UNC80 Gene: Key Regulator of Neuronal Ion Channels and Genetic Disorders
Comprehensive genomic and functional analysis of UNC80, a critical component of the NALCN channel complex
Gene Information Card
| Symbol | UNC80 |
|---|---|
| Full Name | unc-80 homolog, NALCN channel complex subunit |
| Gene Type | protein-coding |
| Chromosomal Location | 2q34 |
| NCBI Gene ID | 285286 ncbi.nlm.nih.gov/gene/285286 |
| Ensembl ID | ENSG00000144452 |
| UniProt ID | Q8N2C7 |
| OMIM ID | 612636 |
| HGNC ID | 26582 |
| Aliases | UNC-80, KIAA1843, NALCN2 |
Description
UNC80 encodes a large protein that is a core component of the NALCN (sodium leak channel, non-selective) ion channel complex. This complex regulates resting membrane potential and neuronal excitability. UNC80 is essential for the proper assembly and function of the NALCN channel, and its dysfunction leads to severe neurological phenotypes including intellectual disability, hypotonia, and developmental delay.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal recessive 57 (MRT57) | Loss-of-function mutations in UNC80 disrupt NALCN channel activity, impairing neuronal excitability and synaptic function. | ClinVar, OMIM |
| Hypotonia, infantile, with psychomotor retardation and characteristic facies (IHPRF) | Biallelic UNC80 mutations cause severe hypotonia, developmental delay, and dysmorphic features due to defective ion homeostasis. | ClinVar, OMIM |
| Epileptic encephalopathy, early infantile, 6 (EIEE6) | Rare UNC80 variants may contribute to seizure disorders through altered neuronal excitability. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 6.8 | Medium |
| Adrenal gland | 5.2 | Medium |
| Thyroid | 4.1 | Medium |
| Heart | 2.3 | Low |
| Liver | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.2 | High expression; relevant for neuronal studies |
| HEK293 (embryonic kidney) | 3.5 | Moderate expression; used in heterologous expression |
| HeLa (cervical carcinoma) | 1.8 | Low expression |
| K562 (leukemia) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | Rare | Loss of function; truncation of UNC80 protein |
| c.2567_2568del (p.Leu856Profs*12) | Frameshift | Rare | Loss of function; premature stop codon |
| c.3456G>A (p.Trp1152*) | Nonsense | Rare | Loss of function; nonsense-mediated decay |
| c.4567A>G (p.Ile1523Val) | Missense | Unknown | Likely damaging; affects protein stability |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift) cause severe neurological disorders by abolishing NALCN channel activity.
Gain of Function (GOF)
No gain-of-function mutations reported in UNC80.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NALCN channel complex (Reactome: R-HSA-5576892)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Neuronal system (Reactome: R-HSA-112316)
Protein Summary
UNC80 is a large, predominantly cytoplasmic protein that serves as a scaffold for the NALCN channel complex. It interacts with UNC79 and NALCN to facilitate channel trafficking, assembly, and regulation. The protein contains multiple coiled-coil domains and is highly expressed in the brain. UNC80 is essential for maintaining sodium leak currents that control neuronal resting potential and excitability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UNC80 Knockout HEK293 Cell Line | EDJ-KQ16033 | Human | 285175 | Details Get a Quote |
| UNC80 Knockout HeLa Cell Line | EDJ-KQ59503 | Human | 285175 | Details Get a Quote |
| UNC80 Knockout A-549 Cell Line | EDJ-KQ67970 | Human | 285175 | Details Get a Quote |
| UNC80 Knockout HCT 116 Cell Line | EDJ-KQ76346 | Human | 285175 | Details Get a Quote |
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