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SIL1 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

SIL1 gene

The SIL1 gene provides instructions for a protein that acts as a nucleotide exchange factor, playing a critical role in protein folding within the endoplasmic reticulum.

Normal Function

The SIL1 gene provides instructions for producing a protein located in a cell structure called the endoplasmic reticulum. Among its many functions, the endoplasmic reticulum folds and modifies newly formed proteins so they have the correct 3-dimensional shape. The SIL1 protein works with BiP, a protein that helps fold newly produced proteins into the proper shape and refold damaged proteins.

To start this process, BiP attaches (binds) to a molecule called adenosine triphosphate (ATP). When BiP folds a protein, the ATP is converted to a similar molecule called adenosine diphosphate (ADP). Then the SIL1 protein releases ADP from BiP so that it can bind to another molecule of ATP and start the protein folding process again. Because of its role in helping BiP exchange ADP for ATP, the SIL1 protein is called a nucleotide exchange factor.

Health Conditions Related to Genetic Changes

Marinesco-Sjögren syndrome

More than a dozen mutations in the SIL1 gene have been found to cause Marinesco-Sjögren syndrome. Most of these mutations result in the production of a protein that has little or no activity. Defective SIL1 protein cannot remove ADP from BiP. BiP is then unable to bind to ATP and re-start the protein folding process. A disruption in protein folding impairs protein transport and causes proteins to accumulate in the endoplasmic reticulum. This accumulation likely damages and destroys cells in many different tissues, leading to:

  • Poor coordination
  • Muscle weakness
  • Other features of Marinesco-Sjögren syndrome

Frequently Asked Questions

Parents should seek evaluation if a child shows a combination of congenital cataracts, delayed motor milestones (poor coordination, ataxia), persistent muscle weakness, and intellectual disability. Additional clues include a characteristic “bird‑like” facial appearance and skeletal anomalies such as scoliosis. When these features cluster, clinicians often order a SIL 1 gene analysis to confirm the diagnosis.
Diagnosis is made by sequencing the SIL1 coding region and exon‑intron boundaries using next‑generation sequencing or Sanger methods. If a pathogenic variant is found, copy‑number analysis (e.g., MLPA) may be added to detect larger deletions. Results are interpreted according to ACMG guidelines and reported to the ordering physician.
Currently there is no cure, but multidisciplinary care can mitigate symptoms. Physical and occupational therapy help maintain strength and balance. Some patients benefit from low‑dose baclofen or other antispastic agents for tone control. Early cataract surgery restores vision, which indirectly supports motor development. Research into chaperone‑enhancing drugs is ongoing, but they remain investigational.
When both parents carry pathogenic SIL1 variants, each pregnancy carries a 25 % chance of an affected child (autosomal‑recessive inheritance), a 50 % chance of a carrier, and a 25 % chance of being unaffected and non‑carrier. Options to discuss include prenatal diagnostic testing (chorionic villus sampling or amniocentesis) and pre‑implantation genetic testing for monogenic disease (PGT‑M) with IVF. Genetic counseling helps the couple understand these risks and make informed decisions.
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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