Meyahealth
HomeGeneticsGeneTYROBP gene
Back to Gene
TYROBP gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

TYROBP gene

The TYROBP gene encodes a protein that acts as an immune signaling adaptor, playing a critical role in bone remodeling and brain health.

Normal Function

The TYROBP gene provides instructions for making the TYRO protein tyrosine kinase binding (TYROBP) protein. Found on the surface of myeloid and lymphoid immune cells, this protein helps transmit chemical signals that activate the cell.

TYROBP forms a complex with other proteins, such as the one produced by the TREM2 gene. This complex is involved in several key biological processes:

  • Immune Response: It activates cells like natural killer cells and dendritic cells to trigger inflammatory responses.
  • Skeletal System: It is found in osteoclasts, cells responsible for breaking down and resorbing bone tissue during the normal process of bone remodeling.
  • Central Nervous System: It functions in microglia, immune cells that protect the brain and spinal cord by removing dead nerve cells and debris.

Health Conditions Related to Genetic Changes

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

Variants in the TYROBP gene are linked to polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL).

  • Mechanism: The condition is caused by defective TYROBP-TREM2 signaling in osteoclasts and microglia.
  • Bone Impact: Malfunctioning osteoclasts are less able to resorb bone tissue, leading to the bone abnormalities characteristic of the disorder.
  • Neurological Impact: Defective signaling causes widespread abnormalities in microglia, which are associated with the neurological problems seen in PLOSL patients.

Other Names for This Gene

  • DAP12
  • DNAX-activation protein 12
  • KAR-associated protein
  • KARAP
  • killer activating receptor associated protein
  • TYOBP_HUMAN

Frequently Asked Questions

Typical findings include diffuse osteosclerosis with cystic lesions on X‑ray or CT of the long bones and skull, and white‑matter changes on brain MRI (hyperintense lesions in the periventricular and subcortical regions). Serum calcium, phosphate, alkaline phosphatase, and parathyroid hormone are usually normal, helping to rule out metabolic bone diseases. Genetic testing confirming biallelic TYROBP (or TREM2) mutations clinches the diagnosis.
Experimental approaches such as CSF‑penetrant anti‑inflammatory agents, microglial colony‑stimulating factor (CSF1R) modulators, or gene‑therapy delivery of functional TYROBP are under investigation. To date, no approved therapy reverses the leukoencephalopathy, but early enrollment in clinical trials may offer neuroprotective benefits.
TYROBP disease follows an autosomal‑recessive pattern. Each sibling of an affected individual has a 25 % chance of being affected, a 50 % chance of being a carrier, and a 25 % chance of being unaffected non‑carrier. Carrier testing for at‑risk relatives, prenatal diagnosis via chorionic villus sampling or amniocentesis, and pre‑implantation genetic testing for embryos are available to prevent recurrence.
Loss‑of‑function TYROBP variants impair DAP12‑mediated signaling in osteoclasts, the cells that resorb bone. Without proper activation, osteoclasts cannot remodel bone efficiently, leading to sclerotic, brittle bone tissue that fractures easily and causes chronic pain. This defective remodeling underlies the polycystic lipomembranous osteodysplasia seen in PLOSL.
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