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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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LRRC26
leucine rich repeat containing 26
Chromosome 9 · 9q34.3
NCBI Gene: 389816Ensembl: ENSG00000184709.7HGNC: HGNC:31409UniProt: Q2I0M4
13PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
voltage-gated potassium channel activityprotein bindingpotassium channel regulator activitytransmembrane transporter bindingneurodegenerative diseaseneoplasmtriple-negative breast cancerbreast cancer
✦AI Summary

LRRC26 (leucine rich repeat containing 26) functions as an auxiliary γ subunit of large-conductance calcium- and voltage-activated potassium (BK) channels, playing critical roles in cellular physiology and disease pathophysiology 1. The protein dramatically enhances BK channel voltage sensitivity by producing a large negative shift (~140 mV) in voltage dependence of activation, converting BK channels from high-voltage to low-voltage activated states under physiological conditions 12. LRRC26 is expressed in diverse tissues including arterial smooth muscle, airway epithelium, and intestinal goblet cells, where it regulates specific physiological functions 345. In arterial smooth muscle cells, LRRC26 associates with plasma membrane BK channels to regulate vascular tone and vasodilation 3. In airway epithelium, LRRC26-regulated BK channels are essential for airway surface liquid homeostasis and mucociliary clearance, with dysfunction contributing to cystic fibrosis pathophysiology 46. In intestinal goblet cells, LRRC26-associated BK channels protect against colitis and regulate mucin secretion 5. Therapeutic targeting of LRRC26 function shows promise, as compounds like nesolicaftor can restore LRRC26-mediated BK channel function in disease states 7. Additionally, LRRC26 may function as a tumor suppressor in colorectal cancer 8.

Sources cited
1
LRRC26 functions as BK channel auxiliary γ subunit causing ~140 mV negative shift in voltage dependence
PMID: 22547800
2
LRRC26 associates with BK channels in arterial smooth muscle cells to regulate vascular tone
PMID: 24906643
3
LRRC26 regulates BK function in airway epithelium critical for mucociliary clearance
PMID: 32732330
4
LRRC26 is important for airway surface liquid homeostasis and mucociliary clearance
PMID: 27115952
5
LRRC26-associated BK channels in goblet cells protect against colitis
PMID: 33431687
6
Structural studies reveal LRRC26's mechanism of BK channel voltage regulation
PMID: 38187713
7
Nesolicaftor can restore LRRC26-mediated BK channel function therapeutically
PMID: 40095970
8
LRRC26 identified as potential tumor suppressor in colorectal cancer
PMID: 32573269
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.28Weak
neoplasmOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.02Suggestive
breast cancerOpen Targets
0.02Suggestive
colitisOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.01Suggestive
gastric cancerOpen Targets
0.01Suggestive
prostate cancerOpen Targets
0.01Suggestive
Crohn's diseaseOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
breast neoplasmOpen Targets
0.01Suggestive
LeishmaniasisOpen Targets
0.01Suggestive
colorectal carcinomaOpen Targets
0.00Suggestive
cystic fibrosisOpen Targets
0.00Suggestive
cystic fibrosis-related diabetesOpen Targets
0.00Suggestive
sessile serrated polypOpen Targets
0.00Suggestive
prostate neoplasmOpen Targets
0.00Suggestive
squamous cell carcinomaOpen Targets
0.00Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KCNK10Shared pathway100%KCNK12Shared pathway100%LRRC38Shared pathway100%LRRC55Shared pathway100%LRRC52Shared pathway100%KCNMA1Protein interaction95%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
17%
Liver
0%
Heart
0%
Ovary
0%
Lung
0%
Gene Interaction Network
Click a node to explore
LRRC26KCNK10KCNK12LRRC38LRRC55LRRC52KCNMA1
PROTEIN STRUCTURE
Preparing viewer…
PDB8VAZ · 2.82 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.99LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF2.81 [1.44–1.99]
RankingsWhere LRRC26 stands among ~20K protein-coding genes
  • #16,211of 20,598
    Most Researched13
  • #17,833of 17,882
    Most Constrained (LOEUF)1.99
Genes detectedLRRC26
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
LRRC26 is a functional BK channel auxiliary γ subunit in arterial smooth muscle cells.
PMID: 24906643
Circ Res · 2014
1.00
2
Hyperglycaemia in cystic fibrosis adversely affects BK channel function critical for mucus clearance.
PMID: 32732330
Eur Respir J · 2021
0.90
3
BK potassium channel modulation by leucine-rich repeat-containing proteins.
PMID: 22547800
Proc Natl Acad Sci U S A · 2012
0.80
4
Airway Hydration, Apical K(+) Secretion, and the Large-Conductance, Ca(2+)-activated and Voltage-dependent Potassium (BK) Channel.
PMID: 27115952
Ann Am Thorac Soc · 2016
0.70
5
High-resolution structures illuminate key principles underlying voltage and LRRC26 regulation of Slo1 channels.
PMID: 38187713
bioRxiv · 2023
0.60