INSL3 (Insulin Like 3)
Key regulator of testicular descent and reproductive function
Gene Information Card
| Symbol | INSL3 |
|---|---|
| Full Name | insulin like 3 |
| Gene Type | protein coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 3640 ncbi.nlm.nih.gov/gene/3640 |
| Ensembl ID | ENSG00000168036 |
| UniProt ID | P51460 |
| OMIM ID | 146738 |
| HGNC ID | 6090 |
| Aliases | RLF, RLN3, Leydig insulin-like peptide, relaxin-like factor |
Description
INSL3 (insulin like 3) encodes a member of the insulin-like hormone superfamily. The protein is primarily produced by Leydig cells in the testis and by theca cells in the ovary. It plays a critical role in testicular descent during embryonic development by mediating the gubernacular reaction. INSL3 also functions in bone metabolism, germ cell survival, and metabolic regulation. Mutations in this gene are associated with cryptorchidism (undescended testis) and may contribute to male infertility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cryptorchidism | Loss-of-function mutations impair INSL3-mediated gubernacular development, preventing normal testicular descent. | OMIM #146738; ClinVar; multiple case-control studies |
| Male infertility | Reduced INSL3 signaling affects spermatogenesis and Leydig cell function. | NCBI Gene; literature review |
| Osteoporosis (potential) | INSL3 modulates bone remodeling via RXFP2 receptor; low levels associated with reduced bone density. | UniProt; experimental studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Ovary | 3.2 | Low |
| Prostate | 1.1 | Not detected |
| Adipose tissue | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Leydig cells (primary) | 45.0 | Highest expression |
| Theca cells (primary) | 8.0 | Ovarian expression |
| HEK293 | 0.1 | No endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.178G>A (p.Gly60Ser) | Missense | Rare | Reduced receptor binding; associated with cryptorchidism |
| c.27C>A (p.Cys9*) | Nonsense | Very rare | Loss of function; premature truncation |
| c.3G>A (p.Met1?) | Start loss | Rare | No protein production; cryptorchidism |
Mutation functional classification
Loss of Function (LOF)
Most INSL3 mutations are loss-of-function, leading to impaired testicular descent and cryptorchidism.
Gain of Function (GOF)
No gain-of-function mutations reported in INSL3.
Dominant Negative (DN)
No dominant-negative mutations described for INSL3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Relaxin signaling pathway (RXFP2 receptor)
• GPCR downstream signaling (cAMP/PKA)
Protein Summary
INSL3 is a 131-amino-acid preproprotein that is processed to a mature A-B heterodimer with structural homology to insulin and relaxin. It is secreted by Leydig cells and binds specifically to the RXFP2 receptor (also known as LGR8 or GREAT). The hormone-receptor interaction activates G-protein-coupled signaling, primarily increasing cAMP levels. INSL3 is essential for the first phase of testicular descent (transabdominal) and has emerging roles in bone metabolism, energy homeostasis, and male fertility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| INSL3 Knockout HEK293 Cell Line | EDJ-KQ4210 | Human | 3640 | Details Get a Quote |
| INSL3 Knockout HeLa Cell Line | EDJ-KQ53667 | Human | 3640 | Details Get a Quote |
| INSL3 Knockout A-549 Cell Line | EDJ-KQ62141 | Human | 3640 | Details Get a Quote |
| INSL3 Knockout HCT 116 Cell Line | EDJ-KQ70631 | Human | 3640 | Details Get a Quote |
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