SLC25A1

Chr 22

solute carrier family 25 member 1

Also known as: CIC, CMS23, CTP, D2L2AD, SEA, SLC20A3

NCBI Gene: 6576 ENSG00000100075 UniProt: P53007

The protein transports citrate across the inner mitochondrial membrane as part of the citrate-malate antiporter system. Autosomal recessive mutations cause combined D-2- and L-2-hydroxyglutaric aciduria and congenital myasthenic syndrome type 23 with presynaptic dysfunction. The pathogenic mechanism appears to involve dominant-negative effects that disrupt normal mitochondrial citrate transport.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the mitochondrial carrier subfamily of solute carrier proteins. Members of this family include nuclear-encoded transporters that translocate small metabolites across the mitochondrial membrane. This protein regulates the movement of citrate across the inner membranes of the mitochondria. Mutations in this gene have been associated with combined D-2- and L-2-hydroxyglutaric aciduria. Pseudogenes of this gene have been identified on chromosomes 7, 11, 16, and 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCombined D-2- and L-2-hydroxyglutaric aciduria

UniProtMyasthenic syndrome, congenital, 23, presynaptic

Clinical highlights

Gene-disease validity (ClinGen)

mitochondrial disease · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

LOF

Mechanism· G2P

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GeneReview available — SLC25A1