KISS1R
Chr 19ADARKISS1 receptor
Also known as: AXOR12, CPPB1, GPR54, HH8, HOT7T175, KISS-1R
The protein encoded by KISS1R is a G protein-coupled receptor that binds kisspeptins and plays a central role in regulating the hypothalamic-pituitary-gonadal reproductive axis by modulating gonadotropin-releasing hormone secretion from hypothalamic neurons. Mutations cause hypogonadotropic hypogonadism and central precocious puberty, conditions affecting pubertal timing and reproductive endocrine function. The gene follows both autosomal dominant and autosomal recessive inheritance patterns depending on the specific condition and variant.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
240 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 7 | 1 | 28 | 0 | 36 |
Likely Pathogenic | 6 | 2 | 4 | 0 | 12 |
VUS | 5 | 100 | 17 | 0 | 122 |
Likely Benign | 0 | 3 | 21 | 24 | 48 |
Benign | 0 | 2 | 11 | 4 | 17 |
Conflicting | — | 3 | |||
| Total | 18 | 108 | 81 | 28 | 238 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KISS1R · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools