NALF1 Gene: Function, Expression, and Clinical Significance
Comprehensive guide to NALF1 (NALCN channel auxiliary factor 1) - genomic information, protein function, expression patterns, and associated diseases.
Gene Information Card
| Symbol | NALF1 |
|---|---|
| Full Name | NALCN channel auxiliary factor 1 |
| Gene Type | gene with protein product |
| Chromosomal Location | 13q33.3 |
| NCBI Gene ID | 728215 ncbi.nlm.nih.gov/gene/728215 |
| Ensembl ID | ENSG00000204442 |
| UniProt ID | B1AL88 |
| OMIM ID | 619899 |
| HGNC ID | HGNC:33877 |
| Aliases | NLF-1, FAM155A |
Description
NALF1 (NALCN channel auxiliary factor 1) is a protein-coding gene located on chromosome 13q33.3. It encodes an auxiliary subunit of the NALCN (sodium leak channel) complex, which plays a critical role in regulating neuronal excitability and pacemaking. NALF1 is essential for proper assembly and function of the NALCN channel, and mutations in this gene have been linked to neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia and characteristic facies (NEDHF) | Loss-of-function mutations in NALF1 disrupt NALCN channel function, leading to altered neuronal excitability and developmental defects. | OMIM 619899; PMID: 32860008 |
| Intellectual disability | Pathogenic variants in NALF1 impair NALCN channel activity, affecting synaptic transmission and cognitive function. | ClinVar; PMID: 32860008 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | Predominantly expressed in the central nervous system, especially in neurons. |
| Testis | Medium | Moderate expression in testicular tissue. |
| Lung | Low | Low expression in lung tissue. |
| Kidney | Low | Low expression in kidney tissue. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal cell line with high NALF1 expression. |
| U-87 MG (glioblastoma) | Medium | Moderate expression in glioblastoma cells. |
| HEK 293 (embryonic kidney) | Low | Low expression in kidney-derived cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare | Loss-of-function; predicted to cause protein truncation. |
| c.1567G>A (p.Gly523Arg) | Missense | Rare | Likely damaging; affects protein function. |
| c.2101delC (p.Leu701TrpfsTer5) | Frameshift | Rare | Loss-of-function; leads to premature stop codon. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in NALF1 are associated with neurodevelopmental disorders, likely due to impaired NALCN channel function.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NALF1.
Dominant Negative (DN)
Dominant-negative effects have not been described for NALF1 mutations.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • plasma membrane (GO:0005886) |
| • ion transport (GO:0006811) | • cation transport (GO:0006812) |
| • membrane (GO:0016020) |
Pathways
• NALCN channel complex
• Ion transport by P-type ATPases
• Neuronal system
Protein Summary
NALF1 encodes an auxiliary subunit of the NALCN (sodium leak channel) complex. This protein is essential for the proper assembly, trafficking, and function of the NALCN channel, which mediates a background sodium leak current that regulates neuronal excitability and pacemaking. NALF1 is predominantly expressed in the brain and is critical for normal neurodevelopment. Mutations in NALF1 lead to a spectrum of neurodevelopmental disorders, including intellectual disability and hypotonia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NALF1 Knockout HEK293 Cell Line | EDJ-KQ13601 | Human | 728215 | Details Get a Quote |
| NALF1 Knockout HeLa Cell Line | EDJ-KQ60692 | Human | 728215 | Details Get a Quote |
| NALF1 Knockout A-549 Cell Line | EDJ-KQ69165 | Human | 728215 | Details Get a Quote |
| NALF1 Knockout HCT 116 Cell Line | EDJ-KQ77519 | Human | 728215 | Details Get a Quote |
