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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TACR3
tachykinin receptor 3
Chromosome 4 Β· 4q24
NCBI Gene: 6870Ensembl: ENSG00000169836.5HGNC: HGNC:11528UniProt: P29371
63PubMed Papers
21Diseases
4Drugs
17Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
sperm midpiecepositive regulation of flagellated sperm motilityphospholipase C-activating tachykinin receptor signaling pathwayplasma membranehypogonadotropic hypogonadism 11 with or without anosmiahypogonadotropic hypogonadismisolated congenital hypogonadotropic hypogonadismmenopause
✦AI Summary

TACR3 encodes tachykinin receptor 3 (NK3R), a G protein-coupled receptor with primary affinity for neuromedin-K, though it also binds substance K/neurokinin A and substance P 1. Ligand binding activates dual signaling pathways: phospholipase C activation via G(q) proteins and adenylate cyclase-mediated cAMP increase 2. Beyond its well-established reproductive function, TACR3 is widely expressed throughout the nervous system and regulates diverse physiological processes including mood, chr4 pain, learning, memory, and neurological conditions such as Alzheimer's and Parkinson's diseases 3. Clinically, loss-of-function TACR3 mutations cause hypogonadotropic hypogonadism with or without anosmia, inherited in autosomal dominant, recessive, or oligogenic patterns, making TACR3 a priority screening target alongside GNRHR in pubertal delay cases 45. Notably, TACR3 mutations appear rare in idiopathic central precocious puberty 6. Recent evidence suggests TACR3 involvement in hypoxic-ischemic encephalopathy through alternative splicing mechanisms 7, and differential TACR3 expression was identified as a biomarker in sepsis-induced acute lung injury 8. These findings indicate TACR3 functions beyond reproduction across multiple organ systems.

Sources cited
1
TACR3 receptor affinity ranking for tachykinins: neuromedin-K > substance K and substance P
PMID: 1312036
2
Neuromedin-K binding triggers G(q) and phospholipase C signaling, and adenylate cyclase activation increasing cAMP
PMID: 37391393
3
TACR3 widely expressed in nervous system; involved in mood disorders, chronic pain, learning, memory, Alzheimer's, Parkinson's disease, schizophrenia, and hypoxic-ischemic encephalopathy
PMID: 32926772
4
TACR3 mutations cause hypogonadotropic hypogonadism; TACR3 should be prioritized for genetic screening alongside GNRHR
PMID: 26680571
5
TACR3 is a G-protein coupled receptor at the top of the HPG axis; loss-of-function variants cause hypogonadotropic hypogonadism in autosomal dominant, recessive, and oligogenic patterns
PMID: 37122876
6
TACR3 gene mutations are not a frequent cause of idiopathic central precocious puberty
PMID: 24434351
7
TACR3 SNP-induced alternative splicing is associated with hypoxic-ischemic encephalopathy in neonatal rats
PMID: 31722250
8
TACR3 identified as a consensus biomarker gene for sepsis-induced acute lung injury diagnosis using machine learning
PMID: 37700323
Disease Associationsβ“˜21
hypogonadotropic hypogonadism 11 with or without anosmiaOpen Targets
0.69Moderate
hypogonadotropic hypogonadismOpen Targets
0.64Moderate
isolated congenital hypogonadotropic hypogonadismOpen Targets
0.63Moderate
menopauseOpen Targets
0.60Moderate
Hot flashesOpen Targets
0.56Moderate
Abnormality of the skeletal systemOpen Targets
0.52Moderate
isolated thyroid-stimulating hormone deficiencyOpen Targets
0.41Moderate
Kallmann syndromeOpen Targets
0.38Weak
AnxietyOpen Targets
0.38Weak
breast neoplasmOpen Targets
0.37Weak
testicular diseaseOpen Targets
0.37Weak
smoking initiationOpen Targets
0.35Weak
hypogonadismOpen Targets
0.33Weak
hypertrophic cardiomyopathyOpen Targets
0.33Weak
menopausal or post-menopausal diseaseOpen Targets
0.32Weak
digestive system neoplasmOpen Targets
0.31Weak
placenta praeviaOpen Targets
0.30Weak
Abnormality of the breastOpen Targets
0.29Weak
atrial fibrillationOpen Targets
0.29Weak
anaphylaxisOpen Targets
0.27Weak
Hypogonadotropic hypogonadism 11 with or without anosmiaUniProt
