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SIX1 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

SIX1 gene

The SIX1 gene provides instructions for a transcription factor that is essential for the normal development of various tissues, including the ears, kidneys, and neck.

Normal Function

The SIX1 gene is part of a group of similar genes known as the SIX gene family. Genes in this family provide instructions for making proteins that bind to DNA and control the activity of other genes. Based on this role, SIX proteins are called transcription factors.

The SIX1 protein interacts with several other proteins, including the protein produced from the EYA1 gene, to regulate the activity of genes that are important for normal development. Before birth, these protein interactions appear to be essential for the normal formation of many tissues, including:

  • The second branchial arch (which gives rise to tissues in the front and side of the neck)
  • The ears
  • The kidneys
  • The nose
  • The thymus (a gland that is part of the immune system)
  • Skeletal muscles (muscles used for movement)

Health Conditions Related to Genetic Changes

Branchiootorenal/branchiootic syndrome

At least nine mutations in the SIX1 gene have been identified in people with branchiootorenal (BOR) syndrome, a condition that disrupts the development of tissues in the neck and causes malformations of the ears and kidneys. A few SIX1 gene mutations have also been found to cause branchiootic (BO) syndrome, which includes many of the same features as BOR syndrome except for kidney (renal) malformations. The two conditions are otherwise so similar that researchers often consider them together (BOR/BO syndrome or branchiootorenal spectrum disorders).

Most of the known SIX1 gene mutations change single protein building blocks (amino acids) in the SIX1 protein. Some of these mutations prevent the SIX1 protein from interacting with other proteins, such as the protein produced from the EYA1 gene. Other mutations affect the ability of SIX1 protein to bind to DNA. Both of these functions are necessary for the SIX1 protein to regulate gene activity during embryonic development. When the SIX1 protein is faulty, it impairs the normal development of many tissues before birth.

Frequently Asked Questions

Management often involves regular hearing tests, kidney function monitoring (including ultrasounds and blood tests), and evaluation for neck cysts or fistulas. Surgical intervention may be needed for severe ear malformations, neck cysts, or kidney issues. A multidisciplinary team including audiologists, nephrologists, and ENTs is often involved.
Key signs include malformations of the ears (e.g., pits, tags, hearing loss), cysts or fistulas in the neck, and kidney problems (ranging from mild to severe, including absence or malformation of kidneys). If you notice any of these features, especially in a newborn or child, consult a doctor for evaluation.
Diagnosis usually begins with a clinical evaluation of symptoms. Genetic testing, often a blood test, is then performed to look for specific mutations in the SIX1 gene. This can confirm the diagnosis and help differentiate between BOR and BO syndrome based on the presence or absence of kidney involvement.
BOR/BO syndrome is typically inherited in an autosomal dominant pattern. This means if one parent has a SIX1 gene mutation, each child has a 50% chance of inheriting the mutation and developing the condition. Genetic counseling can provide a more personalized risk assessment.
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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