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Reviewed July 2014

What is the official name of the FAT4 gene?

The official name of this gene is “FAT atypical cadherin 4.”

FAT4 is the gene's official symbol. The FAT4 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 FAT4 gene?

The FAT4 gene provides instructions for making a protein that is found in most tissues. The protein spans the membrane surrounding cells so that part of the protein is outside the cell and part of the protein is inside the cell. The precise function of the FAT4 protein is largely unknown; however, research shows that the FAT4 protein is likely involved in determining the position of various components within cells (cell polarity). The FAT4 protein is also thought to function as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way.

Does the FAT4 gene share characteristics with other genes?

The FAT4 gene belongs to a family of genes called CDH (cadherins).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? in the Handbook.

How are changes in the FAT4 gene related to health conditions?

Hennekam syndrome - caused by mutations in the FAT4 gene

At least seven mutations in the FAT4 gene have been found to cause Hennekam syndrome, an inherited disorder resulting from malformation of the lymphatic system, which consists of a network of vessels that transport lymph fluid and immune cells throughout the body. The FAT4 gene mutations that cause Hennekam syndrome reduce the activity of the FAT4 protein, which seems to impair normal development of the lymphatic system. However, the mechanism is unknown. A poorly formed lymphatic system leads to lymphatic vessels that are abnormally expanded (lymphangiectasia) and are prone to break open (rupture), puffiness or swelling caused by a buildup of fluid (lymphedema), and other features of Hennekam syndrome. FAT4 gene mutations account for about 25 percent of all cases of Hennekam syndrome.

other disorders - caused by mutations in the FAT4 gene

Mutations in the FAT4 gene have also been found in individuals who have van Maldergem syndrome, a condition characterized by intellectual disability, hearing loss, skeletal abnormalities, and a brain malformation called periventricular heterotopia. The FAT4 gene mutations that cause van Maldergem syndrome lead to a decrease in FAT4 protein function. It is thought that a decrease in FAT4 protein activity in the brain disrupts the polarity of nerve cells in the brain, which leads to periventricular heterotopia.

It is unknown how mutations in the FAT4 gene can cause the signs and symptoms of van Maldergem syndrome in some people but lead to different signs and symptoms in those with Hennekam syndrome (described above). One mutation that replaces the protein building block (amino acid) glutamic acid with the amino acid lysine at position 2375 in the FAT4 protein (written as Glu2375Lys or E2375K) has been found in both individuals with van Maldergem syndrome and those with Hennekam syndrome.

FAT4 gene mutations have also been found in many types of cancers, including a type of skin cancer called head and neck squamous cell carcinoma, an aggressive form of skin cancer called melanoma, a liver cancer called hepatocellular carcinoma, stomach (gastric) cancer, and pancreatic cancer. The FAT4 gene mutations involved in these cancers are different from the ones that cause van Maldergem syndrome and Hennekam syndrome (described above). The FAT4 gene mutations associated with cancers are called somatic mutations; they are found only in cells that become cancerous and are not inherited. It is likely that these mutations prevent the FAT4 protein from acting as a tumor suppressor, contributing to the uncontrollable growth and division of cells that is characteristic of cancer. People with van Maldergem syndrome and Hennekam syndrome are not thought to have an increased risk of developing cancer.

Where is the FAT4 gene located?

Cytogenetic Location: 4q28.1

Molecular Location on chromosome 4: base pairs 125,315,897 to 125,492,932

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBIThis link leads to a site outside Genetics Home Reference.)

The FAT4 gene is located on the long (q) arm of chromosome 4 at position 28.1.

The FAT4 gene is located on the long (q) arm of chromosome 4 at position 28.1.

More precisely, the FAT4 gene is located from base pair 125,315,897 to base pair 125,492,932 on chromosome 4.

See How do geneticists indicate the location of a gene? in the Handbook.

Where can I find additional information about FAT4?

You and your healthcare professional may find the following resources about FAT4 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 FAT4 gene or gene products?

  • cadherin family member 14
  • cadherin-related family member 11
  • CDHF14
  • CDHR11
  • FATJ
  • FAT-J
  • fat-like cadherin protein FAT-J
  • FAT tumor suppressor homolog 4
  • NBLA00548
  • protocadherin Fat 4
  • VMLDS2

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 FAT4?

amino acid ; atypical ; cancer ; carcinoma ; cell ; disability ; gastric ; gene ; glutamic acid ; hepatocellular carcinoma ; inherited ; liver cancer ; lymph ; lymphatic system ; lymphedema ; lysine ; malformation ; melanoma ; mutation ; pancreatic ; protein ; rupture ; stomach ; syndrome ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References (5 links)


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 healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

Reviewed: July 2014
Published: February 1, 2016