AGRP (Agouti Related Neuropeptide) Gene
Key regulator of energy homeostasis, appetite stimulation, and melanocortin signaling
Gene Information Card
| Symbol | AGRP |
|---|---|
| Full Name | Agouti Related Neuropeptide |
| Gene Type | protein-coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 181 ncbi.nlm.nih.gov/gene/181 |
| Ensembl ID | ENSG00000159723 |
| UniProt ID | O00253 |
| OMIM ID | 602311 |
| HGNC ID | 330 |
| Aliases | ART, AGRT, ASIP2, MGC118877 |
Description
AGRP (Agouti Related Neuropeptide) encodes a neuropeptide that acts as an endogenous antagonist of melanocortin receptors MC3R and MC4R. It is primarily expressed in the arcuate nucleus of the hypothalamus and plays a critical role in the central regulation of feeding behavior, energy expenditure, and body weight. AGRP is co-expressed with NPY and is activated under conditions of negative energy balance to stimulate appetite and reduce metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity (susceptibility) | Loss-of-function variants in AGRP may reduce appetite suppression, contributing to hyperphagia and weight gain. | ClinVar, OMIM |
| Anorexia nervosa (protective) | Gain-of-function or overexpression of AGRP increases appetite, potentially counteracting weight loss. | NCBI Gene, literature |
| Cachexia | Elevated AGRP expression in cancer cachexia models promotes appetite and may be a compensatory mechanism. | PubMed, COSMIC |
| Leptin deficiency-related obesity | AGRP expression is upregulated in leptin-deficient states, driving hyperphagia. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Hypothalamus | 12.5 | High |
| Adrenal gland | 0.8 | Low |
| Testis | 0.5 | Low |
| Placenta | 0.3 | Low |
| Cerebellum | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 0.2 | Low expression |
| SK-N-SH (neuroblastoma) | 0.1 | Not detected |
| HMC3 (microglia) | 0.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.199C>T (p.Arg67Cys) | Missense | Rare | Reduced MC4R antagonism; associated with lower BMI |
| c.26G>A (p.Arg9His) | Missense | Rare | Unknown functional effect |
| c.IVS2+1G>A | Splice donor | Rare | Likely loss-of-function; reported in obesity cohorts |
Mutation functional classification
Loss of Function (LOF)
Reduced antagonism of MC3R/MC4R leads to increased melanocortin signaling, promoting satiety and energy expenditure; associated with lower body weight.
Gain of Function (GOF)
Enhanced antagonism of MC3R/MC4R increases appetite and reduces energy expenditure; linked to obesity susceptibility.
Dominant Negative (DN)
Not reported for AGRP.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Melanocortin signaling pathway (MC3R/MC4R antagonism)
• Leptin signaling pathway
• AgRP/NPY neuron pathway in energy homeostasis
• GPCR signaling (via MC3R/MC4R)
Protein Summary
The AGRP protein is a 132-amino acid neuropeptide with a signal peptide and a C-terminal cysteine-rich domain essential for receptor binding. It is synthesized in the arcuate nucleus and released into the paraventricular nucleus to inhibit melanocortin receptors. AGRP is a potent orexigenic factor; its expression is upregulated by ghrelin and downregulated by leptin. The protein circulates in plasma and can cross the blood-brain barrier.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AGRP Knockout HEK293 Cell Line | EDJ-KQ4026 | Human | 181 | Details Get a Quote |
| AGRP Knockout HeLa Cell Line | EDJ-KQ52579 | Human | 181 | Details Get a Quote |
| AGRP Knockout A-549 Cell Line | EDJ-KQ61057 | Human | 181 | Details Get a Quote |
| AGRP Knockout HCT 116 Cell Line | EDJ-KQ69538 | Human | 181 | Details Get a Quote |
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