Pathogenic Variants17
NM_001059.3(TACR3):c.824G>A (p.Trp275Ter)Pathogenic
Hypogonadotropic hypogonadism 11 with or without anosmia|not provided|TACR3-related disorder|Hypogonadotropic hypogonadism
β˜…β˜…β˜†β˜†2026β†’ Residue 275
NM_001059.3(TACR3):c.1057C>T (p.Pro353Ser)Pathogenic
Hypogonadotropic hypogonadism 11 with or without anosmia|not provided|Absence of pubertal development;Hypogonadotropic hypogonadism
β˜…β˜…β˜†β˜†2025β†’ Residue 353
NM_001059.3(TACR3):c.737+1G>APathogenic
Hypogonadotropic hypogonadism 11 with or without anosmia|not provided
β˜…β˜…β˜†β˜†2023
NM_001059.3(TACR3):c.1029G>A (p.Trp343Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 343
NM_001059.3(TACR3):c.992G>A (p.Trp331Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 331
NM_001059.3(TACR3):c.247_267del (p.Trp83_Ser89del)Likely pathogenic
Hypogonadotropic hypogonadism 11 with or without anosmia
β˜…β˜†β˜†β˜†2025β†’ Residue 83
NM_001059.3(TACR3):c.1090C>T (p.Arg364Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 364
NM_001059.3(TACR3):c.737+1G>CLikely pathogenic
TACR3-related disorder
β˜…β˜†β˜†β˜†2023
NM_001059.3(TACR3):c.311_312insTCCTGGATTGCAAGTATGAAATCTTCCTGGATTTGGGAAATCT (p.Leu104_Ile105insProGlyLeuGlnValTer)Likely pathogenic
TACR3-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 104
NM_001059.3(TACR3):c.370del (p.Leu124_Val125insTer)Pathogenic
See cases
β˜…β˜†β˜†β˜†2022β†’ Residue 124
NM_001059.3(TACR3):c.447_448del (p.Ser149fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 149
NM_001059.3(TACR3):c.548+2T>CPathogenic
not provided
β˜…β˜†β˜†β˜†2016
NM_001059.3(TACR3):c.623G>A (p.Trp208Ter)Likely pathogenic
Hypogonadotropic hypogonadism 7 with or without anosmia
β˜…β˜†β˜†β˜†2014β†’ Residue 208
NM_001059.3(TACR3):c.511G>C (p.Ala171Pro)Likely pathogenic
Delayed puberty
β˜…β˜†β˜†β˜†2014β†’ Residue 171
NM_001059.3(TACR3):c.692C>T (p.Thr231Ile)Likely pathogenic
Hypogonadotropic hypogonadism 11 with or without anosmia|Autism spectrum disorder
β˜…β˜†β˜†β˜†β†’ Residue 231
NM_001059.3(TACR3):c.766T>C (p.Tyr256His)Pathogenic
Hypogonadotropic hypogonadism 11 with or without anosmia
β˜†β˜†β˜†β˜†2010β†’ Residue 256
NM_001059.3(TACR3):c.278G>A (p.Gly93Asp)Pathogenic
Hypogonadotropic hypogonadism 11 with or without anosmia|not provided
β˜†β˜†β˜†β˜†2009β†’ Residue 93
View on ClinVar β†—
Drug Targets4
ELINZANETANTApproved
Neurokinin 1 receptor antagonist
breast neoplasm
FEZOLINETANTApproved
Neurokinin 3 receptor antagonist
PAVINETANTPhase II
Neurokinin 3 receptor antagonist
Netherton syndrome
TALNETANTPhase II
Neurokinin 3 receptor antagonist
irritable bowel syndrome
Related Genes
PROK2Protein interaction95%KISS1Protein interaction91%PDYNProtein interaction91%CHD7Protein interaction84%CHKBProtein interaction73%GNRH1Protein interaction72%
Tissue Expression6 tissues
Brain
100%
Lung
6%
Bone Marrow
3%
Ovary
0%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
TACR3PROK2KISS1PDYNCHD7CHKBGNRH1
PROTEIN STRUCTURE
Preparing viewer…
PDB8JBG Β· 2.80 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.21LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.92 [0.71–1.21]
RankingsWhere TACR3 stands among ~20K protein-coding genes
  • #7,412of 20,598
    Most Researched63
  • #641of 1,025
    FDA-Approved Drug Targets2
  • #2,351of 5,498
    Most Pathogenic Variants17
  • #12,721of 17,882
    Most Constrained (LOEUF)1.21
Genes detectedTACR3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A diagnostic model for sepsis-induced acute lung injury using a consensus machine learning approach and its therapeutic implications.
PMID: 37700323
J Transl Med Β· 2023
1.00
2
Tacr3/NK3R: Beyond Their Roles in Reproduction.
PMID: 32926772
ACS Chem Neurosci Β· 2020
0.90
3
Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking.
PMID: 39884015
Ecotoxicol Environ Saf Β· 2025
0.80
4
Association study of TAC3 and TACR3 gene polymorphisms with idiopathic precocious puberty in Chinese girls.
PMID: 25153567
J Pediatr Endocrinol Metab Β· 2015
0.70
5
Genetics of Hypogonadotropic Hypogonadism.
PMID: 26680571
Endocr Dev Β· 2016
0.60