KISS1 Gene: Kisspeptin 1 - Function, Disease Associations, and Expression
Comprehensive biomedical overview of KISS1, encoding kisspeptin, a key regulator of reproduction and cancer metastasis suppressor.
Gene Information Card
| Symbol | KISS1 |
|---|---|
| Full Name | KiSS-1 metastasis suppressor |
| Gene Type | protein-coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 3814 ncbi.nlm.nih.gov/gene/3814 |
| Ensembl ID | ENSG00000170498 |
| UniProt ID | Q15726 |
| OMIM ID | 603286 |
| HGNC ID | 6341 |
| Aliases | KiSS-1, metastin, kisspeptin-1, KISS1 metastasis suppressor |
Description
The KISS1 gene encodes a precursor protein that is proteolytically processed into kisspeptin peptides, including kisspeptin-54 (metastin), kisspeptin-14, kisspeptin-13, and kisspeptin-10. Kisspeptins are endogenous ligands for the G protein-coupled receptor KISS1R (GPR54). They play a critical role in the regulation of the hypothalamic-pituitary-gonadal axis by stimulating gonadotropin-releasing hormone (GnRH) secretion, thereby controlling puberty onset and reproductive function. Additionally, KISS1 functions as a metastasis suppressor in various cancers, inhibiting tumor cell migration and invasion. Mutations in KISS1 are associated with idiopathic hypogonadotropic hypogonadism (IHH) and central precocious puberty (CPP).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Idiopathic Hypogonadotropic Hypogonadism (IHH) | Loss-of-function mutations in KISS1 impair kisspeptin signaling, leading to deficient GnRH secretion and hypogonadotropic hypogonadism. | ClinVar; OMIM (603286); PMID: 20096378 |
| Central Precocious Puberty (CPP) | Gain-of-function mutations in KISS1 (e.g., p.Pro74Ser, p.His90Asp) increase kisspeptin activity, causing early activation of the reproductive axis. | ClinVar; OMIM (603286); PMID: 20096378 |
| Cancer Metastasis Suppression | KISS1 expression is downregulated in metastatic tumors (e.g., melanoma, breast, ovarian, bladder); loss of kisspeptin promotes metastasis. | COSMIC; PMID: 10647956; PMID: 11287908 |
| Kallmann Syndrome (in some cases) | KISS1 mutations may contribute to the phenotype, though primarily associated with other genes. | OMIM; PMID: 20096378 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | High (nTPM ~ 100) | High |
| Hypothalamus | Moderate (nTPM ~ 10-20) | Medium |
| Testis | Low (nTPM ~ 5) | Low |
| Ovary | Low (nTPM ~ 3) | Low |
| Pancreas | Low (nTPM ~ 2) | Low |
| Liver | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | Low | KISS1 expression is reduced in metastatic breast cancer cell lines. |
| MDA-MB-231 (breast cancer) | Very low | Metastatic cell line with low KISS1. |
| HeLa (cervical cancer) | Moderate | Expression present but functional role unclear. |
| HUVEC (endothelial) | Low | Kisspeptin may affect angiogenesis. |
| SH-SY5Y (neuroblastoma) | Moderate | Neuronal cell line expressing KISS1. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.220C>T (p.Pro74Ser) | Missense | Rare (found in CPP) | Gain-of-function; increases kisspeptin potency. |
| c.268C>G (p.His90Asp) | Missense | Rare (found in CPP) | Gain-of-function; enhances receptor activation. |
| c.374G>A (p.Arg125His) | Missense | Rare (found in IHH) | Loss-of-function; impairs kisspeptin signaling. |
| c.1A>G (p.Met1Val) | Start codon loss | Very rare | Loss-of-function; abolishes translation. |
| c.IVS1+1G>A | Splice site | Very rare | Loss-of-function; splicing defect. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or eliminate kisspeptin production or its ability to activate KISS1R, leading to hypogonadotropic hypogonadism and delayed puberty.
Gain of Function (GOF)
Mutations that increase kisspeptin stability or receptor affinity, leading to precocious puberty.
Dominant Negative (DN)
No dominant-negative mutations reported for KISS1; it is a secreted ligand, and mutations are typically recessive or haploinsufficient.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Kisspeptin/KISS1R signaling pathway (GPCR pathway)
• GnRH secretion pathway
• Regulation of puberty
• Metastasis suppression pathway (inhibits tumor invasion)
Protein Summary
The KISS1 gene encodes a 145-amino acid precursor protein that is cleaved into several kisspeptin peptides. Kisspeptin-54 (metastin) is the major product, which binds to the KISS1R (GPR54) receptor, a Gq/11-coupled receptor, leading to phospholipase C activation, intracellular calcium mobilization, and MAPK signaling. In the hypothalamus, kisspeptin stimulates GnRH neurons, triggering the release of GnRH and subsequent gonadotropin secretion. In cancer, kisspeptin acts as a metastasis suppressor by inhibiting tumor cell migration, invasion, and angiogenesis. The protein is expressed in placenta, brain (hypothalamus), and gonads, with lower levels in other tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KISS1 Knockout HEK293 Cell Line | EDJ-KQ5070 | Human | 3814 | Details Get a Quote |
| KISS1R Knockout HEK293 Cell Line | EDJ-KQ10147 | Human | 84634 | Details Get a Quote |
| KISS1R Knockout HCT 116 Cell Line | EDJ-KQ37248 | Human | 84634 | Details Get a Quote |
| KISS1 Knockout HeLa Cell Line | EDJ-KQ53740 | Human | 3814 | Details Get a Quote |
| KISS1R Knockout HeLa Cell Line | EDJ-KQ57624 | Human | 84634 | Details Get a Quote |
| KISS1 Knockout A-549 Cell Line | EDJ-KQ62215 | Human | 3814 | Details Get a Quote |
| KISS1R Knockout A-549 Cell Line | EDJ-KQ66122 | Human | 84634 | Details Get a Quote |
| KISS1 Knockout HCT 116 Cell Line | EDJ-KQ70701 | Human | 3814 | Details Get a Quote |
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