SLC33A1

Chr 3

solute carrier family 33 member 1

Also known as: ACATN, AT-1, AT1, CCHLND, HPBDS, SPG42

NCBI Gene: 9197 ENSG00000169359 UniProt: O00400

This protein is an acetyl-CoA transporter that imports acetyl-CoA into the endoplasmic reticulum for protein acetylation and is necessary for O-acetylation of gangliosides. Mutations cause Huppke-Brendel syndrome (autosomal recessive) and spastic paraplegia 42 (autosomal dominant), affecting the nervous system with spasticity as a key feature. The gene shows low constraint to loss-of-function variation (pLI 0.0001, LOEUF 0.807).

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is required for the formation of O-acetylated (Ac) gangliosides. The encoded protein is predicted to contain 6 to 10 transmembrane domains, and a leucine zipper motif in transmembrane domain III. Defects in this gene have been reported to cause spastic paraplegia autosomal dominant type 42 (SPG42) in one Chinese family, but not in similar patients of European descent. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia 42, autosomal dominant

UniProtHuppke-Brendel syndrome

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.81

LOEUF

LOF

Mechanism· G2P

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GeneReview available — SLC33A1