene has been shown to be responsible for combined pituitary hormone deficiency (for review see Quentien et al., 2006) (see below).

Implicated in

Entity name
Pituitary adenoma
POU1F1 is overexpressed in GH, PRL and TSH pituitary adenomas (Asa et al., 1993; Delhase et al., 1993; Pellegrini et al., 1994) and the increased expression in adenomas is compatible with the role of POU1F1 in cell proliferation. Interestingly, human non-functioning pituitary adenomas also express POU1F1, especially it was expressed in all alpha SU positive nonfunctioning adenomas (Osamura et al., 1999).
Entity name
Combined pituitary hormone deficiency (CPHD)
In humans, mutation in the POU1F1 gene has been shown to be responsible for combined pituitary hormone deficiency. This syndrome is a disease characterized by the lack of PRL, GH, and TSHbeta produced by the somato- lacto- and thyreo-tropes cells. At least sixteen distinct recessive or dominant POU1F1 mutations have been described to date (Cushman et al., 2002; Dattani, 2005). The molecular mechanisms underlying their effects can be dominant inhibition of transcription or inability to bind to DNA. The R271W mutation is the most commonly occurring POU1F1 gene defect (Radovick et al., 1992). Other mutations, such as F135C, show a decreased transactivation activity although the DNA binding property is conserved (Vallette-Kasic et al., 2001).
Atlas Image
Location of the Pit-1 gene mutation.
Entity name
Breast carcinoma
POU1F1 was expressed in normal human breast tissue but its mRNA expression levels is significantly higher in breast adenocarcinoma. This deregulation promotes tumor growth and metastasis (Gil-Puig et al., 2005; Ben-Batalla et al., 2010).
In acute myeloid leukemia POU1F1 has been identified as a new fusion partner of NUP98 gene (Lisboa et al., 2013).


Pubmed IDLast YearTitleAuthors
80773211993Cell type-specific expression of the pituitary transcription activator pit-1 in the human pituitary and pituitary adenomas.Asa SL et al
210601492010Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis.Ben-Batalla I et al
29029271988The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein.Bodner M et al
88799851996Role of Pit-1 in the gene expression of growth hormone, prolactin, and thyrotropin.Cohen LE et al
121736882002Genetic defects in the development and function of the anterior pituitary gland.Cushman LJ et al
160609042005Growth hormone deficiency and combined pituitary hormone deficiency: does the genotype matter?Dattani MT et al
82974691993Pit-1/GHF-1 expression in pituitary adenomas: further analogy between human adenomas and rat SMtTW tumours.Delhase M et al
160618412005Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation.Gil-Puig C et al
23507821990The POU-specific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions.Ingraham HA et al
90092031997Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.Jacobson EM et al
195563462009The 26-amino acid beta-motif of the Pit-1beta transcription factor is a dominant and independent repressor domain.Jonsen MD et al
233320172013POU1F1 is a novel fusion partner of NUP98 in acute myeloid leukemia with t(3;11)(p11;p15).Lisboa S et al
110812071999Pit-1 positive alpha-subunit positive nonfunctioning human pituitary adenomas: a dedifferentiated GH cell lineage?Osamura RY et al
169019732006Involvement of the pituitary-specific transcription factor pit-1 in somatolactotrope cell growth and death: an approach using dominant-negative pit-1 mutants.Pellegrini I et al
111837722000The virtuoso of versatility: POU proteins that flex to fit.Phillips K et al
168791622006Pituitary transcription factors: from congenital deficiencies to gene therapy.Quentien MH et al
15092621992A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency.Radovick S et al
16009471992Differential splicing of the GHF1 primary transcript gives rise to two functionally distinct homeodomain proteins.Theill LE et al
112227422001Combined pituitary hormone deficiency due to the F135C human Pit-1 (pituitary-specific factor 1) gene mutation: functional and structural correlates.Vallette-Kasic S et al

Other Information

Locus ID:

NCBI: 5449
MIM: 173110
HGNC: 9210
Ensembl: ENSG00000064835


dbSNP: 5449
ClinVar: 5449
TCGA: ENSG00000064835


Gene IDTranscript IDUniprot

Expression (GTEx)


Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
185141602008Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function.46
207340642010A large-scale candidate gene association study of age at menarche and age at natural menopause.38
208106042010Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer.34
206341972010Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium.25
204530002010A Large-scale genetic association study of esophageal adenocarcinoma risk.23
194532612009High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men.20
168791622006Pituitary transcription factors: from congenital deficiencies to gene therapy.15
175652742007Sodium-dependent phosphate cotransporters and vascular calcification.15
160618412005Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation.14
210601492010Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis.14


Jean-Louis Franc ; Denis Becquet ; Anne-Marie François-Bellan

POU1F1 (POU class 1 homeobox 1)

Atlas Genet Cytogenet Oncol Haematol. 2014-02-01

Online version: http://atlasgeneticsoncology.org/gene/46362/pou1f1-(pou-class-1-homeobox-1)