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Newly diagnosed or looking for more information on HUWE1-related genetic conditions? Then you're in the right place... Understanding of the impact of changes in the HUWE1 gene is still developing and people can vary in the symptoms they experience such as developmental delays, intellectual disability and growth issues. Guided by the expertise of scientific advisors at Louie's HUWE, the charitable nonprofit for HUWE1, we keep a close watch on new developments. A summary of what we know so far is shown below. You can also find out more in the Louie's HUWE Welcome Guide for Newly Diagnosed Families.

What we know about the HUWE1 gene...

HUWE1 is a gene located on the X chromosome. It holds the chemical instructions (DNA) to create a protein called E3 ubiquitin-protein ligase. This protein is present in all cells in the human body meaning that any variations or mutations in the HUWE1 gene can have significant effects throughout the body.

You can find out more about genes, chromosomes and variants/mutations at Genetic Alliance UK.

What does HUWE1 do?

Understanding of the role of the HUWE1 gene is still developing. Research indicates it has a role in controlling the release of neurotransmitters and in the formation of neurons in the developing brain. It has also been associated with intellectual disability as well as a range of other conditions.

What is a HUWE1 gene variant?

Small changes in the DNA that make up this gene are known as 'variants' or 'mutations' and are associated with a range of features and health issues for people affected by them.  

Important note: Please note the information on this page is based on material in journal publications and has been reviewed by a UK Consultant Clinical Geneticist. This information should not be taken as medical guidance - you should always consult a medical professional for treatments and genetic counselling advice.


HUWE1 gene variants can affect both males and females. Research into the impact of changes in this gene is still developing; here's a summary based on the latest publications...

What are the features?

People affected by HUWE1 variants can have a range of different features and health issues. The most comprehensive study to date reported the following common features:

  • Global developmental delay

  • Speech delay

  • Absence of speech (or less than five words)

  • Moderate to profound intellectual disability in many, mild intellectual disability in some

  • Short stature

  • Hypotonia (low muscle tone)

  • Small hands and feet

  • Microcephaly (small head), although some have larger heads

  • Overlapping toes

  • Epilepsy

  • Hand stereotypies (repetitive movements)

  • Autistic features

  • Walking: most walked at an average age of 2.5 years, although a small number never achieved walking

  • Facial features: broad nasal tip, long face, a short philtrum with thin upper lip and full lower lip, low set ears or posteriorly rotated ears

  • Eyes: deep set eyes, epicanthic folds (skin folds around eyes) and blepharophimosis (small eye openings/under developed eye lids), strabismus (squint), hypermetropia (longsightedness) ± astigmatism and a minority with retinopathy (damage to retina)

Other less common issues include contractures of the knees (tightening of muscles/tendons), scoliosis (curvature of spine), craniosynostosis (abnormally shaped skull), constipation and feeding difficulties.


Families and individuals affected by HUWE1 gene variants can self-report their symptoms as part of the HUWE1 RARE-X Data Collection Program.

Note the effects of HUWE1 variants have been reported in older medical publications under other names, for example 'Mental Retardation X-linked Syndromic Turner-type (MRXST)' or 'Juberg-Marsidi Syndrome (JMS)'. See a list of related conditions on the National Center for Biotechnology Information MedGen database.

How many people are affected?

It is difficult to determine exactly how many people are affected but the largest reported study in 2017 included 21 patients with HUWE1 variants. Previous literature reported on smaller groups or families with inherited HUWE1 variants. The DECIPHER database includes 50 patients with sequence variants matching this gene. We also have an active private Facebook group for families and individuals affected by HUWE1 variants with over 400 members including individuals, parents, siblings and wider family of over 100 individuals with HUWE1 from over 36 countries worldwide.


HUWE1 variants are X-linked meaning that the faulty HUWE1 gene is on the X chromosome. Most HUWE1 variants are new in the child, but in some cases they are inherited. Understanding inheritance of any genetic condition can be complicated and should always be discussed with a geneticist or genetic counsellor.

New/de novo variants
New or 'de novo' HUWE1 variants occur in a child and neither parent has the variant or shows any symptoms. The mutation may have occurred before conception or shortly after. Most HUWE1 variants are de novo.

Inherited variants

HUWE1 variants can also be inherited from a mother who is unaffected or only mildly affected. In this case the mother carries the faulty gene on one of her X chromosomes but usually has few or no symptoms.

What does this mean for future generations?

Females who are unaffected or mildly affected can pass on a HUWE1 gene variant to their children. 

It is theoretically possible that if a severely affected female went on to have children her children would have a 50% chance of being affected.​

An affected male has one X chromosome and one Y chromosome.  If he went on to have a daughter she would have to inherit his X Chromosome and by default the HUWE1 variant.  She could therefore be unaffected, mildly or severely affected.  If an affected male had a son then he would by default pass on his Y chromosome which would mean the child would be unaffected.

However, currently there have been no reported cases of individuals who are significantly affected with HUWE1 related syndrome who have then gone on to have children of their own.

Again, anyone wanting to understand their own situation regarding inheritance would need to discuss this with a geneticist or genetic counsellor.


Download the Louie's HUWE Welcome Guide for newly diagnosed families, or key research publications can be found in the Latest Research section of this site.

The following sites are also useful for further information about rare genetic conditions as well as useful guides to genes, chromosomes and DNA:

To find out more about research and support for families and individuals with HUWE1:

  • Join our Facebook Community for families and individuals affected by HUWE1

  • Learn more about the US charitable nonprofit Louie's Huwe (EIN: 86-1930096).

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