LRRC26

Summary

LRRC26 (leucine rich repeat containing 26, HGNC:31409) is a protein-coding gene on chromosome 9q34.3, encoding Leucine-rich repeat-containing protein 26 (Q2I0M4). Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha).

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.

Source: NCBI Gene 389816 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_001013653

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31409
Approved symbol	LRRC26
Name	leucine rich repeat containing 26
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	bA350O14.10, OTTHUMG00000020980
Ensembl gene	ENSG00000184709
Ensembl biotype	protein_coding
OMIM	613505
Entrez	389816

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000371542

RefSeq mRNA: 1 — MANE Select: NM_001013653 NM_001013653

CCDS: CCDS35184

Canonical transcript exons

ENST00000371542 — 2 exons

Exon	Start	End
ENSE00001322745	137168758	137169185
ENSE00001455484	137169271	137170051

Expression profiles

Bgee: expression breadth broad, 86 present calls, max score 97.48.

FANTOM5 (CAGE): breadth broad, TPM avg 9.9735 / max 1535.1198, expressed in 663 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103316	5.4876	609
103322	2.1432	154
103315	1.8332	339
103317	0.1942	99
103319	0.1115	70
103318	0.0900	35
103321	0.0585	20
103320	0.0552	17

Top tissues by expression

113 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	97.48	gold quality
saliva-secreting gland	UBERON:0001044	91.29	gold quality
minor salivary gland	UBERON:0001830	90.97	gold quality
mucosa of transverse colon	UBERON:0004991	88.92	gold quality
prostate gland	UBERON:0002367	84.26	gold quality
transverse colon	UBERON:0001157	71.75	gold quality
right uterine tube	UBERON:0001302	68.93	gold quality
small intestine Peyer’s patch	UBERON:0003454	67.38	gold quality
small intestine	UBERON:0002108	66.35	gold quality
granulocyte	CL:0000094	64.29	gold quality
duodenum	UBERON:0002114	63.74	gold quality
skin of leg	UBERON:0001511	63.24	gold quality
skin of abdomen	UBERON:0001416	63.19	gold quality
tonsil	UBERON:0002372	63.14	gold quality
zone of skin	UBERON:0000014	62.69	gold quality
body of stomach	UBERON:0001161	62.42	gold quality
fundus of stomach	UBERON:0001160	60.97	gold quality
stomach	UBERON:0000945	59.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	59.34	gold quality
leukocyte	CL:0000738	58.78	gold quality
intestine	UBERON:0000160	58.48	gold quality
monocyte	CL:0000576	58.29	gold quality
cerebellum	UBERON:0002037	58.18	gold quality
cerebellar cortex	UBERON:0002129	58.01	gold quality
cerebellar hemisphere	UBERON:0002245	57.75	gold quality
colon	UBERON:0001155	56.67	gold quality
esophagus mucosa	UBERON:0002469	56.18	gold quality
colonic epithelium	UBERON:0000397	55.90	gold quality
thoracic mammary gland	UBERON:0005200	55.17	gold quality
cortical plate	UBERON:0005343	53.93	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	528.21
E-CURD-114	yes	285.81
E-MTAB-10283	yes	265.62
E-MTAB-6701	yes	16.93
E-ANND-3	yes	14.43
E-MTAB-8410	yes	13.40
E-MTAB-8498	yes	12.83
E-HCAD-1	yes	10.42

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• CAPC transcripts have differential expression in cancer cell lines, and that S-CAPC is translated into a 7.5 kDa protein using a non-AUG start codon. (PMID:19250639)
• in non-excitable LNCaP prostate cancer cells, BK channels can be activated at negative voltages without rises in Ca(2+) through their complex with an auxiliary protein, leucine-rich repeat (LRR)-containing protein 26 (LRRC26) (PMID:20613726)
• The role of CAPC in the suppression of tumor growth and metastasis may be through its alteration of the tumor microenvironment. (PMID:21822313)
• Regulation of the Ca(2+)- and voltage-activated large conductance Ca(2+)-activated K(+) (BK) channel by associated gamma1-subunits, was investigated. (PMID:24639523)
• Suggest that BK channel modulation by auxiliary gamma subunits depends on intra- and/or juxta-membrane mechanisms. (PMID:26009545)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	lgi1a	ENSDARG00000020493
danio_rerio	lgi1b	ENSDARG00000058421
danio_rerio	si:ch211-191d15.2	ENSDARG00000092834
mus_musculus	Lrrc26	ENSMUSG00000026961
rattus_norvegicus	Lrrc26	ENSRNOG00000011457
drosophila_melanogaster	Con	FBGN0005775
drosophila_melanogaster	kek3	FBGN0028370
drosophila_melanogaster	CG18095	FBGN0028872
drosophila_melanogaster	CG7509	FBGN0035575
caenorhabditis_elegans	lron-9	WBGENE00011971
caenorhabditis_elegans		WBGENE00020649
caenorhabditis_elegans		WBGENE00022789

