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TNFRSF11A gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

TNFRSF11A gene

The TNFRSF11A gene provides instructions for a protein essential for bone remodeling and the regulation of bone mass.

Overview

The TNFRSF11A gene provides instructions for making a protein called receptor activator of NF-κB (RANK). This protein is critical for bone remodeling, the process where old bone is broken down and replaced by new bone. RANK is found on the surface of immature osteoclasts—specialized cells that break down bone tissue—and receives signals that trigger these cells to mature and become functional.

Health Conditions Related to Genetic Changes

Familial expansile osteolysis (FEO) and Expansile skeletal hyperphosphatasia (ESH)

These rare bone diseases are caused by duplication mutations in the TNFRSF11A gene. These mutations overactivate RANK, causing an overproduction of osteoclasts that break down bone abnormally. Features include:

  • Skeletal abnormalities
  • Tooth loss
  • Progressive hearing loss

Autosomal recessive osteopetrosis (ARO)

This rare disorder is caused by mutations that prevent the RANK protein from receiving signals, leading to a total absence of mature, functional osteoclasts. Without these cells to break down bone, excess bone forms throughout the skeleton, resulting in:

  • Abnormally dense bones
  • Increased risk of fractures
  • Vision impairment
  • Hearing loss
  • Immune system complications due to defective bone marrow

Other Names

  • CD265
  • RANK
  • Receptor activator of nuclear factor-kappa B
  • Tumor necrosis factor receptor superfamily member 11a

Frequently Asked Questions

Children with this form of osteopetrosis develop excessively dense but brittle bones, leading to frequent fractures, vision problems from optic nerve compression, and hearing loss from inner‑ear bone overgrowth. Bone marrow failure can cause anemia and infections. Management includes regular ophthalmology and audiology evaluations, hematopoietic stem‑cell transplantation (the only curative option for many patients), and supportive care such as physiotherapy, fracture protection, and antibiotics for infections. Early transplant referral improves survival and reduces neurologic complications.
Genetic testing is recommended if you have a close relative (parent, sibling, or child) diagnosed with familial expansile osteolysis (FEO) or expansile skeletal hyperphosphatasia. The test usually involves a blood draw or saliva sample, which is sent to a certified laboratory for DNA sequencing of the TNFRSF11A gene. The lab looks for duplication mutations that cause over‑activation of the RANK protein. Results typically return within 2–4 weeks, and a genetic counselor can help interpret them and discuss implications for you and your family.
Treatment focuses on slowing osteoclast overactivity. The most effective drugs are RANK‑ligand inhibitors such as denosumab, which bind to RANKL and prevent it from activating the overactive RANK receptors. Bisphosphonates may also be used, but they are less targeted. These therapies can stabilize bone density, reduce pain, and lower fracture risk, but they do not fully reverse existing bone loss. Ongoing monitoring with X‑rays or bone density scans is essential to adjust therapy.
Early signs include unexplained tooth loss, increasing bone pain (especially in the jaw, spine, or long bones), new fractures from low‑impact injuries, and progressive hearing loss due to skull bone changes. If you notice sudden severe pain, a fracture after a minor fall, or rapid loss of hearing, seek urgent medical attention, as these may signal accelerated bone destruction that requires prompt treatment to prevent permanent damage.
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.

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