SPTAN1

Chr 9

spectrin alpha, non-erythrocytic 1

Also known as: DEE5, DEVEP, EIEE5, HMN11, HMND11, NEAS, SPG91, SPTA2

NCBI Gene: 6709 ENSG00000197694 UniProt: Q13813

The protein functions as a cytoskeletal scaffold protein that stabilizes the plasma membrane and organizes intracellular organelles, and is also involved in DNA repair and cell cycle regulation. Mutations cause a spectrum of autosomal dominant neurological disorders including developmental and epileptic encephalopathy, developmental delay with or without epilepsy, distal hereditary motor neuronopathy, and spastic paraplegia with or without cerebellar ataxia. The gene is highly intolerant to loss-of-function variants, and mutations can cause disease predominantly through haploinsufficiency, though the broad phenotypic spectrum suggests variant-dependent mechanisms may contribute.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Spectrins are a family of filamentous cytoskeletal proteins that function as essential scaffold proteins that stabilize the plasma membrane and organize intracellular organelles. Spectrins are composed of alpha and beta dimers that associate to form tetramers linked in a head-to-head arrangement. This gene encodes an alpha spectrin that is specifically expressed in nonerythrocytic cells. The encoded protein has been implicated in other cellular functions including DNA repair and cell cycle regulation. Mutations in this gene are the cause of early infantile epileptic encephalopathy-5. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2010]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 5

UniProtDevelopmental delay with or without epilepsy

UniProtNeuronopathy, distal hereditary motor, autosomal dominant 11

UniProtSpastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia

Clinical highlights

Gene-disease validity (ClinGen)

genetic developmental and epileptic encephalopathy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.10

LOEUF· LoF intol.

DN*

Mechanism· G2P

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GeneReview available — SPTAN1