UNC80 (Protein unc-80 homolog) variants and mutations

UNC80 (also known as Protein unc-80 homolog) is a human protein-coding gene encoding a protein unc-80 homolog protein. Within the NALCN complex, it helps control background sodium conductance and neuronal excitability. Biallelic loss-of-function variants cause IHPRF2, with severe hypotonia, developmental impairment, absent or limited speech, and characteristic facial features. This analysis covers 3,484 UNC80 variants and mutations. Of these, 57% have computational variant effect predictions. Disease context includes hypotonia, infantile, with psychomotor retardation and characteristic facies, Intellectual disability, and Encephalopathy. Example UNC80 variants include M1I, V2L, and V2A.

Variant analysis overview

Gene: UNC80
Protein: Protein unc-80 homolog
UniProt accession: Q8N2C7
Organism: Homo sapiens
Variants analyzed: 3484
Variant scope: all variants
Completed: 2026-08-20

Variant and mutation evidence

Variant composition: 3,279 unspecified-consequence records; 105 missense variants; 82 synonymous variants; 7 stop-gained variants; 1 in-frame insertions; 6 frameshift variants; 4 splice-region variants
Prediction scores: 1,984 variants have prediction scores (57% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: hypotonia, infantile, with psychomotor retardation and characteristic facies, Intellectual disability, Encephalopathy, hypotonia, infantile, with psychomotor retardation and characteristic facies 1, Neurodevelopmental delay, self-injurious ideation, Moderate global developmental delay, Anxiety, hereditary disease, neurodegenerative disease, functional laterality, Global developmental delay.

Protein structure and variant hotspots

Protein features: 4 transmembrane segments; 3 post-translational modification sites.
Structural context: 75 variants have structural context.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable UNC80 variants

Examples include M1I, V2L, V2A, V2V, K3R, K3K, R4M, R4R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

UNC80 analysis run — UNC80 (3,484 variants) — completed 2026-08-20