TACR3 (Tachykinin Receptor 3)
A G protein-coupled receptor for neurokinin B, involved in GnRH secretion and puberty onset.
Gene Information Card
| Symbol | TACR3 |
|---|---|
| Full Name | Tachykinin Receptor 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q24 |
| NCBI Gene ID | 6870 ncbi.nlm.nih.gov/gene/6870 |
| Ensembl ID | ENSG00000169836 |
| UniProt ID | P29371 |
| OMIM ID | 162332 |
| HGNC ID | 11526 |
| Aliases | NK3R, NKR, TAC3R, HH11 |
Description
TACR3 encodes the neurokinin B receptor (NK3R), a G protein-coupled receptor that binds neurokinin B (encoded by TAC3). NK3R is expressed in the hypothalamus and plays a critical role in the regulation of gonadotropin-releasing hormone (GnRH) secretion, thereby controlling puberty onset and reproductive function. Loss-of-function mutations in TACR3 cause normosmic isolated hypogonadotropic hypogonadism (nIHH) with delayed or absent puberty.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypogonadotropic Hypogonadism 11 (HH11) | Loss-of-function mutations in TACR3 impair neurokinin B signaling, reducing GnRH secretion and causing delayed puberty or infertility. | OMIM #614840; multiple familial and sporadic cases reported. |
| Normosmic Isolated Hypogonadotropic Hypogonadism (nIHH) | Same mechanism as HH11; TACR3 mutations disrupt the kisspeptin/neurokinin B/dynorphin (KNDy) neuron pathway. | ClinVar; Topaloglu et al. (2009) Nat Genet. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (hypothalamus) | 5.2 | Medium |
| Testis | 1.8 | Low |
| Ovary | 1.5 | Low |
| Placenta | 0.9 | Low |
| Adrenal gland | 0.6 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 3.1 | Moderate expression |
| HEK293 (embryonic kidney) | 0.2 | Very low |
| HepG2 (liver) | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.738_739delCT (p.Cys247*) | Frameshift / nonsense | Rare | Loss of function; truncated protein |
| c.1003C>T (p.Arg335Trp) | Missense | <0.01% (gnomAD) | Impaired receptor activation |
| c.1129G>A (p.Gly377Ser) | Missense | <0.01% | Reduced cell surface expression |
| c.1282C>T (p.Arg428Cys) | Missense | <0.01% | Loss of ligand binding |
Mutation functional classification
Loss of Function (LOF)
Most TACR3 mutations in nIHH are loss-of-function, leading to impaired neurokinin B binding, reduced G protein signaling, or defective trafficking to the cell membrane.
Gain of Function (GOF)
No gain-of-function mutations have been reported in TACR3.
Dominant Negative (DN)
No dominant-negative effects have been described; inheritance is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity (GO:0004930) | • neurokinin B receptor activity (GO:0004996) |
| • neurokinin receptor activity (GO:0008188) | • plasma membrane (GO:0005886) |
| • signal transduction (GO:0007165) | • positive regulation of GnRH secretion (GO:0060224) |
Pathways
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
• GnRH signaling pathway (KEGG: hsa04912)
• Kisspeptin/neurokinin B/dynorphin (KNDy) pathway
Protein Summary
The TACR3 protein (NK3R) is a 465-amino-acid G protein-coupled receptor with seven transmembrane domains. It is activated by neurokinin B, leading to intracellular calcium mobilization and activation of the phospholipase C pathway. NK3R is essential for pulsatile GnRH release; its dysfunction results in hypogonadotropic hypogonadism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TACR3 Knockout HEK293 Cell Line | EDJ-KQ1603 | Human | 6870 | Details Get a Quote |
| TACR3 Knockout HeLa Cell Line | EDJ-KQ54608 | Human | 6870 | Details Get a Quote |
| TACR3 Knockout A-549 Cell Line | EDJ-KQ63088 | Human | 6870 | Details Get a Quote |
| TACR3 Knockout HCT 116 Cell Line | EDJ-KQ71561 | Human | 6870 | Details Get a Quote |
