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5 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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LRRC38
leucine rich repeat containing 38
Chromosome 1 · 1p36.21
NCBI Gene: 126755Ensembl: ENSG00000162494.6HGNC: HGNC:27005UniProt: Q5VT99
4PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
transmembrane transporter bindingvoltage-gated potassium channel complexpotassium channel activator activitypotassium ion transmembrane transportspinal cord injurycoronary artery calcificationneurodegenerative diseaseAlzheimer disease
✦AI Summary

LRRC38 is an auxiliary γ-subunit of large-conductance, voltage- and calcium-activated potassium (BK) channels that modulates their gating properties 1. As a leucine-rich repeat-containing membrane protein, LRRC38 produces a marked hyperpolarizing shift (~20 mV) in the BK channel's voltage dependence of activation in the absence of calcium, distinguishing it from its paralogs LRRC26, LRRC52, and LRRC55 which produce larger shifts 1. The modulatory function of LRRC38 depends on its transmembrane segment and adjacent intracellular positively charged amino acid clusters rather than its extracellular leucine-rich repeat domain 2. LRRC38 shows tissue-specific expression predominantly in secretory glands 1 and is preferentially expressed in skeletal muscle relative to other tissues 3. In cardiac tissue, LRRC38 is upregulated in the left ventricle and associated with cardiac muscle contraction and cellular component movement 4. The gene's role in regulating BK channel function across different tissues suggests physiological importance in controlling electrical signaling, though its specific clinical significance in heart failure and other pathologies requires further investigation.

Sources cited
1
LRRC38 is a BK channel γ-family auxiliary subunit producing ~20 mV hyperpolarizing shift in voltage dependence; expressed mainly in secretory glands
PMID: 22547800
2
BKγ subunit modulation depends on transmembrane segment and intracellular positively charged amino acid clusters
PMID: 26009545
3
LRRC38 is preferentially expressed in skeletal muscle and has associations with muscle disease
PMID: 34968235
4
LRRC38 is upregulated in left ventricle and associated with cardiac muscle contraction
PMID: 38461325
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
spinal cord injuryOpen Targets
0.30Weak
coronary artery calcificationOpen Targets
0.29Weak
neurodegenerative diseaseOpen Targets
0.27Weak
Alzheimer diseaseOpen Targets
0.23Weak
muscle crampOpen Targets
0.23Weak
Abnormality of refractionOpen Targets
0.20Weak
Familial exudative vitreoretinopathyOpen Targets
0.04Suggestive
primary familial polycythemia due to EPO receptor mutationOpen Targets
0.04Suggestive
hemolytic anemia due to diphosphoglycerate mutase deficiencyOpen Targets
0.04Suggestive
Pyruvate kinase hyperactivityOpen Targets
0.04Suggestive
erythrocytosis, familial, 6Open Targets
0.03Suggestive
erythrocytosis, familial, 3Open Targets
0.03Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.03Suggestive
exudative vitreoretinopathy 2, X-linkedOpen Targets
0.03Suggestive
erythrocytosis, familial, 4Open Targets
0.03Suggestive
ovarian neoplasmOpen Targets
0.03Suggestive
46,XX ovotesticular disorder of sex developmentOpen Targets
0.03Suggestive
tetragametic chimerismOpen Targets
0.03Suggestive
hemolytic anemia due to erythrocyte adenosine deaminase overproductionOpen Targets
0.03Suggestive
exudative vitreoretinopathyOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KCNK10Shared pathway100%KCNK12Shared pathway100%LRRC52Shared pathway100%LRRC26Shared pathway100%LRRC55Shared pathway84%KCNMB1Protein interaction73%
Tissue Expression6 tissues
Brain
100%
Heart
65%
Bone Marrow
24%
Ovary
15%
Lung
7%
Liver
0%
Gene Interaction Network
Click a node to explore
LRRC38KCNK10KCNK12LRRC52LRRC26LRRC55KCNMB1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q5VT99
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.61LoF Tolerant
pLIⓘ
0.85Intermediate
Observed/Expected LoF0.29 [0.15–0.61]
RankingsWhere LRRC38 stands among ~20K protein-coding genes
  • #18,608of 20,598
    Most Researched4
  • #4,261of 17,882
    Most Constrained (LOEUF)0.61 · top quartile
Genes detectedLRRC38
Sources retrieved5 papers
Response time—
📄 Sources
5
1
BK potassium channel modulation by leucine-rich repeat-containing proteins.
PMID: 22547800
Proc Natl Acad Sci U S A · 2012
1.00
2
Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure.
PMID: 38461325
Sci Rep · 2024
0.80
3
Epigenetics of Skeletal Muscle-Associated Genes in the
PMID: 34968235
Epigenomes · 2020
0.60
4
Molecular basis for differential modulation of BK channel voltage-dependent gating by auxiliary γ subunits.
PMID: 26009545
J Gen Physiol · 2015
0.40
5
Of BK regulation, painful connections, and versatile neuropeptide signaling.
PMID: 26009540
J Gen Physiol · 2015
0.20