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Gene Review

PROP1  -  PROP paired-like homeobox 1

Homo sapiens

Synonyms: CPHD2, Homeobox protein prophet of Pit-1, PROP-1, Pituitary-specific homeodomain factor
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Disease relevance of PROP1


High impact information on PROP1

  • These mutations in the human PROP1 gene result in a gene product with reduced DNA-binding and transcriptional activation ability in comparison to the product of the murine df mutation [5].
  • Notch signaling is required for maintaining expression of the tissue-specific paired-like homeodomain transcription factor, Prop1, which is required for generation of the Pit1 lineage [6].
  • Mutations in Prophet of PIT1 (Prop1), one of several homeodomain transcription factors that are required for the development of the anterior pituitary gland, are the predominant cause of MPHD (multiple pituitary hormone deficiency) in humans [7].
  • Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia [8].
  • Molecular genetic analyses reveal that Lhx4 and Prop1 have overlapping functions in early pituitary development [8].

Biological context of PROP1

  • Our data indicated that PROP1 expression was observed constantly both in the pituitary tumors and normal human adult pituitary tissues, suggesting that PROP1 is an essential transcriptional factor for pituitary specific gene expression in human [1].
  • The relatively normal expression pattern of GnRH receptor (Gnrhr) suggests that the pituitary gonadotrope cell lineage is appropriately specified, but the ability to synthesize LH and FSH is impaired by excess PROP1 [2].
  • Sequencing of PROP1 revealed homozygosity for a single base-pair substitution (C to T), resulting in the replacement of an Arg by a Cys at codon 120 (R120C) in the third helix of the homeodomain of the Prop-1 protein [9].
  • DESIGN AND PATIENTS: The three coding exons of PROP1, and six exons of POUF-1 in 27 children from 26 families with CPHD, and three exons of HESX1 in 23 children from 22 families with SOD were directly sequenced from a well-characterized regional cohort [3].
  • Molecular analysis of the PROP1 gene revealed compound heterozygotes for two novel missense mutations of the PROP1 gene affecting the same amino acid (Arg71Cys and Arg71His) in the first alpha helix of the Prop-1 homeodomain [10].

Anatomical context of PROP1

  • Cellular determination in the anterior pituitary gland: PIT-1 and PROP-1 mutations as causes of human combined pituitary hormone deficiency [11].
  • We conclude that 1) a large sella turcica and an enlarged pituitary anterior lobe with hyperintense enhanced signal at T1 at MRI can be suggestive of PROP1 deficiency; 2) pituitary morphology can change during follow-up of patients with PROP1 gene mutation; and 3) hormonal deficiencies could include the adrenal axis [12].
  • High level expression of Prop-1 gene in gonadotropic cell lines [13].
  • 2) The PROP-1 gene is also expressed in the adrenal cortex and, when defective, the zona reticularis does not function appropriately [14].

Associations of PROP1 with chemical compounds

  • Some degree of hypocortisolism may necessitate cortisol substitution in patients with PROP1 mutations [15].
  • The common 2-base pair deletion (GA296) in the homozygous state resulted in a Serine to Stop codon (S109X) substitution and generated a truncated Prop-1 protein [16].
  • In addition, isolated deficiencies of follicle stimulating hormone and luteinizing hormone in the corresponding specific beta-subunit genes and PROP1 gene mutations represent pituitary deficiency states, resulting in a phenotype of HH [17].
  • Importantly, 3 tandem repeats of the dinucleotides GA at location 296-302 in the PROP1 gene represent a hot spot for CPHD [18].
  • In conclusion, the substantial linear growth in adult siblings with a PROP-1 mutation illustrates that despite an advanced BA, linear growth potential remains in adulthood in the setting of sex steroid deficiency [19].

Regulatory relationships of PROP1

  • Recently, we reported evidence that Prop-1 directly regulates expression of the porcine FSHbeta gene, thus providing a novel advance in understanding the function of Prop-1 in FSH/LH production and hypogonadism [13].