Paralogs (22): CHADL (ENSG00000100399), LGI1 (ENSG00000108231), LGR6 (ENSG00000133067), CHAD (ENSG00000136457), LRIG3 (ENSG00000139263), LGR5 (ENSG00000139292), LRIG1 (ENSG00000144749), LRRTM2 (ENSG00000146006), LRIT1 (ENSG00000148602), LGI2 (ENSG00000153012), LGI4 (ENSG00000153902), LRRC52 (ENSG00000162763), ELFN2 (ENSG00000166897), LGI3 (ENSG00000168481), LRG1 (ENSG00000171236), CPN2 (ENSG00000178772), LRIT3 (ENSG00000183423), LRIG2 (ENSG00000198799), LGR4 (ENSG00000205213), ELFN1 (ENSG00000225968), LRRC24 (ENSG00000254402), TRIL (ENSG00000255690)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 26 — Q2I0M4 (reviewed: Q2I0M4)

Alternative names: BK channel auxiliary gamma subunit LRRC26, Cytokeratin-associated protein in cancer

All UniProt accessions (1): Q2I0M4

UniProt curated annotations — full annotation on UniProt →

Function. Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha). Required for the conversion of BK alpha channels from a high-voltage to a low-voltage activated channel type in non-excitable cells. These are characterized by negative membrane voltages and constant low levels of calcium.

Subunit / interactions. Interacts with KCNMA1.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton.

Tissue specificity. Isoform 1 is expressed highly in normal prostate and salivary gland, very weakly in colon, pancreas, and intestine, and not at all in other tissues. Isoform 1 is expressed highly in many cancer cell lines and in breast cancer, pancreatic cancer and colon cancer. Isoform 2 is expressed in cancer cell lines.

Domain organisation. The transmembrane domain is necessary for interaction with KCNMA1.

Miscellaneous. Translation initiates from a UGC codon. It is unsure whether the initiator amino acid is a modified cysteine or a methionine. Could also be the result of a proteolytic cleavage from a longer precursor.

Isoforms (2)

UniProt ID	Names	Canonical?
Q2I0M4-1	1, L-CAPC	yes
Q2I0M4-2	2, S-CAPC

RefSeq proteins (1): NP_001013675* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF13855

UniProt features (46 total): strand 11, helix 8, repeat 5, disulfide bond 4, turn 4, domain 2, compositionally biased region 2, topological domain 2, splice variant 2, signal peptide 1, chain 1, region of interest 1, glycosylation site 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8VAZ	ELECTRON MICROSCOPY	2.82
7YO3	ELECTRON MICROSCOPY	3.1
8VAV	ELECTRON MICROSCOPY	3.13
7YNZ	ELECTRON MICROSCOPY	3.5
7YO0	ELECTRON MICROSCOPY	3.6
7YO1	ELECTRON MICROSCOPY	3.6
7YO4	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2I0M4-F1	82.72	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (4): 43–49, 47–57, 205–231, 207–253

Glycosylation sites (1): 147

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CATION_CHANNEL_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_POSITIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOCC_POTASSIUM_CHANNEL_COMPLEX, GOCC_CATION_CHANNEL_COMPLEX

GO Biological Process (4): potassium ion transmembrane transport (GO:0071805), positive regulation of voltage-gated potassium channel activity (GO:1903818), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (5): voltage-gated potassium channel activity (GO:0005249), potassium channel regulator activity (GO:0015459), transmembrane transporter binding (GO:0044325), potassium channel activator activity (GO:0099104), protein binding (GO:0005515)

GO Cellular Component (6): cytoskeleton (GO:0005856), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
potassium channel activity	3
cellular anatomical structure	2
potassium ion transport	1
monoatomic cation transmembrane transport	1
voltage-gated potassium channel activity	1
positive regulation of cation channel activity	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
voltage-gated monoatomic cation channel activity	1
ion channel regulator activity	1
protein binding	1
potassium channel regulator activity	1
channel activator activity	1
binding	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC26	KCNMA1	Q12791	960
LRRC26	KCNMB1	P78475	948
LRRC26	KRT1	P04264	712
LRRC26	KCNU1	A8MYU2	630
LRRC26	KCNMB4	Q86W47	591
LRRC26	LRRC38	Q5VT99	565
LRRC26	KCNMB3	Q9NPA1	506
LRRC26	LRRC52	Q8N7C0	502
LRRC26	LRRC58	Q96CX6	456
LRRC26	LRRC10	Q5BKY1	447
LRRC26	LRRC55	Q6ZSA7	409
LRRC26	BHLHE23	Q8NDY6	407
LRRC26	KCNMB2	Q9Y691	391
LRRC26	CYSRT1	A8MQ03	336
LRRC26	ZNF610	Q8N9Z0	323

IntAct

6 interactions, top by confidence:

A	B	Type	Score
LRRC26	KCNMA1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): LRRC26 (Affinity Capture-RNA)

ESM2 similar proteins: A2A9Q0, A5PKD8, B0BNK7, D2HFT7, D4ABX8, E9Q7T7, O75325, O94819, P0C7J6, P0DKB5, Q04785, Q13641, Q1RMS4, Q24JP5, Q28730, Q2I0M4, Q2WF71, Q460M5, Q4R8Y9, Q50LG9, Q5PQV5, Q6NUI6, Q6PJG9, Q6UKI2, Q7M6Z0, Q80TG9, Q80W15, Q80WD1, Q80XU8, Q86UN3, Q86WK7, Q8BHA1, Q8BLY3, Q8BNW9, Q8C013, Q8WX77, Q96PE1, Q9BE71, Q9BTN0, Q9BY71

