ASIP (Agouti Signaling Protein) Gene
Key regulator of pigmentation and melanocortin signaling
Gene Information Card
| Symbol | ASIP |
|---|---|
| Full Name | agouti signaling protein |
| Gene Type | protein coding |
| Chromosomal Location | 20q11.22 |
| NCBI Gene ID | 434 ncbi.nlm.nih.gov/gene/434 |
| Ensembl ID | ENSG00000101440 |
| UniProt ID | P42127 |
| OMIM ID | 600201 |
| HGNC ID | 742 |
| Aliases | AGTI, AGSW, ASP, SHEP9 |
Description
The ASIP gene encodes agouti signaling protein, a paracrine signaling molecule that antagonizes melanocortin 1 receptor (MC1R) signaling. It regulates eumelanin (black/brown) versus pheomelanin (yellow/red) pigment production in melanocytes. ASIP is also involved in energy homeostasis and adipocyte function through interaction with melanocortin receptors in the hypothalamus.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pigmentation variation (hair/skin color) | ASIP variants alter MC1R antagonism, shifting melanin synthesis toward pheomelanin | OMIM 600201; NCBI Gene |
| Obesity susceptibility | ASIP overexpression in transgenic mice causes yellow coat and obesity; human variants may influence energy balance via MC4R antagonism | OMIM 600201; NCBI Gene |
| Melanoma | ASIP polymorphisms (e.g., rs4911414) are associated with increased melanoma risk, possibly through altered pigmentation and UV sensitivity | ClinVar; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Skin | 8.3 | Medium |
| Testis | 6.1 | Low |
| Brain (hypothalamus) | 4.7 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Melanocytes (primary) | 15.2 | High expression |
| A375 (melanoma) | 9.8 | Moderate expression |
| SK-MEL-28 (melanoma) | 7.4 | Moderate expression |
| HEK293 (embryonic kidney) | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs4911414 (intronic variant) | SNP | 0.25 (European) | Associated with increased melanoma risk and altered ASIP expression |
| rs6058017 (3' UTR variant) | SNP | 0.15 (European) | Associated with darker pigmentation and reduced melanoma risk |
| c.199G>A (p.Ala67Thr) | Missense | Rare | Unknown functional effect; reported in pigmentation studies |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function ASIP variants are rare; predicted to reduce pheomelanin production, leading to darker pigmentation.
Gain of Function (GOF)
Gain-of-function (overexpression) increases pheomelanin synthesis, lightening coat/hair color; linked to obesity in mouse models.
Dominant Negative (DN)
No dominant-negative mutations reported for ASIP.
View complete mutation data：
Gene Ontology (GO)
| • receptor antagonist activity (GO:0005102) | • hormone activity (GO:0005179) |
| • cell-cell signaling (GO:0007267) | • osteoclast differentiation (GO:0030316) |
| • pigmentation (GO:0043473) |
Pathways
• Melanogenesis (KEGG hsa04916)
• GPCR downstream signaling (MC1R pathway)
Protein Summary
Agouti signaling protein (ASIP) is a 132-amino acid secreted protein containing a cysteine-rich C-terminal domain. It functions as an inverse agonist/antagonist of melanocortin receptors (MC1R, MC4R). By blocking MC1R activation, ASIP promotes pheomelanin synthesis. It also modulates energy homeostasis via MC4R in the hypothalamus. ASIP is structurally related to agouti-related protein (AGRP).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ASIP Knockout HEK293 Cell Line | EDJ-KQ4103 | Human | 434 | Details Get a Quote |
| RASIP1 Knockout HEK293 Cell Line | EDJ-KQ14248 | Human | 54922 | Details Get a Quote |
| RASIP1 Knockout HeLa Cell Line | EDJ-KQ45509 | Human | 54922 | Details Get a Quote |
| ASIP Knockout HeLa Cell Line | EDJ-KQ52672 | Human | 434 | Details Get a Quote |
| ASIP Knockout A-549 Cell Line | EDJ-KQ61144 | Human | 434 | Details Get a Quote |
| RASIP1 Knockout A-549 Cell Line | EDJ-KQ64992 | Human | 54922 | Details Get a Quote |
| ASIP Knockout HCT 116 Cell Line | EDJ-KQ69632 | Human | 434 | Details Get a Quote |
| RASIP1 Knockout HCT 116 Cell Line | EDJ-KQ73439 | Human | 54922 | Details Get a Quote |
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