Other interactions of PROP1


Analytical, diagnostic and therapeutic context of PROP1


  1. Prop-1 gene expression in human pituitary tumors. Nakamura, S., Ohtsuru, A., Takamura, N., Kitange, G., Tokunaga, Y., Yasunaga, A., Shibata, S., Yamashita, S. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  2. Role of prophet of Pit1 (PROP1) in gonadotrope differentiation and puberty. Vesper, A.H., Raetzman, L.T., Camper, S.A. Endocrinology (2006) [Pubmed]
  3. 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. Rainbow, L.A., Rees, S.A., Shaikh, M.G., Shaw, N.J., Cole, T., Barrett, T.G., Kirk, J.M. Clin. Endocrinol. (Oxf) (2005) [Pubmed]
  4. Transcription factors regulating pituitary development. Parks, J.S., Brown, M.R. Growth Horm. IGF Res. (1999) [Pubmed]
  5. Mutations in PROP1 cause familial combined pituitary hormone deficiency. Wu, W., Cogan, J.D., Pfäffle, R.W., Dasen, J.S., Frisch, H., O'Connell, S.M., Flynn, S.E., Brown, M.R., Mullis, P.E., Parks, J.S., Phillips, J.A., Rosenfeld, M.G. Nat. Genet. (1998) [Pubmed]
  6. Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesis. Zhu, X., Zhang, J., Tollkuhn, J., Ohsawa, R., Bresnick, E.H., Guillemot, F., Kageyama, R., Rosenfeld, M.G. Genes Dev. (2006) [Pubmed]
  7. Pituitary hypoplasia and respiratory distress syndrome in Prop1 knockout mice. Nasonkin, I.O., Ward, R.D., Raetzman, L.T., Seasholtz, A.F., Saunders, T.L., Gillespie, P.J., Camper, S.A. Hum. Mol. Genet. (2004) [Pubmed]
  8. Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia. Raetzman, L.T., Ward, R., Camper, S.A. Development (2002) [Pubmed]
  9. A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty. Arroyo, A., Pernasetti, F., Vasilyev, V.V., Amato, P., Yen, S.S., Mellon, P.L. Clin. Endocrinol. (Oxf) (2002) [Pubmed]
  10. Two new PROP1 gene mutations responsible for compound pituitary hormone deficiency. Paracchini, R., Giordano, M., Corrias, A., Mellone, S., Matarazzo, P., Bellone, J., Momigliano-Richiardi, P., Bona, G. Clin. Genet. (2003) [Pubmed]
  11. Cellular determination in the anterior pituitary gland: PIT-1 and PROP-1 mutations as causes of human combined pituitary hormone deficiency. Rodriguez, R., Andersen, B. Minerva Endocrinol. (2003) [Pubmed]
  12. Longitudinal hormonal and pituitary imaging changes in two females with combined pituitary hormone deficiency due to deletion of A301,G302 in the PROP1 gene. Mendonca, B.B., Osorio, M.G., Latronico, A.C., Estefan, V., Lo, L.S., Arnhold, I.J. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  13. High level expression of Prop-1 gene in gonadotropic cell lines. Aikawa, S., Sato, T., Ono, T., Kato, T., Kato, Y. J. Reprod. Dev. (2006) [Pubmed]
  14. Insufficient adrenarche in patients with combined pituitary hormone deficiency caused by a PROP-1 gene defect. Voutetakis, A., Livadas, S., Sertedaki, A., Maniati-Christidi, M., Dacou-Voutetakis, C. Journal of pediatric endocrinology & metabolism : JPEM. (2001) [Pubmed]
  15. Combined pituitary hormone deficiency: role of Pit-1 and Prop-1. Pfäffle, R.W., Blankenstein, O., Wüller, S., Kentrup, H. Acta paediatrica (Oslo, Norway : 1992). Supplement. (1999) [Pubmed]
  16. A mutational hot spot in the Prop-1 gene in Russian children with combined pituitary hormone deficiency. Fofanova, O.V., Takamura, N., Kinoshita, E., Parks, J.S., Brown, M.R., Peterkova, V.A., Evgrafov, O.V., Goncharov, N.P., Bulatov, A.A., Dedov, I.I., Yamashita, S. Pituitary (1998) [Pubmed]
  17. The molecular basis of human hypogonadotropic hypogonadism. Layman, L.C. Mol. Genet. Metab. (1999) [Pubmed]
  18. "Hot spot" in the PROP1 gene responsible for combined pituitary hormone deficiency. Deladoëy, J., Flück, C., Büyükgebiz, A., Kuhlmann, B.V., Eblé, A., Hindmarsh, P.C., Wu, W., Mullis, P.E. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  19. Long-term growth hormone therapy in adulthood results in significant linear growth in siblings with a PROP-1 gene mutation. Lee, J.K., Zhu, Y.S., Cordero, J.J., Cai, L.Q., Labour, I., Herrera, C., Imperato-McGinley, J. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  20. Combined pituitary hormone deficiency in Australian children: clinical and genetic correlates. McLennan, K., Jeske, Y., Cotterill, A., Cowley, D., Penfold, J., Jones, T., Howard, N., Thomsett, M., Choong, C. Clin. Endocrinol. (Oxf) (2003) [Pubmed]
  21. Heritable disorders of pituitary development. Parks, J.S., Brown, M.R., Hurley, D.L., Phelps, C.J., Wajnrajch, M.P. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  22. Enhanced repression by HESX1 as a cause of hypopituitarism and septooptic dysplasia. Cohen, R.N., Cohen, L.E., Botero, D., Yu, C., Sagar, A., Jurkiewicz, M., Radovick, S. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  23. A novel PROP1 gene mutation (157delA) in Japanese siblings with combined anterior pituitary hormone deficiency. Tatsumi, K.I., Kikuchi, K., Tsumura, K., Amino, N. Clin. Endocrinol. (Oxf) (2004) [Pubmed]
  24. Functional significance of prop-1 gene expression in pituitary adenomas. Usui, T., Nakamura, Y., Mizuta, H., Murabe, H., Muro, S., Suda, M., Tanaka, K., Tanaka, I., Shimatsu, A., Nakao, K. Endocr. J. (2000) [Pubmed]
  25. The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. Cogan, J.D., Wu, W., Phillips, J.A., Arnhold, I.J., Agapito, A., Fofanova, O.V., Osorio, M.G., Bircan, I., Moreno, A., Mendonca, B.B. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
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