LRRC26

Chr 9

leucine rich repeat containing 26

Also known as: CAPC, bA350O14.10

NCBI Gene: 389816 ENSG00000184709 UniProt: Q2I0M4

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

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

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.68

Clinical Summary— LRRC26

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

73 VUS of 78 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.68LOEUF

pLI 0.013

Z-score 0.53

OE 0.72 (0.32–1.68)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.55Z-score

OE missense 1.16 (0.99–1.35)

115 obs / 99.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.72 (0.32–1.68)

0≤0.351.4

Missense OE?1.16 (0.99–1.35)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 3 / 4.2Missense obs/exp: 115 / 99.5Syn Z: 0.80

This gene — mechanism propensity

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

78 submitted variants in ClinVar

ClinVar

Classification Summary

VUS73

Likely Benign4

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	73	0	73
Likely Benign	2	2	4
Benign	1	0	1
Total	76	2	78

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

93 pathogenic / likely-pathogenic (of 106) ClinVar copy-number / structural variants overlap LRRC26 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →