Meyahealth
Home
ENES
HomeGeneticsGeneRSPO2 gene
Back to Gene
RSPO2 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

RSPO2 gene

The RSPO2 gene provides instructions for the R-spondin-2 protein, which regulates the Wnt signaling pathway critical for tissue development and cell activity.

Normal Function

The RSPO2 gene provides instructions for making a protein called R-spondin-2. This protein plays a role in the Wnt signaling pathway, a series of steps that affect how cells and tissues develop. Wnt signaling is essential for cell division, adhesion, and migration.

During early development, R-spondin-2 increases Wnt signaling by attaching to proteins on the cell surface to inactivate proteins that would otherwise block the Wnt pathway. This process is critical for the growth and development of the skeleton and other tissues.

Health Conditions Related to Genetic Changes

Tetra-amelia syndrome

Variants in the RSPO2 gene have been found to cause tetra-amelia syndrome type 2, a very rare condition characterized by the absence of all four limbs and, typically, a complete absence of both lungs. Most individuals with this condition are stillborn or die shortly after birth.

These variants typically result in a complete lack of functional R-spondin-2 protein. Without this protein to inactivate the blockers of the Wnt pathway, the pathway becomes dysregulated. This irregular signaling during early development leads to the poor development of limbs, organs, and other tissues.

Cancers

Genetic changes involving the RSPO2 gene are associated with various cancers, including those of the colon, stomach, lungs, liver, pancreas, and breast:

  • Chromosomal rearrangements: Translocations can disrupt the region of chromosome 8 containing the RSPO2 gene.
  • Overexpression: Increased activity of the RSPO2 gene leads to increased Wnt signaling. This results in increased cell growth and division, which can contribute to the development of cancer.

Other Names for This Gene

  • cristin2
  • R-spondin family, member 2
  • R-spondin-2

Frequently Asked Questions

Most cases of tetra-amelia syndrome type 2 caused by RSPO2 variants are sporadic, meaning they occur due to new (de novo) genetic changes and are not inherited from a parent. However, if a parent carries a balanced translocation involving the RSPO2 gene, there is a risk of passing an unbalanced chromosome to offspring. Genetic counseling is essential to determine if the case is sporadic or familial and to assess recurrence risks for future pregnancies.
Because tetra-amelia syndrome is extremely rare and often involves complex chromosomal rearrangements or specific loss-of-function variants, it is not typically part of routine prenatal screening panels. Diagnosis is usually suspected when ultrasound imaging reveals the absence of limbs and lungs. Confirmatory diagnosis requires specific genetic testing, such as whole exome sequencing or targeted gene panels, to identify variants in the RSPO2 gene or chromosomal translocations involving chromosome 8.
Mutations in the RSPO2 gene typically result in a complete lack of functional R-spondin-2 protein. This protein is normally required to inactivate blockers of the Wnt signaling pathway. Without it, Wnt signaling becomes dysregulated during early embryonic development, preventing the proper formation of limbs and lungs. Consequently, individuals with tetra-amelia syndrome type 2 are born without all four limbs and usually lack both lungs, which is incompatible with life, leading to stillbirth or death shortly after birth.
RSPO2 overexpression leads to increased Wnt signaling, which promotes uncontrolled cell growth and division, a hallmark of cancer. This gene is associated with various malignancies, including colon, stomach, lung, liver, pancreatic, and breast cancers. In many cases, this overexpression is driven by chromosomal rearrangements or translocations that disrupt the region of chromosome 8 containing the RSPO2 gene, rather than simple point mutations.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

Meyahealth

Ⓒ 2026. All rights reserved by MEYA

About UsTerms & PolicyFAQ