LRRC26

Chr 9

leucine rich repeat containing 26

Also known as: CAPC, bA350O14.10

The protein is an auxiliary subunit of large-conductance calcium and voltage-activated potassium (BK) channels that converts BK alpha channels from high-voltage to low-voltage activation in non-excitable cells. Mutations in this gene cause autosomal recessive epileptic encephalopathy with developmental delay and seizures typically beginning in infancy or early childhood. The gene shows low constraint to loss-of-function variation (pLI 0.01, LOEUF 1.68), suggesting tolerance to protein-truncating variants.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.68
Clinical SummaryLRRC26
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.68LOEUF
pLI 0.013
Z-score 0.53
OE 0.72 (0.321.68)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.55Z-score
OE missense 1.16 (0.991.35)
115 obs / 99.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.72 (0.321.68)
00.351.4
Missense OE1.16 (0.991.35)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 3 / 4.2Missense obs/exp: 115 / 99.5Syn Z: 0.80
DN
0.6938th %ile
GOF
0.84top 5%
LOF
0.3258th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LRRC26 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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