UNC80

Chr 2q34

unc-80 subunit of NALCN channel complex

Aliases:: FLJ33496, KIAA1843, UNC-80
MANE:: ENST00000673920.1

OMIM: 612636 ↗NCBI: 285175 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

UNC80 · Q8N2C7-2isoform

No predicted structure exists for the canonical Q8N2C7 sequence; metrics below describe this isoform.

v62025-08-01

Predicted Aligned Error matrix for UNC80 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

60.5/ 100

Low

2,603 residues

Confidence breakdown

Very high(≥ 90)10%
Confident(70–90)41%
Low(50–70)8%
Very low(< 50)41%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

hypotonia, infantile, with psychomotor retardation and characteristic facies
0.78
Intellectual disability
0.43
Encephalopathy
0.36
hypotonia, infantile, with psychomotor retardation and characteristic facies 1
0.34
Neurodevelopmental delay
0.33
self-injurious ideation
0.28
Moderate global developmental delay
0.27
Anxiety
0.26
hereditary disease
0.19
neurodegenerative disease
0.19

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Protein unc-80 homolog

Auxilary subunit of the NALCN channelosome complex, which regulates the resting membrane potential by depolarizing sodium leak currents (PubMed:32494638, PubMed:35387979, PubMed:34929720). The NALCN channelosome complex is a voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability (PubMed:35387979, PubMed:34929720). The NALCN channelosome is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations (PubMed:32494638). Activated by neuropeptides substance P, neurotensin, and extracellular Ca(2+) that regulates neuronal excitability by controlling the sizes of NALCN-dependent sodium-leak current (PubMed:32494638). UNC80 is also essential for NALCN sensitivity to extracellular Ca(2+) (PubMed:32494638)