The Rory Belle Foundation

Cycle 3

Web:

Contact:

The NARS1 gene is responsible for creating proteins that help cells grow and develop throughout your body. A mutation or mutations on this gene leave those impacted with cognitive, physical, and neurological issues. It can cause speech delays, abnormal brain MRI's, difficulty balancing and walking, seizures, feeding issues, and many other symptoms.

Last updated 04/30/2026

Clinical

Disease Class

Epilepsy and seizure disorders

Genetic diseases

Inherited metabolic disorder

Muscular and neuromuscular diseases

Neurological diseases

Protein synthesis and tRNA disorders

Body Systems

Cardiovascular / Circulatory

Digestive

Metabolic

Muscular / Skeletal

Nervous / Sensory

Organs

Bones

Brain

Connective tissue / joints

Ears

Eyes

Heart

Intestines

Liver

Mouth / teeth

Muscles

Nerves

Stomach

Throat/pharynx

Known Genetic Link

Yes, one or more genes directly cause the condition

Causative Genes

NARS1

Contributory Genes

None specified / unknown

Type of Inheritance

Autosomal dominant

Autosomal recessive

De novo

Newborn Screening

Disease Mechanism(s)

Aberrant immune response

Enzyme deficiency

tRNA charging/aminoacylation defect (aminoacyl-tRNA synthetase disorders)

Age of Onset

Adulthood (age 18-64)

Infancy (age 0-1)

Prebirth

Average Age at Diagnosis

Adolescence (12-17)

Adulthood (age 18-64)

Early childhood (age 1+-5)

Infancy (age 0-1)

Middle childhood (6-11)

Life Expectancy

Adolescence (12-17)

Adulthood (age 18-64)

Early childhood (age 1+-5)

Affected Sex(es)

Female

Male

National Prevalence

11-50

Global Prevalence

101-1000

National Incidence

Less than 10

Global Incidence

Less than 10

Populations and/or ancestry with higher prevalence

There appears to be founder homozygous autosomal recessive variants that are expressed in several families of Libyan and Pakistani origin.

Symptoms / Phenotypes

abnormal eye contact

abnormal heart morphology

abnormal skeletal morphology

abnormality of the dentition

anxiety

attention disorders / ADHD

autism

brain imaging abnormality

constipation

craniofacial abnormalities

delayed ability to walk

diarrhea

drooling

dyskinesia

dystonia

EEG abnormality

exaggerated startle response

failure to thrive

feeding difficulties

functional motor deficit

gastroesophageal reflux

gastrointestinal dysmotility

growth delay / deficiency

hearing loss / hearing impairment

hyperlaxity / joint laxity

hypertonia

hypotonia

impairment of activities of daily living

impulsivity

intellectual delay / global developmental delay

intellectual disability

kidney disease / nephropathy

liver disease

microcephaly

motor delay

movement disorders / ataxia / tremor

nystagmus

peripheral neuropathy

pica

recurrent hand flapping

recurrent maladaptive behavior

seizures / epilepsy

sensory processing disorder / sensory hypersensitivity

sensory seeking

sleep disorders

spasticity

speech delay

speech problems / apraxia

tube feeding

vertigo

vision problems

vomiting / nausea

Biomarkers

Diagnostic

· A variant identified in NARS1

Monitoring

· EMG, EEG

Other

Prognostic

Therapeutic

Existing Therapies

Other

· OT, PT, Speech therapy

Regulatory Agency-Approved for Symptom Relief

· seizure, (treatment and rescue) spasticity, agitation, GI, medications

Therapies in Development

Antisense oligonucleotide (ASO) therapy

Dietary & metabolic therapies (medical food, dietary restriction, supplements, etc.)

Gene therapy

RNA interference (RNAi) therapy (siRNA, etc.)

Repurposed drug

Small molecule therapy (novel small molecule drugs)

Therapeutic Development Stages

In clinical trials (Phase I, II, III, or IV)

In preclinical development

In research/exploratory phase

Therapeutic Development Role

Access to registry or natural history study

Funding

Outcome measures development

Recruitment and outreach to patients

Recruitment and outreach to trial sites / physicians

Results dissemination (including publications)

Sample provision

Study protocol design and/or review (includes selection of outcome measures)

Organizational & Research

Cell Lines

Fibroblasts

iPSCs

Other

Plasma

Cell Lines, Institution

Applied StemCell, Inc

COMBINEDBrain

University College London (UCL)

Vanderbilt University

Cell Lines, Involvement

Consulted

Funded

Own

Cell Lines, share

All our cell lines are freely available

Disease Model

Mouse

Disease Model, Involvement

Consulted

Funded

Own

Disease Model, share

Some of our disease models are freely available

Organizational Challenges

Animal model viability, Biomarker identification and development

Clinical Trial Role

Funding

Outcome measures, development

Recruitment and outreach, patients

Recruitment and outreach, trial sites/physicians

Study protocol design, review

Clinical Trial Types

Other

Biobank, Institution

Van Andel Institute

Biobank, Involvement

Consulted

Designed

Funded

Own

Center of Excellence, Institution

None

Registry

Yes, we have a registry that we created

Data Collected, Registry

Genetic data

Patient contact info

Data Entered by, Registry

Patients

Platform, Registry

Other

Natural History Study

Yes, we have collaborated on a natural history study

Data Collected, Natural History Study

Clinical endpoints (outcomes)

Genetic data

Medication usage

Patient-reported outcomes

Prospective data

Retrospective data

Platform, Natural History Study

RARE-X

FDA Patient Listening Session

FDA Patient-Focused Drug Development (PFDD) Program

ICD Codes

No, we do not have any ICD codes

Diagnostic Guidelines

Science Advisory Board Policies

Yes, willing to share SAB policies

Research Network Policies

Has CRN but no policies

Patient Priority Survey

Yes

Patient Priority Survey, share

Yes, will share

Research Roadmap

Yes we have a Research Roadmap, and will share policies

Europe

None

Europe