RTN2

Chr 19

reticulon 2

Also known as: HMNR11, NSP2, NSPL1, NSPLI, SPG12

NCBI Gene: 6253 ENSG00000125744 UniProt: O75298

The RTN2 protein localizes to the endoplasmic reticulum where it inhibits amyloid precursor protein processing and enhances trafficking of transporters including glutamate and glucose transporters to the cell surface. Mutations cause either autosomal dominant spastic paraplegia-12 or autosomal recessive distal hereditary motor neuronopathy with spasticity, both affecting motor neurons and causing progressive spasticity. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.417), and the differing inheritance patterns suggest distinct pathogenic mechanisms for different mutation types.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene belongs to the family of reticulon encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. Reticulon proteins also play an important role in the replication of positive-strand RNA (ssRNA) viruses. Mutations at this locus have been associated with autosomal dominant spastic paraplegia-12. [provided by RefSeq, Aug 2020]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia 12, autosomal dominant

UniProtNeuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — RTN2