• OMIM 603286
  • Located at chromosome 1q32.1
  • Encodes kisspeptins, G protein-coupled receptor ligands (Ohtaki, Shintani et al. 2001).
  • KISS1 comprises 3 exons. The transcript, KISS1-001 ENST00000367194 (NM_002256.3), encodes a 138 amino acid precursor peptide, which is cleaved to a 54 amino acid peptide and may be further truncated to 14, 13 or 10 amino acid carboxyl-terminal fragments. These truncated peptides are known as the kisspeptins and act as ligands for the G protein-coupled receptor GPR54 (Ohtaki, Shintani et al. 2001).

Human genetics

  • KISS1 was originally identified as a human metastasis suppressor gene that has the ability to suppress melanoma and breast cancer metastases (Lee, Miele et al. 1996). Later, it became clear that kisspeptin-GPR54 signaling plays an important role in initiating secretion of the gonadotropin-releasing hormone (GnRH) at puberty (Navarro, Castellano et al. 2005; Shahab, Mastronardi et al. 2005).
  • Several missense mutations in KISS1 have been identified in GnRH-deficient patients (Chan, Broder-Fingert et al. 2011; Topaloglu, Tello et al. 2012).
  • Mutations in KISS1 are associated with familial cases of normosmic congenital hypogonadotropic hypogonadism (Gurbuz, Kotan et al. 2012). They account for less than 2% of the cases.


Chan, Y. M., S. Broder-Fingert, et al. (2011). "GnRH-deficient phenotypes in humans and mice with heterozygous variants in KISS1/Kiss1." J Clin Endocrinol Metab96(11): E1771-1781.

Gurbuz, F., L. D. Kotan, et al. (2012). "Distribution of gene mutations associated with familial normosmic idiopathic hypogonadotropic hypogonadism." J Clin Res Pediatr Endocrinol4(3): 121-126.

Lee, J. H., M. E. Miele, et al. (1996). "KiSS-1, a novel human malignant melanoma metastasis-suppressor gene." J Natl Cancer Inst88(23): 1731-1737.

Navarro, V. M., J. M. Castellano, et al. (2005). "Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54." Endocrinology146(1): 156-163.

Ohtaki, T., Y. Shintani, et al. (2001). "Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor." Nature411(6837): 613-617.

Shahab, M., C. Mastronardi, et al. (2005). "Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates." Proc Natl Acad Sci U S A102(6): 2129-2134.

Topaloglu, A. K., J. A. Tello, et al. (2012). "Inactivating KISS1 mutation and hypogonadotropic hypogonadism." N Engl J Med366(7): 629-635.

 Last updated on 17/06/2018 at 14:39