Channeling Hope Foundation
Cycle 3
Genetic mutations of the NALCN Channel (also known as the Sodium Leak Channel) and associated proteins (UNC79, UNC80, FAM155) are very rare genetic disorders. The NALCN Channel plays a crucial role in regulating the electrical activity of neurons and other cells.
Last updated 04/30/2026
Clinical
Disease Class
Channelopathies
Endocrine diseases
Epilepsy and seizure disorders
Genetic diseases
Intellectual disability and developmental syndromes
Multi-system genetic syndromes
Neurological diseases
Body Systems
Cardiovascular / Circulatory
Digestive
Endocrine
Muscular / Skeletal
Nervous / Sensory
Respiratory
Organs
Brain
Connective tissue / joints
Eyes
Heart
Intestines
Lungs
Muscles
Nerves
Pancreas
Pituitary glands
Known Genetic Link
Yes, one or more genes directly cause the condition
Causative Genes
NALCN
NALF1 (FAM155A)
UNC79
UNC80
Contributory Genes
None specified / unknown
Type of Inheritance
Autosomal recessive
De novo
Newborn Screening
No
Disease Mechanism(s)
Abnormal channel conductance
Altered channel kinetics
Ion channel dysfunction
Age of Onset
Infancy (age 0-1)
Prebirth
Average Age at Diagnosis
Adulthood (age 18-64)
Early childhood (age 1+-5)
Infancy (age 0-1)
Middle childhood (6-11)
Life Expectancy
Adulthood (age 18-64)
Early childhood (age 1+-5)
Infancy (age 0-1)
Affected Sex(es)
Female
Male
National Prevalence
101-1000
Global Prevalence
101-1000
National Incidence
Less than 10
Global Incidence
Less than 10
Populations and/or ancestry with higher prevalence
IHPRF 1 and IHPRF 2 appear to have higher prevalence in Middle Eastern populations; none known for CLIFAHDD or UNC-79 related disease
Symptoms / Phenotypes
abnormal brain features
abnormal facial shape
abnormal hand morphology
adducted thumbs
breathing difficulties
cardiac abnormalities
clubfoot/talipes equinovarus
constipation
delayed ability to walk
developmental delay
excessive salivation
feeding difficulties
gastroesophageal reflux
growth delay / deficiency
hip dysplasia
hypertonia
hypotonia
intellectual disability
seizures / epilepsy
short stature
speech delay
vision problems
vomiting / nausea
Biomarkers
Diagnostic
· Mutation in the NALCN channelsome (including associated proteins UNC79 and UNC80) or NALCN gene
Monitoring
· developmental milestones, Brain MRI
Existing Therapies
None
Therapies in Development
Antibody-based therapy (monoclonal antibodies, biologics)
Antisense oligonucleotide (ASO) therapy
Repurposed drug
· 2 - aprepitant, nefopam
Small molecule therapy (novel small molecule drugs)
Therapeutic Development Stages
In preclinical development
In research/exploratory phase
Therapeutic Development Role
Data analysis
Sample provision
Organizational & Research
Cell Lines
Fibroblasts
iPSCs
Plasma
Cell Lines, Institution
Baylor College of Medicine
French National Centre for Scientific Research (CNRS)
Cell Lines, Involvement
Consulted
Designed
Funded
Own
Cell Lines, share
Some of our cell lines are freely available
Disease Model
C. elegans
Mouse
Organoids
Other
Disease Model, Involvement
Consulted
Disease Model, share
Some of our disease models are freely available
Organizational Challenges
(1) Genetic therapies are a goal but have been a challenge to launch. We would be interested in partnering to develop capacity and infrastructure to facilitate gene therapy development in the future. In line of this, we have to generate iPSCs (3 available, though more needed) and isogenic controls of iPSCs, which are costly. (2) Biomarker discovery has been a challenge. It would be great to be able to pool experiences and efforts in this or enable further collaboration with COMBINEDBrain, as it would be much more cost effective to perform multiomic testing with multiple diseases rather than just each pursuing individually (3) Natural history study data and clinical outcomes remain a challenge. It would be ideal to foster tools that can be used across diseases with similar phenotypes. (4) Funding and personnel to champion research, therapy development, and synergistic efforts across organizations. While there are many great ideas, having champions within the research community who can take the lead on enacting and implementing and applying for funding has been a barrier as all the organizational leads are already stretched thin.
Clinical Trial Role
Not involved
Biobank, Institution
University of Texas San Antonio
Biobank, Involvement
Consulted
Designed
Funded
Own
Center of Excellence, Institution
None
Registry
Yes, we have collaborated on a registry
Data Collected, Registry
Clinical data
Genetic data
Longitudinal natural history data
Medication usage
Patient contact info
Patient-reported data
Data Entered by, Registry
Both
Platform, Registry
Citizen Health
Matrix
RARE-X
REDCap
Natural History Study
Yes, we have a natural history study that we created
Data Collected, Natural History Study
Clinical endpoints (outcomes)
Electronic health records/electronic medical records
Genetic data
Medication usage
Patient-reported outcomes
Prospective data
Retrospective data
Platform, Natural History Study
Citizen Health
Matrix
REDCap
FDA Patient Listening Session
No
FDA Patient-Focused Drug Development (PFDD) Program
No
ICD Codes
No, we do not have any ICD codes
Diagnostic Guidelines
No
Science Advisory Board Policies
No 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
International Chapters
None
International Partners
Europe
Other International Research Initiatives
Europe