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Sorting nexin-14 (SNX14)
- Target
- SNX14
- Molecular classification
- Sorting nexin family protein, Regulator of G protein signaling (RGS) domain-containing protein, endoplasmic reticulum–associated scaffold/cargo sorting protein
01
Overview
Sorting nexin-14 (SNX14) is a member of the sorting nexin protein family characterized by a modified Phox (PX) domain and a regulator of G protein signaling (RGS) domain. Unlike other sorting nexins, SNX14’s PX domain does not directly bind phosphoinositide membranes, but instead organizes inter-organelle contact sites, especially between the endoplasmic reticulum and lipid droplets, supporting lipid metabolism and cellular homeostasis. SNX14 plays a crucial role in neuronal function, autophagosome clearance, and neural development, and its loss leads to lysosomal dysfunction, delayed autophagy, increased apoptosis, and neurodegeneration. Biallelic SNX14 mutations cause the pediatric-onset neurological disorder SCAR20, which is marked by cerebellar atrophy, ataxia, intellectual disability, and sometimes autistic features. Experimental studies are exploring SNX14’s potential roles in cancer biology via its circular RNA derivative (circSNX14), but it is not currently a direct therapeutic target.
- Other names
- SNX14Sorting nexin-14RGS-PX2SCAR20
02
Biological functions
Intracellular trafficking (with atypical PX domain)Regulation of autophagy (required for autophagosome clearance)Maintaining neuronal excitability and synaptic transmissionEndoplasmic reticulum–lipid droplet contact site formationNeutral lipid and cholesterol homeostasisRegulation of cell death and apoptosis via lysosomal/autophagic pathwayInter-organelle crosstalk (ER, lysosomes, lipid droplets)
03
Disease associations
Neurodevelopmental disorder: mutations cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20)—characterized by cerebellar atrophy, ataxia, intellectual disability, coarsened facial features, and, variably, autistic behaviorLysosomal/autophagic dysfunction syndromesIntellectual disabilityAutism spectrum disorder (risk gene)Potential cancer involvement: emerging evidence implicates SNX14 and circSNX14 as a tumor suppressor in hepatocellular carcinoma and possibly in breast cancer, based on preliminary data
04
Biomarkers
SCAR20 mutations/variants (for diagnosis and possibly research stratification in neurodevelopmental or lysosomal/autophagic disorders)circSNX14 for cancer prognosis or research
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