Reviewed March 2015
What is the official name of the FBN1 gene?
The official name of this gene is “fibrillin 1.”
FBN1 is the gene's official symbol. The FBN1 gene is also known by other names, listed below.
Read more about gene names and symbols on the About page.
What is the normal function of the FBN1 gene?
The FBN1 gene provides instructions for making a large protein called fibrillin-1. This protein is transported out of cells into the extracellular matrix, which is an intricate lattice of proteins and other molecules that forms in the spaces between cells. In this matrix, molecules of fibrillin-1 attach (bind) to each other and to other proteins to form threadlike filaments called microfibrils. Microfibrils form elastic fibers, which enable the skin, ligaments, and blood vessels to stretch. Microfibrils also provide support to more rigid tissues such as bones and the tissues that support the nerves, muscles, and lenses of the eyes.
Microfibrils store a protein called transforming growth factor beta (TGF-β), a critical growth factor. TGF-β affects development by helping to control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). Microfibrils help regulate the availability of TGF-β, which is turned off (inactivated) when stored in microfibrils and turned on (activated) when released.
How are changes in the FBN1 gene related to health conditions?
acromicric dysplasia - caused by mutations in the FBN1 gene
At least nine FBN1 gene mutations have been identified in people with acromicric dysplasia. This condition is characterized by severely short stature, short limbs, stiff joints, and distinctive facial features.
FBN1 gene mutations that cause acromicric dysplasia are located in an area of the gene called exons 41 and 42, and change single protein building blocks (amino acids) in a region of the fibrillin-1 protein called TGF-β binding-protein-like domain 5. The mutations result in a reduction and disorganization of the microfibrils. Without enough normal microfibrils to store TGF-β, the growth factor is abnormally active. These effects likely contribute to the physical abnormalities that occur in acromicric dysplasia, but the mechanisms are unclear.
It is unknown why the FBN1 gene mutations that cause acromicric dysplasia lead to short stature, while certain other FBN1 gene mutations that also increase TGF-β activity cause a disorder called Marfan syndrome (see below), which is characterized by tall stature.
isolated ectopia lentis - caused by mutations in the FBN1 gene
More than 30 mutations in the FBN1 gene have been found to cause isolated ectopia lentis. In this condition, the lens in one or both eyes is off-center (displaced), which leads to vision problems. Most of the FBN1 gene mutations that cause this condition change single amino acids in the fibrillin-1 protein. As a result, the production of normal fibrillin-1 protein is reduced, leading to a decrease in microfibril formation or the formation of impaired microfibrils. Without enough functional microfibrils to anchor the lens in its central position at the front of the eye, the lens becomes displaced, resulting in isolated ectopia lentis and related vision problems.
Ectopia lentis is classified as isolated when it occurs alone, without signs and symptoms affecting other body systems. However, some people initially diagnosed with isolated ectopia lentis caused by FBN1 gene mutations later develop additional features typical of a condition called Marfan syndrome (described below), such as abnormalities of the large blood vessel that distributes blood from the heart to the rest of the body (the aorta). In these cases, the diagnosis often changes from isolated ectopia lentis to Marfan syndrome.
Marfan syndrome - caused by mutations in the FBN1 gene
Researchers have identified more than 1,300 FBN1 gene mutations that cause Marfan syndrome, a disorder that affects the connective tissue supporting the body's joints and organs. Abnormalities in the connective tissue lead to heart and eye problems in people with this disorder. In addition, affected individuals are usually tall and slender with elongated fingers and toes and other skeletal abnormalities. Most of the mutations that cause Marfan syndrome change a single amino acid in the fibrillin-1 protein. The remaining FBN1 gene mutations result in an abnormal fibrillin-1 protein that cannot function properly. FBN1 gene mutations that cause Marfan syndrome reduce the amount of fibrillin-1 produced by the cell, alter the structure or stability of fibrillin-1, or impair the transport of fibrillin-1 out of the cell. These mutations lead to a severe reduction in the amount of fibrillin-1 available to form microfibrils. Without enough microfibrils, excess TGF-β growth factors are activated and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues and the signs and symptoms of Marfan syndrome.
Weill-Marchesani syndrome - caused by mutations in the FBN1 gene
Mutations in the FBN1 gene have also been identified in Weill-Marchesani syndrome. One of the identified mutations deletes part of the gene, leading to the production of an unstable version of the fibrillin-1 protein. The unstable protein likely interferes with the assembly of microfibrils. Abnormal microfibrils weaken connective tissue, which causes the eye, heart, and skeletal abnormalities associated with Weill-Marchesani syndrome.
- other disorders - caused by mutations in the FBN1 gene
Mutations in the FBN1 gene can cause a condition called stiff skin syndrome. This condition is characterized by very hard, thick skin covering most of the body. The abnormal skin limits movement and can lead to joint deformities called contractures that restrict the movement of certain joints. The signs and symptoms of stiff skin syndrome usually become apparent in infancy to mid-childhood.
Mutations in the FBN1 gene can cause another condition called MASS syndrome. This condition involves abnormalities in several parts of the body, including the mitral valve (one of the valves that controls blood flow through the heart), the aorta (a large blood vessel that distributes blood from the heart to the rest of the body), the skeleton, and the skin.
It is unknown why different mutations in the FBN1 gene cause such a variety of disorders.
Genetics Home Reference provides additional information about these conditions associated with changes in the FBN1 gene:
Where is the FBN1 gene located?
Cytogenetic Location: 15q21.1
Molecular Location on chromosome 15: base pairs 48,408,306 to 48,645,788
The FBN1 gene is located on the long (q) arm of chromosome 15 at position 21.1.
More precisely, the FBN1 gene is located from base pair 48,408,306 to base pair 48,645,788 on chromosome 15.
See How do geneticists indicate the location of a gene? in the Handbook.
Where can I find additional information about FBN1?
You and your healthcare professional may find the following resources about FBN1 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
What other names do people use for the FBN1 gene or gene products?
- fibrillin 1 (Marfan syndrome)
Where can I find general information about genes?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding FBN1?
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? in the Handbook.