NOG gene
The NOG gene provides instructions for making the noggin protein, which is essential for proper bone and joint development.
Normal Function
The NOG gene provides instructions for making a protein called noggin. This protein is involved in the development of many body tissues, including nerve tissue, muscles, and bones. Noggin's role in bone development makes it important for proper joint formation.
Noggin interacts with members of a group of proteins called bone morphogenetic proteins (BMPs). These proteins help control the development of bone and other tissues. In order to begin these developmental processes, BMPs attach (bind) to other proteins called receptors, and this binding stimulates specific cellular processes. The noggin protein regulates the activity of certain BMPs by attaching to them and blocking them from binding to the receptor, which leads to a decrease in BMP signaling.
Health Conditions Related to Genetic Changes
Tarsal-carpal coalition syndrome
Several mutations in the NOG gene have been identified in people with a condition called tarsal-carpal coalition syndrome. This condition is characterized by fusion of the individual bones in the wrists (the carpal bones) and in the ankles (the tarsal bones) as well as fusion at the joints between the bones that make up each finger and toe (symphalangism). Symphalangism makes the fingers and toes stiff and difficult to bend.
This condition is caused by mutations in the NOG gene that change single protein building blocks (amino acids) in the noggin protein. These mutations alter the structure or stability of noggin, impair the transport of noggin out of the cell, or reduce the protein's ability to bind to BMPs, resulting in a reduction of functional noggin protein. With decreased noggin function, BMPs abnormally stimulate bone formation in joint areas, where there should be no bone, causing the bone fusions seen in people with tarsal-carpal coalition syndrome.
Other disorders
Several other bone-related disorders are caused by mutations in the NOG gene. These gene mutations change single protein building blocks (amino acids) in the noggin protein:
- Proximal symphalangism: Characterized by fusion at the joints between the bones in the fingers and toes, particularly at the joint at the base of the digit. Other signs include abnormally short middle fingers, webbed toes, and hearing loss due to fusion of the bones in the ears (stapes fixation).
- Multiple synostoses syndrome 1: Characterized by symphalangism and characteristic facial features, such as a broad nose and thin lips. Affected individuals can have fusion of the bones in the hands, feet, hips, and upper part of the spine (cervical vertebrae).
- Stapes ankylosis with broad thumb and toes (Teunissen-Cremers syndrome): Individuals have hearing loss due to stapes fixation, farsightedness, and broad thumbs and big toes.
- Brachydactyly type B2: Characterized by short fingers and toes because the middle bone of the digit or the bone that forms the tip of the digit is abnormally small or absent.
As in tarsal-carpal coalition syndrome, the NOG gene mutations that cause these conditions reduce the amount of functional noggin protein. Because of a shared genetic cause and overlapping features, researchers have suggested that these conditions represent a spectrum of related conditions referred to as NOG-related-symphalangism spectrum disorder (NOG-SSD).