KISS1R

Chr 19p13.3

KISS1 receptor

Aliases:: HOT7T175, AXOR12
MANE:: ENST00000234371.10

OMIM: 604161 ↗NCBI: 84634 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

KISS1R · Q969F8

v62025-08-01

Predicted Aligned Error matrix for KISS1R — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

75.3/ 100

Confident

398 residues

Confidence breakdown

Very high(≥ 90)33%
Confident(70–90)35%
Low(50–70)10%
Very low(< 50)21%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Hypogonadotropic hypogonadism
BIALLELIC, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism (GMS)
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Inherited non-medullary thyroid cancer
Unknown

Disease associations (Open Targets)

Kallmann syndrome
0.76
hypogonadotropic hypogonadism 8 with or without anosmia
0.58
central precocious puberty
0.47
hypogonadotropic hypogonadism
0.47
central precocious puberty 1
0.44
neurodegenerative disease
0.37
pituitary stalk interruption syndrome
0.28
urogenital tract malformation
0.27
disease of genitourinary system
0.27
hereditary disease
0.19

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

KiSS-1 receptor

Receptor for kisspeptins (kisspeptin-10, kisspeptin-13, kisspeptin-14 and metastin/kisspeptin-54) (PubMed:11457843, PubMed:11527393, PubMed:15020672, PubMed:15596153). The hypothalamic KISS1/KISS1R signaling system plays a central role in the regulation of the hypothalamic-pituitary-gonadal reproductive axis by modulating the secretion of gonadotropin-releasing hormone (GnRH) from GnRH neurons (PubMed:12944565, PubMed:14573733, PubMed:15598687, PubMed:17164310, PubMed:18272894). In these neurons, kisspeptin binding to its receptor activates G(q)-dependent signaling, leading to phospholipase C (PLC) activation, and hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:14573733, PubMed:15598687, PubMed:39151001). The subsequent rise in intracellular calcium levels results in the inhibition of inward rectifier potassium channels and activation of TRPC-like cation channels, leading to GnRH neurons depolarization and stimulation (By similarity). In addition to this pathway, kisspeptin also triggers G(q)-independent signaling via beta-arrestin, leading to MAPK cascade activation and ERK1/ERK2 phosphorylation (PubMed:25147978). Furthermore, activation of KISS1R by kisspeptin-10 recruits phosphatase DUSP18 and SRC to the KISS1R C-terminus through a G(q)-dependent signaling pathway, leading to DUSP18-mediated dephosphorylation of SRC (PubMed:38346942). In bone tissue, this results in down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption (By similarity). KISS1R is also involved in the regulation of other processes, including cell proliferation and cell migration (PubMed:11457843, PubMed:11527393, PubMed:15020672, PubMed:15596153, PubMed:38512807)