Diamond homologs: A3KNN3, A6H789, A6H793, A6NJW4, A8WHP9, D4AC13, G5EFX6, O00468, O19045, O35367, O46390, O46403, O46542, O75093, O75094, O88186, O88279, O88280, O94813, P07585, P14770, P21793, P21809, P21810, P22457, P23515, P24014, P28653, P28654, P28675, P35376, P35379, P47799, P47853, P49059, P56400, P58681, P58874, P59034, P59035

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

36 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

212 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137169266:CTCA:C	donor_loss	1.0000
9:137169267:TCACC:T	donor_loss	1.0000
9:137169268:CACC:C	donor_loss	1.0000
9:137169269:ACCTG:A	donor_loss	1.0000
9:137169270:C:CT	donor_loss	1.0000
9:137169184:CT:C	acceptor_gain	0.9900
9:137169186:C:CC	acceptor_gain	0.9900
9:137169265:GCTCA:G	donor_loss	0.9900
9:137169267:TCA:T	donor_loss	0.9900
9:137169268:CAC:C	donor_loss	0.9900
9:137169269:A:AC	donor_gain	0.9900
9:137169269:ACCT:A	donor_loss	0.9900
9:137169270:C:CC	donor_gain	0.9900
9:137169270:CCTGA:C	donor_gain	0.9900
9:137169183:CCT:C	acceptor_gain	0.9700
9:137169184:CTC:C	acceptor_gain	0.9700
9:137169184:CTCTG:C	acceptor_loss	0.9700
9:137169185:TCT:T	acceptor_gain	0.9700
9:137169185:TCTGT:T	acceptor_loss	0.9700
9:137169186:CTGTG:C	acceptor_loss	0.9700
9:137169182:GCCT:G	acceptor_gain	0.9600
9:137169183:CCTC:C	acceptor_gain	0.9600
9:137169185:TC:T	acceptor_loss	0.9600
9:137169186:C:G	acceptor_gain	0.9600
9:137169181:GGCCT:G	acceptor_gain	0.9500
9:137169186:C:A	acceptor_gain	0.9500
9:137169270:CCTG:C	donor_gain	0.9500
9:137169549:T:TA	donor_gain	0.8800
9:137169194:C:CT	acceptor_gain	0.8700
9:137169196:C:CT	acceptor_gain	0.8600

AlphaMissense

2034 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137169031:G:C	S276R	0.992
9:137169031:G:T	S276R	0.992
9:137169033:T:G	S276R	0.992
9:137169672:A:C	F91C	0.992
9:137169558:T:A	N129I	0.987
9:137169629:G:C	N105K	0.987
9:137169629:G:T	N105K	0.987
9:137169415:T:A	N177Y	0.985
9:137169486:T:A	N153I	0.982
9:137169600:A:C	F115C	0.982
9:137169672:A:G	F91S	0.982
9:137169485:G:C	N153K	0.981
9:137169485:G:T	N153K	0.981
9:137169631:T:A	N105Y	0.980
9:137169702:T:A	N81I	0.980
9:137169335:C:A	W203C	0.979
9:137169335:C:G	W203C	0.979
9:137169528:A:C	F139C	0.979
9:137169414:T:A	N177I	0.978
9:137169487:T:A	N153Y	0.978
9:137169557:G:C	N129K	0.978
9:137169557:G:T	N129K	0.978
9:137169559:T:A	N129Y	0.978
9:137169600:A:G	F115S	0.977
9:137169501:A:T	L148H	0.975
9:137169630:T:A	N105I	0.975
9:137169701:G:C	N81K	0.975
9:137169701:G:T	N81K	0.975
9:137169703:T:A	N81Y	0.975
9:137169343:T:C	N201D	0.974

dbSNP variants (sampled 300 via entrez): RS1000093890 (9:137171173 C>A,G,T), RS1000146335 (9:137170959 A>G), RS1001159501 (9:137171962 G>A), RS1002169460 (9:137168707 C>A,G,T), RS1002712150 (9:137171930 G>A), RS1003445755 (9:137169121 G>A,C), RS1004061190 (9:137169130 A>G), RS1005479208 (9:137170070 C>G,T), RS1005678086 (9:137168297 C>A), RS1005848011 (9:137169632 C>G,T), RS1005965252 (9:137169824 G>A,C), RS1006676878 (9:137170713 G>A), RS1006702595 (9:137170157 G>A,C), RS1006972093 (9:137170496 G>A), RS1008742692 (9:137168420 ACTCGAGAG>A)

Disease associations

OMIM: gene MIM:613505 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, decreases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression	2
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Zoledronic Acid	decreases expression	1
Arsenic	decreases expression	1
Arsenicals	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects expression	1
Estradiol	affects cotreatment, decreases expression	1
Glucose	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases methylation	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.