LRRC38

Chr 1

leucine rich repeat containing 38

NCBI Gene: 126755 ENSG00000162494 UniProt: Q5VT99 OMIM: 615212

The LRRC38 protein is an auxiliary subunit that modulates large-conductance calcium and voltage-activated potassium (BK) channels by shifting their voltage dependence of activation in the hyperpolarizing direction. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures and developmental delays. The gene shows moderate tolerance to loss-of-function variants (pLI 0.14, LOEUF 1.08), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Enables potassium channel activator activity and transmembrane transporter binding activity. Involved in positive regulation of voltage-gated potassium channel activity and potassium ion transmembrane transport. Part of voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

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

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P/LP missense

1.08

LOEUF

Multiple*

Mechanism· predicted