What is SETBP1?

What is SETBP1?

The SETBP1 gene is located on the long (q) arm of chromosome 18 at position 12.3. This gene contains the instructions to produce SETBP1 protein. The protein is shown to be active in numerous tissues, predominantly in the brain. This suggests that changes involving this gene may impact the development and/or function of brain cells. The overall function of the SETBP1 protein is still largely unknown — more research is necessary. DNA changes that lead to a decreased amount of the SETBP1 protein are associated with SETBP1 disorder.

SETBP1 gene 18q12.3
Image provided by NCBI

SETBP1 disorder

SETBP1 disorder is a  very rare disorder caused by a loss-of-function mutation in one of the two copies of the SETBP1 gene. The one copy of the SETBP1 gene does not produce a sufficient amount of SETBP1 protein for the body to function normally.  Individuals with a full or a partial deletion of chromosome 18q12.3 may also have SETBP1 disorder. Those reporting a loss-of-function of the SETBP1 gene are reported as de novo. De novo mutations are spontaneous mutations and occur where the family has no history of the disorder. We still do not know the full function of the SETBP1 gene or why a loss of SETBP1 genetic material causes a genetic disease. Individuals with SETBP1 disorder are expressive speech impaired and have mild-moderate developmental delay.

The symptoms vary for those impacted by SETBP1 disorder. Not all individuals impacted by a loss-of-function of the SETBP1 gene will exhibit all the symptoms. Reported Symptoms:

  • speech language difficulties ranging from absent speech to apraxia to expressive language delay
  • intellectual disability – ranging from mild to severe
  • delayed motor skills
  • decreased fine motor skills
  • behavior challenges
  • autistic-like traits
  • autism
  • seizures or EEG abnormalities
  • ADHD
  • low muscle tone, hypotonia
  • subtle facial differences including a long chin, longer face, dolichocephaly, brachycephaly, downslanting palpebral fissures, thin upper lip, etc.

Listen to Dr Siddharth Srivastava, a pediatric neurologist from Boston Children’s Hospital, talk about the features of SETBP1 disorder – Watch the video.

SETBP1 disorder is also known as SETBP1-related disorder; SETBP1-related intellectual disability; SETBP1-related developmental delay; Autosomal dominant mental retardation 29 (MRD 29)

Schinzel-Giedion Syndrome (SGS)

A different type of mutation within SETBP1 results in an overproduction of SETBP1 protein. These gain-of-function or dominant-negative mutations cause a different disorder called Schinzel-Giedion syndrome (SGS). Schinzel-Giedion syndrome is a severe multi-organ disorder characterized by distinct facial features, neurodevelopmental and structural anomalies. For more information about SGS or to connect with other families impacted by SGS, please contact us so we can help connect you.

Learn more about the differences between SETBP1 disorder and SGS – Watch the Video.