SLC12A6

Chr 15ARAD

solute carrier family 12 member 6

Also known as: ACCPN, CMT2II, KCC3, KCC3A, KCC3B

NCBI Gene: 9990 ENSG00000140199 UniProt: Q9UHW9 OMIM: 604878

This gene encodes a potassium-chloride cotransporter that maintains cellular chloride concentrations and contributes to cell volume regulation by mediating electroneutral ion transport when cells swell. Mutations cause agenesis of the corpus callosum with peripheral neuropathy and Charcot-Marie-Tooth disease type 2II, inherited in both autosomal recessive and autosomal dominant patterns. The gene is highly intolerant to loss-of-function variants (LOEUF 0.395), indicating that complete protein loss is likely deleterious.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Agenesis of the corpus callosum with peripheral neuropathyMIM #218000

Charcot-Marie-Tooth disease, axonal, type 2IIMIM #620068

Clinical highlights

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

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P/LP missense

0.40

LOEUF

LOF

Mechanism· G2P

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GeneReview available — SLC12A6